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Caterina LONGO

Professore Ordinario
Dipartimento Chirurgico, Medico, Odontoiatrico e di Scienze Morfologiche con interesse Trapiantologico, Oncologico e di Medicina Rigenerativa

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Pubblicazioni

2024 - A rapidly growing nodule on the face during pregnancy [Articolo su rivista]
Lai, Michela; Piana, Simonetta; Mirra, Marica; Raucci, Margherita; Pampena, Riccardo; Longo, Caterina
abstract

: It is well known that adnexal skin tumors can simulate other cutaneous neoplasia and that various types of benign and malignant skin tumors can develop or modify during pregnancy. Here, we report a case of trichoblastoma mimicking a keratoacanthoma arising in a nevus sebaceous during pregnancy. Given its unique clinical and dermoscopic features, this case highlights the pivotal role of clinicopathological correlation in the diagnosis of adnexal tumors with an atypical clinical presentation.

2024 - BAUSSS biomarker further validated as a key risk staging tool for patients with primary melanoma [Articolo su rivista]
Dixon, Anthony J; Kyrgidis, Athanassios; Sladden, Michael; Nirenberg, Alexander; Steinman, Howard K; Smith, Harvey; Zachary, Christopher B; Anderson, Stuart; Leiter-Stöppke, Ulrike; Longo, Caterina; Apalla, Zoe
abstract

2024 - Confocal Assessment of Pigmented-Mucosal Lesions: A Monocentric, Retrospective Evaluation of Lip and Genital Area [Articolo su rivista]
Coco, Valeria; Cappilli, Simone; Di Stefani, Alessandro; Ricci, Costantino; Perino, Francesca; Di Nardo, Lucia; Longo, Caterina; Peris, Ketty
abstract

Introduction: Pigmentation of lip and/or genitalia is mainly due to the development of benign melanotic macules, with a less occurrence of melanocytic and other non-melanocytic lesions. Mucosal melanoma has worse prognosis compared with cutaneous counterpart, hence identification of atypical features for an early diagnosis is crucial. Objectives: The aim of this study was to report further data of confocal features characterizing pigmented mucosal lesions of genital area and of the lips and test the diagnostic role of the reflectance confocal microscopy (RCM)lip score. Methods: Clinical, dermoscopic and RCM images of histologically proven pigmented lesions, involving the genital area (vulva or glans penis) and lip, were retrospectively reviewed. RCM images were evaluated for malignant criteria, and statistical analysis was conducted for categorical variables. Results: Seventy pigmented lesions were included in the study and divided into two groups based on the body area location: lip (17) and genital area (53). Architectural disarray (P = 0.002), dendritic (P = 0.031) and roundish cells in epidermis (P < 0.0001), interpapillary dendritic cells (P = 0.039) and junctional atypical cells (P = 0.002) were associated to genital melanoma. Melanoma involving the lip was characterized by roundish cells in epidermis, a criterion found in one labial benign lesion, only (P = 0.005). Main limitations of the study are the inclusion of low melanomas and the presence of epidermal dendritic cells in melanosis and melanoma, as a confusing factor in imaging. Conclusions: Dermatologists should consider confocal microscopy as an adjunctive tool to dermoscopy in the differential diagnosis of pigmented mucosal lesions, especially in presence of clinical and dermoscopic findings suspicious for malignancy.

2024 - Dermatoscopy and reflectance confocal microscopy for basal cell carcinoma diagnosis and diagnosis prediction score: A prospective and multicenter study on 1005 lesions [Articolo su rivista]
Longo, Caterina; Guida, Stefania; Mirra, Marica; Pampena, Riccardo; Ciardo, Silvana; Bassoli, Sara; Casari, Alice; Rongioletti, Franco; Spadafora, Marco; Chester, Johanna; Kaleci, Shaniko; Lai, Michela; Magi, Serena; Mazzoni, Laura; Farnetani, Francesca; Stanganelli, Ignazio; Pellacani, Giovanni
abstract

Background: Basal cell carcinoma (BCC) is usually diagnosed by clinical and dermatoscopy examination, but diagnostic accuracy may be suboptimal. Reflectance confocal microscopy (RCM) imaging increases skin cancer diagnostic accuracy. Objective: To evaluate additional benefit in diagnostic accuracy of handheld RCM in a prospective controlled clinical setting. Methods: A prospective, multicenter study in 3 skin cancer reference centers in Italy enrolling consecutive lesions with clinical-dermatoscopic suspicion of BCC (ClinicalTrials.gov: NCT04789421). Results: A total of 1005 lesions were included, of which 474 histopathologically confirmed versus 531 diagnosed by clinical-dermatoscopic-RCM correlation, confirmed with 2 years of follow-up. Specifically, 740 were confirmed BCCs. Sensitivity and specificity for dermatoscopy alone was 93.2% (95% CI, 91.2-94.9) and 51.7% (95% CI, 45.5-57.9); positive predictive value was 84.4 (95% CI, 81.7-86.8) and negative predictive value 73.3 (95% CI, 66.3-79.5). Adjunctive RCM reported higher rates: 97.8 (95% CI, 96.5-98.8) sensitivity and 86.8 (95% CI, 82.1-90.6) specificity, with positive predictive value of 95.4 (95% CI, 93.6-96.8) and negative predictive value 93.5 (95% CI, 89.7-96.2). Limitations: Study conducted in a single country. Conclusions: Adjunctive handheld RCM assessment of lesions clinically suspicious for BCC permits higher diagnostic accuracy with minimal false negative lesions.

2024 - Dermoscopic, Histological, Confocal Microscopy Correlation of Atypical-Dysplastic Melanocytic Nevi [Articolo su rivista]
Cantisani, Carmen; Ambrosio, Luca; Annessi, Emanuele; Longo, Caterina; Farnetani, Francesca; Pezzini, Claudia; Condorelli, Alessandra; Annessi, Giorgio; Bonetti, Luca Reggiani; Guida, Stefania; Cota, Carlo; Tammaro, Antonella; Chello, Camilla; Pellacani, Giovanni
abstract

Introduction: The term "atypical melanocytic nevus" (AMN) is used as a synonym for dysplastic nevus (DN) in clinical practice. Although the criteria for diagnosis of AMN/DN by the Agency for Research on Cancer helps to differentiate AMN/DN from common acquired nevi, they do not have high degrees of specificity, as they are similar to those used for the diagnosis of melanoma. Objectives: In this retrospective study we evaluated the correlation and diagnostic concordance of dermoscopy, confocal microscopy, and histological examination in 50 AMN. Methods: A graded scale was used to compare histological examination with dermoscopy and confocal microscopy. Low magnification histological images of only the central part of lesions were examined. This allowed histological diagnoses based almost exclusively on architectural criteria instead of simultaneously architectural and cytological, as in the global histological examination. Results: Our data demonstrate that the diagnostic accuracy of dermoscopy and confocal microscopy diagnosis of the clinical aspects of AMN/DN as nevi or melanomas tends to be equivalent, being fair for nevi and excellent for melanomas. The total percentage of AMN suggested that the accuracy of confocal microscopy in the diagnosis of melanoma (86.7%) is greater than that of dermoscopy (73.3%). Conclusions: This study demonstrated that diagnostic assessments of AMN/DN by dermoscopy and confocal microscopy are accurate and often coincide with those of histological examination and that their combined use helps to better manage and monitor these patients by facilitating early detection of melanomas and reducing unnecessary excisions of benign melanocytic lesions.

2024 - Diagnostic Imaging of Agminated Blue Lesions and Blue Lesions with Satellitosis: Case Series with a Concise Review of the Current Literature [Articolo su rivista]
Cantisani, Carmen; Paolino, Giovanni; Di Guardo, Antonio; Gomes, Vito; Carugno, Andrea; Greco, Maria Elisabetta; Musolff, Noah; Azzella, Giulia; Rossi, Giovanni; Soda, Giuseppe; Longo, Caterina; Pellacani, Giovanni
abstract

Background: Agmination and/or satellitosis in pigmented blue lesions is a phenomenon rarely mentioned in the literature and not well known. This phenomenon can be expressed by several benign and malignant pigmented blue lesions, such as blue nevi, Spitz nevi, melanocytoma and melanoma. On this spectrum, dermoscopy, reflectance confocal microscopy (RCM) and dynamic Optical coherence tomography (D-OCT) represent non-invasive imaging technologies, which may help clinicians in the diagnosis of melanoma and non-melanoma skin cancers in daily clinical practice. Methods: Currently, in the literature there is a lack of new data about agminated blue lesions and blues lesions with satellitosis, as well as the lack of a recent and updated review of the literature about this topic. Therefore, considering that clinicians must be confident with the diagnosis of these rare skin lesions, we decided to carry out this work. Results: In this paper, four new cases of agminated pigmented cutaneous lesions were described. Moreover, a review of the current literature on this topic was performed. Conclusions: A clinical-pathological correlation is often needed to reach a correct diagnosis; currently, dermoscopy and non-invasive diagnostic techniques, such as reflectance confocal microscopy and optical coherence tomography, due to the depth of these skin lesions in the dermis, can only make a partial and limited contribution.

2024 - Melanocortin-1 receptor (MC1R): a review for dermatologists [Articolo su rivista]
Guida, Stefania; Puig, Susana; DI Resta, Chiara; Sallustio, Fabio; Mangano, Eleonora; Stabile, Giorgio; Longo, Caterina; Pellacani, Giovanni; Guida, Gabriella; Rongioletti, Franco
abstract

: Melanocortin-1 receptor (MC1R) and its variants have a pivotal role in melanin synthesis. However, MC1R has been associated to non-pigmentary pathways related to DNA-repair activities and inflammation. The aim of this review is to provide an up-to-date overview about the role of MC1R in the skin. Specifically, after summarizing the current knowledge about MC1R structure and polymorphisms, we report data concerning the correlation between MC1R, phenotypic traits, skin aging, other diseases and skin cancers and their risk assessment through genetic testing.

2024 - Sentinel lymph node biopsy is unreliable in predicting melanoma mortality for both younger and older patients [Articolo su rivista]
Dixon, Anthony J; Kyrgidis, Athanassios; Steinman, Howard K; Dixon, John B; Sladden, Michael; Garbe, Claus; Lallas, Aimilios; Zachary, Christopher B; Leiter-Stöppke, Ulrike; Smith, Harvey; Nirenberg, Alexander; Zouboulis, Christos C; Longo, Caterina; Argenziano, Giuseppe; Apalla, Zoe; Popescu, Catalin; Tzellos, Thrasyvoulos; Anderson, Stuart; Nanz, Lena; Cleaver, Lloyd; Thomas, J Meirion
abstract

Background: Melanoma disease patterns vary with patient age. Aim: To evaluate sentinel lymph node biopsy (SLNB) in managing melanoma at differing patient ages. Methods: Online prediction tools were applied to compare SLNB positivity (SLNB+ ) and survival risk at patient ages 20-80. Tübingen melanoma data were used to determine variations in the hazard ratio of SLNB+ for mortality at different patient ages. Results: Regardless of tumour thickness, predicted SLNB+ rates were markedly higher than mortality rates for 20-year-old patients. For 80-year-old patients, it is the opposite. Discussion: If 1000 20-year-olds with a 0.4 mm thickness non-ulcerated melanoma underwent SLNB, 100 would likely be positive. If all 100 were to be offered adjuvant drug therapy (ADT), fewer than three more melanoma deaths in those 1000 patients would be avoided. In total, 97 patients would have received medication they may never have needed. If 1000 80-year-olds with a 3 mm thickness non-ulcerated melanoma underwent SLNB, only 40 would likely be positive. In total, 274 patients would be predicted to die of melanoma, 245 being SLNB negative and 29 SLNB+ . ADT linked to SLNB+ could deny treatment to 89% of these high-risk patients. Limitations: The authors relied on published risk data. Conclusion: SLNB has poor specificity at predicting mortality in young melanoma patients and poor sensitivity in older patients. SLNB is not indicated in managing cutaneous melanoma for patients under 40 or over 60 years of age. Many such patients could be managed with wide local excision alone in their clinician's office-based practice. For all cutaneous melanoma patients at all ages, linking ADT to BAUSSS biomarker, (an algorithm of Breslow thickness, age, ulceration, subtype, sex and Site) rather than SLNB+ is likely more appropriate. BAUSSS provides a more accurate melanoma-specific mortality risk assessment for patients without burdening them with added surgery, hospitalization, costs or morbidity risk.

2023 - A reinforcement learning model for AI-based decision support in skin cancer [Articolo su rivista]
Barata, Catarina; Rotemberg, Veronica; Codella, Noel C F; Tschandl, Philipp; Rinner, Christoph; Akay, Bengu Nisa; Apalla, Zoe; Argenziano, Giuseppe; Halpern, Allan; Lallas, Aimilios; Longo, Caterina; Malvehy, Josep; Puig, Susana; Rosendahl, Cliff; Soyer, H Peter; Zalaudek, Iris; Kittler, Harald
abstract

: We investigated whether human preferences hold the potential to improve diagnostic artificial intelligence (AI)-based decision support using skin cancer diagnosis as a use case. We utilized nonuniform rewards and penalties based on expert-generated tables, balancing the benefits and harms of various diagnostic errors, which were applied using reinforcement learning. Compared with supervised learning, the reinforcement learning model improved the sensitivity for melanoma from 61.4% to 79.5% (95% confidence interval (CI): 73.5-85.6%) and for basal cell carcinoma from 79.4% to 87.1% (95% CI: 80.3-93.9%). AI overconfidence was also reduced while simultaneously maintaining accuracy. Reinforcement learning increased the rate of correct diagnoses made by dermatologists by 12.0% (95% CI: 8.8-15.1%) and improved the rate of optimal management decisions from 57.4% to 65.3% (95% CI: 61.7-68.9%). We further demonstrated that the reward-adjusted reinforcement learning model and a threshold-based model outperformed naïve supervised learning in various clinical scenarios. Our findings suggest the potential for incorporating human preferences into image-based diagnostic algorithms.

2023 - A risk-scoring model for the differential diagnosis of lentigo maligna and other atypical pigmented facial lesions of the face: The facial iDScore [Articolo su rivista]
Tognetti, Linda; Cartocci, Alessandra; Żychowska, Magdalena; Savarese, Imma; Cinotti, Elisa; Pizzichetta, Maria Antonietta; Moscarella, Elvira; Longo, Caterina; Farnetani, Francesca; Guida, Stefania; Paoli, John; Lallas, Aimilios; Tiodorovic, Danica; Stanganelli, Ignazio; Magi, Serena; Dika, Emi; Zalaudek, Iris; Suppa, Mariano; Argenziano, Giuseppe; Pellacani, Giovanni; Perrot, Jean Luc; Miracapillo, Chiara; Rubegni, Giovanni; Cevenini, Gabriele; Rubegni, Pietro
abstract

BackgroundDue to progressive ageing of the population, the incidence of facial lentigo maligna (LM) of the face is increasing. Many benign simulators of LM and LMM, known as atypical pigmented facial lesions (aPFLs-pigmented actinic keratosis, solar lentigo, seborrheic keratosis, seborrheic-lichenoid keratosis, atypical nevus) may be found on photodamaged skin. This generates many diagnostic issues and increases the number of biopsies, with a subsequent impact on aesthetic outcome and health insurance costs. ObjectivesOur aim was to develop a risk-scoring classifier-based algorithm to estimate the probability of an aPFL being malignant. A second aim was to compare its diagnostic accuracy with that of dermoscopists so as to define the advantages of using the model in patient management. Materials and MethodsA total of 154 dermatologists analysed 1111 aPFLs and their management in a teledermatology setting: They performed pattern analysis, gave an intuitive clinical diagnosis and proposed lesion management options (follow-up/reflectance confocal microscopy/biopsy). Each case was composed of a dermoscopic and/or clinical picture plus metadata (histology, age, sex, location, diameter). The risk-scoring classifier was developed and tested on this dataset and then validated on 86 additional aPFLs. ResultsThe facial Integrated Dermoscopic Score (iDScore) model consisted of seven dermoscopic variables and three objective parameters (diameter & GE; 8 mm, age & GE; 70 years, male sex); the score ranged from 0 to 16. In the testing set, the facial iDScore-aided diagnosis was more accurate (AUC = 0.79 [IC 95% 0.757-0.843]) than the intuitive diagnosis proposed by dermatologists (average of 43.5%). In the management study, the score model reduced the number of benign lesions sent for biopsies by 41.5% and increased the number of LM/LMM cases sent for reflectance confocal microscopy or biopsy instead of follow-up by 66%. ConclusionsThe facial iDScore can be proposed as a feasible tool for managing patients with aPFLs.

2023 - Advanced Cutaneous Squamous Cell Carcinoma: Italian Multicentric Retrospective Analysis of Patient Profiles and Therapeutic Approaches [Articolo su rivista]
Mannino, Maria; Piccerillo, Alfredo; Dika, Emi; Vaccari, Sabina; Quaglino, Pietro; Rubatto, Marco; Longo, Caterina; Borsari, Stefania; Pellacani, Giovanni; Fargnoli, Maria Concetta; Caponio, Chiara; Argenziano, Giuseppe; Briatico, Giulia; Bianchi, Luca; Di Raimondo, Cosimo; Calzavara Pinton, Pier Giacomo; Zalaudek, Iris; Di Stefani, Alessandro; Peris, Ketty
abstract

Background: Advanced cutaneous squamous cell carcinoma (aCSCC) represents an area of unmet clinical need, with no standardized treatments until the recent approval of immune checkpoint inhibitors (ICIs). Objectives: The aim of the study was to describe clinical characteristics and therapeutic strategies of a real-life Italian cohort of aCSCC patients managed at the beginning of cemiplimab approval as compassionate use in Italy. Methods: A multicenter retrospective study was performed by 10 Italian centers in the period January 1, 2018-May 31, 2020. Patients aged >= 18 years and diagnosed with aCSCC (locally aCSCC and metastatic CSCC) were eligible for the study. Analysis of patients' characteristics and treatment strategies was performed. Results: 239 patients were initially recruited in the study: 19 patients were excluded due to incomplete data collection, yielding a final cohort of 220 patients, of which 191 and 220 were included for patients' clinical characteristics and therapeutic intervention analysis, respectively. Median age at the time of diagnosis was 81 years (range: 72-86); nodal metastases were detected in 64/220 (29%) patients, and distant metastatic spread was reported in 33/220 (15%) patients. Most of our patients referred chronic occupational and/or recreational sun exposure, experienced >= 1 sunburn during their lifetime, never wore hats or used photoprotective filters, and presented with signs of cumulative sun damage (solar lentigines and/or actinic keratosis). Majority of our cohort received at least one intervention directed to the primary tumor (n = 212, 96.3%); surgery and radiotherapy were the most common therapeutic choices. Immunotherapy was administered to a small number of patients as compassionate use, especially in the metastatic setting. Conclusions: Our study outlines the complex and heterogeneous clinical and therapeutic landscape of aCSCC patients at the beginning of ICI era, highlighting the need of a standardized care for this fragile and high-need patient population.

2023 - Blue skin: intravascular melanoma metastasis detected by means of dermoscopy [Articolo su rivista]
Zaffonato, M; Moscarella, E; Piana, S; Banzi, M; Lai, M; Argenziano, G; Longo, C
abstract

2023 - Capillaritis as cutaneous adverse reaction to SARS-COV-2 primary and booster vaccination: A series of eight cases [Articolo su rivista]
Di Bartolomeo, Luca; Vaccaro, Federico; Borgia, Francesco; Lentini, Maria; Longo, Caterina; Vaccaro, Mario
abstract

2023 - Case Report: Sequential postzygotic HRAS mutation and gains of the paternal chromosome 11 carrying the mutated allele in a patient with epidermal nevus and rhabdomyosarcoma: evidence of a multiple-hit mechanism involving HRAS in oncogenic transformation [Articolo su rivista]
Zuntini, Roberta; Cattani, Chiara; Pedace, Lucia; Miele, Evelina; Caraffi, Stefano Giuseppe; Gardini, Stefano; Ficarelli, Elena; Pizzi, Simone; Radio, Francesca Clementina; Barone, Angelica; Piana, Simonetta; Bertolini, Patrizia; Corradi, Domenico; Marinelli, Maria; Longo, Caterina; Motolese, Alberico; Zuffardi, Orsetta; Tartaglia, Marco; Garavelli, Livia
abstract

We report a 7-year-old boy born with epidermal nevi (EN) arranged according to Blaschko's lines involving the face and head, right upper limb, chest, and left lower limb, who developed a left paratesticular embryonal rhabdomyosarcoma at 18 months of age. Parallel sequencing identified a gain-of-function variant (c.37G>C, p.Gly13Arg) of HRAS in both epidermal nevus and tumor but not in leukocytes or buccal mucosal epithelial cells, indicating its postzygotic origin. The variant accounted for 33% and 92% of the total reads in the nevus and tumor DNA specimens, respectively, supporting additional somatic hits in the latter. DNA methylation (DNAm) profiling of the tumor documented a signature consistent with embryonal rhabdomyosarcoma and CNV array analysis inferred from the DNAm arrays and subsequent MLPA analysis demonstrated copy number gains of the entire paternal chromosome 11 carrying the mutated HRAS allele, likely as the result of paternal unidisomy followed by subsequent gain(s) of the paternal chromosome in the tumor. Other structural rearrangements were observed in the tumours, while no additional pathogenic variants affecting genes with role in the RAS-MAPK and PI3K-AKT-MTOR pathways were identified. Our findings provide further evidence of the contribution of "gene dosage" to the multistep process driving cell transformation associated with hyperactive HRAS function.

2023 - Clinical Review of Mucosal Melanoma: The 11-Year Experience of a Referral Center [Articolo su rivista]
Spadafora, Marco; Santandrea, Giacomo; Lai, Michela; Borsari, Stafania; Kaleci, Shaniko; Banzi, Chiara; Mandato, Vincenzo Dario; Pellacani, Giovanni; Piana, Simonetta; Longo, Caterina
abstract

Introduction: Mucosal melanoma is a rare neoplasm. Late diagnosis is caused by occult anatomic sites and scarcity of symptoms. Novel biological therapies have now become available. Demographic, therapeutical and survival records on mucosal melanoma are scarce. Objectives: To provide an 11-year retrospective clinical review of real-world data on mucosal melanomas managed in a tertiary referral center in Italy. Methods: We included patients with histopathological mucosal melanoma diagnoses from January 2011 to December 2021. Data were collected until the last known follow-up or death. Survival analysis was performed. Results: Among 33 patients, we found 9 sinonasal, 13 anorectal and 11 urogenital mucosal melanomas (median age 82, females 66.7%). Eighteen cases (54.5%) presented with metastasis (p<0.05). In the urogenital subgroup, only 4 patients (36.4%) had metastasis at diagnosis, all in regional lymph nodes. Sinonasal melanomas were surgically managed with a debulking procedure (44.4%); every case of anorectal and urogenital melanomas underwent radical surgery (30.8% and 45.5%). Fifteen patients were treated with biological therapy (p<0.05). Radiation therapy was used in all melanomas of the sinonasal region (p<0.05). Overall survival was longer for urogenital melanomas (26 months). Univariate analysis showed an increased hazard ratio for death in patients with metastasis. A negative prognostic value of metastatic status was reported by the multivariate model, while administration of first-line immunotherapy demonstrated a protective role. Conclusions: At diagnosis, the absence of metastatic disease is the most relevant factor that influences the survival of mucosal melanomas. Moreover, the use of immunotherapy might prolong the survival of metastatic mucosal melanoma patients.

2023 - Clinical characteristics of an Italian patient population with advanced BCC and real-life evaluation of HHI safety and effectiveness [Articolo su rivista]
Mannino, Maria; Piccerillo, Alfredo; Fabbrocini, Gabriella; Quaglino, Pietro; Argenziano, Giuseppe; Dika, Emi; Ascierto, Paolo Antonio; Pellacani, Giovanni; Longo, Caterina; Fargnoli, Maria Concetta; Bianchi, Luca; Calzavara-Pinton, Piergiacomo; Zalaudek, Iris; Fava, Paolo; Scalvenzi, Massimiliano; Bocchino, Enrico; Di Stefani, Alessandro; Peris, Ketty
abstract

Background: Advanced basal cell carcinoma (aBCC) represents a complex and clinically heterogeneous group of lesions for which curative surgery and/or radiotherapy is unlikely. Systemic therapy with hedgehog pathway inhibitors (HHI) changed the treatment landscape for this complex patient population.Objectives: to describe the clinical characteristics of a real-life Italian cohort diagnosed with aBCC, and to investigate effectiveness and safety of HHI.Methods: a multicenter observational study was performed by twelve Italian centers in the period January 1, 2016 - October 15, 2022. Patients aged >= 18 years and diagnosed with aBCC (locally advanced and metastatic BCC) were eligible for the study. Methods for investigating tumor response to HHI included clinical and dermatoscopic evaluation, radiological imaging, and histopathology. For HHI safety assessment, therapy-related adverse events (AEs) were reported and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.Results: we enrolled 178 patients under treatment with HHI: 126 (70.8%) and 52 patients (29.2%) received sonidegib and vismodegib, respectively. Comprehensive data on HHI effectiveness and disease outcome was available for 132 (74.1%) of 178 patients: 129 patients had a diagnosis of locally advanced BCC (laBCC) (n=84, sonidegib; n=45, vismodegib), and 3 patients of metastatic BCC (mBCC) (n=2, vismodegib; n=1, sonidegib, off-label). Objective response rate (ORR) was 76.7% (95% CI: 82.3-68.7) and 33.3% (95% CI: 88.2-1.7) for laBCC (CR: 43/129; PR: 56/129) and mBCC (CR: 0/3; PR: 1/3), respectively. High-risk aBCC histopathological subtypes and occurrence of >2 therapy-related AEs were significantly associated with non-response to HHI therapy [(OR: 2.61; 95% CI: 1.09-6.05; p:0.03) and (OR: 2.74; 95% CI: 1.03-7.9; p:0.04)], respectively. Majority of our cohort (54.5%) developed at least 1 therapy-related AE, most of which were mild-moderate in severity.Conclusions: our results demonstrate the effectiveness and safety profile of HHI and confirm the reproducibility of pivotal trial results in real-life clinical setting.

2023 - Congenital Multiple Nevoid Hypertrichosis [Articolo su rivista]
Lippolis, Nicola; Curti, Alex; Longo, Caterina; Di Lernia, Vito
abstract

2023 - Delphi Consensus Among International Experts on the Diagnosis, Management, and Surveillance for Lentigo Maligna [Articolo su rivista]
Longo, Caterina; Navarrete-Dechent, Cristian; Tschandl, Philipp; Apalla, Zoe; Argenziano, Giuseppe; Braun, Ralph P; Bataille, Veronique; Cabo, Horacio; Hoffmann-Wellhenhof, Rainer; Forsea, Ana Maria; Garbe, Claus; Guitera, Pascale; Raimond, Karls; Marghoob, Ashfaq A; Malvehy, Josep; Del Marmol, Veronique; Moreno, David; Nehal, Kishwer S; Nagore, Eduardo; Paoli, John; Pellacani, Giovanni; Peris, Ketty; Puig, Susana; Soyer, H Peter; Swetter, Susan; Stratigos, Alexander; Stolz, Wilhelm; Thomas, Luc; Tiodorovic, Danica; Zalaudek, Iris; Kittler, Harald; Lallas, Aimilios
abstract

Introduction: Melanoma of the lentigo maligna (LM) type is challenging. There is lack of consensus on the optimal diagnosis, treatment, and follow-up. Objectives: To obtain general consensus on the diagnosis, treatment, and follow-up for LM. Methods: A modified Delphi method was used. The invited participants were either members of the International Dermoscopy Society, academic experts, or authors of published articles relating to skin cancer and melanoma. Participants were required to respond across three rounds using a 4-point Likert scale). Consensus was defined as >75% of participants agreeing/strongly agreeing or disagreeing/strongly disagreeing. Results: Of the 31 experts invited to participate in this Delphi study, 29 participants completed Round 1 (89.9% response rate), 25/31 completed Round 2 (77.5% response rate), and 25/31 completed Round 3 (77.5% response rate). Experts agreed that LM diagnosis should be based on a clinical and dermatoscopic approach (92%) followed by a biopsy. The most appropriate primary treatment of LM was deemed to be margin-controlled surgery (83.3%), although non-surgical modalities, especially imiquimod, were commonly used either as alternative off-label primary treatment in selected patients or as adjuvant therapy following surgery; 62% participants responded life-long clinical follow-up was needed for LM. Conclusions: Clinical and histological diagnosis of LM is challenging and should be based on macroscopic, dermatoscopic, and RCM examination followed by a biopsy. Different treatment modalities and follow-up should be carefully discussed with the patient.

2023 - Dermoscopic features of trichoepithelioma: A multicentre observational case-control study conducted by the International Dermoscopy Society [Articolo su rivista]
Longo, Caterina; Lippolis, Nicola; Lai, Michela; Spadafora, Marco; Kaleci, Shaniko; Condorelli, Alessandra Grazia; Lombardi, Mara; Pampena, Riccardo; Argenziano, Giuseppe; Nazzaro, Gianluca; Scalvenzi, Massimiliano; Akay, Bengü Nisa; Broganelli, Paolo; Fargnoli, Maria Concetta; Paoli, John; Yélamos, Oriol; Pellacani, Giovanni; Borsari, Stefania; Lallas, Aimilios
abstract

2023 - Dermoscopy of atypical pigmented lesions of the face: Variation according to facial areas [Articolo su rivista]
Tognetti, Linda; Cartocci, Alessandra; Cinotti, Elisa; D'Onghia, Martina; Żychowska, Magdalena; Moscarella, Elvira; Dika, Emi; Farnetani, Francesca; Guida, Stefania; Paoli, John; Lallas, Aimilios; Tiodorovic, Danica; Stanganelli, Ignazio; Longo, Caterina; Suppa, Mariano; Zalaudek, Iris; Argenziano, Giuseppe; Perrot, Jean Luc; Rubegni, Giovanni; Cataldo, Gennaro; Rubegni, Pietro
abstract

Atypical pigmented facial lesions (aPFLs)-including lentigo maligna (LM) and lentigo maligna melanoma (LMM), solar lentigo (SL), pigmented actinic keratosis (PAK), atypical nevi (AN), seborrheic keratosis (SK) and lichen planus-like keratosis (LPLK)-can exhibit clinical and dermoscopic overlapping features. We aimed to investigate if and how 14 dermoscopic features suggestive for the aforementioned aPFLs vary according to six facial sites among 1197 aPFLs cases (excised to rule out malignancy) along with lesion and patients' metadata. According to distribution and association analysis, aPFLs on the forehead of a male patient aged > 69 years displaying the obliterated follicular openings pattern, appear to be more at risk of malignancy. Of converse, aPFLs of the orbital/cheek/nose area with evident and regular follicular openings with diameter < 10 mm in a female aged below 68 are probably benign. The obliterated follicular openings, keratin plugs, evident and regular follicular openings and target-like pattern features differed significantly among six facial areas in all aPFLs cases. Lesion of the nose may show both features suggestive of malignancy and benignity (e.g. many SL and PAK may display target-like pattern and some LM/LMM cases display keratin plugs and evident and follicular openings), making these features less specific.

2023 - Dermoscopy of melanoma according to different body sites: Head and neck, trunk, limbs, nail, mucosal and acral [Articolo su rivista]
Longo, Caterina; Pampena, Riccardo; Moscarella, Elvira; Chester, Johanna; Starace, Michela; Cinotti, Elisa; Piraccini, Bianca Maria; Argenziano, Giuseppe; Peris, Ketty; Pellacani, Giovanni
abstract

Effective cancer screening detects early-stage tumours, leading to a lower incidence of late-stage disease over time. Dermoscopy is the gold standard for skin cancer diagnosis as diagnostic accuracy is improved compared to naked eye examinations. As melanoma dermoscopic features are often body site specific, awareness of common features according to their location is imperative for improved melanoma diagnostic accuracy. Several criteria have been identified according to the anatomical location of the melanoma. This review provides a comprehensive and contemporary review of dermoscopic melanoma criteria according to specific body sites, including frequently observed melanoma of the head/neck, trunk and limbs and special site melanomas, located on the nail, mucosal and acral region.

2023 - Development and Implementation of a Web-based International Registry Dedicated to Atypical Pigmented Skin Lesions of the Face: Teledermatologic Investigation on Epidemiology and Risk Factors [Articolo su rivista]
Tognetti, Linda; Cinotti, Elisa; Farnetani, Francesca; Lallas, Aimilios; Paoli, John; Longo, Caterina; Pampena, Riccardo; Moscarella, Elvira; Argenziano, Giuseppe; Tiodorovic, Danica; Stanganelli, Ignazio; Magi, Serena; Suppa, Mariano; Del Marmol, Veronique; Dika, Emi; Zelin, Enrico; Zalaudeck, Iris; Pizzichetta, Maria Antonietta; Pellacani, Giovanni; Perrot, Jean Luc; Bertello, Martina; Cataldo, Gennaro; Cevenini, Gabriele; Rubegni, Pietro; Cartocci, Alessandra
abstract

Background: Atypical pigmented facial lesions (aPFLs) often display clinical and dermoscopic equivocal and/or overlapping features, thus causing a challenging and delayed diagnosis and/or inappropriate excisions. No specific registry dedicated to aPFL paired with clinical data is available to date.Methods: The dataset is hosted on a specifically designed web platform. Each complete case was composed of the following data: (1) one dermoscopic picture; (2) one clinical picture; (3) two lesion data, that is, maximum diameter and facial location (e.g., orbital area/forehead/nose/cheek/chin/mouth); (4) patient's demographics: family history of melanoma, history of sunburns in childhood, phototype, pheomelanine, eyes/hair color, multiple nevi/dysplastic nevi on the body; and (5) acquisition device (videodermatoscope/camera-based/smartphone-based system).Results: A total of 11 dermatologic centers contributed to a final teledermoscopy database of 1,197 aPFL with a distribution of 353 lentigo maligna (LM), 146 lentigo maligna melanoma (LMM), 231 pigmented actinic keratoses, 266 solar lentigo, 125 atypical nevi, 48 seborrheic keratosis, and 28 seborrheic-lichenoid keratoses. The cheek site was involved in half of aPFL cases (50%). Compared with those with the other aPFL cases, patients with LM/LMM were predominantly men, older (69.32 +/- 12.9 years on average vs. 62.69 +/- 14.51), exhibited larger lesions (11.88 +/- 7.74 mm average maximum diameter vs. 9.33 +/- 6.46 mm), and reported a positive history of sunburn in childhood.Conclusions: The iDScore facial dataset currently represents a precious source of data suitable for the design of diagnostic support tools based on risk scoring classifiers to help dermatologists in recognizing LM/LMM among challenging aPFL in clinical practice.

2023 - Diving Into the Blue: A Case of Melanoma Arising in a Giant Congenital Blue Nevus During Pregnancy [Articolo su rivista]
Curti, Alex; Piana, Simonetta; Banzi, Maria; Castagnetti, Fabio; Lai, Michela; Longo, Caterina
abstract

2023 - Ex vivo mapping of enhancer networks that define the transcriptional program driving melanoma metastasis [Articolo su rivista]
Manicardi, Veronica; Gugnoni, Mila; Sauta, Elisabetta; Donati, Benedetta; Vitale, Emanuele; Torricelli, Federica; Manzotti, Gloria; Piana, Simonetta; Longo, Caterina; Ghini, Francesco; Ciarrocchi, Alessia
abstract

: Mortality from vmelanoma is associated with metastatic disease, but the mechanisms leading to spreading of the cancer cells remain obscure. Spatial profiling revealed that melanoma is characterized by a high degree of heterogeneity, which is established by the ability of melanoma cells to switch between different phenotypical stages. This plasticity, likely a heritage from embryonic pathways, accounts for a relevant part of the metastatic potential of these lesions, and requires the rapid and efficient reorganization of the transcriptional landscape of melanoma cells. A large part of the non-coding genome cooperates to control gene expression, specifically through the activity of enhancers (ENHs). In this study, we aimed to identify ex vivo the network of active ENHs and to outline their cooperative interactions in supporting transcriptional adaptation during melanoma metastatic progression. We conducted a genome-wide analysis to map active ENHs distribution in a retrospective cohort of 39 melanoma patients, comparing the profiles obtained in primary (N = 19) and metastatic (N = 20) melanoma lesions. Unsupervised clustering showed that the profile for acetylated histone H3 at lysine 27 (H3K27ac) efficiently segregates lesions into three different clusters corresponding to progressive stages of the disease. We reconstructed the map of super-ENHs (SEs) and cooperative ENHs that associate with metastatic progression in melanoma, which showed that cooperation among regulatory elements is a mandatory requirement for transcriptional plasticity. We also showed that these elements carry out specialized and non-redundant functions, and indicated the existence of a hierarchical organization, with SEs on top as masterminds of the entire transcriptional program and classical ENHs as executors. By providing an innovative vision of how the chromatin landscape of melanoma works during metastatic spreading, our data also point out the need to integrate functional profiling in the analysis of cancer lesions to increase definition and improve interpretation of tumor heterogeneity.

2023 - Expert agreement on the presence and spatial localization of melanocytic features in dermoscopy [Articolo su rivista]
Liopyris, Konstantinos; Navarrete-Dechent, Cristian; Marchetti, Michael A; Rotemberg, Veronica; Apalla, Zoe; Argenziano, Giuseppe; Blum, Andreas; Braun, Ralph P; Carrera, Cristina; Codella, Noel C F; Combalia, Marc; Dusza, Stephen W; Gutman, David A; Helba, Brian; Hofmann-Wellenhof, Rainer; Jaimes, Natalia; Kittler, Harald; Kose, Kivanc; Lallas, Aimilios; Longo, Caterina; Malvehy, Josep; Menzies, Scott; Nelson, Kelly C; Paoli, John; Puig, Susana; Rabinovitz, Harold S; Rishpon, Ayelet; Russo, Teresa; Scope, Alon; Soyer, H Peter; Stein, Jennifer A; Stolz, Willhelm; Sgouros, Dimitrios; Stratigos, Alexander J; Swanson, David L; Thomas, Luc; Tschandl, Philipp; Zalaudek, Iris; Weber, Jochen; Halpern, Allan C; Marghoob, Ashfaq A
abstract

: Dermoscopy aids in melanoma detection; however, agreement on dermoscopic features, including those of high clinical relevance, remains poor. Herein we attempted to evaluate agreement among experts on 'exemplar images' not only for the presence of melanocytic-specific features but also for spatial localization. This was a cross-sectional, multicenter, observational study. Dermoscopy images exhibiting at least one of 31 melanocytic-specific features were submitted by 25 world experts as 'exemplars'. Using a web-based platform that allows for image mark-up of specific contrast-defined regions (superpixels), 20 expert readers annotated 248 dermoscopic images in collections of 62 images. Each collection was reviewed by five independent readers. A total of 4,507 feature observations were performed. Good-to-excellent agreement was found for 14 of 31 features (45.2%), with 8 achieving excellent agreement (Gwet's AC >0.75) and 7 of them being melanoma-specific features. These features were: 'Peppering /Granularity' (0.91); 'Shiny White Streaks' (0.89); 'Typical Pigment network' (0.83); 'Blotch Irregular' (0.82); 'Negative Network' (0.81); 'Irregular Globules' (0.78); 'Dotted Vessels' (0.77) and 'Blue Whitish Veil' (0.76). By utilizing an exemplar dataset, good-to-excellent agreement was found for 14 features that have previously been shown useful in discriminating nevi from melanoma. All images are public (www.isic-archive.com) and can be used for education, scientific communication and machine learning experiments.

2023 - Gamified Learning in Dermatology and Dermoscopy Education: A Paradigm Shift [Articolo su rivista]
Donoso, Francisca; Peirano, Dominga; Longo, Caterina; Apalla, Zoe; Lallas, Aimilios; Jaimes, Natalia; Navarrete-Dechent, Cristian
abstract

'Gamification' and 'serious games' are methodologies that use the principles of games to facilitate learning processes and the acquisition of skills and knowledge. Gamified learning has been increasingly used in dermatological education and dermatological meetings.Teaching methods in medical education have been changing. More recent teaching modalities have gone beyond the traditional delivery of knowledge, promoting learning motivation, and improving teaching and learning outcomes. 'Gamification' and 'serious games' are methodologies that use the principles of games to facilitate learning processes and the acquisition of skills and knowledge, thereby improving attitudes towards learning when compared with traditional teaching methods. As dermatology is a visual field, images are a key component of different teaching strategies. Likewise, dermoscopy, a noninvasive diagnostic technique that allows the visualization of structures within the epidermis and upper dermis, also uses images and pattern recognition strategies. A series of Apps using game-based strategy have been created to teach and facilitate dermoscopy learning; however, studies are required to demonstrate their effectiveness. This review summarizes the current evidence of game-based learning strategies in medical education, including dermatology and dermoscopy.

2023 - Improved methodology in determining melanoma mortality and selecting patients for immunotherapy [Articolo su rivista]
Dixon, A J; Steinman, H K; Kyrgidis, A; Smith, H; Sladden, M; Zouboulis, C; Argenziano, G; Apalla, Z; Lallas, A; Longo, C; Nirenberg, A; Popescu, C; Dixon, J B; Tzellos, T; Zachary, C; Cleaver, L; Anderson, S; Zagarella, S; Thomas, J M
abstract

2023 - Indications for adjuvant radiotherapy in high-risk squamous cell carcinoma with clear margins: a Delphi consensus [Articolo su rivista]
Moscarella, Elvira; Di Brizzi, Eugenia Veronica; Alpi, Paolo; Arcelli, Alessandra; Badellino, Serena; Bossi, Paolo; Calzavara-Pinton, Pier Giacomo; Di Stefani, Alessandro; Dika, Emi; Eibenschutz, Laura; Fargnoli, Maria Concetta; Bruno, Fionda; Gravina, Giovanni Luca; Grilli Leonulli, Barbara; Longo, Caterina; Lospalluti, Lucia; Nardone, Valerio; Pimpinelli, Nicola; Quaglino, Pietro; Queirolo, Paola; Rubegni, Pietro; Tagliaferri, Luca; Troiani, Teresa; Vavassori, Andrea; Argenziano, Giuseppe
abstract

2023 - Is reflectance confocal microscopy useful in the differential diagnosis of extra facial lentigo maligna? A retrospective multicentric case-control study [Articolo su rivista]
Licata, Gaetano; Brancaccio, Gabriella; Ronchi, Andrea; Borsari, Stefania; Longo, Caterina; Piana, Simonetta; Cinotti, Elisa; Dragotto, Martina; Rubegni, Pietro; Argenziano, Giuseppe; Moscarella, Elvira
abstract

Background: Extra facial lentigo maligna (EF-LM) arises outside the head and neck area. EF-LM presents the classic histological features of lentigo maligna. The dermoscopic aspects of EF-LM have been poorly studied. Objective: The primary aims of our study were to analyse and describe the clinical, dermoscopic and confocal microscopy features of a series of histologically confirmed EF-LM. Method: We conducted a retrospective and multicentric study. From our database, we selected 48 cases of thin melanomas on photodamaged skin with histological features of EF-LM of which clinical, dermoscopic and confocal microscopy images were available, and a control group of 45 lesions, that can be subjected to differential diagnosis such as solar lentigo, lichenoid keratosis, seborrheic keratosis and melanocytic nevi, of which dermoscopic and confocal microscope images were available. Results: Extra facial lentigo maligna had a higher prevalence of lentigo-like pigment patterns, angulated lines and zigzag structures. At confocal microscopy, LM-EF cases showed a higher prevalence of pagetoid spreading, round cells, dendritic cells in the epidermis, atypical cells at the dermo-epidermal junction, dendritic cells at the junction, meshwork pattern and elastosis. Our study shows that reflectance confocal microscopy (RCM) has a sensitivity of 90% and a specificity of 97% for the differential diagnosis of this type of melanoma. Conclusions: Extra facial lentigo maligna does not have the classic dermoscopic features of superficial spreading melanoma, the most observed dermoscopic criteria are angulated lines and lentigo-like pigment patterns without lentigo-like border. RCM can be a valuable imaging tool for the evaluation of all those suspicion skin lesions at dermoscopy highlighting cellular atypia suggestive for melanoma.

2023 - Laser Treatment Monitoring with Reflectance Confocal Microscopy [Articolo su rivista]
Guida, Stefania; Longo, Caterina; Amato, Simone; Rossi, Anthony M; Manfredini, Marco; Ciardo, Silvana; Spadafora, Marco; Nisticò, Steven P; Mercuri, Santo R; Rongioletti, Franco; Zerbinati, Nicola; Pellacani, Giovanni
abstract

Laser treatments have become popular in Dermatology. In parallel to technologic development enabling the availability of different laser wavelengths, non-invasive skin imaging techniques, such as reflectance confocal microscopy (RCM), have been used to explore morphologic and qualitative skin characteristics. Specifically, RCM can be applied to cosmetically sensitive skin areas such as the face, without the need for skin biopsies. For these reasons, apart from its current use in skin cancer diagnosis, our systematic review reveals how RCM can be employed in the field of laser treatment monitoring, being particularly suitable for the evaluation of variations in epidermis and dermis, and pigmentary and vascular characteristics of the skin. This systematic review article aims to provide an overview on current applications of RCM laser treatment monitoring, while describing RCM features identified for different applications. Studies on human subjects treated with laser treatments, monitored with RCM, were included in the current systematic review. Five groups of treatments were identified and described: skin rejuvenation, scar tissue, pigmentary disorders, vascular disorders and other. Interestingly, RCM can assist treatments with lasers targeting all chromophores in the skin and exploiting laser induced optical breakdown. Treatment monitoring encompasses assessment at baseline and examination of changes after treatment, therefore revealing details in morphologic alterations underlying different skin conditions and mechanisms of actions of laser therapy, as well as objectify results after treatment.

2023 - Lentigo maligna and lentigo maligna melanoma in patients younger than 50 years old: A multicentric international clinical-dermoscopic study [Articolo su rivista]
Longo, Caterina; Sticchi, Alberto; Curti, Alex; Kaleci, Shaniko; Moscarella, Elvira; Argenziano, Giuseppe; Thomas, Luc; Guitera, Pascale; Huang, Chen; Tiodorovic, Danika; Apalla, Zoe; Peris, Ketty; Del Regno, Laura; Guida, Stefania; Lallas, Aimilios; Kittler, Harald; Pellacani, Giovanni; Navarrete-Dechent, Cristian
abstract

Background: LM/LMM is usually diagnosed in elderly patients when it is a large lesion. However, it is important to detect it at an earlier stage to minimize the size of the surgical procedure. Objective: To determine the clinical, dermoscopic and confocal features of LM/LMM in patients <50 years old. Method: This study included cases of consecutively excised LM/LMM arising in patients younger than 50 years if clinical and dermoscopic images were available; confocal images were considered when present. Multicenter study involving tertiary referral centers for skin cancer management. Consecutive patients younger than 50 years with a complete set of clinical and dermoscopic images and histopathological diagnosis of LM/LMM. The aim of this study to define clinical and dermoscopic features related to young age group such as size, dermoscopic criteria and when available, confocal features. Results: A total of 85 LM/LMM of the face from 85 patients younger than 50 years were included in the study. A regression model showed a direct association with the size of the lesion (R2 = 0.08, p-value = 0.01) and with the number of dermoscopic criteria at diagnosis (R2 = 0.12, p-value < 0.01). In a multi variable analysis an increasing number of dermoscopic criteria was correlated with increased age of the patients (p-value < 0.01), while the presence of grey color was a predictor of a younger age at diagnosis (p-value = 0.03). RCM revealed the presence of melanoma diagnostic criteria in all cases (pagetoid cells and atypical nesting). Conclusions: LM is not a disease limited to the elderly as previously thought. LM presenting in young adults tends to be smaller and with fewer dermoscopic criteria making its diagnosis challenging. Careful evaluation of facial pigmented lesions prior to cosmetic procedures is mandatory to avoid incorrectly treating early LM as a benign lesion.

2023 - Melanoma in children: A systematic review and individual patient meta-analysis [Articolo su rivista]
Pampena, Riccardo; Piccolo, Vincenzo; Muscianese, Marta; Kyrgidis, Athanassios; Lai, Michela; Russo, Teresa; Briatico, Giulia; Di Brizzi, Eugenia Veronica; Cascone, Giovanni; Pellerone, Sebastiano; Longo, Caterina; Moscarella, Elvira; Argenziano, Giuseppe
abstract

The current evidence on paediatric melanoma is heterogeneous, especially regarding the prognosis of different histological subtypes. We sought to systematically review the evidence on paediatric melanoma, highlighting the major sources of heterogeneity and focusing on available data on single patients. A systematic search was performed from 1948 to 25 January 2021. Only studies reporting at least one case of cutaneous melanoma in patients aged <= 18 years were included. Unknown primary and uncertain malignant melanomas were excluded. Three couples of authors independently performed title/abstract screening and two different authors reviewed all the relevant full texts. The selected articles were manually cross-checked for overlapping data for qualitative synthesis. Subsequently data on single patients were extracted to perform a patient-level meta-analysis. PROSPERO registration number: CRD42021233248. The main outcomes were melanoma-specific survival (MSS) and progression-free survival (PFS) outcomes. Separate analyses were done of cases with complete information on histologic subtype, focusing on superficial spreading (SSM), nodular (NM) and spitzoid melanomas, as well as of those classified as de-novo (DNM) and acquired or congenital nevus-associated melanomas (NAM). The qualitative synthesis covered 266 studies; however, data on single patients were available from 213 studies including 1002 patients. Among histologic subtypes, NM had a lower MSS than both SSM and spitzoid melanoma, and a lower PFS than SSM. Spitzoid melanoma had a significantly higher progression risk than SSM and trended toward lower mortality. Focusing on nevus-associated status, DNM demonstrated better MSS after progression than congenital NAM, and no differences were highlighted in PFS. Our findings describe the existence of different biological patterns in paediatric melanoma. Specifically, spitzoid melanomas demonstrated intermediate behaviour between SSM and NM and showed a high risk of nodal progression but low mortality. This raises the question of whether spitzoid lesions are being over-diagnosed as melanoma in childhood.

2023 - Online prediction tools for melanoma survival: A comparison [Articolo su rivista]
Dixon, A; Steinman, H K; Kyrgidis, A; Smith, H; Sladden, M; Zouboulis, C; Argenziano, G; Apalla, Z; Lallas, A; Longo, C; Nirenberg, A; Popescu, C; Tzellos, T; Cleaver, L; Zachary, C; Anderson, S; Thomas, J M
abstract

BackgroundBreslow thickness, patient age and ulceration are the three most valuable clinical and pathological predictors of melanoma survival. A readily available reliable online tool that accurately considers these and other predictors could be valuable for clinicians managing melanoma patients. ObjectiveTo compare online melanoma survival prediction tools that request user input on clinical and pathological features. MethodsSearch engines were used to identify available predictive nomograms. For each, clinical and pathological predictors were compared. ResultsThree tools were identified. The American Joint Committee on Cancer tool inappropriately rated thin tumours as higher risk than intermediate tumours. The University of Louisville tool was found to have six shortcomings: a requirement for sentinel node biopsy, unavailable input of thin melanoma or patients over 70 years of age and less reliable hazard ratio calculations for age, ulceration and tumour thickness. The LifeMath.net tool was found to appropriately consider tumour thickness, ulceration, age, sex, site and tumour subtype in predicting survival. LimitationsThe authors did not have access to the base data used to compile various prediction tools. ConclusionThe LifeMath.net prediction tool is the most reliable for clinicians in counselling patients with newly diagnosed primary cutaneous melanoma regarding their survival prospects.

2023 - Skin ageing: Clinical aspects and in vivo microscopic patterns observed with reflectance confocal microscopy and optical coherence tomography [Articolo su rivista]
Pezzini, Claudia; Ciardo, Silvana; Guida, Stefania; Kaleci, Shaniko; Chester, Johanna; Casari, Alice; Manfredini, Marco; Longo, Caterina; Farnetani, Francesca; Brugués, Ariadna Ortiz; Pellacani, Giovanni
abstract

Few studies have combined high-resolution, non-invasive imaging, such as standardized clinical images, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), for age-related skin change characterization according to age groups. This study aimed to correlate clinical manifestations of ageing with skin cytoarchitectural background observed with high-resolution, non-invasive imaging according to age-related skin pattern distribution. A set of 140 non-pathological facial skin images were retrospectively retrieved from a research database. Subjects, aged between 20 and 89, were divided into 7 age groups. Clinical features were explored with VISIA, including hyperpigmentation, skin texture, wrinkles, pores and red areas, quantified and expressed as automated absolute scores. Previously described RCM and OCT epidermal and dermal features associated with ageing were investigated. All features were assessed for distribution and correlation among age groups. Significant direct correlations between age and clinical features were proven for cutaneous hyperpigmentation, skin texture, wrinkles and red areas. As age advances, RCM epidermal irregular honeycomb and mottled pigmentation are more frequently observed and collagen is more frequently coarse, huddled and curled, while the epidermis in OCT is thickened and the dermal density is decreased with more disrupted collagen fibres. RCM and OCT feature changes correlate directly and indirectly as well as correlating directly and indirectly with standardized clinical images. Clinical manifestations of ageing correlate with skin cytoarchitectural background observed with RCM and OCT. In conclusion, complimentary information between standardized clinical images and high-resolution, non-invasive imaging will assist in the development of future studies dedicated to skin ageing assessment and treatment effectiveness.

2023 - Synthesis of Brominated Lactones Related to Mycalin A: Selective Antiproliferative Activity on Metastatic Melanoma Cells and Inhibition of the Cell Migration [Articolo su rivista]
Capasso, Domenica; Marino, Paola; Di Gaetano, Sonia; Borbone, Nicola; Terracciano, Monica; Trani, Roberta; Longo, Caterina; Piccialli, Vincenzo
abstract

Starting from D-xylonolactone and D-ribonolactone, several five-membered bromolactones, related to the C1-C5 portion of mycalin A lactone, have been synthesized. The bromination of D-ribonolactone with HBr/AcOH, without a subsequent transesterification step, has been studied for the first time, giving us most of the acetylated lactones investigated in the present study. For each compound, where possible, both the C-3 alcohol and the corresponding acetate were prepared. Evaluation of their anti-tumor activity showed that all the acetates possess a good cytotoxicity towards human melanoma (A375), human cervical adenocarcinoma (HeLa) and human metastatic melanoma (WM266) cancer cells, comparable or even higher than that displayed by the original mycalin A lactone. Lactone acetates derived from D-ribonolactone showed the higher selectivity of action, exhibiting a strong cytotoxicity on all the tested tumor cells but only a limited toxicity on healthy human dermal fibroblast (HDF) cells, used as a control. Wound healing assays showed that two of these substances inhibit the migration of the WM266 cells.

2023 - The combination of oral and topical photoprotection with a standardized Polypodium leucotomos extract is beneficial against actinic keratosis [Articolo su rivista]
Pellacani, Giovanni; Peris, Ketty; Ciardo, Silvana; Pezzini, Claudia; Tambone, Sara; Farnetani, Francesca; Longo, Caterina; Chello, Camilla; González, Salvador
abstract

IntroductionThis study describes a prospective, multicentre, randomized controlled, open-label study with three arms aimed at studying the differences between: [Cnt], self-administered sun protection; [T], topical treatment; and [TO], topical + oral treatment; for the management of Actinic Keratosis (AK) in a cohort of subjects of advanced age displaying severe actinic damage (SAD). MethodsTreatments administered to groups [T] and [TO] had a common component, which is a botanical extract, Fernblock, with demonstrated photoprotective activity. ResultsIn total, 131 subjects were distributed randomly in the three groups, and followed up clinically at three separate time points, beginning of the study (t = 0) and after 6 and 12 months. Analysis of clinical data and examination using reflectance confocal microscopy (RCM) revealed that group [T] and [TO] displayed decreased clinical AK and field cancerization parameters, including the number of new lesions, and reduced the need for additional interventions in these patients. RCM revealed normalization of the keratinocyte layer. Improvements in AK and field cancerization parameters were greatest in the group [TO], suggesting that topical and oral photoprotection improves the clinical and anatomical outcome compared to control conditions. ConclusionsThe combination of topical and oral immune photoprotection provides an advantage compared to topical photoprotection alone.

2023 - Visualizing Touton Giant Cells Under Reflectance Confocal Microscopy in Two Cases of Juvenile Xanthogranuloma [Articolo su rivista]
Peirano, Dominga; Donoso, Francisca; Vargas, Sebastián; Hidalgo, Leonel; Feuerhake, Teo; Scope, Alon; Longo, Caterina; Navarrete-Dechent, Cristian
abstract

2022 - Characteristics and management of skin cancers in very elderly patients: A real-world challenge for clinicians [Articolo su rivista]
Lai, Michela; Pampena, Riccardo; Mirra, Marica; Raucci, Margherita; Benati, Elisa; Borsari, Stefania; Lombardi, Mara; Banzi, Maria; Castagnetti, Fabio; Palmieri, Tamara; Piana, Simonetta; Ramundo, Dafne; Pellacani, Giovanni; Longo, Caterina
abstract

The increase life expectancy led to an expected increase in skin cancer incidence in older patients. Their treatment can require a complex decision-making process. Limited data are available on characteristics, management and outcome of skin tumours in nonagenarian and centenarian patients. The aim of our study was to describe epidemiology, clinical-pathological features and treatment strategies of skin cancers in a cohort of patients aged >= 95 years. A total of 116 patients >= 95 years of age presented for the evaluation of 225 skin lesions (mean of 1.94 lesions per patient). The mean age was 97.4 years, 57.8% were women. Most patients had an ECOG score of 3 (49.3%) or 4 (32%). Lesions were mainly located on the head and neck area (74.2%), upper (7.1%) and lower (6,2%) limbs. The majority of patients presented with non-melanoma skin cancers (183/225; 81.3%), 25/225 (11.1%) had actinic keratosis, 5 (2.2%) melanoma and 2 (0.9%) atypical fibroxanthoma. Forty-eight lesions (21.3%) were treated with surgery, 58 (25.8%) with radiotherapy. The management of 73 lesion (32.4%) was discussed at the multidisciplinary tumour board meeting. One patient died for the progression of a squamous cell carcinoma; 74 patients died for causes unrelated to skin tumours, 36 are still alive after a mean follow-up of 27.27 months. This cohort study confirms that age is not per se a contraindication for treatment of skin cancers in elderly patients. Our results support the importance of a patient-centred care approach that should take into consideration patient's preferences, comorbidities, compliance and possible adverse events.

2022 - Clark level could be still a useful prognostic marker in scalp melanoma: a multicentric cross-sectional study [Articolo su rivista]
Brancaccio, Gabriella; Di Brizzi, Eugenia Veronica; Kittler, Harald; Lallas, Aimilios; Longo, Caterina; Malvehy, Josep; Moscarella, Elvira; Pellerone, Sebastiano; Puig, Susana; Ronchi, Andrea; Thomas, Luc; Argenziano, Giuseppe
abstract

2022 - Clinically unquestionable but histologically deceptive melanomas in acral skin grafts: PRAME confirms its role [Articolo su rivista]
Santandrea, Giacomo; Valli, Riccardo; Ragazzi, Moira; Castagnetti, Fabio; Lai, Michela; Longo, Caterina; Piana, Simonetta
abstract

The aim of this study was to investigate the role of PRAME in reducing the risk of an underestimation of tumour margins, in a consecutive series of acral melanomas recurring on skin grafts.

2022 - Comparative Analysis of PRAME Expression in 127 Acral and Nail Melanocytic Lesions [Articolo su rivista]
Santandrea, Giacomo; Valli, Riccardo; Zanetti, Eleonora; Ragazzi, Moira; Pampena, Riccardo; Longo, Caterina; Lai, Michela; Piana, Simonetta; Cesinaro, Anna M
abstract

: PRAME (PReferentially expressed Antigen in MElanoma), a cancer testis antigen expressed in low levels in gonadal, endometrial, and adrenal gland tissues, has been recently considered a valuable tool in the differential diagnosis between benign and malignant melanocytic lesions. The aim of the current study is to perform PRAME immunostaining on a large series of benign and malignant acral lesions to evaluate the reproducibility of data reported in the literature and to validate PRAME as an affordable tool in the differential diagnosis between benign and malignant acral melanocytic tumors. Immunohistochemical analysis for PRAME was performed in 127 benign and malignant acral and nail melanocytic lesions. To better correlate PRAME expression with the nature (benign vs. malignant) of the lesions, we categorized PRAME tumor cells percentage positivity and intensity in a cumulative score obtained by adding the quartile of positive tumor cells (0, 1+, 2+, 3+, 4+) to PRAME expression intensity in tumor cells (0, 1+, 2+, 3+). Adopting an arbitrary PRAME expression score of < 5 versus ≥5 resulted in a correct identification of 82.5% of benign and 87.1% of malignant lesions. PRAME immunohistochemistry demonstrated good sensitivity and specificity in the diagnosis of acral melanocytic lesions, however, in line with the previous literature, we identified a subset of challenging cases such as acral Spitz nevi, in situ melanomas, and small, thin, invasive melanomas in which PRAME did not correlate with morphologic features. This suggests that PRAME can be a valid tool to be incorporated in a diagnostic clinicopathologic algorithm, subject to morphologic characteristics.

2022 - Cutaneous Melanoma Systematic Diagnostic Workflows and Integrated Reflectance Confocal Microscopy Assessed with a Retrospective, Comparative Longitudinal (2009–2018) Study [Articolo su rivista]
Pellacani, G.; Farnetani, F.; Chester, J.; Kaleci, S.; Ciardo, S.; Bassoli, S.; Casari, A.; Longo, C.; Manfredini, M.; Cesinaro, A. M.; Giusti, F.; Iacuzio, A.; Migaldi, M.
abstract

Background: The increasing global burden of melanoma demands efficient health services. Accurate early melanoma diagnosis improves prognosis. Objectives: To assess melanoma prevention strategies and a systematic diagnostic-therapeutical workflow (improved patient access and high-performance technology integration) and estimate cost savings. Methods: Retrospective analysis of epidemiological data of an entire province over a 10-year period of all excised lesions suspicious for melanoma (melanoma or benign), registered according to excision location: reference hospital (DP) or other (NDP). A systematic diagnostic-therapeutical workflow, including direct patient access, primary care physician education and high-performance technology (reflectance confocal microscopy (RCM)) integration, was implemented. Impact was assessed with the number of lesions needed to excise (NNE). Results: From 40,832 suspicious lesions excised, 7.5% (n = 3054) were melanoma. There was a 279% increase in the number of melanomas excised (n = 203 (2009) to n = 567 (2018)). Identification precision improved more than 100% (5.1% in 2009 to 12.0% in 2018). After RCM implementation, NNE decreased almost 3-fold at DP and by half at NDP. Overall NNE for DP was significantly lower (NNE = 8) than for NDP (NNE = 20), p < 0.001. Cost savings amounted to EUR 1,476,392.00. Conclusions: Melanoma prevention strategies combined with systematic.

2022 - Dendritic cells in reflectance confocal microscopy are a clue for early melanoma diagnosis in extrafacial flat pigmented melanocytic lesions [Articolo su rivista]
Guiducci, L.; Kaleci, S.; Chester, J.; Longo, C.; Ciardo, S.; Farnetani, F.; Pellacani, G.
abstract

Differential diagnosis of extrafacial flat pigmented lesions with dermoscopic reticular and/or homogeneous pattern is challenging. Dendritic cells upon reflectance confocal microscopy (RCM) still represent a pitfall. This study aims to determine the role of dendritic cells upon RCM in the epidermis and dermo-epidermal junction (DEJ), together with common RCM features for melanoma and nevi, in dermoscopically equivocal extrafacial flat pigmented lesions. A retrospective evaluation of RCM images of melanocytic extrafacial flat pigmented lesions with reticular and/or homogeneous dermoscopic pattern and with histopathological diagnosis, was performed. A multivariate model of RCM features was used to obtain a score of independent risk factors. A total of 698 lesions were included. Increasing patient age, epidermal dendritic cells, many dendritic cells in the DEJ (>30%) and many (>5/mm2) round atypical cells were independent risk factors for melanoma. Edged papillae and melanophages were indicative of nevus. A score based on these features was developed to assist in melanoma differential diagnosis. The RCM observation of abundant (>30%) dendritic cells in the DEJ is highly suggestive of malignity. This independent risk factor should also be considered for improved differential diagnosis of extrafacial melanoma.

2022 - Dermatological and Dermoscopic Baselines in BRCA Mutation Carriers [Articolo su rivista]
Paolino, Giovanni; Pampena, Riccardo; Di Nicola, Matteo Riccardo; Longo, Caterina; Rognone, Alessia; Zambelli, Stefania; Bianchini, Giampaolo; Mercuri, Santo Raffaele
abstract

Breast cancer-associated genes 1 and 2 (BRCA1 and BRCA2) are tumor suppressor genes encoding a large protein that is involved in many essential biological processes. BRCA mutated patients show an increased risk to develop several malignancies, including cutaneous malignancies, although inconsistently across multiple studies. We carried out an observational study on the main dermatological and dermoscopic aspects in a population of patients with BRCA 1/2 mutations, to identify the main clinical and dermoscopical features in this class of patients. A total of 52 patients with BRCA mutations were included in the current analysis. Clinical, dermoscopical, and pathological data were obtained during the dermatologic visits. Out of the entire cohort, 67.3% of patients showed brown hairs and 63.5% of patients showed brown eyes, with phototype III as the most frequent phototype (69.2%). A total of 2.017 melanocytic lesions in all patients were analyzed; specifically, 40 patients (76.9%) showed a total number of nevi > 10, while regarding the main observed dermoscopic features, a prevalence of reticular pattern in 63% of cases was observed, followed by a mixed pattern in 19.2% of cases. Regarding the cutaneous examination, eruptive angiomas (eCAs) were the main dermatologic manifestations in 46.2% of patients. Out of 52 patients and during a follow-up of 24 months one patient developed an in situ melanoma. Interestingly, none of the patients with eCAs showed a TN > 10, highlighting an inverse correlation. To date, there is insufficient evidence to warrant increased surveillance in patients with BRCA mutations or with a positive family history for BRCA mutations, in the absence of standard cutaneous risk factors. Further studies with larger samples of patients are needed to better investigate dermatological and dermatoscopic features in BRCA mutation carriers.

2022 - Dermatoscopy of nodular/plaque-type primary cutaneous T- and B-cell lymphomas: A retrospective comparative study with pseudolymphomas and tumoral/inflammatory mimickers by the International Dermoscopy Society [Articolo su rivista]
Errichetti, Enzo; Geller, Shamir; Zalaudek, Iris; Longo, Caterina; Kyrgidis, Athanassios; Akay, Bengu Nisa; Piccolo, Vincenzo; Myskowski, Patricia; Vitiello, Paola; Russo, Teresa; Argenziano, Giuseppe; Sławińska, Martyna; Sokołowska-Wojdyło, Małgorzata; Sobjanek, Michał; Toncic, Ruzica Jurakic; Rados, Jaka; Drvar, Daniela Ledic; Ceovic, Romana; Kaminska-Winciorek, Grażyna; Zaballos, Pedro; Reggiani, Camilla; Kremic, Zorana; Lanssens, Sven; Güleç, Ayşe Tülin; Lobato-Berezo, Alejandro; Damiani, Giovanni; Maione, Vincenzo; Calzavara-Pinton, Piergiacomo; Sotiriou, Elena; Stinco, Giuseppe; Apalla, Zoe; Lallas, Aimilios
abstract

Limited data on dermatoscopy of nodular/plaque-type T-/B-cell primary cutaneous lymphomas (PCLs) is available.

2022 - Dermoscopic spectrum of mycosis fungoides: a retrospective observational study by the International Dermoscopy Society [Articolo su rivista]
Errichetti, Enzo; Apalla, Zoe; Geller, Shamir; Sławińska, Martyna; Kyrgidis, Athanassios; Kaminska-Winciorek, Grażyna; Jurakic Toncic, Ruzica; Bobos, Mattheos; Rados, Jaka; Ledic Drvar, Daniela; Ceovic, Romana; Akay, Bengu Nisa; Piccolo, Vincenzo; Myskowski, Patricia; Vitiello, Paola; Russo, Teresa; Argenziano, Giuseppe; Sokołowska-Wojdyło, Małgorzata; Sobjanek, Michał; Stoikovic-Filipovic, Jelena; Longo, Caterina; Pellacani, Giovanni; Stinco, Giuseppe; Lallas, Aimilios
abstract

Background: The dermoscopic features of classic patch stage mycosis fungoides (MF) have been described, but data on plaque and tumoral stage as well as rarer MF subtypes is limited. Objective: To evaluate dermoscopic morphology and dermoscopic-pathological correlations of classic MF stages and investigate dermoscopic features of MF variants. Methods: Patients with histopathologically confirmed lesions of classic MF (patch, plaque and tumoral stage) or folliculotropic, erythrodermic and poikilodermatous MF were included. Standardized evaluation of dermoscopic pictures of the included MF variants and comparative analysis and dermoscopic-pathological correlation assessment of different stages of classic MF were performed. Results: A total of 118 instances were included (75 classic MF, 26 folliculotropic MF, 9 erythrodermic MF, and 8 poikilodermatous MF). Linear/linear-curved vessels and white scales in the skin furrows were significantly associated with patch-stage MF, while clustered dotted vessels were related to plaque-stage MF and peripheral linear vessels with branches, ulceration and red globules separated by white lines to tumor-stage MF. Moreover, patchy white scales were significantly more common in patches and plaques compared to tumors, whereas focal bright white structureless areas were related to plaque and tumoral stage. Vessels histopathologically corresponded to dilated vascular structures in the dermis, orange structureless areas to either dermal hemosiderin (patch/plaque stage) or dense cellular infiltration (tumors), bright white lines/structureless areas to dermal fibrosis, and ulceration to loss of epidermis. The main dermoscopic findings of folliculotropic MF were lack of hairs, dilated follicles and follicular plugs, while erythrodermic MF was mainly characterized by linear/dotted vessels, patchy white scales and focal orange structureless areas and poikilodermatous MF by focal white and brown structureless areas, white patchy scales and brown reticular lines. Conclusion: Dermoscopy may allow a more precise characterization of classic MF and reveal clues suggestive of the main MF variants.

2022 - Dermoscopy of cutaneous adnexal tumours: a systematic review of the literature [Articolo su rivista]
Lai, M; Muscianese, M; Piana, S; Chester, J; Borsari, S; Paolino, G; Pellacani, G; Longo, C; Pampena, R
abstract

Cutaneous adnexal tumours (ATs) encompass a variegated group of hamartomas and benign or malignant tumours, originating from the hair follicle, sebaceous, eccrine or apocrine glands that may simulate other cutaneous neoplasms. This study aims to provide a comprehensive overview of the spectrum of clinical and dermoscopic features of ATs, to better define these lesions and assist in the differential diagnosis. We performed a two-step systematic search of the literature in PubMed, Embase and Cochrane Library databases from inception until 4 September 2020. In the first step, we aimed to define histological variants of ATs with descriptions of dermoscopic criteria. The second step included a search for the name of each previously identified AT variants in the same databases adding 'AND (epilum* or dermosc* or dermatosc*)'. All study types in English language reporting dermoscopic images of ATs were included. Collisions between ATs and other inflammatory or neoplastic skin lesions were excluded, with the exception of collisions with a sebaceous nevus. The protocol of this study was prospectively registered in PROSPERO (CRD42021244677). In total, 206 articles met our inclusion criteria, encompassing 372 ATs in 365 patients. Most ATs were apocrine-eccrine (n = 217, 58.3%, n = 173 benign) with a prevalence of poromas (n = 82), followed by follicular ATs (n = 88, 23.7%, n = 83 benign) and sebaceous ATs (n = 67, 18.0%, n = 49 benign). Most patients had a single AT lesion (320, 86.0%), while 42 (11.3%) had multiple ATs. A syndrome causing multiple ATs was identified in 15 patients. Histopathological analysis revealed 82% benign (n = 305) and 18.0% malignant (n = 67). ATs were classified according to their ability to mimic four groups of more common skin tumours: basal cell carcinoma, squamous cell carcinoma, melanocytic lesions and benign cutaneous lesions. Moreover, we have highlighted the ability of malignant variants of ATs to simulate benign skin lesions. This systematic review offers a comprehensive overview of the common clinical and dermoscopic features of follicular, sebaceous and apocrine-eccrine ATs and details possible differential dermoscopic features.

2022 - Dermoscopy of early melanomas: variation according to the anatomic site [Articolo su rivista]
Tognetti, Linda; Cartocci, Alessandra; Cinotti, Elisa; Moscarella, Elvira; Farnetani, Francesca; Carrera, Cristina; Lallas, Aimilios; Tiodorovic, Danica; Longo, Caterina; Puig, Susana; Perrot, Jean Luc; Argenziano, Giuseppe; Pellacani, Giovanni; Cataldo, Gennaro; Balistreri, Alberto; Cevenini, Gabriele; Rubegni, Pietro
abstract

To date, is yet to be elucidated whether the body location of cutaneous melanoma can significantly affect an early dermoscopic diagnosis and, consequently, if it can be regarded as a prognostic factor. To investigate the dermoscopic appearance of early melanomas (EMs) at different body sites; to test the ability of dermoscopists in recognizing specific dermoscopic features in EMs. A pool of 106 experienced dermoscopists evaluated the presence of 10 dermoscopic features assumed as suggestive of malignancy among 268 images of EMs with ambiguous appearance located at 16 body sites. According to 720 evaluations, EMs of the "upper extremities" showed a prevalence of early atypical lentiginous features. EMs of the "anterior trunk" exhibited the lower rate of recognition for all features. EMs of the "rear trunk" can be regarded as an intermediate area, showing high recognition rates of regression-related and chronic-traumatism-related features.

2022 - Dermoscopy, confocal microscopy and optical coherence tomography features of main inflammatory and autoimmune skin diseases: A systematic review [Articolo su rivista]
Guida, S.; Longhitano, S.; Ardigo, M.; Pampena, R.; Ciardo, S.; Bigi, L.; Mandel, V. D.; Vaschieri, C.; Manfredini, M.; Pezzini, C.; Arginelli, F.; Farnetani, F.; Zerbinati, N.; Longo, C.; Pellacani, G.
abstract

Background/Objectives: Non-invasive skin imaging features of main skin inflammatory and autoimmune diseases have been reported, although a comprehensive review of their correlation with histopathologic features is currently lacking. Therefore, the aim of this paper was to review the correlation of dermoscopic, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) criteria of main inflammatory and autoimmune skin diseases with their corresponding histopathologic criteria correlation. Methods: Studies on human subjects affected by main inflammatory and autoimmune diseases, defining the correlation of dermoscopic, RCM or OCT with histopathologic criteria, were included in the review. Five groups of diseases were identified and described: psoriasiform, spongiotic and interface dermatitis, bullous diseases and scleroderma. Results: Psoriasiform dermatitis was typified by white scales, corresponding to hyperkeratosis, and vessels, observed with RCM and OCT. Spongiosis, corresponding to dark areas within the epidermis with RCM and OCT, was the main feature of spongiotic dermatitis. Interface dermatitis was characterised by dermoepidermal junction obscuration. Blisters, typical of bullous diseases, were visualised as dark areas with RCM and OCT while scleroderma lesions were characterised by dermoscopic fibrotic beams, related to dermal thickness variations, with specific OCT and histopathologic correlations. Conclusions: Although the role of RCM and OCT has yet to be defined in clinical practice, non-invasive skin imaging shows promising results on inflammatory and autoimmune skin diseases, due to the correlation with histopathologic features.

2022 - Dynamic dermoscopic and reflectance confocal microscopic changes of melanocytic lesions excised during follow-up [Articolo su rivista]
Condorelli, Alessandra Grazia; Farnetani, Francesca; Ciardo, Silvana; Chester, Johanna; Kaleci, Shaniko; Stanganelli, Ignazio; Mazzoni, Laura; Magi, Serena; Mandel, Victor Desmond; Mirra, Marica; Pampena, Riccardo; Raucci, Margherita; Longo, Caterina; Pellacani, Giovanni
abstract

BACKGROUND: Digital dermoscopy follow-up (DDF) is useful in improving melanoma recognition, catching early changes over time, although benign nevi can also show changes. Reflectance confocal microscopy (RCM) improves melanoma diagnostic accuracy and decreases the number of unnecessary resections.OBJECTIVES: To evaluate dynamic dermoscopic and RCM changes during follow-up of equivocal melanocytic lesions and assess the impact of adjunctive RCM to DDF for melanoma diagnosis.METHODS: A retrospective, multicenter study of extra-facial atypical melanocytic lesions excised during follow-up was performed. Morphological changes were evaluated comparing dermoscopy and RCM baseline and follow-up images.RESULTS: 137 atypical melanocytic lesions were studied, including 14 melanomas and 123 benign nevi. Significantly greater changes in DDF of atypical network, regression, atypical streaks and asymmetrical growth and in dynamic RCM of atypical cells and dermal-epidermal junction (DEJ) disarray were note in melanomas. With adjunctive dynamic RCM and major changes at DDF, sensitivity reached 100% with 40.6% specificity.LIMITATIONS: Selected series of "difficult to recognize" lesions, with both DDF and dynamic RCM images.CONCLUSION: Adjunctive dynamic RCM improves early melanoma recognition sensitivity.

2022 - Effect of Reflectance Confocal Microscopy for Suspect Lesions on Diagnostic Accuracy in Melanoma: A Randomized Clinical Trial [Articolo su rivista]
Pellacani, Giovanni; Farnetani, Francesca; Ciardo, Silvana; Chester, Johanna; Kaleci, Shaniko; Mazzoni, Laura; Bassoli, Sara; Casari, Alice; Pampena, Riccardo; Mirra, Marica; Lai, Michela; Magi, Serena; Mandel, Victor D; Di Matteo, Sergio; Colombo, Giorgio Lorenzo; Stanganelli, Ignazio; Longo, Caterina
abstract

IMPORTANCE Previous systematic reviews and meta-analyses have concluded that given data paucity, a comparison of reflectance confocal microscopy (RCM) with dermoscopy is complex. They recommend comparative prospective studies in a real-world setting of suspect lesions.OBJECTIVE To test the hypothesis that RCM reduces unnecessary lesion excision by more than 30% and identifies all melanoma lesions thicker than 0.5 mm at baseline.DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial included 3165 patients enrolled from 3 dermatology referral centers in Italy between January 2017 and December 2019, with a mean (SD) follow-up of 9.6 (6.9) months (range, 1.9-37.0 months). The consecutive sample of 3165 suspect lesions determined through dermoscopy were eligible for inclusion (10 patients refused). Diagnostic analysis included 3078 patients (48 lost, 39 refused excision). Data were analyzed between April and September 2021.INTERVENTIONS Patients were randomly assigned 1:1 to standard therapeutic care (clinical and dermoscopy evaluation) with or without adjunctive RCM. Information available guided prospective clinical decision-making (excision or follow-up).MAIN OUTCOMES AND MEASURES Hypotheses were defined prior to study initiation. All lesions excised (baseline and follow-up) were registered, including histopathological diagnoses/no change at dermoscopy follow-up (with or without adjunctive RCM). Number needed to excise (total number of excised lesions/number of melanomas) and Breslow thickness of delayed diagnosed melanomas were calculated based on real-life, prospective, clinical decision-making.RESULTS Among the 3165 participants, 1608 (50.8%) were male, and mean (SD) age was 49.3 (14.9) years. When compared with standard therapeutic care only, adjunctive RCM was associated with a higher positive predictive value (18.9 vs 33.3), lower benign to malignant ratio (3.7:1.0 vs 1.8:1.0), and a number needed to excise reduction of 43.4% (5.3 vs 3.0). All lesions (n = 15) with delayed melanoma diagnoses were thinner than 0.5 mm.CONCLUSIONS AND RELEVANCE This randomized clinical trial shows that adjunctive use of RCM for suspect lesions reduces unnecessary excisions and assures the removal of aggressive melanomas at baseline in a real-life, clinical decision-making application for referral centers with RCM.

2022 - Evaluation of the dermatoscopic criteria for the early detection of SCC arising on an AK [Articolo su rivista]
Papageorgiou, Chryssoula; Lallas, Aimilios; Manoli, Sofia Magdalini; Longo, Caterina; Lai, Michela; Liopyris, Konstantinos; Lallas, Konstantinos; Lazaridou, Elizabeth; Apalla, Zoe
abstract

BACKGROUND: Advanced squamous cell carcinoma (SCC) can easily be discriminated from actinic keratosis (AK), based on clinical and dermatoscopic features. However, at the initial stage of dermal invasion, an SCC might still be clinically flat and its discrimination from AK remains challenging, even with the addition of dermatoscopy.OBJECTIVE: The aim of the present study was to investigate the clinical and dermatoscopic criteria that could suggest early invasion and serve as potent predictors to discriminate early SCC from AK.METHODS: Clinical and dermatoscopic images of histopathologically diagnosed AKs and early SCCs were evaluated by three independent investigators for the presence of predefined criteria.RESULTS: A total of 50 early SCCs and 45 AKs were included. The main positive dermatoscopic predictors of early SCC were dotted/glomerular vessels (OR=3.83), hairpin vessels (OR=12.12) and white structureless areas (OR=3.58), whereas background erythema represented a negative SCC predictor (OR=0.22).LIMITATIONS: The retrospective evaluation of images. Moreover, the differential diagnosis included in the study is restricted between AK and early SCC.CONCLUSIONS: We identified potent predictors for the discrimination of AK and early SCC that may better guide management decisions in the everyday clinical practice.

2022 - Multicentre Selective Lymphadenectomy Trial 1: key primary data remain unavailable [Articolo su rivista]
Dixon, Anthony; Kyrgidis, Athanassios; Zachary, Christopher; Dixon, John; Popescu, Catalin; Sladden, Michael; Apalla, Zoe; Anderson, Stuart; Argenziano, Giuseppe; Ioannides, Demitrios; Nirenberg, Alexander; Lallas, Aimillios; Zagarella, Samuel; Longo, Caterina; Smith, Harvey; Steinman, Howard; Tzellos, Thrasivoulos; Cleaver, Lloyd; Leahey, Ken; Zouboulis, Christos C; Thomas, J Meirion
abstract

2022 - Non-Melanoma Skin Cancer Clearance after Medical Treatment Detected with Noninvasive Skin Imaging: A Systematic Review and Meta-Analysis [Articolo su rivista]
Guida, Stefania; Alma, Antonio; Kaleci, Shaniko; Chester, Johanna; Ciardo, Silvana; Proietti, Ilaria; Giuffrida, Roberta; Zalaudek, Iris; Manfredini, Marco; Longo, Caterina; Farnetani, Francesca; Pellacani, Giovanni
abstract

Simple Summary Non-melanoma skin cancers (NMSC) represent about one-third of all malignancies. While surgery is the current gold standard treatment, many nonsurgical approaches are available for selected cases. Currently, there are no studies concerning the overall impact of dermoscopy, optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) for NMSC treatment monitoring. Therefore, we aim to review the current literature and provide an updated summary of noninvasive skin imaging in NMSC medical treatment management and the diagnostic accuracy of the most advanced technologies. Background/Objectives: Non-melanoma skin cancer (NMSC) treated with nonsurgical therapies can be monitored with noninvasive skin imaging. The precision of dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) in detecting clearance is unclear. We aim to report the proportion of persisting tumors identified with noninvasive technologies available in the literature. Methods: A systematic literature search was conducted on the PubMed and Cochrane Public Library Databases for articles published prior to November 2021. Statistical analyses were conducted with MedCalc 14.8.1 software. Results: A total of eight studies (352 lesions) reporting noninvasive imaging for NMSC clearance following nonsurgical treatment were included. Most (n = 7) reported basal cell carcinoma (BCC), and one study reported squamous cell carcinoma (SCC) clearance. A meta-analysis of the BCC clearance revealed that the summary effect for RCM was higher, as compared to the other techniques. Interestingly, the sensitivity and specificity for OCT were 86.4% (95% CI: 65.1-97.1) and 100% (95% CI: 94.8-100.0), respectively, whilst, for RCM, they reached 100% (95%CI: 86.8-100) and 72.5% (95% CI: 64.4-79.7), respectively. Conclusions: Routine clinical examination and dermoscopy underperform when employed for NMSC clearance monitoring, although they represent the first approach to the patient. OCT and RCM seem to improve the detection of persistent BCC after medical treatment.

2022 - Photodistributed eruptive telangiectasias: an uncommon adverse drug reaction. A retrospective case series [Articolo su rivista]
Vaccaro, Mario; Di Bartolomeo, Luca; Borgia, F; Longo, Caterina; Vaccaro, Federico; Gangemi, Sebastiano; Lentini, Maria; Caradonna, Emanuela
abstract

Drug-induced photodistributed telangiectasia (PT) is cutaneous side effects resulting from the interaction of ultraviolet (UV) radiation with pharmacotherapy. Reports of PT in literature are scarce. We report twenty-five cases of drug-induced photodistributed telangiectasias, highlighting the potential relationship between the onset of skin lesions, drug-intake and photo-exposure. We alert practitioners that telangiectasia is a possible dermatological phototoxic side-effect to many drugs.

2022 - Pigmented Actinic Keratosis Versus In Situ Melanoma: PRAME May Be Helpful [Articolo su rivista]
Santandrea, Giacomo; Longo, Caterina; Borsari, Stefania; Lai, Michela; Piana, Simonetta
abstract

2022 - Prevalence and clinical-pathological features of nevus-associated versus de novo melanoma: a retrospective cross-sectional study of 2806 cases [Articolo su rivista]
Lai, Michela; Piana, Simonetta; Pellacani, Giovanni; Longo, Caterina; Pampena, Riccardo
abstract

Introduction:Nevus-associated melanoma (NAM) accounts for almost one third of all cutaneous melanomas; it is often associated with younger age, trunk location and lower Breslow's thickness compared to de novo melanoma (DNM). Objectives:To define the prevalence of NAM in a tertiary referral Center in Italy and to analyze its distribution according to demographics, clinical and histopathological variables Methods:Data were retrospectively retrieved from the archive of the Pathology Unit from June 2011 to August 2020. NAMs were compared with DNMs according to demographic, clinical and histo-pathological variables Results:A total of 2806 consecutive cases of melanoma were excised in 2537 patients. Of these, 431 (15.4%) were NAM. NAM patients were significantly younger than DNM patients (55.1 +/- 14.1 vs. 62.0 +/- 15.0 years, p<0.001); they were predominantly located on the trunk (64.0% vs. 47.9% of DNMs). Melanoma located on the head and neck, trunk and upper limbs respectively had 2.3 (95%CI:1.2-4.5, p:0.014), 3.2 (95%CI:2.1-5.1, p<0.001) and 3.5 (95%CI:2.0-6.1, p<0.001) more odds to be NAM than those on the lower limbs Conclusions:Our results confirm the association of NAM with younger age and trunk location. We also demonstrated that body site differences of NAM distribution are enhanced before the sixth decade of life.

2022 - Screening for skin cancer in special populations: testicular germ-cell cancer survivors [Articolo su rivista]
Navarrete-Dechent, C; Longo, C
abstract

2022 - Self-reported measure of subjective distress in response to COVID-19 pandemic in patients referred to our skin cancer unit during the first wave [Articolo su rivista]
Borsari, S.; Pampena, R.; Benati, M.; Raucci, M.; Mirra, M.; Lai, M.; Lombardi, M.; Pellacani, G.; Longo, C.
abstract

During the Italian first wave of the COVID-19 pandemic, social restrictions and bad news spread daily by mass media inevitably had a huge influence on the mental state of the population. To assess how much the COVID-19 outbreak impacted the psychologic state of patients referring to our Skin Cancer Unit from March 9 to May 31, 2020, we administered to them a self-report questionnaire, the Impact of Event Scale-Revised (IES-R). To evaluate the trend of the IES-R score over time, we set a temporal cutoff of March 27 (the day with the highest number of deaths for COVID-19 in Italy during the first wave). Three hundred fifty-five patients completed the questionnaire, reporting an average IES-R score of 25.5 (±16.4); 32.4% of participants reached a total IES-R score >32. Patients who visited after March 27, 2020 reported a higher psychologic impact, since the IES-R score significantly increased from 23.6 (±15.6) to 28.3 (±17.2). A group reported higher scores (of participants reaching an IES-R score >32, 57.4% were women and 33.9% were men). We gathered that, at an early stage of events of this magnitude, it could be useful to submit the IES-R questionnaire in high-risk and oncologic patients: we could potentially identify individuals at risk of developing post-traumatic stress disorders, who might be tempted to postpone necessary medical consultations. This could be also the basis for increasing targeted psychologic support in selected patients.

2022 - The Value of In Vivo Reflectance Confocal Microscopy as an Assessment Tool in Chemotherapy-Induced Peripheral Neuropathy: A Pilot Study [Articolo su rivista]
Ramnarine, Sabrina R; Dougherty, Patrick M; Rolke, Roman; Williams, Linda J; Alessi-Fox, Christi; Coleman, Andrew J; Longo, Caterina; Colvin, Lesley A; Fallon, Marie T
abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting toxicity with significant sequelae. There is a lack of standardized objective and reliable assessment tools in CIPN. In vivo reflectance confocal microscopy (RCM) imaging offers a non-invasive method to identify peripheral neuropathy markers, namely Meissner's corpuscles. This article reports on the feasibility and value of RCM in CIPN.Background There is a lack of standardized objective and reliable assessment tools for chemotherapy-induced peripheral neuropathy (CIPN). In vivo reflectance confocal microscopy (RCM) imaging offers a non-invasive method to identify peripheral neuropathy markers, namely Meissner's corpuscles (MC). This study investigated the feasibility and value of RCM in CIPN. Patients and Methods Reflectance confocal microscopy was performed on the fingertip to evaluate MC density in 45 healthy controls and 9 patients with cancer (prior, during, and post-chemotherapy). Quantification was completed by 2 reviewers (one blinded), with maximum MC count/3 x 3 mm image reported. Quantitative Sensory Testing (QST; thermal and mechanical detection thresholds), Grooved pegboard test, and patient-reported outcomes measures (PROMS) were conducted for comparison. Results In controls (25 females, 20 males; 24-81 years), females exhibited greater mean MC density compared with males (49.9 +/- 7.1 vs 30.9 +/- 4.2 MC/3 x 3 mm; P = .03). Differences existed across age by decade (P < .0001). Meissner's corpuscle density was correlated with mechanical detection (rho = -0.51), warm detection (rho = -0.47), cold pain (rho = 0.49) thresholds (P < .01); and completion time on the Grooved pegboard test in both hands (P <= .02). At baseline, patients had reduced MC density vs age and gender-matched controls (P = .03). Longitudinal assessment of MC density revealed significant relationships with QST and PROMS. Inter-rater reliability of MC count showed an intraclass correlation of 0.96 (P < .0001). Conclusions The findings support the clinical utility of RCM in CIPN as it provides meaningful markers of sensory nerve dysfunction. Novel, prospective assessment demonstrated the ability to detect subclinical deficits in patients at risk of CIPN and potential to monitor neuropathy progression.

2022 - The association between COVID-19 lockdowns and melanoma diagnosis and thickness: A multicenter retrospective study from Europe [Articolo su rivista]
Scharf, Camila; Brancaccio, Gabriella; Di Stefani, Alessandro; Fargnoli, Maria Concetta; Kittler, Harald; Kyrgidis, Athanassios; Lallas, Aimilios; Longo, Caterina; Malvehy, Josep; Moscarella, Elvira; Peris, Ketty; Piana, Simonetta; Puig, Susana; Thomas, Luc; Argenziano, Giuseppe
abstract

2022 - The role of reflectance confocal microscopy in the diagnosis of eccrine poroma: A retrospective case–control study [Articolo su rivista]
Di Tullio, F.; Mandel, V. D.; Ignazio, S.; Cinotti, E.; Kaleci, S.; Ciardo, S.; Peccerillo, F.; Longo, C.; Farnetani, F.; Pellacani, G.
abstract

Eccrine poroma (EP) is a rare benign adnexal tumor that may mimic benign or malignant tumors and differential diagnosis may be difficult under clinical and dermoscopic examination. Reflectance confocal microscopy (RCM) examination may add important information to diagnosis and subsequent management of solitary lesions for which dermoscopy can be challenging. The aim of the present study was to investigate features of EP at RCM in order to detect the characteristics that might aid in the differential diagnosis of EP versus other solitary lesions (benign or malignant). Secondary objective was to correlate the resulting features with histopathological findings. This monocentric retrospective observational case–control study included all EPs registered with RCM between January 2007 and May 2018. Control cases were benign or malignant lesions similar in clinical appearance, morphology, and dermoscopic features to EPs. RCM evaluators were blinded to clinical-dermoscopic images and to final histopathological diagnoses. Finally, RCM-histopathological correlation was performed. A total of 11 EPs and 33 controls were included in the present study. Among RCM parameters, “cords without palisading,” “dark holes,” “prominent vascularization” and “abundant stroma” resulted positively associated with EP in univariate analysis. RCM features correspond to the histopathological diagnosis of EP in 97% of cases, as illustrated by the cluster analysis. An excellent correlation between diagnostic features of conventional histopathology and RCM was observed. RCM assists in the differential diagnosis of solitary lesions, allowing to reach a correct diagnosis of EP through the identification of its four characteristics.

2022 - The role of stereotactic radiotherapy in addition to immunotherapy in the management of melanoma brain metastases: results of a systematic review [Articolo su rivista]
Lancellotta, Valentina; Del Regno, Laura; Di Stefani, Alessandro; Fionda, Bruno; Marazzi, Fabio; Rossi, Ernesto; Balducci, Mario; Pampena, Riccardo; Morganti, Alessio Giuseppe; Mangoni, Monica; Lebbe, Celeste; Garbe, Claus; Longo, Caterina; Schinzari, Giovanni; Tagliaferri, Luca; Peris, Ketty
abstract

Aim of this study was to systematically review the literature to assess efficacy and safety of stereotactic radiotherapy (SRT) in combination with immunotherapy for the treatment of melanoma brain metastases (MBM). The literature was searched using PubMed, Scopus, and Embase. Studies comparing SRT plus immunotherapy versus SRT or immunotherapy alone were deemed eligible for inclusion. Two studies showed improved overall survival after SRT plus immunotherapy in melanoma cancer patients with brain metastases. Three studies reported data on LC and DFS showing as SRT plus immunotherapy did not improve local control and DFS rates. G3-G4 toxicity was reported in only one study (20% in the SRT plus immunotherapy group versus 23% in the immunotherapy group). Despite SRT plus concurrent immunotherapy seems associated with possible survival advantage and low >= G3 late toxicity rates, the quality of evidence is very low. Therefore, in patients with brain metastases from melanoma, SRT plus immunotherapy should be evaluated on an individual basis after discussion by a multidisciplinary team.

2022 - Trends in cutaneous melanoma mortality in Italy from 1982 to 2016 [Articolo su rivista]
Briatico, Giulia; Mancuso, Pamela; Argenziano, Giuseppe; Longo, Caterina; Mangone, Lucia; Moscarella, Elvira; Brancaccio, Gabriella; Pampena, Riccardo
abstract

Background In Italy, comprehensive national studies, about mortality rates for cutaneous melanoma, are missing. The aim of this study was to analyze the trend of cutaneous melanoma mortality in Italy from 1982 to 2016. Methods Data on death certificates were obtained from Italian National Institute of Statistics (ISTAT: Istituto nazionale di STATistica, Indagine sulle cause di morte). Mortality rates were age-standardized on the European population 2013 and presented per 100,000 individuals. Age-adjusted mortality rates (AMRs) were calculated by sex, age group, and geographic areas. To identify changes in mortality rate trends, a joinpoint regression model was used, and the annual percent change (APC) was estimated. Results In Italy, a total number of 49,312 patients (44.0% women) died for cutaneous melanoma from 1982 to 2016. Melanoma mortality rates significantly increased in the study period in both sexes, with higher AMR values and a steeper increase in men (from 2.71 to 4.02; APC: 1.43; 95% CI 1.26-1.61) than women (from 1.94-2.10; APC: 0.23; 95% CI 0.00-0.46). The largest difference between men and women was observed in patients aged >= 65 years with APC of 2.17 in men (95% CI 1.97-2.37) and 0.37 in women (95% CI 0.08-0.66). Conclusion In conclusion, the melanoma mortality rate in Italy progressively increased especially in elderly men. Several hypotheses might explain the observed age and geographic differences such as sun exposure habits or different strategies of prevention campaigns.

2022 - Unusual dermoscopic patterns of basal cell carcinoma mimicking melanoma [Articolo su rivista]
Di Matteo, E.; Pampena, R.; Pizzichetta, M. A.; Cinotti, E.; Chester, J.; Kaleci, S.; Manfredini, M.; Guida, S.; Dika, E.; Moscarella, E.; Lallas, A.; Apalla, Z.; Argenziano, G.; Perrot, J. L.; Tognetti, L.; Lai, M.; Cantisani, C.; Roberti, V.; Fiorani, D.; Baraldi, C.; Veneziano, L.; Papageorgiou, C.; Ciardo, S.; Rubegni, P.; Zalaudek, I.; Patrizi, A.; Longo, C.; Bianchi, L.; Pellacani, G.; Farnetani, F.
abstract

Background: Basal cell carcinoma can simulate melanoma and specific dermoscopic criteria have not yet been defined in a large cohort. Objective: To identify dermoscopic “trump” characteristics for differential diagnosis, identify cluster groups and assess the clinical impact of this study's findings. Methods: Retrospective, multicentric comparative study of atypical, non-facial basal cell carcinoma (≥1 seven-point checklist criteria) and melanoma (with at least one BCC criteria) at dermoscopy. Observed dermoscopic features were used to develop a proposed score. Lesion clusters were defined with hierarchical analysis. Clinical impact was assessed with a blinded reader study following this study's results. Results: A total of 146 basal cell carcinoma and 76 melanoma were included. Atypical vascular pattern was common to most lesions (74.5%). Twelve trump features were included in the proposed score (sensitivity 94.1% and specificity 79.5%). Cluster analysis identified 3 basal cell carcinoma and 3 melanoma clusters. Findings improved overall diagnostic accuracy and confidence (26.8% and 13.8%, respectively; p < 0.001). Conclusions: These findings support the notion that atypical vascular pattern should be considered a shared feature of both melanoma and atypical basal cell carcinoma. Our proposed score improves diagnostic accuracy and confidence. Absence of pigmented features was associated with lower diagnostic accuracy and confidence.

2021 - A new deep learning approach integrated with clinical data for the dermoscopic differentiation of early melanomas from atypical nevi [Articolo su rivista]
Tognetti, Linda; Bonechi, Simone; Andreini, Paolo; Bianchini, Monica; Scarselli, Franco; Cevenini, Gabriele; Moscarella, Elvira; Farnetani, Francesca; Longo, Caterina; Lallas, Aimilios; Carrera, Cristina; Puig, Susana; Tiodorovic, Danica; Perrot, Jean Luc; Pellacani, Giovanni; Argenziano, Giuseppe; Cinotti, Elisa; Cataldo, Gennaro; Balistreri, Alberto; Mecocci, Alessandro; Gori, Marco; Rubegni, Pietro; Cartocci, Alessandra
abstract

Timely recognition of malignant melanoma (MM) is challenging for dermatologists worldwide and represents the main determinant for mortality. Dermoscopic examination is influenced by dermatologists' experience and fails to achieve adequate accuracy and reproducibility in discriminating atypical nevi (AN) from early melanomas (EM).

2021 - A plea for standardization of confocal microscopy and optical coherence tomography parameters to evaluate physiological and para-physiological skin conditions in cosmetic science [Articolo su rivista]
Ciardo, Silvana; Pezzini, Claudia; Guida, Stefania; Del Duca, Ester; Ungar, Jonathan; Guttman-Yassky, Emma; Manfredini, Marco; Farnetani, Francesca; Longo, Caterina; Pellacani, Giovanni
abstract

Non-invasive Reflectance Confocal Microscopy (RCM) and Optical Coherence Tomography (OCT) have been extended to the dermo-cosmetic field, for skin pathophysiology understanding and therapeutics monitoring. However, standardized methodology and parameters to interpret structures and changes in these settings are still lacking.

2021 - An international 3-center training and reading study to assess basal cell carcinoma surgical margins with ex-vivo fluorescence confocal microscopy [Articolo su rivista]
Kose, Kivanc; Alessi Fox, Christi; Rossi, Anthony; Jain, Manu; Cordova, Miguel; Dusza, Stephen W; Ragazzi, Moira; Gardini, Stefano; Moscarella, Elvira; Diaz, Alba; Pigem, Ramon; Gonzalez, Salvador; Bennassar, Antoni; Carrera, Cristina; Longo, Caterina; Rajadhyaksha, Milind; Nehal, Kishwer
abstract

Novel solutions are needed for expediting margin assessment to guide BCC surgeries. Ex-vivo fluorescence confocal microscopy (FCM) is starting to be used in freshly-excised surgical specimens to examine BCC margins in real-time. Training and educational process are needed for this novel technology to be implemented into clinic.

2021 - Are we born and do we die without nevi? A cross-sectional study [Articolo su rivista]
Di Brizzi, E. V.; Pampena, R.; Licata, G.; Calabrese, G.; Longo, C.; Argenziano, G.
abstract

Background: It is well known that the number of nevi varies with age. However, there are a few data in the literature concerning total nevus count at different ages. The aim of this study was to assess and compare the total nevus count among different age groups. Methods: The total nevus count was assessed in consecutive patients belonging to nine age groups. Median nevus count was calculated and compared for each age group. Multivariate logistic regression analysis was used to define the influence of sex and phototype on the association between nevus count and age. Results: We enrolled 900 patients (461, 51.2% females), with a median age of 46 years and a total of 18,136 nevi. Significant differences were found in the median total nevus count among all age groups (P < 0.001), with a significant increase in the first two decades and a significant decrease after the age of 50 years. A similar trend was also observed in subgroups. The differences observed in the total body nevus count among age groups were independent of sex and phototype. Conclusions: We demonstrate that the total nevus count significantly increases during childhood and gradually decreases in the elderly.

2021 - Atypical fibroxanthoma: in-vivo and ex-vivo confocal features [Articolo su rivista]
Pampena, Riccardo; Peccerillo, Francesca; Piana, Simonetta; Paolino, Giovanni; Mercuri, Santo R; Pellacani, Giovanni; Longo, Caterina
abstract

N/A

2021 - Circulating mucosal-associated invariant T cells identify patients responding to anti-PD-1 therapy [Articolo su rivista]
De Biasi, S.; Gibellini, L.; Lo Tartaro, D.; Puccio, S.; Rabacchi, C.; Mazza, E. M. C.; Brummelman, J.; Williams, B.; Kaihara, K.; Forcato, M.; Bicciato, S.; Pinti, M.; Depenni, R.; Sabbatini, R.; Longo, C.; Dominici, M.; Pellacani, G.; Lugli, E.; Cossarizza, A.
abstract

Immune checkpoint inhibitors are used for treating patients with metastatic melanoma. Since the response to treatment is variable, biomarkers are urgently needed to identify patients who may benefit from such therapy. Here, we combine single-cell RNA-sequencing and multiparameter flow cytometry to assess changes in circulating CD8+ T cells in 28 patients with metastatic melanoma starting anti-PD-1 therapy, followed for 6 months: 17 responded to therapy, whilst 11 did not. Proportions of activated and proliferating CD8+ T cells and of mucosal-associated invariant T (MAIT) cells are significantly higher in responders, prior to and throughout therapy duration. MAIT cells from responders express higher level of CXCR4 and produce more granzyme B. In silico analysis support MAIT presence in the tumor microenvironment. Finally, patients with >1.7% of MAIT among peripheral CD8+ population show a better response to treatment. Our results thus suggest that MAIT cells may be considered a biomarker for patients responding to anti-PD-1 therapy.

2021 - Clinical and Dermoscopic Factors for the Identification of Aggressive Histologic Subtypes of Basal Cell Carcinoma [Articolo su rivista]
Pampena, R.; Parisi, G.; Benati, M.; Borsari, S.; Lai, M.; Paolino, G.; Cesinaro, A. M.; Ciardo, S.; Farnetani, F.; Bassoli, S.; Argenziano, G.; Pellacani, G.; Longo, C.
abstract

Background: Infiltrative basal cell carcinoma (BCC) has a higher risk for post-surgical recurrence as compared to the most common low-aggressive superficial and nodular BCC. Independent diagnostic criteria for infiltrative BCC diagnosis have not been still defined. Improving the pre-surgical recognition of infiltrative BCC might significantly reduce the risk of incomplete excision and recurrence. Objective: The aim of this study is to define clinical and dermoscopic criteria that can differentiate infiltrative BCC from the most common low-aggressive superficial and nodular BCC. Methods: Clinical and dermoscopic images of infiltrative, superficial, and nodular BCC were retrospectively retrieved from our database and jointly evaluated by two experienced dermoscopists, blinded for the histologic subtype. Pairwise comparisons between the three histologic subtypes were performed and multivariable logistic regression models were constructed in order to define clinical and dermoscopic factors independently associated with each subtype. To validate our findings, two experienced dermoscopists not previously involved in the study were asked to evaluate clinical and dermoscopic images from an external dataset, guessing the proper BCC subtype between infiltrative, nodular and superficial, before and after being provided with the study results. Result: A total of 481 histopathologically proven BCCs (51.4% nodular, 33.9% superficial, and 14.8% infiltrative) were included. We found that infiltrative BCC mostly appeared on the head and neck as an amelanotic hypopigmented plaque or papule, displaying ulceration on dermoscopic examination, along with arborizing and fine superficial telangiectasia. Shiny white structures were also frequently observed. Multivariate regression analysis allowed us to define a clinical-dermoscopic profile of infiltrative BCC. Conclusions: We defined the clinical-dermoscopic profile of infiltrative BCC, allowing to differentiate this variant from superficial and nodular BCC. This will improve pre-surgical recognition of infiltrative forms, reducing the risk for post-surgical recurrence.

2021 - Clinical and dermatoscopic predictors of squamous cell carcinoma of the lips: A case-control, multicentric study [Articolo su rivista]
Lallas, A; Martínez, G; Arceu, M; Kyrgidis, A; Liopyris, K; Brancaccio, G; Longo, C; Errichetti, E; Sgouros, D; Papageorgiou, C; Fotiadou, C; Siskou, S; Manoli, S M; Sotiriou, E; Ioannides, D; Katoulis, A; Lazaridou, E; Todorovska, V; Argenziano, G; Apalla, Z
abstract

Squamous cell carcinoma of the lip accounts for 20% of all oral carcinomas. Its diagnosis may be challenging because of it clinical resembles actinic cheilitis and inflammatory lesions of the lips.

2021 - Clinical applications of in vivo and ex vivo confocal microscopy [Articolo su rivista]
Guida, S.; Arginelli, F.; Farnetani, F.; Ciardo, S.; Bertoni, L.; Manfredini, M.; Zerbinati, N.; Longo, C.; Pellacani, G.
abstract

Confocal laser scanning microscopy (CLSM) has been introduced in clinical settings as a tool enabling a quasi-histologic view of a given tissue, without performing a biopsy. It has been applied to many fields of medicine mainly to the skin and to the analysis of skin cancers for both in vivo and ex vivo CLSM. In vivo CLSM involves reflectance mode, which is based on refractive index of cell structures serving as endogenous chromophores, reaching a depth of exploration of 200 µm. It has been proven to increase the diagnostic accuracy of skin cancers, both melanoma and nonmelanoma. While histopathologic examination is the gold standard for diagnosis, in vivo CLSM alone and in addition to dermoscopy, contributes to the reduction of the number of excised lesions to exclude a melanoma, and to improve margin recognition in lentigo maligna, enabling tissue sparing for excisions. Ex vivo CLSM can be performed in reflectance and fluorescent mode. Fluorescence confocal microscopy is applied for “real-time” pathological examination of freshly excised specimens for diagnostic purposes and for the evaluation of margin clearance after excision in Mohs surgery. Further prospective interventional studies using CLSM might contribute to increase the knowledge about its application, reproducing real-life settings.

2021 - Combined PARP1-targeted nuclear contrast and reflectance contrast enhances confocal microscopic detection of basal cell carcinoma [Articolo su rivista]
Sahu, Aditi; Cordero, Jose; Wu, Xiancheng; Kossatz, Susanne; Harris, Ucalene; Demetrio Desouza Franca, Paula; Kurtansky, Nicholas R; Everett, Niasia; Dusza, Stephen; Monnier, Jilliana; Kumar, Piyush; Alessi-Fox, Christi; Brand, Christian; Roberts, Sheryl; Kose, Kivanc; Phillip, William; Lee, Erica; Jason Chen, Chih-Shan; Rossi, Anthony; Nehal, Kishwer; Pulitzer, Melissa; Longo, Caterina; Halpern, Allan; Reiner, Thomas; Rajadhyaksha, Milind; Jain, Manu
abstract

Reflectance confocal microscopy (RCM) with endogenous backscattered contrast can noninvasively image basal cell carcinomas (BCCs) in skin. However, BCCs present with high nuclear density and the relatively weak backscattering from nuclei impose a fundamental limit on contrast, detectability, and diagnostic accuracy. We investigated PARPi-FL, an exogenous nuclear poly (ADP-ribose) polymerase (PARP1)-targeted fluorescent contrast agent and fluorescence confocal microscopy (FCM) towards improving BCC diagnosis. Methods: We tested PARP1 expression in 95 BCC tissues using immunohistochemistry, followed by PARPi-FL staining in 32 fresh surgical BCC specimens. Diagnostic accuracy of PARPi-FL contrast was evaluated in 83 surgical specimens. Optimal parameters for trans-epidermal permeability of PARPi-FL through intact skin was tested ex vivo on 5 human skin specimens and in vivo in 3 adult Yorkshire pigs. Results: We found significantly higher PARP1 expression and PARPi-FL binding in BCCs, as compared to normal skin structures. Blinded reading of RCM-and-FCM images by two experts demonstrated a higher diagnostic accuracy for BCCs with combined fluorescence and reflectance contrast, as compared to RCM-alone. Optimal parameters (time and concentration) for PARPi-FL trans-epidermal permeation through intact skin were successfully determined. Conclusion: Combined fluorescence and reflectance contrast may improve noninvasive BCC diagnosis with confocal microscopy.

2021 - Combining PARPi-FL fluorescence and reflectance contrast for improved detection of basal cell carcinoma (BCC) [Relazione in Atti di Convegno]
Sahu, A.; Cordero, J.; Wu, X.; Franca, P. D. D.; Kossatz, S.; Harris, U.; Kurtansky, N.; Everett, N.; Dusza, S.; Monnier, J.; Kumar, P.; Fox, C.; Brand, C.; Roberts, S.; Kose, K.; Phillips, W.; Lee, E.; Chen, C. -S. J.; Rossi, A.; Nehal, K.; Pulitzer, M.; Longo, C.; Halpern, A.; Reiner, T.; Rajadhyaksha, M.; Jain, M.
abstract

Towa rds improving non-invasive BCC diagnosis, we demonstrate successful PARPi-FL (PARP1-ta rgeted nuclear contrast) la beling in tumors, permeability through stratum corneum, and high dia gnostic accuracy with combined PARPi-FL a nd reflectance contrast.

2021 - Cutaneous localization of classic hodgkin lymphoma associated with mycosis fungoides: Report of a rare event and review of the literature [Articolo su rivista]
Zanelli, M.; Ricci, S.; Sanguedolce, F.; Palicelli, A.; Farnetti, E.; Tafuni, A.; Zizzo, M.; Valli, R.; De Celis, M. I. A.; Cavazza, A.; Longo, C.; Ascani, S.
abstract

Mycosis fungoides and nodal classic Hodgkin lymphoma (cHL) have been reported to occur concurrently or sequentially in the same patient. A long-lasting mycosis fungoides more often precedes the onset of nodal cHL, although few cases of nodal cHL followed by mycosis fungoides have been observed. Skin involvement is a rare manifestation of cHL that may be observed in the setting of advanced disease. The decrease in skin involvement in cHL is mainly due to the improved therapeutic strategies. The concurrent presence of mycosis fungoides and cutaneous localization of classic Hodgkin lymphoma represents a very uncommon event, with only two cases reported so far. Herein, we describe the case of a 71-year-old man, with a history of recurrent nodal cHL, who developed MF and, subsequently, the cutaneous localization of cHL. The clinicopathological features of the two diseases are described focusing on the main differential diagnoses to be taken into consideration, and a review of the literature is performed.

2021 - Cutaneous squamous cell carcinoma in patients with chronic lymphocytic leukemia: a systematic review of the literature [Articolo su rivista]
Lai, M.; Pampena, R.; Cornacchia, L.; Odorici, G.; Piccerillo, A.; Pellacani, G.; Peris, K.; Longo, C.
abstract

The continuous improvement of life expectancy of patients with chronic lymphocytic leukemia (CLL) has resulted in increased risk of second primary malignancy that potentially may affect survival and quality of life of CLL patients. We performed a systematic review to assess the risk and the clinical-pathological features and prognosis of cutaneous squamous cell carcinoma (cSCC) in patients with CLL. We searched PubMed, Embase, and Cochrane Central Register of Control Trials databases for articles published from database inception to December 31, 2019. English-language studies reporting original data on patients with a specific diagnosis of CLL and cSCC were included. Data were extracted using a standardized extraction form, and any discordance was resolved by consensus. Descriptive data were generated by pooling patients from eligible studies. Of the 4588 non-duplicate records identified, 55 articles met our inclusion criteria. These studies reported that CLL patients have a 3.2% prevalence of cSCC, with an 11.5% cSCC-related lethality and an overall risk of metastasis of 5.7% (7.3% for regional lymph node involvement and 3.8% for distant metastasis). The quality of evidence was limited by the high heterogeneity in the design, populations, and objectives of the included studies. This systematic review suggests that cSCC in CLL patients tends to behave less aggressively compared with the solid organ transplant recipients but has a higher morbidity and mortality than in the general population. Future prospective studies are needed to increase the quality of evidence and to determine the best treatment modalities and screening intervals for these patients.

2021 - Deep Learning for Basal Cell Carcinoma Detection for Reflectance Confocal Microscopy [Articolo su rivista]
Campanella, Gabriele; Navarrete-Dechent, Cristian; Liopyris, Konstantinos; Monnier, Jilliana; Aleissa, Saud; Minas, Bramhteg; Scope, Alon; Longo, Caterina; Guitera, Pascale; Pellacani, Giovanni; Kose, Kivanc; Halpern, Allan C; Fuchs, Thomas J; Jain, Manu
abstract

Basal cell carcinoma (BCC) is the most common skin cancer, with over 2 million cases diagnosed annually in the United States. Conventionally, BCC is diagnosed by naked eye examination and dermoscopy. Suspicious lesions are either removed or biopsied for histopathological confirmation, thus lowering the specificity of non-invasive BCC diagnosis. Recently, reflectance confocal microscopy (RCM), a non-invasive diagnostic technique that can image skin lesions at cellular level resolution, has shown to improve specificity in BCC diagnosis and reduced the number needed to biopsy by 2-to-3 times. In this study, we developed and evaluated a deep learning-based artificial intelligence model to automatically detect BCC in RCM images. The proposed model achieved an area under the curve (AUC) for the receiver operator characteristic (ROC) curve of 89.7% (stack-level) and 88.3% (lesion level), a performance on par with that of RCM experts. Furthermore, the model achieved an AUC of 86.1% on a held-out test set from international collaborators, demonstrating the reproducibility and generalizability of the proposed automated diagnostic approach. These results provide a clear indication that the clinical deployment of decision support systems for the detection of BCC in RCM images has the potential for optimizing the evaluation and diagnosis of skin cancer patients.

2021 - Flat scalp melanoma dermoscopic and reflectance confocal microscopy features correspond to histopathologic type and lesion location [Articolo su rivista]
Garbarino, F; Pampena, R; Lai, M; Pereira, A R; Piana, S; Cesinaro, A M; Cinotti, E; Fiorani, D; Ciardo, S; Farnetani, F; Chester, J; Pellacani, G; Guitera, P; Longo, C
abstract

Dermoscopy and Reflectance Confocal Microscopy (RCM) features of scalp melanoma according to lesion location and histopathology have not been fully investigated.

2021 - Glioblastoma and malignant melanoma: Serendipitous or anticipated association? [Articolo su rivista]
Fiondella, L.; Cavallieri, F.; Napoli, M.; Froio, E.; Serra, S.; Borsari, S.; Giaccherini, L.; Ghadirpour, R.; Cozzi, S.; Pascarella, R.; Longo, C.; Valzania, F.; Pisanello, A.
abstract

2021 - Italian expert-based recommendations on the use of photo(chemo)therapy in the management of Mycosis Fungoides: results of an E-Delphi consensus [Articolo su rivista]
Grandi, V; Baldo, A; Berti, E; Quaglino, P; Rupoli, S; Alaibac, M; Alberti-Violetti, S; Amerio, P; Brazzelli, V; Bruni, P L; Calzavara-Pinton, P; Parodi, A; Cozzani, E; Burlando, M; Fargnoli, M; Gambini, D; Iacovelli, P; Pacifico, A; Longo, C; Monfrecola, G; Motolese, A; Mozzicafreddo, G; Cota, C; Pigatto, P; Pileri, A; Savoia, P; Simonacci, M; Venturini, M; Offidani, A; Molinelli, E; Pellegrino, M; Trovato, E; Piccinno, R; Lawrence, K; Pimpinelli, N
abstract

Phototherapy is a mainstay for the treatment of MF. However, there is scarce evidence for its use, mostly due to the lack of a unified schedule. The primary aim of this study was to establish the first structured, expert-based consensus regarding the indications and technical schedules of NB-UVB and PUVA for MF. The secondary aim was to determine the consensus level for each specific item.

2021 - Melanoma diagnosis at the time of COVID-19 [Articolo su rivista]
Longo, C.; Pampena, R.; Fossati, B.; Pellacani, G.; Peris, K.
abstract

2021 - New systemic therapies for cutaneous melanoma: why, who and what [Articolo su rivista]
Pampena, Riccardo; Michelini, Simone; Lai, Michela; Chester, Johanna; Pellacani, Giovanni; Longo, Caterina
abstract

Incidence of melanoma has been increasing in both sexes in the last decades. Advanced melanoma has always been one of the deadliest cancer worldwide due to his high metastatic capacity. In the last ten years, progresses in the knowledge of the molecular mechanisms involved in the melanoma development and progression, and in immune-response against melanoma, empowered the development of two new classes of systemic therapeutic agents: target-therapies and immunotherapies. Both of these classes consist of monoclonal antibodies inhibiting specific molecules. Target-therapies are selectively directed against cells harbouring the BRAFV600-mutation, while immunotherapies target the two molecules involved in immune-checkpoint regulation, enhancing the immune response against the tumor: cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 receptor (PD-1). Target- and immunotherapy demonstrated to improve both progression-free and overall survival in melanoma patients either in metastatic or in adjuvant settings. Several drugs have been approved in recent years as monotherapy or in combination, and many other drugs are currently under investigation in clinical trials. In the current review on new systemic therapies for cutaneous melanoma, we revise the molecular basis and the mechanisms of actions of both target- and immunotherapy (why). We discuss who are the best candidate to receive such therapies in both the adjuvant and metastatic setting (who) and which are the most important efficacy and safety data on these drugs (what).

2021 - Real-Time Confocal Imaging for Hidradenitis Suppurativa: Description of Morphological Aspects and Focus on the Role of Follicular Ostia [Articolo su rivista]
Cappilli, S.; Giovanardi, G.; Di Stefani, A.; Longo, C.; Perino, F.; Chiricozzi, A.; Peris, K.
abstract

Background: Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory skin disease involving the follicular unit. Growing evidence suggests a crucial role of hyperkeratosis, infundibular plugging and perifolliculitis in its pathogenesis. Objectives: To characterize the microscopic morphology of open comedos using in vivo reflectance confocal microscopy (RCM) and define alterations occurring in HS normal-Appearing perilesional skin compared to healthy skin of a control group, discussing therefore microscopic differences. Materials and Methods: Twenty patients (11 males, 9 females; aged 19-51 years) affected by HS were recruited. RCM was performed on open comedos of axillary/inguinal regions and on normal-Appearing skin areas distant at least 1.5 cm from HS lesions. Ten healthy individuals (6 males, 4 females) were included as control group. Results: RCM aspects of 78 open comedos were explored, observing circular/ovoidal structures disclosing a hyperrefractive amorphous material (72/78, 92.3%) within the infundibular cavity surrounded with a bright (51/78, 65.4%) and regular (52/78, 66.2%) border. Follicular ostia of HS perilesional skin (n = 541) compared to follicular ostia of a control group (n = 321) were characterized by a larger infundibular diameter (183.4 vs. 85.8 μm) and diverged in terms of material collected inside infundibula (44.5 vs. 21%) and keratinization of the border (47.6 vs. 25.5%). Conclusion: In vivo characterization of open comedos and the recognition of microscopic subclinical alterations of HS normal-Appearing skin, compared to healthy skin, could add further insights into the definition of biological events leading to HS manifestations, including the dysregulated process of keratinization.

2021 - Real-life experience with oral oxybutynin long-term continuous therapy in severe hyperhidrosis and systematic review of the literature [Articolo su rivista]
Briatico, G.; Pampena, R.; Fulgione, E.; Babino, G.; Giorgio, C. M.; D'Ambra, I.; Caccavale, S.; Longo, C.; Argenziano, G.
abstract

Hyperhidrosis is a disorder of excessive sweating severely impacting on patient's quality of life (Qol). Several studies have been published about oral oxybutynin, but no studies focused on the achievement of complete clinical and Qol response. The aim of this study was to report our real-life experience with oral oxybutynin in patients with severe hyperhidrosis significantly affecting their Qol. In this cohort retrospective study, we enrolled, in a 3-year period, patients affected by severe hyperhidrosis with poor Qol, continuously treated with oral oxybutynin. Our outcome was the obtainment of complete clinical and Qol improvement. A systematic review of the literature was also performed reporting efficacy and safety of oral oxybutynin for primary hyperhidrosis. We enrolled 62 patients, of which 53 (85.5%) received a mean daily dose of 10 mg and nine (15.5%) of 5 mg. Complete clinical response was achieved in 77.4% (48/62) of cases, while complete Qol improvement occurred in 51.6% (32/62) of cases. Adverse events were only reported as mild, with dry mouth being the most frequently observed (16.1%). Kaplan-Meier survival analysis highlighted that both median clinical and Qol complete responses were reached after 1 year of continuous therapy with oral oxybutynin. The main limitation of our study is the small number of patients enrolled. Long-term therapy with oral oxybutynin for severe hyperhidrosis, continuously administered at a mean daily dosage of 5 to 10 mg, allowed the majority of our patients to reach both clinical and Qol complete improvement, without significant adverse events.

2021 - Real-world experience on off-label use of imiquimod 5% as an adjuvant therapy after surgery or as a monotherapy for lentigo maligna [Articolo su rivista]
Lallas, A; Moscarella, E; Kittler, H; Longo, C; Thomas, L; Zalaudek, I; Kyrgidis, A; Manoli, S M; di Meo, N; Papageorgiou, C; Apalla, Z; Argenziano, G
abstract

Because of the tendency of lentigo maligna (LM) for subclinical extension, staged excisions with margin control achieve lower recurrence rates than conventional wide local excision (0-9.5% vs 8-20%). However, these surgical techniques are limited by their requirement in time, costs and training.

2021 - Reflectance Confocal Microscopy of Aging Skin and Skin Cancer [Articolo su rivista]
Guida, Stefania; Pellacani, Giovanni; Ciardo, Silvana; Longo, Caterina
abstract

Skin aging is a complex process that causes morphologic variations. Some of these variations have been hypothesized to be involved in skin cancer development. This paper reviews current knowledge of the features of aged skin as seen with reflectance confocal microscopy (RCM). Basic principles of the technique are described, and the RCM features of healthy skin and skin cancer are briefly discussed. Moreover, the RCM features at different layers of young and elderly skin are described, as are the variations that occur with passing years and in relation to sun exposure that contribute to photoaging and the development of skin cancer. RCM enables the noninvasive evaluation, at quasi-histologic resolution, of aging-related skin changes, some of which are shared with skin cancer; this ability helps avoid skin biopsy. Further research is needed to understand the relation between skin aging and skin cancer development.

2021 - Reflectance confocal microscopy features of uncommon histopathological variants of cutaneous melanoma [Articolo su rivista]
Lai, M.; Pampena, R.; Piana, S.; Pellacani, G.; Longo, C.
abstract

2021 - Reflectance confocal microscopy role in mycosis fungoides follow-up [Articolo su rivista]
Melhoranse Gouveia, B.; Wells, J.; Kim, J.; Collgros, H.; Guitera, P.; Longo, C.; Fernandez-Penas, P.
abstract

Background: Reflectance confocal microscopy (RCM) is a useful tool for many skin cancers, allowing non-invasive evaluation over time and identifying areas of active disease. Its role to follow-up mycosis fungoides (MF) patients has not yet been evaluated. Objective: To assess the level of agreement between RCM and histopathology and to develop a RCM checklist that could help monitoring MF patients. Method: Prospective study in a cutaneous lymphoma clinic of a tertiary hospital in Australia. RCM and biopsies were performed on the same area at baseline, before commencing or changing treatment, and at 6 months after starting treatment. Normal skin sites were also analysed and acted as controls. RCM features and histopathological findings were blindly evaluated by the confocalist and pathologist. Correlation between RCM and histology was measured by overall per cent of agreement (OPA), kappa and ROC curves. Additionally, RCM images before and after treatment were assessed blinded from clinical information and correlated to clinical assessment. Results: Thirty-eight MF lesions were included. Nineteen of these 38 were re-assessed by RCM 6 months later. Fifty biopsies were performed (38 at baseline and 12 after 6 months). The combination of four RCM features corresponding to Pautrier's microabscess, epidermal and junctional lymphocytes and interface dermatitis formed the RCM checklist for MF that predicted the severity of disease with AUC of 0.95 (P =.003). Conclusion: Reflectance confocal microscopy can assess activity within a lesion and over time and assist in the clinical management of patients with MF.

2021 - Sutton’s naevi as a pitfall for reflectance confocal microscopy: marked inflamed naevi could not be suitable for teleconfocal examination [Articolo su rivista]
Brugues, A.; Ribero, S.; Barreiro, A.; Bassoli, S.; Garcia, A. P.; Longo, C.; Segura, S.; Alos, L.; Malvehy, J.; Puig, S.; Carrera, C.
abstract

2021 - The role of ultrasound examination for early identification of lymph-node metastasis of cutaneous squamous cell carcinoma: results from a single institutional center [Articolo su rivista]
Pampena, Riccardo; Raucci, Margherita; Mirra, Marica; Lombardi, Mara; Piana, Simonetta; Kyrgidis, Athanassios; Peccerillo, Francesca; Paganelli, Alessia; Garbarino, Federico; Pellacani, Giovanni; Longo, Caterina
abstract

Metastasis from cutaneous squamous cell carcinoma (cSCC) mainly involve the regional nodal basin, with an incidence ranging from 2%-4% until 15% in case of high-risk tumors. When dealing with high-risk cSCC, ultrasound examination is recommended every 3- 4 months during follow up. We aimed to determine the role of US examination in the early diagnosis of nodal metastasis from cSCC.

2021 - The spectrum of morphologic patterns of nodular melanoma: a study of the International Dermoscopy Society [Articolo su rivista]
Niforou, A; Sgouros, D; Lallas, A; Zaras, A; Scope, A; Tsao, H; Argenziano, G; Longo, C; Kittler, H; Stratigos, A
abstract

2021 - Thumb up for a false alarm! [Articolo su rivista]
Pampena, Riccardo; Piana, Simonetta; Lai, Michela; Pellacani, Giovanni; Longo, Caterina
abstract

2021 - Treatment of Advanced Basal Cell Carcinoma with Hedgehog Pathway Inhibitors: A Multidisciplinary Expert Meeting [Articolo su rivista]
De Giorgi, Vincenzo; Scarfì, Federica; Trane, Luciana; Silvestri, Flavia; Venturi, Federico; Zuccaro, Biancamaria; Spinelli, Giuseppe; Scoccianti, Silvia; De Rosa, Francesco; Dika, Emi; Longo, Caterina
abstract

Despite recent progress and the publishing of several clinical guidelines on the management of advanced basal cell carcinoma, there is still no comprehensive set of clinical guidelines addressing the complexity inherent to the use of Hedgehog pathway inhibitors in the treatment of advanced basal cell carcinoma in real-world clinical practice. To develop practical and valuable tools that help specialists improve the clinical management of these patients, we sought the opinion of expert physicians with extensive knowledge and experience in the treatment of advanced basal cell carcinoma.

2020 - A meta-analysis on the influence of partial biopsy of primary melanoma on disease recurrence and patient survival [Articolo su rivista]
Moscarella, E; Pampena, R; Palmiotti, G; Bonamonte, D; Brancaccio, G; Piccolo, V; Longo, C; Argenziano, G
abstract

Complete surgical excision is the preferred biopsy type for suspicious melanocytic lesions. However, partial biopsy is sometimes used in special situations. Previous studies have explored the effect of partial biopsy of a primary melanoma on patient outcome with controversial results.

2020 - A survey on the use of reflectance confocal microscopy among dermatologists in Italy [Articolo su rivista]
Moscarella, Elvira; Agozzino, Marina; Longo, Caterina; Pellacani, Giovanni; Argenziano, Giuseppe
abstract

2020 - Adjuvant therapy for cutaneous melanoma: a systematic review and network meta-analysis of new therapies [Articolo su rivista]
Longo, C; Pampena, R; Lallas, A; Kyrgidis, A; Stratigos, A; Peris, K; Garbe, C; Pellacani, G
abstract

New drugs have been recently approved as adjuvant therapies for melanoma. In this Bayesian network meta-analysis, we aimed to assess the best therapeutic option in terms of Recurrence Free Survival (RFS), Overall Survival (OS) and adverse events (AEs). PubMed, Embase, Cochrane library and the American Society of Clinical Oncology databases were searched from inception until August the 20th 2018. We estimated adjusted hazard ratios (HRs) for RFS and OS and relative odds ratios (ORs) for AEs and surface under the cumulative ranking (SUCRA) probabilities were calculated. A number of 872 records were identified and six were finally included in the meta-analysis. A total of 4244 patients in 6 studies were randomized. The following therapies were considered in the selected studies: combined dabrafenib and trametinib, vemurafenib, nivolumab, ipilimumab, pembrolizumab. Nivolumab demonstrated the highest probability (75.1%) of being the best in term of RFS, followed by dabrafenib+trametinib, pembrolizumab, ipilimumab and vemurafenib; however, OS was not estimable. Concerning AEs, pembrolizumab and nivolumab showed the highest probability to be less associated with any and 3-4 grade AEs (83.1% and 64.4%, respectively). In conclusion, all new drugs are highly effective in adjuvant setting and the best choice is dependent of patient's context.

2020 - An intraoperative study with ex vivo fluorescence confocal microscopy: diagnostic accuracy of the three visualization modalities [Articolo su rivista]
Reggiani, C.; Pellacani, G.; Reggiani Bonetti, L.; Zanelli, G.; Azzoni, P.; Chester, J.; Kaleci, S.; Ferrari, B.; Bellini, P.; Longo, C.; Bertoni, L.; Magnoni, C.
abstract

Ex-vivo fluorescence confocal microscopy (FCM) is an imaging technique that captures real time digital images of freshly excised tissue with quasi histopathological resolution. FCM reduces time to image acquisition compared to hematoxylin and eosin (H&E) frozen section analysis.

2020 - Basal cell carcinoma or melanoma, that is the question! [Articolo su rivista]
Pampena, R; Lai, M; Piana, S; Pellacani, G; Longo, C
abstract

Both dermoscopy and in-vivo reflectance confocal microscopy (RCM) demonstrated high levels of diagnostic accuracy for basal cell carcinoma (BCC) diagnosis.1,2 Although specific dermoscopic criteria have been described, BCC may simulate other benign and malignant cutaneous tumors, with melanoma representing one of the most common differential diagnosis.3 RCM has been largely employed for both BCC diagnosis and management in in-vivo and ex-vivo settings.4 However, in few cases, RCM features could be misinterpreted especially by novices leading to delayed surgical excision.

2020 - Clinical and Dermoscopic Features Associated With Difficult-to-Recognize Variants of Cutaneous Melanoma: A Systematic Review [Articolo su rivista]
Pampena, Riccardo; Lai, Michela; Lombardi, Mara; Mirra, Marica; Raucci, Margherita; Lallas, Aimilios; Apalla, Zoe; Argenziano, Giuseppe; Pellacani, Giovanni; Longo, Caterina
abstract

The clinical and dermoscopic features of the vast majority of uncommon variants of cutaneous melanoma have been rarely reported, leading to difficulty in making accurate diagnoses.

2020 - Clinical and dermoscopic characteristics of congenital and noncongenital nevus-associated melanomas [Articolo su rivista]
Zalaudek, I.; Conforti, C.; Guarneri, F.; Vezzoni, R.; Deinlein, T.; Hofmann-Wellenhof, R.; Longo, C.; Moscarella, E.; Kittler, H.; Argenziano, G.; Giuffrida, R.
abstract

Background: No specific features of nevus-associated melanoma (NAM) are currently defined. Objective: To identify clinical/dermoscopic features of NAM. Methods: Retrospective evaluation of histopathologically diagnosed NAM. Results: Eighty of 165 NAMs had a clinically recognizable nevus component, often raised or nodular, most frequently characterized by different morphologic clones and/or colors. In 111 of 165 NAMs, dermoscopy showed a nevus component, prevalently characterized by regular dots/clods and structureless brown areas. Clinically, the melanoma component was eccentric/peripheral in 45 of 80 cases and central in 35 of 80; dermoscopically, the figures were 59 of 111 and 52 of 111, respectively. Melanomas associated with congenital nevi (C-NAMs) occur at a younger age and have a thicker Breslow depth than melanomas associated with acquired nevi (NC-NAMs). Dermoscopically, regular dots/globules characterize C-NAMs, and hypopigmented structureless areas characterize NC-NAMs. Limitations: Retrospective analysis. Conclusion: C-NAMs are more often central to a congenital nevus, with a clod/globular or structureless brown pattern, typical of young patients. NC-NAMs are frequently hypopigmented nodules/plaques, eccentric/peripheral, with hypopigmented structureless areas, typical of older patients.

2020 - Clinicopathological and dermoscopic features of amelanotic and hypomelanotic melanoma: a retrospective multicentric study [Articolo su rivista]
Paolino, G.; Bearzi, P.; Pampena, R.; Longo, C.; Frascione, P.; Rizzo, N.; Raucci, M.; Carbone, A.; Cantisani, C.; Ricci, F.; Didona, D.; Frattini, F.; Bulotta, A.; Gregorc, V.; Mercuri, S. R.
abstract

Background: Amelanotic and hypomelanotic melanoma (AHM) has a higher risk of delayed diagnosis and a significant lower 5-year melanoma-specific survival compared to pigmented melanoma. Our aim was the evaluation of the clinicopathological/dermoscopic features of amelanotic melanoma (AM) and hypomelanotic melanoma (HM). Methods: All participants had a personal history of AHM. We defined HM as showing clinical/dermoscopic pigmentation in < 25% of the lesion’s surface and histopathological focal pigmentation, while AM as melanomas with clinical/dermoscopic and histopathological absence of pigmentation. Results: The most common phenotypic traits among the 145 AHM patients were as follows: phototype II, blue-grey eyes, and dark brown hair. Red hair was present in 23.8% AHM cases (AM = 22.60%; HM = 25.80%). The most affected area was the back (29.5%). A total of 67.1% were classified as AM and 32.9% as HM. The most represented hair colors in AM and HM were, respectively, blonde and dark brown hair. Median Breslow thickness was 1.7 mm, superficial spreading melanoma (SSM) and nodular melanoma (NM) were the most represented histotypes, and mitotic rate > 1 × mm2 was reported in 73.3% cases, and regression was significantly more present in HM. Dermoscopy showed high prevalence of white structureless zones (63.4%), linear looped vessels (58.8%), linear irregular vessels (50.0%), and arborizing vessels (47.2%). Multivariate logistic regression confirmed the association between the presence of pigmentation and the following: histological regression, dermoscopic globules, and arborizing vessels. Conclusions: Predominance of red hair in AHM patients was not confirmed. AHM affects mostly intermittent sun-exposed body areas. The deeper median Breslow thickness (versus pigmented melanoma), the association of AM with the nodular histotype, and the high mitotic rate highlight the AHM’s aggressiveness. HM’s higher levels of regression can be explained by the presence of pigmentation, driving the underlying immune response. AHM showed a polymorphous vascular pattern and significant presence of arborizing vessels (especially HM).

2020 - Color Atlas of Dermoscopy [Curatela]
Argenziano, G.; Moscarella, E.; Piccolo, V.; Agozzino, M.; Longo, C.; Pellacani, G.
abstract

A trip to the dermatologist’s office on a regular basis is always useful. Should we notice one of our moles changing its appearance, for example, we’d better have it checked. Don’t be afraid. Dermatologists have now a reliable, non-invasive method at their disposal: DERMOSCOPY. Dermoscopy has been defined the millennium method, since it is fast, easy to apply and convenient. There is also a hint of oriental wisdom at the basis of Dermoscopy. According to traditional oriental medicine, a good doctor should be able to make a diagnosis even just looking at the patient. Indeed, the careful and methodical observation, with the help of a dermatoscope (a simple optical lens) of skin lesions, has allowed dermatologists to discover many new models of pigmented and-non pigmented lesions and today Dermoscopy represents the standard for the diagnosis of melanoma and skin tumors in general diagnosis of lesions and skin cancers.

2020 - Correlation Between Dermoscopic and Histologic Features of Uncommon Cutaneous Melanoma Variants-Reply [Articolo su rivista]
Longo, Caterina; Lai, Michela; Pampena, Riccardo
abstract

2020 - Dark pigmented lesions: diagnostic accuracy of dermatoscopy and reflectance confocal microscopy in a tertiary referral center for skin cancer diagnosis [Articolo su rivista]
Longo, Caterina; Mazzeo, Mauro; Raucci, Margherita; Cornacchia, Luigi; Lai, Michela; Bianchi, Luca; Peris, Ketty; Pampena, Riccardo; Pellacani, Giovanni
abstract

There is lack of studies on the diagnostic accuracy of dermatoscopy and reflectance confocal microscopy (RCM) for dark pigmented lesions.

2020 - Dermatoscopic features of thin (≤ 2mm Breslow thickness) versus thick (> 2mm Breslow thickness) nodular melanoma and predictors of nodular melanoma versus nodular non-melanoma tumors: a multicentric collaborative study by the International Dermoscopy Society [Articolo su rivista]
Sgouros, D; Lallas, A; Kittler, H; Zarras, A; Kyrgidis, A; Papageorgiou, C; Puig, S; Scope, A; Argenziano, G; Zalaudek, I; Pizzichetta, M A; Marghoob, A; Liopyris, K; Malvehy, J; Oikonomou, C; Flórez, A; Braun, R; Cabo, H; Nazzaro, G; Lanssens, S; Menzies, S; Paoli, J; Kaminska-Winciorek, G; Longo, C; Katoulis, A; Apalla, Z; Ioannides, D; Thomas, L; Tromme, I; Ogata, D; Desinioti, C; Geller, A; Stratigos, A
abstract

Thin nodular melanoma (NM) often lacks conspicuous melanoma-specific dermatoscopic criteria, and escapes clinical detection until it progresses to a thicker and more advanced tumor.

2020 - Dermatoscopy of combined blue nevi: A multicenter study of the International Dermoscopy Society [Articolo su rivista]
Stojkovic-Filipovic, J; Tiodorovic, D; Lallas, A; Akay, B N; Longo, C; Rosendahl, C; Dobrosavljevic, D; Nazzaro, G; Argenziano, G; Zalaudek, I; Tromme, I; Tschandl, P; Puig, S; Lanssens, S; Kittler, H
abstract

BACKGROUND: Combined blue nevi may mimic melanoma and are relatively often biopsied for diagnostic reasons.OBJECTIVE: To better characterize combined blue nevi and to compare it with melanoma.METHODS: We collected clinical and dermatoscopic images of 111 histologically confirmed combined blue nevi and contrasted their dermatoscopic characteristics with 132 partly blue colored melanomas. Furthermore, we compared the accuracy of human experts using pattern analysis with a computer algorithm based on deep learning.RESULTS: Combined blue nevi are usually flat or slightly elevated and, in comparison to melanoma, more frequent on the head and neck. Dermatoscopically, they are typified by a blue structureless part in combination with either brown clods (n=52, 46.8%), lines (n=28, 25.2%), or skin-colored or brown structureless areas (n=31, 27.9%). In contrast to melanoma, the blue part of combined blue nevi is more often well defined (18.9% versus 4.5%, p<0.001) and more often located in the center (22.5% versus 5.3%, p<0.001). Melanomas are more often chaotic (OR: 28.7, 95% CI: 14.8-55.7, p<0.001), have at least one melanoma clue (OR: 10.8, 95% CI: 5.2-22.2 p<0.001) in particular white lines (OR: 37.1, 95% CI: 13.4-102.9, p<0.001). Using simplified pattern analysis (chaos and clues), two raters reached sensitivities of 93.9% (95% CI: 88.4-97.3%) and 92.4% (95% CI: 86.5-96.3%) at corresponding specificities of 59.5% (95% CI: 49.7-68.7%) and 65.8% (95% CI: 56.2-74.5%). The human accuracy with pattern analysis was on par with a state-of-the-art computer algorithm based on deep learning that achieved an area under the curve of (0.92, 95% CI: 0.87-0.96) and a specificity of 85.3% (95% CI: 76.5-91.7%) at a given sensitivity of 83.6% (95% CI: 72.5-91.5%).CONCLUSION: Combined blue nevi usually lack melanoma clues, in particular white lines. The accuracy of pattern analysis for combined nevi is acceptable and histopathologic confirmation may not be necessary in exemplary cases.

2020 - Dermoscopic and clinical predictors of reflectance confocal microscopy patterns of typical nevi on the back and legs: A cross-sectional study [Articolo su rivista]
Scope, Alon; Farnetani, Francesca; Haupt, Sara; Schechtman, Edna; Longo, Caterina; Pellacani, Giovanni
abstract

Nevus phenotype is a marker of melanoma risk. In-vivo prediction of microscopic pattern is needed to more precisely classify nevi.

2020 - Dermoscopy and confocal microscopy of small sized basal cell carcinoma (diameter less than 5 mm): a report of 12 cases [Articolo su rivista]
Pampena, Riccardo; Specchio, Francesca; Ragazzi, Moira; Pellacani, Giovanni; Longo, Caterina
abstract

NA

2020 - Dermoscopy comparative approach for early diagnosis in familial melanoma: influence of MC1R genotype [Articolo su rivista]
Longo, C; Barquet, V; Hernandez, E; Marghoob, A A; Potrony, M; Carrera, C; Aguilera, P; Badenas, C; Malvehy, J; Puig, S
abstract

MC1R polymorphisms interact with CDKN2A mutations modulating melanoma risk and contribute to a less suspicious clinical and dermoscopic appearance of melanomas. Different strategies, including dermoscopic comparative approach and digital monitoring, are used for the melanoma diagnosis in this context.

2020 - Development of a Core Outcome Set for Cutaneous Squamous Cell Carcinoma Trials: Identification of Core Domains and Outcomes [Articolo su rivista]
Reynolds, K A; Schlessinger, D I; Yanes, A F; Godinez-Puig, V; Chen, B R; Kurta, A O; Cotseones, J K; Chiren, S G; Iyengar, S; Ibrahim, S A; Kang, B Y; Worley, B; Behshad, R; DeHoratius, D M; Denes, P; Drucker, A M; Dzubow, L M; Etzkorn, J R; Harwood, C A; Kim, J Y S; Lawrence, N; Lee, E H; Lissner, G S; Marghoob, A A; Matin, R N; Mattox, A R; Mittal, B B; Thomas, J R; Zhou, X A; Zloty, D; Hughes, B G M; Nottage, M K; Green, A C; Testori, A A E; Argenziano, G; Longo, C; Zalaudek, I; Lebbe, C; Malvehy, J; Saiag, P; Cernea, S S; Schmitt, J; Kirkham, J J; Poon, E; Sobanko, J F; Cartee, T V; Maher, I A; Alam, M
abstract

BACKGROUND: The lack of uniformity in the outcomes reported in clinical studies of the treatment of cutaneous squamous cell carcinoma (cSCC) complicates efforts to compare treatment effectiveness across trials.OBJECTIVE: To develop a core outcome set (COS), a minimum set of agreed-upon outcomes to be measured in all clinical trials of a given disease or outcome, for the treatment of cSCC.METHODS: One hundred nine outcomes were identified via a systematic literature review and interviews with 28 stakeholders. After consolidation of this long list, 55 candidate outcomes were rated by 19 physician and 10 patient stakeholders, respectively, in two rounds of Delphi exercises. Outcomes scored 'critically important' (scored 7,8, or 9) by 70% of patients and 70% of physicians were provisionally included. At the consensus meeting, after discussion and voting of 44 international experts and patients, the provisional list was reduced to a final core set, for which consensus was achieved among all meeting participants.RESULTS: A core set of seven outcomes was finalized at the consensus meeting: serious or persistent adverse events, patient-reported quality of life, complete response, partial response, recurrence-free survival, progression-free survival, and disease-specific survival.CONCLUSIONS: In order to increase the comparability of results across trials and to reduce selective reporting bias, cSCC researchers should consider reporting these core outcomes. Further work needs to be performed to identify the measures that should be reported for each of these outcomes.

2020 - Digital dermoscopic changes during follow-up of de-novo and nevus-associated melanoma: a cohort study [Articolo su rivista]
Pampena, Riccardo; Manfreda, Valeria; Kyrgidis, Athanassios; Lai, Michela; Borsari, Stefania; Benati, Elisa; Lombardi, Mara; Bianchi, Luca; Zalaudek, Iris; Moscarella, Elvira; Lallas, Aimilios; Argenziano, Giuseppe; Pellacani, Giovanni; Longo, Caterina
abstract

Nevus-associated melanoma (NAM) has been regarded as a distinct biological entity from de-novo melanoma (DNM); however, static dermoscopy often fails in differentiating these entities. Digital dermoscopic monitoring allows to identify dynamic changes occurring during follow-up; this may improve diagnostic accuracy and potentially our knowledge on NAM biology. We aimed to define main independent factors associated with NAM diagnosis and those influencing follow-up time in a population of melanomas excised at follow-up.

2020 - Digital follow-up by means of dermatoscopy and reflectance confocal microscopy of actinic keratosis treated with Imiquimod 3.75% cream [Articolo su rivista]
Benati, E.; Longhitano, S.; Pampena, R.; Mirra, M.; Raucci, M.; Pellacani, G.; Longo, C.
abstract

Background: Imiquimod 3.75% cream (Zyclara® Meda, Stockholm, Sweden) is a new field-directed therapy for actinic keratosis (AK). Objectives: The aim is to evaluate efficacy and the morphologic dynamic changes induced by this treatment by means of dermatoscopy and reflectance confocal microscopy (RCM) of imiquimod 3.75% cream for the treatment of AKs of the face or scalp and to evaluate. Methods: Thirty-two patients were treated with Imiquimod 3.75% cream. Demographic parameters, AK-FAS and AKASI scores and side-effects were collected. RCM and dermatoscopy on one target AKs were performed at each visit. We collected images at baseline (T0), after 1 week from the end of the first 2-week cycle (T1), after 1 week from the end of the entire treatment (T2) and 2 months after the end of treatment (T3). Results: One target representative AK in the selected area of treatment of each patient was analysed. All dermoscopic and confocal parameters were reduced 2 months after the end of the therapy (T3) with a substantial reduction of AKASI and AK-FAS scores, and 17 cases (54.8%) were completely solved. Confocal microscopic analysis showed a reduction of keratinocytes disarray in 77.4% of cases; none showed crusts and parakeratosis. Inflammation was considerably decreased and was observed only in 12.9% of patients at the last visit. This improvement was not assessed on dermatoscopy because of inflammation and background erythema, which adversely influenced the assessments. LSRs were observed in almost all the patients during treatment being more severe after the first cycle of treatment (T1). Conclusions: Imiquimod 3.75% cream is effective in treating clinical and subclinical AKs with an easy management of side-effects. Dermatoscopy and mostly RCM allow non-invasive monitoring of treatment response in vivo.

2020 - Factors Affecting Sentinel Node Metastasis in Thin (T1) Cutaneous Melanomas: Development and External Validation of a Predictive Nomogram [Articolo su rivista]
Maurichi, Andrea; Miceli, Rosalba; Eriksson, Hanna; Newton-Bishop, Julia; Nsengimana, Jérémie; Chan, May; Hayes, Andrew J.; Heelan, Kara; Adams, David; Patuzzo, Roberto; Barretta, Francesco; Gallino, Gianfranco; Harwood, Catherine; Bergamaschi, Daniele; Bennett, Dorothy; Lasithiotakis, Konstantinos; Ghiorzo, Paola; Dalmasso, Bruna; Manganoni, Ausilia; Consoli, Francesca; Mattavelli, Ilaria; Barbieri, Consuelo; Leva, Andrea; Cortinovis, Umberto; Espeli, Vittoria; Mangas, Cristina; Quaglino, Pietro; Ribero, Simone; Broganelli, Paolo; Pellacani, Giovanni; Longo, Caterina; Del Forno, Corrado; Borgognoni, Lorenzo; Sestini, Serena; Pimpinelli, Nicola; Fortunato, Sara; Chiarugi, Alessandra; Nardini, Paolo; Morittu, Elena; Florita, Antonio; Cossa, Mara; Valeri, Barbara; Milione, Massimo; Pruneri, Giancarlo; Zoras, Odysseas; Anichini, Andrea; Mortarini, Roberta; Santinami, Mario
abstract

Thin melanomas (T1; # 1 mm) constitute 70% of newly diagnosed cutaneous melanomas. Regional node metastasis determined by sentinel node biopsy (SNB) is an important prognostic factor for T1 melanoma. However, current melanoma guidelines do not provide clear indications on when to perform SNB in T1 disease and stress an individualized approach to SNB that considers all clinicopathologic risk factors. We aimed to identify determinants of sentinel node (SN) status for incorporation into an externally validated nomogram to better select patients with T1 disease for SNB.

2020 - Flat-pigmented facial lesions without highly specific melanocytic dermoscopy features: the role of dermoscopic globules and dots in differential diagnosis with corresponding reflectance confocal microscopy substrates [Articolo su rivista]
Guida, S; Farnetani, F; De Pace, B; Shaniko, K; Chester, J; Stanganelli, I; Ciardo, S; De Carvalho, N; Longo, C; Pellacani, G
abstract

Dermoscopy is the first and often only level of non-invasive diagnostic investigation for cutaneous disease. However, differential diagnosis of lentigo maligna (LM) is difficult with dermoscopy because of shared dermoscopic features with flat-pigmented non-melanocytic skin neoplasms (NMSN).1-3 Previous authors have identified some dermoscopic features as suggestive for melanocytic lesions and highly suggestive for LM; grey rhomboidal structures, non-evident follicles, grey circles and intense pigmentation.

2020 - Human–computer collaboration for skin cancer recognition [Articolo su rivista]
Tschandl, P.; Rinner, C.; Apalla, Z.; Argenziano, G.; Codella, N.; Halpern, A.; Janda, M.; Lallas, A.; Longo, C.; Malvehy, J.; Paoli, J.; Puig, S.; Rosendahl, C.; Soyer, H. P.; Zalaudek, I.; Kittler, H.
abstract

The rapid increase in telemedicine coupled with recent advances in diagnostic artificial intelligence (AI) create the imperative to consider the opportunities and risks of inserting AI-based support into new paradigms of care. Here we build on recent achievements in the accuracy of image-based AI for skin cancer diagnosis to address the effects of varied representations of AI-based support across different levels of clinical expertise and multiple clinical workflows. We find that good quality AI-based support of clinical decision-making improves diagnostic accuracy over that of either AI or physicians alone, and that the least experienced clinicians gain the most from AI-based support. We further find that AI-based multiclass probabilities outperformed content-based image retrieval (CBIR) representations of AI in the mobile technology environment, and AI-based support had utility in simulations of second opinions and of telemedicine triage. In addition to demonstrating the potential benefits associated with good quality AI in the hands of non-expert clinicians, we find that faulty AI can mislead the entire spectrum of clinicians, including experts. Lastly, we show that insights derived from AI class-activation maps can inform improvements in human diagnosis. Together, our approach and findings offer a framework for future studies across the spectrum of image-based diagnostics to improve human–computer collaboration in clinical practice.

2020 - In-vivo confocal microscopy: the role of comparative approach in patients with multiple atypical nevi [Articolo su rivista]
Longhitano, Sabrina; Pampena, Riccardo; Guida, Stefania; De Pace, Barbara; Ciardo, Silvana; Chester, Johanna; Longo, Caterina; Farnetani, Francesca; Pellacani, Giovanni
abstract

In-vivo reflectance confocal microscopy (RCM) increases diagnostic accuracy for melanoma diagnosis when combined with dermoscopy. In patients with multiple atypical nevi a comparative dermoscopic approach improves melanoma recognition and saves unnecessary excision. The performance of a comparative approach combining dermoscopy and RCM has not been yet investigated.

2020 - Looking horizontally at disseminated superficial actinic porokeratosis: Correlations between in-vivo reflectance confocal microscopy and histopathology [Articolo su rivista]
Mazzeo, M.; Longo, C.; Manfreda, V.; Piana, S.; Bianchi, L.; Pellacani, G.; Pampena, R.
abstract

2020 - Lost in Translation: True Clinical Impact of RCM Overlooked in "Biopsy outperforms Reflectance Confocal Microscopy in Diagnosing and Subtyping Basal Cell Carcinoma: Results and Experiences from a Randomized Controlled Multicentre Trial" [Articolo su rivista]
Gill, M; Pellacani, G; Grant-Kels, J M; Ardigò, M; Chen, C-S J; Gonzalez, S; Guitera, P; Longo, C; Malvehy, J; Markowitz, O; Puig, S; Rabinovitz, H; Rao, B K; Scope, A; Ulrich, M
abstract

In 'Biopsy Outperforms Reflectance Confocal Microscopy in Diagnosing and Subtyping Basal Cell Carcinoma: Results and Experiences from a Randomized Controlled Multicentre Trial', the authors found that reflectance confocal microscopy (RCM) identifies basal cell carcinoma (BCC) with 99% sensitivity and, impressively, distinguishes superficial BCCs from more aggressive BCCs with 88.9% sensitivity compared to punch biopsy (PB) at 91%,1 a difference without statistical significance.

2020 - Management of cutaneous melanoma: comparison of the leading international guidelines updated to the 8th American Joint Committee on Cancer staging system and workup proposal by the Italian Society of Dermatology [Articolo su rivista]
Argenziano, Giuseppe; Brancaccio, Gabriella; Moscarella, Elvira; Dika, Emi; Fargnoli, Maria C; Ferrara, Gerardo; Longo, Caterina; Pellacani, Giovanni; Peris, Ketty; Pimpinelli, Nicola; Quaglino, Pietro; Rongioletti, Franco; Simonacci, Marco; Zalaudek, Iris; Calzavara Pinton, Piergiacomo
abstract

2020 - Melanomas of the scalp: is hair coverage preventing early diagnosis? [Articolo su rivista]
Pereira, A. R.; Collgros, H.; Guitera, P.; Benati, E.; Longo, C.; Argenziano, G.; Dika, E.; Lambertini, M.; Menzies, S. W.; Lobato Williams, A.; Gallo, B. M.; Hirata, S. H.
abstract

Background: Scalp melanomas are usually thicker and show worse prognosis than other sites and other head and neck melanomas. One hypothesis to explain this aggressive behavior could be diagnosis delay attributed to hair concealment of lesions. Methods: Primary melanomas of the scalp diagnosed over two decades at four reference centers in Australia and Italy were included. Hair coverage and visibility of the lesions were assessed on preoperative photographic documentation by two investigators and correlated with some prognostic factors (Breslow thickness, mitotic rate, and ulceration). Patients records and pathology reports provided clinical and histological data. Results: The majority of 113 melanomas included were located on easily visible areas of the scalp – hairless scalp (49%) or hairline (15%). The remaining ones (36%), considered to be hair-covered, showed more frequently thinning of hair (63%) than a dense hair coverage (37%). Melanomas of “hairy scalps” were more frequently invasive (81%) and had higher median Breslow (0.8 ± 1.3 mm) than those arising on bald scalps or areas with thinning of hair (43%; 0 ± 0.6 mm), P = 0.004. However, when considering only the invasive cases (n = 55), Breslow thickness and mitotic rate were not statistically different between concealed and easily visible areas. Melanomas detected by a doctor were thinner than those first noticed by the patient, relatives, or a hairdresser (P < 0.001). Conclusions: Most scalp melanomas arose on easily visible areas, which are more prone to ultraviolet damage. Hair-covered ones, despite rare, could be overlooked during examination. Proactive screening of the scalp area should be encouraged.

2020 - Molecular genetics of cutaneous squamous cell carcinoma: perspective for treatment strategies [Articolo su rivista]
Di Nardo, Lucia; Pellegrini, Cristina; Di Stefani, Alessandro; Del Regno, Laura; Sollena, Pietro; Piccerillo, Alfredo; Longo, Caterina; Garbe, Claus; Fargnoli, Maria Concetta; Peris, Ketty
abstract

Cutaneous squamous cell carcinoma (cSCC) represents 20% of all skin cancers. Although primary cSCCs can be successfully treated with surgery, a subset of highly aggressive lesions may progress to advanced disease, representing a public health care problem with significant cancer-related morbidity and mortality. A complex network of genes (TP53, CDKN2A, NOTCH1 and NOTCH2, EGFR and TERT) and molecular pathways (RAS/RAF/MEK/ERK and PI3K/AKT/mTOR) have been shown to play an important role in the pathogenesis of cSCC. The epigenetic regulation of TP53 and CDKN2A is an attractive therapeutic target for the treatment of cSCC, as well as NOTCH activating agents capable to restore its tumour-suppressor function. EGFR inhibitors including both monoclonal antibodies (cetuximab and panitumumab) and tyrosine kinase inhibitors (erlotinib, gefitinib and dasatinib) have been used in clinical trials for the treatment of advanced cSCC, achieving only partial clinical benefit. Recently, an immune-modulatory drug (cemiplimab) has been introduced for the treatment of advanced cSCC with good clinical results and a favourable safety profile, while other PD1/PD-L1 inhibitors, either as monotherapy or in combination with targeted therapies, are currently under investigation. This review focuses on molecular findings involved in the pathogenesis of cSCC and their implications for the future development of new treatment strategies. In addition, current and ongoing treatments on targeted therapies and/or immunotherapy are illustrated.

2020 - Neck Melanoma: Clinical, Dermoscopic and Confocal Features [Articolo su rivista]
Borsari, Stefania; Pampena, Riccardo; Raucci, Margherita; Mirra, Marica; Piana, Simonetta; Pellacani, Giovanni; Longo, Caterina
abstract

The head and neck are considered one single anatomical unit. No data on clinical, dermoscopic and confocal aspects of neck melanoma are currently available.

2020 - Nevus-associated melanoma: facts and controversies [Articolo su rivista]
Pampena, Riccardo; Lai, Michela; Piana, Simonetta; Lallas, Aimilios; Pellacani, Giovanni; Longo, Caterina
abstract

Nevus-associated melanoma (NAM) is defined on histopathological basis by the coexistence of melanoma and nevus components. Melanomas developing on pre-existing congenital or acquired nevi are usually of the superficial spreading subtype and harbor the BRAFV600E mutation. NAM accounts for almost one-third of melanoma cases As compared to de novo melanoma, NAM develops on younger patients, is more frequently located on the trunk, and is associated with a high nevus count, light eye color and history of frequent sunburns. NAM has been regarded as a model to investigate melanoma origin. Molecular analysis defining the mutation profile of NAM's nevus and melanoma components supported the existence of two pathways of melanoma development, the first not involving clinically visible precursors, the second involving melanocytic nevi as precursors. Concerning diagnosis, dermatoscopy may identify nevus and melanoma components when located side-by-side, but no specific criteria have been described when superimposed. In-vivo reflectance confocal microscopy significantly enhances the recognition of NAM by allowing the detection of nevus remnants when superficially located. Regarding prognosis, NAM is generally thinner and more frequently in-situ than de-novo melanoma. Furthermore, studies reporting survival analysis demonstrated a trend towards better overall, distant-metastasis-free and recurrence-free survival. Although a clinical, phenotypic and molecular profile of NAM has been defined, controversies still exist. In the current review, we widely report and discuss facts and controversies on NAM.

2020 - Reflectance confocal microscopy diagnostic accuracy for malignant melanoma in different clinical settings: systematic review and meta-analysis [Articolo su rivista]
Pezzini, C.; Kaleci, S.; Chester, J.; Farnetani, F.; Longo, C.; Pellacani, G.
abstract

Background: The diagnostic accuracy of reflectance confocal microscopy (RCM) of cutaneous malignant melanoma (MM) seems promising. However, clinical scenarios in which RCM is most useful are still to be established. Objectives: To assess the diagnostic accuracy of RCM for MM diagnosis according to study design, lesion type and diagnostic modality. Secondary outcomes include a comparison with dermoscopy. Methods: A systematic literature search was conducted on PubMed, Embase, Scopus and Cochrane Public Library Databases for English articles published prior to January 2019. Statistical analyses were conducted with Meta-Disc v. 1.4, STATA 14.0 software and the QUADAS-2 tool. Results: A total of 32 studies (7352 lesions) were included in the meta-analysis. Pooled sensitivity and specificity resulted 92% (95% CI: 0.91–0.93) and 70% (95% CI: 0.69–0.71), respectively. According to study design, diagnostic sensitivity was high for all study types, confirming a lower specificity for prospective interventional studies. Diagnostic accuracy remained high for all lesion types, with the highest specificity obtained for consecutive lesions of 77% (95% CI: 0.75–0.78) vs. 65% (95% CI: 0.63–0.66) for lesions highly suspicious for MM. RCM diagnostic accuracy was superior to dermoscopy, most notably in terms of specificity of 56% (95% CI: 0.52–0.60) vs. 38% (95% CI: 0.34–0.42), respectively. Studies were generally assessed across all domains as low or unclear risk of bias with a mainly low concern regarding applicability of evidence. Publication bias was asymmetrical (11.2 ± 4.0; 95% CI 2.97–19.43; P < 0.01). Conclusions: Independent of study design, RCM has a high diagnostic power for MM detection, and unnecessary excisions are reduced compared to dermoscopy. This reduction is most evident in non-decisional RCM scenarios and for lesions analysed at RCM consecutively compared to those selected highly suspicious for MM. However, the scarcity, heterogeneity and bias associated with the data in literature should be considered when interpreting present conclusions.

2020 - Reflectance confocal microscopy for striae distansae treatment monitoring after CO2 fractional laser [Articolo su rivista]
Guida, Stefania; Losi, Amanda; Greco, Maurizio; Ciardo, Silvana; Pellacani, Giovanni; Longo, Caterina
abstract

The aim of this study is to describe the efficacy and safety of CO2 fractional laser to treat striae distensae (SD), before (T0) and 1 month after the last laser session (T1), in patients following different protocols based on the number of laser sessions, ≤4 and > 4. Efficacy was estimated with global assessment improvement scale (GAIS) performed by both physicians and patients, reflectance confocal microscopy (RCM), dermatology life quality index (DLQI). Safety was evaluated through pain assessment and adverse events. Eighteen patients with SD were enrolled. Clinical improvement of SD was observed in all patients at T1, as compared to T0. Furthermore, a reduction of RCM features of SD was observed at T1, above all in patients receiving >4 treatments, as compared to T0. Interestingly, we describe herein a new RCM feature of SD, the "neat-wall", corresponding to a distortion of the normal DEJ, with a well-demarcated margin. A significant improvement of DLQI (P-value = 0.007) was also registered after SD treatment. Adverse events included temporary erythema and edema. In conclusion, the current study confirms the efficacy and safety of fractional CO2 laser, proposing RCM features, such as parallel collagen fibers and the neat-wall, as potential markers of SD treatment response. This article is protected by copyright. All rights reserved.

2020 - Reflectance confocal microscopy terminology glossary for melanocytic skin lesions: A systematic review [Articolo su rivista]
Navarrete-Dechent, Cristian; Liopyris, Konstantinos; Monnier, Jilliana; Aleissa, Saud; Boyce, Lindsay M; Longo, Caterina; Oliviero, Margaret; Rabinovitz, Harold; Marghoob, Ashfaq A; Halpern, Allan C; Pellacani, Giovanni; Scope, Alon; Jain, Manu
abstract

There is lack of uniformity in the reflectance confocal microscopy (RCM) terminology for melanocytic lesions.

2020 - Reply to E. Hindié [Articolo su rivista]
Maurichi, Andrea; Miceli, Rosalba; Eriksson, Hanna; Newton-Bishop, Julia; Nsengimana, Jérémie; Chan, May; Hayes, Andrew J; Heelan, Kara; Adams, David; Patuzzo, Roberto; Barretta, Francesco; Gallino, Gianfranco; Harwood, Catherine; Bergamaschi, Daniele; Bennett, Dorothy; Lasithiotakis, Konstantinos; Ghiorzo, Paola; Dalmasso, Bruna; Manganoni, Ausilia; Consoli, Francesca; Mattavelli, Ilaria; Barbieri, Consuelo; Leva, Andrea; Cortinovis, Umberto; Espeli, Vittoria; Mangas, Cristina; Quaglino, Pietro; Ribero, Simone; Broganelli, Paolo; Pellacani, Giovanni; Longo, Caterina; Del Forno, Corrado; Borgognoni, Lorenzo; Sestini, Serena; Pimpinelli, Nicola; Fortunato, Sara; Chiarugi, Alessandra; Nardini, Paolo; Morittu, Elena; Florita, Antonio; Cossa, Mara; Valeri, Barbara; Milione, Massimo; Pruneri, Giancarlo; Zoras, Odysseas; Anichini, Andrea; Mortarini, Roberta; Santinami, Mario
abstract

2020 - Segmentation of cellular patterns in confocal images of melanocytic lesions in vivo via a multiscale encoder-decoder network (MED-Net) [Articolo su rivista]
Kose, K.; Bozkurt, A.; Alessi-Fox, C.; Gill, M.; Longo, C.; Pellacani, G.; Dy, J. G.; Brooks, D. H.; Rajadhyaksha, M.
abstract

In-vivo optical microscopy is advancing into routine clinical practice for non-invasively guiding diagnosis and treatment of cancer and other diseases, and thus beginning to reduce the need for traditional biopsy. However, reading and analysis of the optical microscopic images are generally still qualitative, relying mainly on visual examination. Here we present an automated semantic segmentation method called “Multiscale Encoder-Decoder Network (MED-Net)” that provides pixel-wise labeling into classes of patterns in a quantitative manner. The novelty in our approach is the modeling of textural patterns at multiple scales (magnifications, resolutions). This mimics the traditional procedure for examining pathology images, which routinely starts with low magnification (low resolution, large field of view) followed by closer inspection of suspicious areas with higher magnification (higher resolution, smaller fields of view). We trained and tested our model on non-overlapping partitions of 117 reflectance confocal microscopy (RCM) mosaics of melanocytic lesions, an extensive dataset for this application, collected at four clinics in the US, and two in Italy. With patient-wise cross-validation, we achieved pixel-wise mean sensitivity and specificity of 74% and 92%, respectively, with 0.74 Dice coefficient over six classes. In the scenario, we partitioned the data clinic-wise and tested the generalizability of the model over multiple clinics. In this setting, we achieved pixel-wise mean sensitivity and specificity of 77% and 94%, respectively, with 0.77 Dice coefficient. We compared MED-Net against the state-of-the-art semantic segmentation models and achieved better quantitative segmentation performance. Our results also suggest that, due to its nested multiscale architecture, the MED-Net model annotated RCM mosaics more coherently, avoiding unrealistic-fragmented annotations.

2020 - Standardization of dermoscopic terminology and basic dermoscopic parameters to evaluate in general dermatology (non-neoplastic dermatoses): an expert consensus on behalf of the International Dermoscopy Society [Articolo su rivista]
Errichetti, E; Zalaudek, I; Kittler, H; Apalla, Z; Argenziano, G; Bakos, R; Blum, A; Braun, R; Ioannides, D; Lacarrubba, F; Lazaridou, E; Longo, C; Micali, G; Moscarella, E; Paoli, J; Papageorgiou, C; Russo, T; Scope, A; Stinco, G; Thomas, L; Toncic, R J; Tschandl, P; Cabo, H; Hallpern, A; Hofmann-Wellenhof, R; Malvehy, J; Marghoob, A; Menzies, S; Pellacani, G; Puig, S; Rabinovitz, H; Rudnicka, L; Vakirlis, E; Soyer, P; Stolz, W; Tanaka, M; Lallas, A
abstract

Over the last few years, several articles on dermoscopy of non-neoplastic dermatoses have been published, yet there is poor consistency in the terminology among different studies.

2020 - Systematic review and proposal of an in vivo reflectance confocal microscopy assessment tool for cutaneous lymphoma [Articolo su rivista]
Melhoranse Gouveia, B.; Wells, J.; Kim, J.; Consuegra, G.; Longo, C.; Fernandez-Penas, P.
abstract

Background Reflectance confocal microscopy (RCM) is a non-invasive imaging technique that provides dynamic information and allows in vivo monitoring, with excellent histologic correlation. In the last decade, the use of RCM for cutaneous T-cell lymphomas (CTCL) has been reported. CTCL may require multiple biopsies for diagnosis due to its equivocal clinical presentation. RCM was described as a possible tool to help determine the best site for skin biopsy. This study aims to systematically review all RCM features reported in literature for CTCL. Method A systematic literature search concerning CTCL evaluated by RCM was performed in eight electronic databases until May 2019 following PRISMA-DTA quality assessment. Results Eighteen RCM features were described in patients with CTCL. The most frequent were: interface dermatitis (89%), epidermal lymphocytes (82%), epidermal architectural disarray (81%), and vesicle-like structure (Pautrier microabscess) (51%). Conclusion In order to establish comparable parameters among the studies identified, we proposed descriptors for CTCL features and a grading system to quantify them. This will facilitate to define the role of RCM in the diagnosis and monitoring of CTCL patients.

2020 - The Comparative Use of Multiple Electronic Devices in the Teledermoscopic Diagnosis of Early Melanoma [Articolo su rivista]
Tognetti, Linda; Cartocci, Alessandra; Balistreri, Alberto; Cataldo, Gennaro; Cinotti, Elisa; Moscarella, Elvira; Farnetani, Francesca; Lallas, Aimilios; Tiodorovic, Danica; Carrera, Cristina; Longo, Caterina; Puig, Susanna; Perrot, Jean Luc; Argenziano, Giuseppe; Pellacani, Giovanni; Rubegni, Pietro; Cevenini, Gabriele
abstract

Background: The use of mobile electronic devices as support to medical activity was largely implemented in the past decade. Introduction: Our first aim was to evaluate the frequency of use of different electronic devices, that is, personal computer (PC), notebook, tablet, smartphone, in a pool of dermatologists recruited to perform multiple online testing session on difficult melanocytic skin lesions (MSLs) cases. The second aim was to evaluate the feasibility of each device in terms of teledermatologic diagnostic performance; the use of four different diagnostic methods, that is, intuitive diagnosis and three dermoscopic algorithms, was also investigated. Materials and Methods: A total of 111 dermatologists with 4 different levels of experience in dermoscopy, performed 4 tests (intuitive diagnosis and iDScore, ABCD rule, 7-point-checklist-based diagnosis) on 979 MSLs blinded cases. Each testing session was performed with a preferred device. Results: The overall highest areas under the receiver operating characteristic (AUROC) (82%) was obtained by young generation dermoscopists 1-4 years experience) when using an integrated clinical dermoscopic algorithm (iDScore) on a notebook. The average dermatologist using the iDScore obtained AUROC 77.40% with large screen devices (PC and notebook) 77.6% with small screen (tablet, smartphone) and 78.2% by combining the two. Discussion: Young generation of dermoscopists alternately use different devices, whereas elderly generation still prefer to use the PC. The diagnostic performances obtained with small/large screen were not statistically different from those obtained with fixed/mobile devices. Conclusions: Mobile devices were feasible tools to achieve adequate diagnostic accuracy in difficult MSLs, on a teledermatology setting, independently from participant skill level/age.

2020 - The dermatoscopic inverse approach significantly improves the accuracy of human readers for lentigo maligna diagnosis [Articolo su rivista]
Lallas, Aimilios; Lallas, Konstantinos; Tschandl, Philipp; Kittler, Harald; Apalla, Zoe; Longo, Caterina; Argenziano, Giuseppe
abstract

A recently introduced dermatoscopic method for diagnosis of early lentigo maligna (LM) is based on the absence of prevalent patterns of pigmented actinic keratosis (PAK) and solar lentigo/flat seborrheic keratosis (SL/SK). We term this the "inverse approach" OBJECTIVE: To determine whether training on the inverse approach increases the diagnostic accuracy of readers as compared to classic pattern analysis.

2020 - The dermoscopic pattern of blue nevi involving the nail apparatus [Articolo su rivista]
Apalla, Zoe; Lallas, Aimilios; Longo, Caterina; Bobos, Matthaios; Starace, Michela; Lazaridou, Elizabeth; Piraccini, Bianca Maria
abstract

N/A

2020 - The impact of anatomical location and sun-exposure on the dermoscopic recognition of atypical nevi and early melanomas: usefulness of an integrated clinical-dermoscopic method (iDScore) [Articolo su rivista]
Tognetti, L; Cartocci, A; Cinotti, E; Moscarella, E; Farnetani, F; Lallas, A; Tiodorovic, D; Carrera, C; Longo, C; Puig, S; Perrot, J L; Argenziano, G; Pellacani, G; Cataldo, G; Balistreri, A; Cevenini, G; Rubegni, P
abstract

The anatomical location of atypical melanocytic skin lesion (aMSL) was never combined into an algorithm for discriminating early melanomas (EM) from atypical nevi (AN).

2020 - The presence of eccentric hyperpigmentation should raise the suspicion of melanoma [Articolo su rivista]
Borsari, S; Peccerillo, F; Pampena, R; Lai, M; Spadafora, M; Moscarella, E; Lallas, A; Pizzichetta, M A; Zalaudek, I; Del Regno, L; Peris, K; Pellacani, G; Longo, C
abstract

Melanocytic lesions with eccentric hyperpigmentation (EH), even though without other dermatoscopic features of melanoma, are often excised.

2020 - The prevailing dermoscopic vascular pattern in melanoma is influenced by tumor thickness and pigmentation type [Articolo su rivista]
Deinlein, T; Longo, C; Schulter, G; Pizzichetta, M A; Zalaudek, I
abstract

In non-pigmented skin tumors the diagnosis is mainly based on the evaluation of the vascular morphology and vessels´ distribution dermoscopically [1-4]. However, up to date, no study formally correlated the prevailing vascular morphology with the thickness of melanoma according to Breslow and amount of pigmentation.

2020 - Too small to be true! [Articolo su rivista]
Pampena, R.; Piana, S.; Manfreda, V.; Bianchi, L.; Pellacani, G.; Longo, C.
abstract

2020 - Treatment monitoring of 5-Fluorouracil 0.5%/Salicylic Acid 10% lesion-directed therapy for actinic keratosis using dermoscopy and in-vivo reflectance confocal microscopy [Articolo su rivista]
Pampena, Riccardo; Condorelli, Alessandra; Cornacchia, Luigi; Guiducci, Laura; Raucci, Margherita; Benati, Elisa; Mirra, Marica; Peris, Ketty; Lai, Michela; Pellacani, Giovanni; Longo, Caterina
abstract

Recently 5-fluorouracil 0.5% / salicylic acid 10% (5-FU/SA) topical solution has been included in the National Italian portfolio for lesion-directed treatment of grade I/II actinic keratosis (AKs) located on the face or scalp. To describe the utility of dermoscopy and RCM in treatment response monitoring of a series of AKs treated with 5-FU/SA as lesion-directed therapy. Consecutive patients were prospectively treated for a maximum of 12 weeks with 5-FU/SA for AKs located on the face or scalp. Clinical, dermoscopic and confocal images of one index AK were acquired at each visit and pre-specified criteria were evaluated. Clinical, dermoscopic and confocal responses were evaluated at last follow up visit. Fourteen patients were enrolled, of which five were treated for 12 weeks, 7 for 8 and 2 for 4 weeks. At a median follow up of 30 weeks, 64.3% (9/14) index AKs achieved complete clinical, 50% (7/14) complete dermoscopic and 42.9% (6/14) complete confocal clearance. Local skin reaction was mild and significantly decreased during therapy administration. Although the small number of cases, our study underlines the utility of both dermoscopy and in-vivo RCM in 5-FU/SA treatment response monitoring for AKs located on the face or scalp. This article is protected by copyright. All rights reserved.

2020 - Treatments of actinic cheilitis: a systematic review of the literature [Articolo su rivista]
Lai, Michela; Pampena, Riccardo; Cornacchia, Luigi; Pellacani, Giovanni; Peris, Ketty; Longo, Caterina
abstract

No large studies defined the best treatment for actinic cheilitis.

2020 - Validation of an integrated dermoscopic scoring method in an European teledermoscopy web platform: the iDScore project for early detection of melanoma [Articolo su rivista]
Tognetti, L.; Cevenini, G.; Moscarella, E.; Cinotti, E.; Farnetani, F.; Lallas, A.; Tiodorovic, D.; Carrera, C.; Puig, S.; Perrot, J. L.; Longo, C.; Argenziano, G.; Pellacani, G.; Smargiassi, E.; Cataldo, G.; Cartocci, A.; Balistreri, A.; Rubegni, P.
abstract

BackgroundAlthough live and teledermoscopic examination has been successfully used to achieve non-invasive diagnosis of melanocytic skin lesions (MSLs), early melanoma (EM) and atypical nevi (AN) continue to be a challenge, and none of the various algorithms proposed have been sufficiently accurate. We designed a scoring classifier diagnostic method, the iDScore that combines clinical data of the patient with dermoscopic features of the MSL.ObjectiveTo test the accuracy of the iDScore in differentiating EM from AN in a teledermoscopy setting and to compare it with intuitive diagnosis, the ABCD rule and the seven-point checklist.Materials and methodsA dedicated teledermoscopy web platform was designed. This involved the following: (i) collecting a large integrated clinical-historical-dermoscopic data set of difficult MSLs from eight European dermatology centres; (ii) online testing, education and training in using the iDScore. A total of 904 images were combined with age, sex, lesion diameter and body site data and evaluated on the platform by 111 participants with four levels of skill in dermoscopy. Each testing session consisted of 30 blind cases to examine consecutively by the above four methods. 'Management decisions' and personal participant data were also recorded.ResultsiDScore-aided diagnosis achieved satisfactory diagnostic accuracy for all lesions, irrespective of centre of affiliation, showing an average AUC of 0.776 in all participant testing sessions. All skill groups improved their accuracy by 10-16% with respect to intuitive diagnosis and the other methods, showing high concordance and avoiding wrong management decisions.ConclusionWe demonstrated the validity of the iDScore method for managing suspicious MSLs in a large multicentric data set and a teledermoscopic setting. The platform designed for the iDScore project provides ready support for physicians of any dermoscopy skill level and is useful for education and training.

2019 - A comparative dermoscopic and reflectance confocal microscopy study of naevi and melanoma with negative pigment network [Articolo su rivista]
Farnetani, Francesca; Scope, Alon; Mazzoni, Laura; Mandel, Victor Desmond; Manfredini, Marco; Magi, Serena; Vaschieri, Cristina; Kaleci, Shaniko; Longo, Caterina; Ciardo, Silvana; Stanganelli, Ignazio; Pellacani, Giovanni
abstract

Background: Negative pigment network (NPN) is a dermoscopic structure observed more frequently among melanomas than naevi. Precise tissue correlates of NPN are still elusive. Objective: To describe the reflectance confocal microscopy (RCM) findings underlying NPN in melanocytic neoplasms. Methods: We retrospectively identified all melanocytic neoplasms displaying dermoscopic NPN that were imaged with RCM and subsequently biopsied between 2011 and 2015. Images from study lesions (n = 50) were evaluated for dermoscopic and RCM Criteria. Histopathological correlational study was performed in a subset of cases (n = 15). Results: The study data set consisted of 21 melanomas (42%) and 29 naevi (58%). Melanomas showed more frequently irregularly shaped globules than naevi (62% vs. 28%, P = 0.03); NPN also tended to be more asymmetrically located among melanomas (86%) than naevi (62%), albeit not significant (P = 0.06). Under RCM, we observed three patterns of dermal papillae (DP): (i) 'Dark DP' - whereby DP were devoid of nests and often surrounded by a junctional proliferation as thick-Rings - this pattern was less common among melanomas (n = 10, 48%) than naevi (n = 23, 79%, P = 0.02); (ii) 'Bulging DP' - whereby junctional nests of melanocytes protrude into the DP, often in association with junctional proliferation as Meshwork - with comparable frequency among melanomas (n = 12, 57%) and naevi (n = 23, 79%, P = 0.09) and (iii) 'Expanded DP' - whereby junctional and/or dermal nests filled and expanded the DP, often in association with dermal-epidermal junction (DEJ) Clod pattern - seen more commonly among melanomas (n = 15, 71%) than naevi (n = 6, 21%, P < 0.001). Dermoscopy-RCM correlation and comparison to histopathological findings show that the hypo-pigmented lines of NPN correlate with broadened epidermal retes, which often show overlying surface dells and wedge-shaped hypergranulosis, while the pigmented globules of NPN correlate with a predominantly-junctiona of melanocytes along and between the elongated retes. Conclusions: Dermoscopic NPN correlates with three DEJ RCM patterns with differing frequency between naevi and melanomas.

2019 - Alopecia neoplastica as a sign of visceral malignancies: a systematic review [Articolo su rivista]
Paolino, G.; Pampena, R.; Grassi, S.; Mercuri, S. R.; Cardone, M.; Corsetti, P.; Moliterni, E.; Muscianese, M.; Rossi, A.; Frascione, P.; Longo, C.
abstract

Alopecia neoplastica (AN) from visceral tumours is a rare form of cutaneous metastasis in which internal malignancies spread to the scalp. The diagnosis of AN may be very challenging, especially when its onset precedes the diagnosis of the primary tumour. We aimed to improve the knowledge on AN, highlighting that in case of scarring localized alopecia, a differential diagnosis with metastasis should always be considered. We performed a systematic review to describe the main demographic and clinical features associated with AN from visceral malignancies; a survival analysis was also performed. In 118 reports, accounting for 123 patients, we found that women were more affected by AN than men (53.7% vs. 46.3%). The most frequent site of the primary tumour was the gastrointestinal tract (24.4%), followed by breast (17.9%), kidney (8.1%), lung (7.3%), thyroid (7.3%), uterus (6.5%), central nervous system (6.5%), liver (3.3%) and other anatomic areas for 18.7% of cases. Furthermore, in more than half of the cases (66.1%), AN lesions were single and were mainly diagnosed after the primary visceral tumour (71.5%). Finally, survival analysis highlighted a lower progression-free survival in men; while, no significant differences in overall survival were reported among genders. In conclusion, metastatic skin disease should always be taken into consideration when dealing with patients with localized scarring alopecia.

2019 - Atlante di Dermoscopia [Monografia/Trattato scientifico]
Argenziano, G; Moscarella, E; Piccolo, V; Agozzino, M; Longo, C; Pellacani, G.
abstract

LA FILOSOFIA DELLA DERMATOSCOPIA “Ecco il mio segreto. È molto semplice. È solo con il cuore che si vede bene. L’essenziale è invisibile all’occhio” (Antoine de Saint Exupéry). Per secoli, l’unico strumento diagnostico a disposizione del dermatologo è stato lo sguardo attento e l’esperienza nell’individuare e interpretare i cambiamenti strutturali della superficie cutanea. Anche se il microcosmo dei colori e delle strutture dermatoscopiche oggi conosciuti è sempre stato probabilmente davanti agli occhi delle generazioni precedenti di dermatologi, i loro occhi non riuscivano a riconoscerli. La citazione “la bellezza sta nel nascosto” descrive mirabilmente come la dermatoscopia abbia influenzato la storia della dermatologia. Con l’aiuto di una semplice lente ottica, chiamata dermatoscopio, si è aperta al dermatologo osservatore una dimensione morfologica delle lesioni cutanee completamente nuova e finora sconosciuta. Da allora i ricercatori hanno approfondito lo studio di questa nuova dimensione morfologica, con la costante scoperta di nuovi modelli morfologici di lesioni cutanee pigmentate e non pigmentate. La dermatoscopia può giustamente essere considerata il metodo del millennio. Il fatto che sia veloce, affidabile, facile da trasportare, da applicare e conveniente spiega il successo del metodo in tutto il mondo. Oggi rappresenta lo standard nella diagnosi di tumori cutanei e delle lesioni cutanee in dermatologia generale. Una volta che avrete iniziato ad usare la dermatoscopia, non la lascerete andare. Come possiamo spiegare che un metodo così semplice è tanto coinvolgente e contagioso? Potremmo rispondere a questa domanda da un punto di vista scientifico oggettivo o personale. Ci sono sempre più prove che la dermatoscopia ha migliorato l’accuratezza diagnostica dei medici, influenzando positivamente la gestione del paziente e aumentando la confidenza diagnostica. Inoltre, la dermatoscopia permette l’osservazione dei tumori della pelle in vivo e la loro osservazione nel tempo, il che ha aperto nuove conoscenze sul comportamento e la biologia dei tumori melanocitici. Ma qual è il valore della dermatoscopia per coloro che la utilizzano? Qui trovate un estratto delle risposte alla domanda “perché amate la dermatoscopia” da parte degli specializzandi, dei membri del comitato editoriale di Dermatology Practical & Conceptual e dei membri del comitato esecutivo della International Dermoscopy Society: “è una scienza particolare e in continua evoluzione - il suo potenziale salvavita - è lo studio del dettaglio - è un ponte tra dermatologia e patologia - non sono bravo in nient’altro - diagnosi rapida, semplice, sicura e accurata, cosa si può chiedere di più - è pieno di sorprese - è un modo di vivere e di pensare - è la passione e l’amore puro per quello che si fa - è l’amore per la morfologia - è un modo semplice per spiegare la fisiopatologia di una malattia - è un impegno analitico ed estetico - ci rende migliori clinici e scienziati - può essere applicato da tutti - è veloce - è magico - guardare qualsiasi cosa attraverso una lente d’ingrandimento è divertente ed emozionante - le persone e il senso di comunità - mi ha permesso di incontrare molti amici e migliora le mie capacità ogni giorno, mese, anno - non amo la dermatoscopia ma la pratico. Quello che amo, tuttavia, è il popolo della dermatoscopia - soddisfa le 3 B in lingua spagnola: bueno, bonito y barato - la comunità che ha creato - mi aiuta a fornire le migliori cure per i miei pazienti. In sostanza, ha contribuito notevolmente a rendere le mie giornate lavorative più piacevoli e meno stressanti - è parte integrante della mia vita. Mi ha permesso di dare una migliore cura al paziente, tenere conferenze in tutto il mondo, collaborare con altri che sono diventati cari amici, quindi amo quello che la dermatoscopia ha fatto per me - Il love d

2019 - Blue lesions of the ears: When dermoscopy is not enough! [Articolo su rivista]
Bombonato, C.; Piana, S.; Pampena, R.; Benati, E.; Longo, C.
abstract

NA

2019 - Broadening the List of Basal Cell Carcinoma Mimickers: Dermoscopic Features of Trichoadenoma [Articolo su rivista]
Pampena, Riccardo; Borsari, Stefania; Piana, Simonetta; Longo, Caterina
abstract

N/A

2019 - Capecitabine-induced eruptive acral hyperpigmentation: Clinical and dermoscopic evaluation of two cases [Articolo su rivista]
Peccerillo, Francesca; Pampena, Riccardo; Giannetti, Luca; Pellacani, Giovanni; Longo, Caterina
abstract

nd

2019 - Clinical and dermoscopic features of pleomorphic dermal sarcoma [Articolo su rivista]
Di Brizzi, E. V.; Moscarella, E.; Piana, S.; Longo, C.; Franco, R.; Alfano, R.; Argenziano, G.
abstract

NA

2019 - Comparison of the accuracy of human readers versus machine-learning algorithms for pigmented skin lesion classification: an open, web-based, international, diagnostic study [Articolo su rivista]
Tschandl, P.; Codella, N.; Akay, B. N.; Argenziano, G.; Braun, R. P.; Cabo, H.; Gutman, D.; Halpern, A.; Helba, B.; Hofmann-Wellenhof, R.; Lallas, A.; Lapins, J.; Longo, C.; Malvehy, J.; Marchetti, M. A.; Marghoob, A.; Menzies, S.; Oakley, A.; Paoli, J.; Puig, S.; Rinner, C.; Rosendahl, C.; Scope, A.; Sinz, C.; Soyer, H. P.; Thomas, L.; Zalaudek, I.; Kittler, H.
abstract

Background: Whether machine-learning algorithms can diagnose all pigmented skin lesions as accurately as human experts is unclear. The aim of this study was to compare the diagnostic accuracy of state-of-the-art machine-learning algorithms with human readers for all clinically relevant types of benign and malignant pigmented skin lesions. Methods: For this open, web-based, international, diagnostic study, human readers were asked to diagnose dermatoscopic images selected randomly in 30-image batches from a test set of 1511 images. The diagnoses from human readers were compared with those of 139 algorithms created by 77 machine-learning labs, who participated in the International Skin Imaging Collaboration 2018 challenge and received a training set of 10 015 images in advance. The ground truth of each lesion fell into one of seven predefined disease categories: intraepithelial carcinoma including actinic keratoses and Bowen's disease; basal cell carcinoma; benign keratinocytic lesions including solar lentigo, seborrheic keratosis and lichen planus-like keratosis; dermatofibroma; melanoma; melanocytic nevus; and vascular lesions. The two main outcomes were the differences in the number of correct specific diagnoses per batch between all human readers and the top three algorithms, and between human experts and the top three algorithms. Findings: Between Aug 4, 2018, and Sept 30, 2018, 511 human readers from 63 countries had at least one attempt in the reader study. 283 (55·4%) of 511 human readers were board-certified dermatologists, 118 (23·1%) were dermatology residents, and 83 (16·2%) were general practitioners. When comparing all human readers with all machine-learning algorithms, the algorithms achieved a mean of 2·01 (95% CI 1·97 to 2·04; p<0·0001) more correct diagnoses (17·91 [SD 3·42] vs 19·92 [4·27]). 27 human experts with more than 10 years of experience achieved a mean of 18·78 (SD 3·15) correct answers, compared with 25·43 (1·95) correct answers for the top three machine algorithms (mean difference 6·65, 95% CI 6·06–7·25; p<0·0001). The difference between human experts and the top three algorithms was significantly lower for images in the test set that were collected from sources not included in the training set (human underperformance of 11·4%, 95% CI 9·9–12·9 vs 3·6%, 0·8–6·3; p<0·0001). Interpretation: State-of-the-art machine-learning classifiers outperformed human experts in the diagnosis of pigmented skin lesions and should have a more important role in clinical practice. However, a possible limitation of these algorithms is their decreased performance for out-of-distribution images, which should be addressed in future research. Funding: None.

2019 - Dermoscopic features of mammary Paget’s disease: a retrospective case-control study by the International Dermoscopy Society [Articolo su rivista]
Apalla, Z.; Errichetti, E.; Kyrgidis, A.; Stolz, W.; Puig, S.; Malvehy, J.; Zalaudek, I.; Moscarella, E.; Longo, C.; Blum, A.; Lanssens, S.; Savoia, Francesco; Tschandl, P.; Kittler, H.; Sinz, C.; Stinco, G.; Argenziano, G.; Lazaridou, E.; Lallas, A.
abstract

Background: Mammary Paget’s disease (MPD) is a rare intraepidermal adenocarcinoma of the nipple-areola complex, associated with an underlying breast cancer in approximately 90% of cases. Delayed diagnosis of MPD is common. Its dermoscopic features have been ill defined in the literature. Objectives: To determine the clinical and dermoscopic features of MPD versus other dermatologic entities that involve nipple and areola. Methods: Members of the IDS were invited to submit any case of histologically confirmed MPD, as well as other benign and malignant dermatoses that involve the nipple and areola complex. A standardized evaluation of the dermoscopic images was performed and the results were statistically analyzed. Results: Sixty-five lesions were included in the study, 22 (33.8%) of them MPD and 43 (66.2%) controls. The most frequent dermoscopic criteria of MPD were white scales (86.4%) and pink structureless areas (81.8%), followed by dotted vessels (72.7%), erosion/ulceration (68.2%) and white shiny lines (63.6%). The multivariate analysis showed that white scales and pink structureless areas were significant predictors of MPD, posing a 68-fold and a 31-fold probability of MPD, respectively. Split of the population into pigmented and non-pigmented lesions showed that in pigmented MPD, pink structureless areas, white lines and grey granules and dots are positive predictors of the disease. Among non-pigmented lesions, pink structureless areas, white lines, erosion/ulceration and white scales served as predictors of MPD. Conclusions: The most frequent profile of an individual with MPD is an elderly female with unilateral, asymptomatic, erythematous plaque of the nipple, dermoscopically displaying pink structureless areas, fine white scales, dotted and a few short linear vessels. In case of pigmentation we may also observe brown structureless areas and pigmented granules. Limitations: Small sample size, retrospective design.

2019 - Dermoscopic similarity is an independent predictor of BRAF mutational concordance in multiple melanomas [Articolo su rivista]
Moscarella, E.; Pellegrini, C.; Pampena, R.; Argenziano, G.; Manfredini, M.; Martorelli, C.; Ciarrocchi, A.; Dika, E.; Peris, K.; Antonini, Alfredo; Cipolloni, G.; Alfano, R.; Longo, C.; Fargnoli, M. C.
abstract

Background: The association of clinical and dermoscopic features with BRAF mutational status has been poorly analysed in multiple primary melanomas (MPM). Objective: To investigate whether concordance of BRAF mutational status is associated with dermoscopic similarity in multiple melanomas of the same patient. Methods: Dermoscopic images and corresponding tissue sections of 124 melanomas from 62 patients with MPM were selected at four Italian Dermatology Departments. Similarity of dermoscopic appearance between multiple melanomas was evaluated according to the presence of the same prevalent dermoscopic feature. The BRAFV600 mutational status was analysed with allele-specific TaqManTM assays or pyrosequencing. Spearman's correlation and univariate and multivariate regression analysis were used for statistical analysis. Results: A similar dermoscopic appearance was identified in 38.7% (24/62) of patients with MPM and was correlated with older age at first diagnosis (rho: 0.26; P: 0.042) and occurrence on sun-damaged skin (rho: 0.27; P: 0.037). The BRAFV600 mutation was detected in 39.5% (49/124) of the tumors and a concordant BRAF mutational status between melanomas in 33/62 (53.2%) MPM patients. Dermoscopically similar melanomas showed 5.7-fold higher odds to be concordant for BRAF mutational status compared to dissimilar lesions (OR: 5.7; 95% CI 1.7-19.5; P: 0.005). Conclusion: Dermoscopic similarity of multiple melanomas represents an independent clinical predictor of a concordant BRAF mutational status in MPM patients.

2019 - Diagnosing the Less Common Skin Tumors Clinical Appearance and Dermoscopy Correlation [Monografia/Trattato scientifico]
Longo, Caterina; Annetta, Alessandro; Argenziano, Giuseppe; Benati, Elisa; Bombonato, Caterina; Borsari, Stefania; Di Brizzi Eugenia, Veronica; Ferrara, Gerardo; La Viola, Giorgio; Lombardi, Mara; Moscarella, Elvira; Pampena, Riccardo; Paolino, Giovanni; Piana, Simonetta
abstract

Many texts deal with how to diagnose the straightforward melanomas of the skin, but there are many less common skin tumors that a clinician needs to be aware of because these are still likely to be encountered at some point in a clinical setting and many of them have serious implications. This highly illustrated text from an internationally acclaimed researcher provides a reliable guide to how to proceed with diagnosis of these more challenging entities. Contents: Tumors of the Epidermis: Nevoid basal cell carcinoma syndrome * Fibroepithelioma of Pinkus * Basosquamous carcinoma * Verrucous carcinoma * Sarcomatoid squamous cell carcinoma * Lentigines, Nevi, and Melanoma: Atypical Spitz nevus (tumor) * Halo Spitz nevus * Desmoplastic nevus * Pigmented epithelioid melanocytoma * Animal-type melanoma * Nevoid melanoma * Balloon cell melanoma * Desmoplastic melanoma * Special site melanoma (mucosal, acral) * Tumors of Cutaneous Appendages: Trichoadenoma * Trichoepithelioma and Brooke-Spiegler syndrome * Desmoplastic trichoepithelioma * Trichoblastoma * Tumors of the follicular infundibulum * Tricholemmoma and tricholemmal carcinoma and Cowden syndrome * Pilomatrixoma * Fibrofolliculoma/trichodiscoma and Birt—Hogg-Dubè syndrome * Sebaceous tumors *Syringocystadenoma papilliferum * Hidradenoma * Cylindroma and familial cylindromatosis and Brooke-Spiegler syndrome * Spiradenoma * Mammary and extramammary Paget’s disease * Syringoma * Eccrine poroma and eccrine porocarcinoma * Mesenchymal Tumors: Dermatofibrosarcoma protuberans * Atypical fibroxanthoma * Malignant fibrous histiocytoma (pleomorphic undifferentiated sarcoma) * Other Uncommon Tumors: Merkel cell carcinoma * Kaposi’s sarcoma * Angiosarcoma * Retiform hemangioendothelioma

2019 - Diagnostic accuracy of ex vivo fluorescence confocal microscopy in Mohs surgery of basal cell carcinomas: a prospective study on 753 margins [Articolo su rivista]
Longo, C.; Pampena, R.; Bombonato, C.; Gardini, S.; Piana, S.; Mirra, M.; Raucci, M.; Kyrgidis, A.; Pellacani, G.; Ragazzi, M.
abstract

Background: Frozen histological sections are used for intraoperative margin assessment during Mohs surgery. Fluorescence confocal microscopy (FCM) is a new tool that offers a promising and faster alternative to frozen histology. Objectives: To evaluate prospectively in a clinical setting the accuracy of FCM vs. frozen sections in margin assessment of basal cell carcinoma (BCC). Methods: Patients with BCC scheduled for Mohs surgery were prospectively enrolled. Freshly excised surgical specimens were examined by FCM and then frozen sections were evaluated. Permanent sections were obtained, in order to validate the sample technique. A blind re-evaluation was also performed for discordant cases. Sensitivity and specificity levels, as well as positive and negative predictive values (PPV and NPV, respectively), were calculated and receiver–operating characteristic curves generated. Results: We enrolled 127 BCCs in as many patients (40·2% females). Seven hundred and fifty-three sections were examined. All BCCs were located in the head and neck area. In evaluating the performance of FCM vs. frozen sections, sensitivity was 79·8%, specificity was 95·8%, PPV was 80·5% and NPV was 95·7% [area under the curve 0·88, 95% confidence interval 0·84–0·92 (P < 0·001)]. Forty-nine discordant cases were re-evaluated; 24 were false positive and 25 false negative. The performance of FCM and frozen sections was also evaluated according to the final histopathological assessment. Conclusions: We found high levels of accuracy for FCM vs. frozen section evaluation in intraoperative BCC margin assessment during Mohs surgery. Some technical issues prevent the wide use of this technique, but new devices promise to overcome these limitations.

2019 - Diffuse melanosis and melanuria [Articolo su rivista]
Piana, S.; Longo, C.
abstract

N/A

2019 - Digital ex-vivo confocal imaging for fast Mohs surgery in nonmelanoma skin cancers: An emerging technique in dermatologic surgery [Articolo su rivista]
Mercuri, Santo R; Rizzo, Nathalie; Bellinzona, Federica; Pampena, Riccardo; Brianti, Pina; Moffa, Giada; Colombo Flink, Laetitia; Bearzi, Pietro; Longo, Caterina; Paolino, Giovanni
abstract

2019 - Ex-vivo Fluorescence Confocal Microscopy: The First Application For Real-Time Pathologic Examination of Prostatic Tissue [Articolo su rivista]
Puliatti, Stefano; Bertoni, Laura; Pirola, Giacomo Maria; Azzoni, Paola; Bevilacqua, Luigi; Eissa, Ahmed; Elsherbiny, Ahmed; Sighinolfi, Maria Chiara; Chester, Johanna; Rocco, Bernardo; Micali, Salvatore; Bagni, Ilaria; Reggiani Bonetti, Luca; Maiorana, Antonino; Malvehy, Josep; Longo, Caterina; Montironi, Rodolfo; Bianchi, Giampaolo; Pellacani, Giovanni
abstract

Prostate cancer "real time" intra-operative pathological examination currently utilizes frozen section, despite the many inherent limitations of this procedure. Ex vivo Fluorescence Confocal Microscopy (FCM) is a novel technology, which provides fast microscopic fluorescence and reflectance tissue imaging. FCM has been proven beneficial in colorectal, breast, thyroid and skin lesions. However, it was never applied in urology. The aim of our study is to report the first application of FCM in the urologic field assessing its diagnostic accuracy for non-neoplastic and cancerous prostate tissue (prostatic adenocarcinoma) compared to the gold standard histopathological diagnoses.

2019 - External validation and comparison of four confocal microscopic scores for melanoma diagnosis on a retrospective series of highly suspicious melanocytic lesions [Articolo su rivista]
Pampena, R.; Borsari, S.; Lai, M.; Benati, E.; Longhitano, S.; Mirra, M.; Kyrgidis, A.; Pellacani, G.; Longo, C.
abstract

Background: In vivo reflectance confocal microscopy significantly improves melanoma diagnosis as compared to clinical/dermoscopic examination alone. Several confocal criteria have been described allowing to differentiate melanoma from nevi; by combining different criteria, three pure confocal scores (Pellacani 2005, Segura 2009 and Pellacani 2012) and one mixed dermoscopic/confocal score (Borsari 2018) were constructed. Objective: Our aim was to externally validate and compare the performance of these confocal scores. Methods: We retrospectively enrolled excised melanocytic lesions which underwent confocal examination in a 2-year period. Lesions located on the face and acral sites were excluded. Both dermoscopic and confocal criteria considered in the four scores were evaluated by experts. Subsequently, specificity and sensitivity levels for each score were calculated, together with the positive and negative predictive values and likelihood ratios; also, receiver operating characteristic curves were constructed. Results: A total of 389 patients with 422 lesions were retrospectively enrolled, of which 162 (38.4%) were melanomas and 260 (61.6%) were nevi (189 common and 71 Spitz/Reed nevi). The highest sensitivity levels were recorded for Segura 2009 with cut-off ≥−1 (92.0%), while Pellacani 2005 with cut-off ≥5 achieved the highest specificity (69.6%). The score by Borsari et al. showed the highest levels of positive and negative predictive values (59.8% and 91.5%) and likelihood ratios (2.4 and 0.1) as well as the highest area under the curve values (0.76; 95% CI 0.72–0.81; P < 0.001). Conclusions: High levels of accuracy were found for each of the four considered scores. No differences were found among scores in confirming melanoma diagnosis when positive; however, the score by Borsari 2018 was the best in excluding melanoma diagnosis when negative.

2019 - Five-point checklist for skin cancer detection in primary care [Articolo su rivista]
Moscarella, Elvira; Lallas, Aimilios; Longo, Caterina; Alfano, Roberto; Argenziano, Giuseppe
abstract

Skin cancer screening interventions often relay on the involvement of general practitioners (GPs). Many interventions up to now have been directed to training approaches focusing on the clinical features of skin malignancies to increase GPs skill in skin cancer recognition.

2019 - Food and beverage consumption and melanoma risk: a population-based case-control study in Northern Italy [Articolo su rivista]
Malagoli, C; Malavolti, M; Agnoli, C; Farnetani, F; Longo, C; Filippini, T; Pellacani, G; Vinceti, M
abstract

It has been suggested that diet may influence the risk of melanoma, but few studies are available on this topic. We assessed the relation between food consumption and the risk of cutaneous melanoma in a Northern Italy population. We carried out a population-based case-control study involving 380 cases of melanoma and 719 age- and sex-matched controls. Dietary habits were established through a self-administered semi-quantitative food frequency questionnaire. We computed the odds ratios (ORs) of melanoma and the corresponding 95% confidence intervals (CIs) according to tertiles of daily intake of each food item, using multiple logistic regression models adjusted for major confounding factors. We observed an indication of a positive association between melanoma risk and consumption of cereals and cereal products (OR = 1.32; 95% CI 0.89–1.96, higher vs. lowest tertile), sweets (OR = 1.22; 95% CI 0.84–1.76), chocolate, candy bars. etc., (OR = 1.51; 95% CI 1.09–2.09) and cabbages (OR = 1.51; 95% CI 1.09–2.09). Conversely, an inverse association with disease risk was found for the intake of legumes (OR = 0.77; 95% CI 0.52–1.13), olive oil (OR = 0.77; 95% CI 0.51–1.16), eggs (OR = 0.58; 95% CI 0.41–0.82), and onion and garlic (OR = 0.80; 95% CI 0.52–1.14). No relationship was observed with beverage consumption. Our results suggest potentially adverse effects on melanoma risk of foods characterized by high contents of refined flours and sugars, while suggesting a protective role for eggs and two key components of the Mediterranean diet, legumes and olive oil. These associations warrant further investigation and, if confirmed, they might have important public health implications for the reduction of melanoma incidence through dietary modification.

2019 - Melanoma types by in vivo reflectance confocal microscopy correlated with protein and molecular genetic alterations: A pilot study [Articolo su rivista]
Beretti, F.; Bertoni, L.; Farnetani, F.; Pellegrini, C.; Gorelli, G.; Cesinaro, A. M.; Reggiani Bonetti, L.; Di Nardo, L.; Kaleci, S.; Chester, J.; Longo, C.; Massi, D.; Fargnoli, M. C.; Pellacani, G.
abstract

Cutaneous melanoma (CM) is one of the most prevalent skin cancers, which lacks both a prognostic marker and a specific and lasting treatment, due to the complexity of the disease and heterogeneity of patients. Reflectance confocal microscopy (RCM) in vivo analysis is a versatile approach offering immediate morphological information, enabling the identification of four primary cutaneous RCM CM types. Whether RCM CM types are associated with a specific protein and molecular genetic profiles at the tissue level remains unclear. The current pilot study was designed to identify potential correlations between RCM CM types and specific biological characteristics, combining immunohistochemistry (IHC) and molecular analyses. Eighty primary CMs evaluated at patient bedside with RCM (type 1 [19, 24%], type 2 [12, 15%], type 3 [7, 9%] and type 4 [42, 52%]) were retrospectively evaluated by IHC stains (CD271, CD20, CD31, cyclin D1), fluorescence in situ hybridization FISH for MYC gain and CDKN2A loss and molecular analysis for somatic mutations (BRAF, NRAS and KIT). RCM CM types correlated with markers of stemness property, density of intra-tumoral lymphocytic B infiltrate and cyclin D1 expression, while no significant association was found with blood vessel density nor molecular findings. RCM CM types show a different marker profile expression, suggestive of a progression and an increase in aggressiveness, according to RCM morphologies.

2019 - Morphological classification of melanoma metastasis with reflectance confocal microscopy [Articolo su rivista]
Farnetani, F; Manfredini, M; Longhitano, S; Chester, J; Shaniko, K; Cinotti, E; Mazzoni, L; Venturini, M; Manganoni, A; Longo, C; Reggiani-Bonetti, L; Giannetti, L; Rubegni, P; Calzavara-Pinton, P; Stanganelli, I; Perrot, J L; Pellacani, G
abstract

Cutaneous malignant melanoma metastases differential diagnosis is challenging, as clinical and dermoscopic features can simulate primary melanoma or other benign or malignant skin neoplasms, and in-vivo reflectance confocal microscopy could assist. Our aim was to identify specific reflectance confocal microscopy features for cutaneous malignant melanoma metastases, and epidermal and dermal involvement.

2019 - Nipple and areola lesions: Dermoscopy and reflectance confocal microscopy features [Articolo su rivista]
Cinotti, Elisa; Galluccio, Danila; Ardigò, Marco; Gonzalez, Salvador; Manganoni, Ausila Maria; Venturini, Marina; Broganelli, Paolo; Ribero, Simone; Farnetani, Francesca; Mandel, Victor Desmond; Pellacani, Giovanni; Tognetti, Linda; Lacarrubba, Francesco; Guitera, Pascale; Stanganelli, Ignazio; Zalaudek, Iris; Arzberger, Edith Johanna; Bahadoran, Philippe; Longo, Caterina; Spataro, Giuseppe; Perrot, Jean-Luc; Rubegni, Pietro
abstract

[No abstract available]

2019 - Peritumoural clefting as a key feature in differentiating basal cell carcinoma from trichoblastoma through in vivo reflectance confocal microscopy [Articolo su rivista]
Pampena, R.; Peccerillo, F.; Marghoob, N. G.; Piana, S.; Longo, C.
abstract

NA

2019 - Physician–patient communication and patient-reported outcomes in the actinic keratosis treatment adherence initiative (AK-TRAIN): a multicenter, prospective, real-life study of treatment satisfaction, quality of life and adherence to topical field-directed therapy for the treatment of actinic keratosis in Italy [Articolo su rivista]
Neri, L.; Peris, K.; Longo, C.; Calvieri, S.; Frascione, P.; Parodi, A.; Eibenschuz, L.; Bottoni, U.; Pellacani, G.; Ayala, F.; Quaglino, P.; Cannavo, S.; Rubegni, P.; Ferreli, C.; Girolomoni, Giampiero; Bongiorno, M. R.; Potenza, C.; Micali, G.; Pimpinelli, N.; Romanelli, M.; Stanganelli, I.; Bonamonte, D.; Peserico, A.; Fargnoli, M. C.; Pinton, P. C.; Costanzo, D.; Cantisani, C.; Borsari, S.; Ricci, F.; Izzi, S.; Chiara, F.; Cozzani, E.; Carboni, Anna Rita; Amoruso, G. F.; Dastoli, S.; Scalvenzi, M.; Deboli, T.; Francesco, B.; Casari, A.; Nami, N.; Ferreli, C.; Camilla Delle Vedove, C. S.; Viola, L.; La Carrubba, F.; Grandi, V.; Dini, V.; Mazzoni, L.; Vestita, M. L.; Fabiano, A.; Zane, C.; Orsini, D.
abstract

Background: Patients with multiple actinic keratoses (AKs) should be treated with field-directed therapy. Such treatments challenge patients’ adherence due to out-of-pocket costs, length of treatment and severity of local skin reactions (LSRs). Effective physician–patient communication (PPC) may buffer therapy-related distress, thus improving quality of life, treatment satisfaction and adherence. Objectives: We evaluated the interplay between PPC, LSR intensity (safety) and lesion clearance rates (effectiveness) on treatment satisfaction, quality of life and treatment adherence among patients with multiple AKs receiving topical field-directed therapies. Methods: In this observational, multicentre, longitudinal, cohort study, we included 1136 adult patients with discrete, clinically detectable, visible, multiple (three or more lesions in a 25 cm 2 area), Grade I/II AKs, for whom the attending dermatologist has prescribed treatment with a topical field-directed therapy. We matched self-reported data and medical information recorded by dermatologists in standard clinical forms. Patients were followed up at two time points (T1: 8 days; T2: 25–30 days). Results: Most patients were elderly, married, men with poor socio-economic status and multiple lesions of the scalp or face. The majority (n = 961) had a prescription of ingenol mebutate (IMB) and 175 received either diclofenac 3% in hyaluronic acid (DHA) or imiquimod 5% (IMQ). Clearance rate at 1 month was 84%. Most patients felt very supported (n = 819, 73%) and rated dermatologist's explanations very clear (n = 608, 54%). Treatment satisfaction (effectiveness and convenience scales) increased along the follow-up, especially for those on IMB (Δ pre-post  = −4.00; other: Δ pre-post  = −0.25; interaction P < 0.001). Communication clarity was associated with higher treatment satisfaction scores (β = 0.4–0.6, P < 0.01) and lower risk of non-adherence among IMB patients (risk difference: 16%, P < 0.01). Conclusion: Communication clarity was associated with patient-reported outcomes and adherence beyond AK-related clinical parameters. Our study questions the current episodic approach to AK management and provides the rationale to develop chronic care models fostering patients’ engagement and treatment alliance.

2019 - Pigmented skin lesions displaying regression features: Dermoscopy and reflectance confocal microscopy criteria for diagnosis [Articolo su rivista]
Moscarella, E.; Bombonato, C.; Pampena, R.; Kyrgidis, A.; Benati, E.; Piana, S.; Borsari, S.; Lallas, A.; Pellacani, G.; Argenziano, G.; Longo, C.
abstract

Melanomas and nevi displaying regression features can be difficult to differentiate. To describe reflectance confocal microscopy features in benign and malignant pigmented skin lesions characterized by regression features in dermoscopy. Observational retrospective study. Inclusion criteria were presence of dermoscopic features of regression; availability of clinical, dermoscopic and RCM imaging; definite histopathologic diagnosis. The study sample comprised 217 lesions; 108 (49.8%) melanomas and 109 were benign lesions, of which 102 (47.0%) nevi and 7 (3.2%) lichen planus-like keratosis (lplk). Patients with melanoma were significantly older than those with benign lesions (61.9 ± 15.4 vs 46.1 ± 14.8; P < 0.001) and a higher proportion of melanomas displayed dermoscopic regression structures in more than 50% of lesion surface (n = 83/108; 76.9%; P < 0.001). On RCM examination, pagetoid cells were significantly more reported in melanoma group, than in benign lesions (86.1% vs 59.6%; P < 0.001) and were more frequently widespread distributed (65.6% vs 20.0%; P < 0.001) and both dendritic and roundish (36.6% vs 15.4%; P < 0.001) in shape. Aspecific architecture at the dermo-epidermal junction (DEJ) was more commonly seen among melanomas than benign lesions (23.1% vs 11.9%; P = 0.002) with higher presence of dendritic and both dendritic and roundish atypical cells at the DEJ (28.7% vs 18.3% and 19.4% vs 3.7%; P < 0.001, respectively). Focal pagetoid infiltration and ringed or clod patterns were more commonly seen in benign lesion. In conclusion, the correct interpretation of regressing lesions remains a challenge, assessing carefully the extent and characteristics of architectural and cytologic atypia on RCM is an additional piece of the complex puzzle of melanoma diagnosis.

2019 - Reflectance confocal microscopy made easy: The 4 must-know key features for the diagnosis of melanoma and nonmelanoma skin cancers [Articolo su rivista]
Pellacani, G.; Scope, A.; Gonzalez, S.; Guitera, P.; Farnetani, F.; Malvehy, J.; Witkowski, A.; De Carvalho, N.; Lupi, O.; Longo, C.
abstract

Background: Reflectance confocal microscopy (RCM)-based skin cancer diagnosis requires proficiency. Objective: To identify a short list of key RCM features of skin cancers and test their diagnostic utility. Methods: We identified key RCM features through consensus among 6 experts using a modified Delphi method. To test the diagnostic utility of these RCM key features, 10 novice RCM readers evaluated a subset of 100 RCM cases from a retrospective data set of benign and malignant skin neoplasms. Results: From 56 features reported in the literature, the experts identified 18 RCM features as highly valuable for skin cancer diagnosis. On the basis of consensus definitions, these RCM features were further clustered into 2 melanoma-specific key features (atypical cells and dermoepidermal junction disarray), 1 basal cell carcinoma–specific key feature (basaloid cords/islands), and 1 squamous cell carcinoma–specific key feature (keratinocyte disarray). The novice reading study showed that the presence of at least 1 of the 4 key features was associated with an overall sensitivity for skin cancer diagnosis of 91%, with a sensitivity for melanoma of 93%, a sensitivity for basal cell carcinoma of 92%, and a sensitivity for squamous cell carcinoma of 67%, and an overall specificity of 57%. Limitations: The consensus was based on only six RCM experts and the validation study was retrospective. Conclusions: A consensus terminology short list identifying the 4 RCM key features for skin cancer diagnosis may facilitate dissemination of RCM to novice users.

2019 - Reflectance confocal microscopy terminology glossary for nonmelanocytic skin lesions: A systematic review [Articolo su rivista]
Navarrete-Dechent, C.; DeRosa, A. P.; Longo, C.; Liopyris, K.; Oliviero, M.; Rabinovitz, H.; Marghoob, A. A.; Halpern, A. C.; Pellacani, G.; Scope, A.; Jain, M.
abstract

Background: There is lack of uniformity in reflectance confocal microscopy (RCM) terminology for nonmelanocytic lesions (NMLs). Objective: To review published RCM terms for NMLs and identify likely synonymous terms. Methods: We conducted a systematic review of original research articles published up to August 19, 2017, adhering to Preferred Reporting Items for Systemic Reviews and Meta-Analyses guidelines. Two investigators gathered all published RCM terms used to describe basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and seborrheic keratosis/solar lentigo/lichen planus–like keratosis (SK/SL/LPLK). Synonymous terms were grouped on the basis of similarity in definition and histopathologic correlates. Results: The inclusion criteria was met by 31 studies. Average frequency of use per term was 1.6 (range 1-8). By grouping synonymous terms, the number of terms could be reduced from 58 to 18 for BCC, 58 to 36 for SCC, 23 to 12 for SK/SL/LPLK, and from 139 to 66 terms (52.5% reduction) in total. The frequency of term usage stratified by anatomic layer (suprabasal epidermis vs epidermal basal layer, dermoepidermal junction, and superficial dermis) was 27 (25.7%) versus 78 (74.2%) for BCC; 60 (64.5%) versus 33 (34.5%) for SCC, and 15 (45.4%) versus 18 (54.5%) for SK/SL/LPLK, respectively. Limitations: Articles that were not peer reviewed were excluded. Conclusion: Systematic review of published RCM terms provides the basis for future NMLs terminology consensus.

2019 - Sclerosing nevus with pseudomelanomatous features: dermoscopic and confocal aspects [Articolo su rivista]
Bombonato, C.; Pampena, R.; Franceschini, C.; Piana, S.; Perino, F.; Di Stefani, A.; Ardigo, M.; Fargnoli, M. C.; Frascione, P.; Borsari, S.; Pellacani, G.; Peris, K.; Longo, C.
abstract

Background: Sclerosing nevus with pseudomelanomatous features (SNPFs) is a clinical and pathologic entity that mimics melanoma both clinically and histologically. The lesion is a melanocytic nevus, histologically characterized by fibrosis and a pseudomelanomatous proliferation. It is typically seen in young to middle-aged individuals, mainly on the back, where microtrauma or inflammatory changes are more frequent. Dermoscopic description of SNPF has been reported so far in one case series. Objective: The aim of our study was to describe the dermoscopic and confocal features of SNPF. Methods: Histopathologically confirmed cases of SNPF were retrospectively collected from three referral centres in Italy. Only lesions with available clinical, dermoscopic and histopathological data were included; confocal images were also retrieved, when available. Lesions were evaluated for the presence of 12 dermoscopic and five confocal criteria previously described. Results: The study population included 93 lesions in as many patients (71 men and 22 women; median age: 38 years). Dermoscopically, we found a predominance of dark colours, in particular brown and blue, which were found in all lesions and the vast majority of the lesions (86/93; 92.5%) displayed at least one structureless area. By the combination of colours and structures, we observed that the majority of the lesions (67/92; 72%) were characterized by more than one structure and more than one colour. Confocal evaluation was performed on a subset of 24/93 lesions showing a regular architecture pattern (19/24 cases, 79%), with a predominance of the ringed pattern. The presence of focal cytologic atypia at the dermal-epidermal junction was present in 12/24 cases (50%) with a prevalent dendritic-shaped cell proliferation. Conclusions: The current study demonstrated that SNPF was frequently characterized, on dermoscopic examination, by more than one structure and more than one colour and on confocal microscopy by a regular ringed pattern with focal dendritic atypical cells.

2019 - The prevalent dermoscopic criterion to distinguish between benign and suspicious pink tumours [Articolo su rivista]
Russo, T.; Pampena, R.; Piccolo, V.; Alfano, R.; Papageorgiou, C.; Apalla, Z.; Longo, C.; Lallas, A.; Argenziano, G.
abstract

Background: Pink skin tumours are difficult to differentiate, clinically and dermoscopically. In previous studies, mainly focused on pigmented lesions, pattern analysis provided the best sensitivity and specificity values, as compared to other algorithms. These findings suggest that the global dermoscopic appearance, based on the evaluation of prevalent features, could represent a valuable and practical approach even when dealing with pink lesions. Objective: In this study, we aimed to evaluate the diagnostic accuracy of a new dermoscopic approach for pink tumours based on the prevalent criterion, as compared to a standard diagnostic method (Menzies algorithm). Methods: The databases of two referral centres were retrospectively evaluated to retrieve dermoscopic images of amelanotic/hypomelanotic skin lesions. Two experts in dermoscopy, blinded for the final diagnosis and for clinical and demographic information, evaluated separately dermoscopic pictures of 1000 lesions according to the Menzies score and to the prevalent criterion method. Results: According to the high sensitivity model of the Menzies score, 129 (12.9%) lesions were considered as non-suspicious (of which 16 were false negative) and 871 (87.1%) as suspicious (of which 212 were false positive), with 97.6% sensitivity and 34.8% specificity. According to the high specificity model, 370 (37%) lesions were evaluated as non-suspicious (of which 105 were false negative) and 630 (63%) as suspicious (of which 60 were false positive), with 84.4% sensitivity and 81.5% specificity. Concerning the prevalent criterion method, 316 (31.6%) lesions were evaluated as non-suspicious (of which 46 were false negative) and 684 (68.4) as suspicious (of which 55 were false positive), with 93.2% sensitivity and 83.1% specificity. Conclusions: This study demonstrated that focusing on the prevalent dermoscopic features could allow to detect malignant pink tumours with similar sensitivity but higher specificity than using the conventional Menzies scoring system.

2019 - Tumor of the follicular infundibulum: Dermoscopic and confocal features [Articolo su rivista]
Pampena, R.; Lai, M.; Piana, S.; Pellacani, G.; Longo, C.
abstract

N/A

2019 - When follow-up is telling you the truth [Articolo su rivista]
Longo, C.; Pampena, R.; Piana, S.; Pellacani, G.; Ragazzi, M.
abstract

NA

2019 - Worsening alopecia in an elderly woman [Articolo su rivista]
Piana, S.; Longo, C.; Valli, R.
abstract

NA

2019 - ‘Eternal sunshine of the spotless islands’: how dermoscopy may influence confocal microscopy when dealing with squamous cells carcinoma simulating basal cell carcinoma [Articolo su rivista]
Cornacchia, L.; Longo, C.; Piana, S.; Lai, M.; Pellacani, G.; Peris, K.; Pampena, R.
abstract

NA

2018 - A new dermoscopic algorithm for the differential diagnosis of facial lentigo maligna and pigmented actinic keratosis [Articolo su rivista]
Micantonio, T.; Neri, L.; Longo, C.; Grassi, S.; Di Stefani, A.; Antonini, A.; Coco, V.; Fargnoli, M. C.; Argenziano, G.; Peris, K.
abstract

Background: The clinical and dermoscopic diagnosis of facial lentigo maligna (LM) and pigmented actinic keratosis (PAK) remains challenging, particularly at the early disease stages. Objectives: To identify dermoscopic criteria that might be useful to differentiate LM from PAK, and to elaborate and validate an automated diagnostic algorithm for facial LM/PAK. Materials & Methods: We performed a retrospective multicentre study to evaluate dermoscopic images of histologically-proven LM and PAK, and assess previously described dermoscopic criteria. Results: In the first part of the study, 61 cases of LM and 74 PAK were examined and a parsimonious algorithm was elaborated using stepwise discriminant analysis. The following eight dermoscopic criteria achieved the greatest discriminative power: (1) light brown colour; (2) a structureless zone, varying in colour from brown to brown/tan, to black; (3) in-focus, discontinuous brown lines; (4) incomplete brown or grey circles; (5) a structureless brown or black zone, obscuring the hair follicles; (6) a brown (tan), eccentric, structureless zone; (7) a blue structureless zone; and (8) scales. The newly developed algorithm was subsequently validated using an additional series of 110LMand 75 PAKcases. Diagnostic accuracy was 86.5% (k: 0.73, 95% CI: 0.63-0.83). For the diagnosis of LM vs PAK, sensitivity was 82.7% (95% CI: 75.7-89.8%), specificity was 92.0% (95% CI: 85.9-98.1%), positive predictive value was 93.8% (95% CI: 89.0-98.6%), and negative predictive value was 78.4% (95% CI: 68.4-86.5%). Conclusions: This algorithm may represent an additional tool for clinicians to distinguish between facial LM and PAK.

2018 - Accuracy of Dermoscopic Criteria for the Diagnosis of Melanoma In Situ [Articolo su rivista]
Lallas, Aimilios; Longo, Caterina; Manfredini, Marco; Benati, Elisa; Babino, Graziella; Chinazzo, Chiara; Apalla, Zoe; Papageorgiou, Chryssoula; Moscarella, Elvira; Kyrgidis, Athanassios; Argenziano, Giuseppe
abstract

The accuracy of melanoma-specific dermoscopic criteria has been tested mainly in studies including invasive tumors. Scarce evidence exists on the usefulness of these criteria for the diagnosis of melanoma in situ (MIS).

2018 - An integrated clinical-dermoscopic risk scoring system for the differentiation between early melanoma and atypical nevi: the iDScore [Articolo su rivista]
Tognetti, L.; Cevenini, G.; Moscarella, E.; Cinotti, E.; Farnetani, F.; Mahlvey, J.; Perrot, J. L.; Longo, C.; Pellacani, G.; Argenziano, G.; Fimiani, M.; Rubegni, P.
abstract

Background Dermoscopy revealed to be extremely useful in the diagnosis of early melanoma, the most important limitation being its subjectivity in giving a final diagnosis. To overcome this problem, several algorithms and checklists have been proposed. However, they generally demonstrated modest level of diagnostic accuracy, unsatisfactory concordance between dermoscopists and/or poor specificity. Objective Methods To test a new methodological approach for the differentiation between early melanoma and atypical nevi, based on an integrated clinical-anamnestic dermoscopic risk scoring system (iDScore). We selected a total of 435 standardized dermoscopic images of clinically atypical melanocytic skin lesion (MSL) excised in the suspect of malignancy (i.e. 134 early melanomas - MM - and 301 atypical nevi). Data concerning patient age and sex and lesion dimension and site were collected. A scoring classifier was designed based on this data set integrated with the dermoscopic evaluations performed by three experts blinded to histological diagnosis. Results Conclusion A total of seven dermoscopic structures, three age groups (30-40 years, 41-60 years and >60 years), two maximum diameter categories (5-10 mm and >10 mm) and three body areas (i.e. frequently, chronically and seldom photoexposed sites) were selected by the scoring classifier as interdependently significant variables. The total risk score (S) of a lesion resulted from the simple sum of partial scores assigned to each selected variable. The iDScore-aided diagnosis showed an high accuracy (receiver operating characteristic-area under the curve = 0.903; IC: 95% = 0.887-0.918). A risk-based criticality scale corresponding to different S ranges was proposed. The iDScore checklist is proposed as a feasible and efficient tool to support dermatologists in non-invasive differentiation between atypical nevi and early MM on the basis of few selected clinical-anamnestic data and standardized dermoscopic features.

2018 - Atlas of Diagnostically Challenging Melanocytic Neoplasms [Monografia/Trattato scientifico]
Longo, Caterina; Argenziano, Giuseppe; Lallas, Aimilios; Moscarella, Elvira; Piana, Simonetta
abstract

This atlas provides a clear, concise overview of the most challenging circumstances faced by clinicians and pathologists when dealing with melanocytic neoplasms. The book is structured as a case series; for each case, the clinical and dermoscopic appearances are presented, accompanied by a brief but comprehensive description and compelling histopathologic images. When available, in vivo confocal microscopy images are also included to highlight additional diagnostic clues. Identification of key messages and selected references will further guide the reader in the diagnosis and management of the neoplasm under consideration. It is well known that melanocytic lesions can be difficult to interpret. Some lesions show an ambiguous combination of morphologic criteria, and in these cases interpretation entails a high degree of subjectivity that results in low interobserver agreement even among expert pathologists. This atlas demonstrates how the addition of clinical information, including that provided by dermoscopy, can assist in reaching a more confident diagnosis.

2018 - Basal cell carcinoma: the utility of in vivo and ex vivo confocal microscopy [Articolo su rivista]
Longo, C.; Borsari, S.; Pampena, R.; Benati, E.; Bombonato, C.; Raucci, M.; Mirra, M.; Di Stefani, A.; Peris, K.; Pellacani, G.
abstract

The use of confocal microscopy is possible using two different modalities: first, at patient's bedside for a rapid in vivo diagnosis of basal cell carcinoma and second, in the operating room directly on freshly excised specimen for a fast ex vivo margin-controlled surgery. In the current review, we report the main application of confocal microscopy for basal cell carcinoma diagnosis and management in both modalities.

2018 - Clinical, dermoscopic, and confocal features of nevi and melanomas in a multiple primary melanoma patient with the MITF p.E318K homozygous mutation [Articolo su rivista]
Bassoli, S.; Pellegrini, Camilla; Longo, C.; Di Nardo, L.; Farnetani, F.; Cesinaro, A. M.; Pellacani, G.; Fargnoli, M. C.
abstract

NA

2018 - Cutaneous squamous cell carcinoma. Italian Guidelines by SIDeMaST adapted to and updating EADO/EDF/EORTC guidelines [Articolo su rivista]
Peris, K.; Alaibac, M.; Argenziano, G.; Di Stefani, A.; Fargnoli, M. C.; Frascione, P.; Gualdi, G.; Longo, C.; Moscarella, E.; Naldi, L.; Pellacani, G.; Pimpinelli, N.; Quaglino, P.; Salgarello, M.; Sollena, P.; Valentini, V.; Zalaudek, I.; Calzavara-Pinton, P.
abstract

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, accounting for 20% of all cutaneous malignancies, and has an increasing incidence in the elderly as well as in the younger population. Although most cSCC is treated with simple therapeutic procedures, advanced cSCC can lead a significant risk for morbidity, negative impact on quality of life, and death. Proper management includes distinguishing between high-risk and low-risk lesions and determining treatment accordingly. A collaboration of multidisciplinary Italian experts has given birth to these recommendations on cSCC diagnosis and management, based on a critical review of the literature, existing European (EADO- EDF-EORTC) guidelines and the expert's experience. Topics covered include diagnostic path and histopathologic assessment, tumor staging, surgical and nonsurgical procedures, follow-up and management of localized and advanced disease.

2018 - Dermoscopic Features of Basal Cell Carcinoma on the Lower Limbs: A Chameleon! [Articolo su rivista]
Lombardi, M.; Pampena, R.; Borsari, S.; Bombonato, C.; Benati, E.; Pellacani, G.; Longo, C.
abstract

Background: Lower limbs represent an uncommon location for basal cell carcinoma (BCC) and only few reports have described dermoscopic features of BCC in this body site. Since BCCs of the lower limbs frequently display nonclassic BCC dermoscopic criteria, they can simulate other benign or malignant lesions. Objective: Our aim was to describe the dermoscopic features of BCC located on lower limbs and to define which criteria were more associated with their benign-or malignant-looking appearance. Methods: We conducted a retrospective study enrolling consecutive patients with histologically confirmed BCCs of the lower limbs. Lesions were classified in 7 categories according to the clinical and dermoscopic global appearance. Clear BCC, squamous cell carcinoma (SCC) or Bowen disease-like, Kaposi disease-like, melanoma-like, and aspecific pattern were considered malignant-looking lesions; however, seborrheic keratosis-like and dermatofibroma-like were considered benign-looking. To define which dermoscopic criteria were independently associated with benign-or malignant-looking appearance, we conducted a multivariate logistic regression analysis. Results: A total of 81 BCCs were enrolled: 18 (22%) were benign-looking lesions (of which 11 were seborrheic keratosis-like and 7 dermatofibroma-like) and 63 (78%) were malignant-looking BCCs (of which 24 were clear-cut BCCs, 23 SCC-like, 2 Kaposi disease-like, 9 melanoma-like, and 5 had aspecific pattern). Multivariate regression analysis showed that erosions/ulceration and vessels were independently associated with malignant-looking appearance. The most represented vessels were glomerular and polymorphic, which are more frequently encountered in SCC, together with ulceration. Conclusion: BCC of the lower legs frequently simulates other benign or malignant lesions, with SCC being the main differential diagnosis.

2018 - Dermoscopy Improves the Diagnostic Accuracy of Melanomas Clinically Resembling Seborrheic Keratosis: Cross-Sectional Study of the Ability to Detect Seborrheic Keratosis-Like Melanomas by a Group of Dermatologists with Varying Degrees of Experience [Articolo su rivista]
Carrera, C.; Segura, S.; Aguilera, P.; Takigami, C. M.; Gomes, A.; Barreiro, A.; Scalvenzi, M.; Longo, C.; Cavicchini, S.; Thomas, L.; Malvehy, J.; Puig, S.; Zalaudek, I.
abstract

Background: Malignant melanomas mimicking seborrheic keratosis (SK-like MMs) carry the risk of delayed diagnosis and inadequate treatment. The value of dermoscopy to improve the correct detection of these mimickers has not been previously studied. Objective: To evaluate the diagnostic accuracy of clinically SK-like MMs with and without dermoscopy. Methods: Clinical and dermoscopic images of histopathologically proven SK-like MMs (n = 134) intermingled with other melanomas and benign tumors were randomly presented to clinicians with different levels of experience, blinded to the diagnosis and goal of the study. Each participant classified each lesion as melanoma or benign tumor. The clinical and clinical-dermoscopic diagnostic accuracies were measured separately. Results: Overall, 54 participants with a mean clinical experience of 15.8 years (SD 11.8) evaluated 231 tumors. Almost 40% of SK-like melanomas were clinically misclassified as benign tumor. Dermoscopy improved diagnostic accuracy for all participants, independently of experience, from 60.9 to 68.1% (p < 0.001), mostly due to a significant increase in the sensitivity (clinical 61.9% vs. dermoscopic 74.5%) (p < 0.001). Dermoscopy did not significantly affect specificity among the experienced participants (≥6 years of experience) compared to clinical examination (61.1 vs. 59.6%, respectively); in contrast, dermoscopy was associated with a decrease in specificity compared to clinical diagnosis among novice participants (< 6 years) (45.6 vs. 61.1%, respectively; p = 0.02). Conclusion: Melanomas can be clinically indistinguishable from SKs despite being evaluated by expert dermatologists. Dermoscopy, even in nonexpert hands, significantly improves their recognition.

2018 - Dermoscopy and Diagnosis of Benign and Malignant Skin Lesions [Curatela]
Heinitz, I; Wilkinson, D; Argenziano, G; Lallas, A; Blum, A; Hofmann-Wellenhof, R; Kittler, H; Longo, C; Marghoob, Aa; Moscarella, E; Rosendahl, C; Tanaka, M; Thomas, L; Tschandl, P; Zalaudek, I
abstract

As we know from numerous studies, the effective use of dermoscopy by trained and experienced clinicians markedly improves diagnostic accuracy and reduces the number of unnecessary excisions of skin lesions. The Definitive Guide to Dermoscopy and Diagnosis of Benign and Malignant Skin Lesions is based on the HealthCert online Professional Diploma of Dermoscopy developed in collaboration with the International Dermoscopy Society (IDS). Featuring real patient case studies, thousands of illustrations and practical advice on skin cancer diagnosis and treatment, this comprehensive reference is a true “Dermoscopy Bible” comprising the extensive expertise of the 14 most influential experts and global pioneers in Dermoscopy. Aimed at primary care practitioners, skin cancer specialists, dermatologists and any medical professional with an interest in skin cancer medicine or general dermatology, this 540-page guide provides the substantial knowledge required to diagnose a wide range of lesions on any body part, skin type and patient group.

2018 - Dermoscopy and reflectance confocal microscopy for monitoring the treatment of actinic cheilitis with ingenol mebutate gel: Report of three cases [Articolo su rivista]
Benati, E.; Pampena, R.; Bombonato, C.; Borsari, S.; Lombardi, M.; Longo, C.
abstract

Actinic cheilitis (AC) can precede the development of squamous cell carcinoma (SCC) of the lip, a location with higher risk of invasiveness and metastasis. Herein, we reported the use of ingenol mebutate (IngMeb) 0.015% gel on three consecutive days to treat three patients suffering from AC. All the three patients achieved complete clearance of AC with rapid clinical effect, favorable safety profile, good patient's compliance related to short time of applications, and few local skin reactions. So IngMeb is an attractive new therapy for AC. Moreover, the present case report adds further evidence to the usefulness of dermoscopy and Reflectance confocal microscopy (RCM) in the assessment and monitoring of treatment outcome.

2018 - Dermoscopy features of atypical fibroxanthoma: A multicenter study of the International Dermoscopy Society [Articolo su rivista]
Moscarella, E.; Piana, S.; Specchio, F.; Kyrgidis, A.; Nazzaro, G.; Eliceche, M. L.; Savoia, F.; Bugatti, L.; Filosa, G.; Zalaudek, I.; Scarfi, F.; Inskip, M.; Rosendahl, C.; Pyne, J. H.; Siggs, G.; Togral, A. K.; Cabo, H.; Drlik, L.; Lallas, A.; Longo, C.; Argenziano, G.
abstract

Background/Objectives: Little is known about the dermoscopic features of atypical fibroxanthoma. Methods: This was a case-control study. Atypical fibroxanthoma lesions were compared with a control group with non-melanoma skin cancer. Results: Altogether 40 atypical fibroxanthoma were collected. Most developed in men (93%), appearing mainly as nodular (63%), amelanotic (93%) and ulcerated (78%) lesions. Most lesions were located on the scalp (55%) and the ears (13%). Dermoscopically, most atypical fibroxanthoma displayed red (83%) and white (70%) structureless areas and irregular linear vessels (43%). A series of features achieved statistical significance when comparing atypical fibroxanthoma with non-melanoma skin cancer. The presence of red and white structureless areas and white lines, and the absence of yellowish-white opaque scales, hairpin vessels and arborising vessels were predictive of atypical fibroxanthoma in univariate analysis. However, when squamous cell carcinoma was excluded from the analysis, none of the criteria achieved statistical significance. When basal cell carcinoma was excluded, three variables achieved statistical significance in predicting atypical fibroxanthoma: red, structureless areas, the absence of opaque yellowish-white scales and absence of white circles. Conclusions: Atypical fibroxanthomas seem to be barely distinguishable from basal cell carcinoma dermoscopically, but they are more easily distinguishable from a well to moderately differentiated squamous cell carcinoma. A histopathological examination is needed for the final diagnosis.

2018 - Dermoscopy of Lymphomas and Pseudolymphomas [Articolo su rivista]
Bombonato, C.; Pampena, R.; Lallas, A.; Pellacani, G.; Longo, C.
abstract

Primary cutaneous lymphomas are a heterogeneous group that includes 2 main groups of primary T- and B-cell lymphomas, which can involve the skin with distinct variability in clinical presentation, histopathology, immunophenotypes, molecular signature, and prognosis. We sought to describe the clinical and dermoscopic features of the most frequent clinical forms of cutaneous lymphomas. The diagnosis of these entities is still based on a cellular level and there are very few reports in literature about dermoscopy of cutaneous lymphomas. Nevertheless, we think that their dermoscopic features can be useful for helping in clinical diagnosis.

2018 - Dermoscopy of syringocystadenoma papilliferum [Articolo su rivista]
Lombardi, Mara; Piana, Simonetta; Longo, Caterina; Borsari, Stefania; Persechino, Flavia; Argenziano, Giuseppe; Moscarella, Elvira
abstract

Syringocystadenoma papilliferum is a benign adnexal neoplasm frequently seen in association with other adnexal tumours. We report the dermoscopic features of three cases of syringocystadenoma papilliferum developing in naevus sebaceus. Clinically the lesions were characterised by exophytic papillary structures. Dermoscopically, polymorphous vessels were the prevalent feature.

2018 - Dermoscopy vs. reflectance confocal microscopy for the diagnosis of lentigo maligna [Articolo su rivista]
Cinotti, E.; Labeille, B.; Debarbieux, S.; Carrera, C.; Lacarrubba, F.; Witkowski, A. M.; Moscarella, E.; Arzberger, E.; Kittler, H.; Bahadoran, P.; Gonzalez, S.; Guitera, P.; Agozzino, M.; Farnetani, F.; Hofmann-Wellenhof, R.; Ardigò, M.; Rubegni, P.; Tognetti, L.; Ludzik, J.; Zalaudek, I.; Argenziano, G.; Longo, C.; Ribero, S.; Malvehy, J.; Pellacani, G.; Cambazard, F.; Perrot, J. L.
abstract

Background: Several dermoscopic and in vivo reflectance confocal microscopy (RCM) diagnostic criteria of lentigo maligna (LM)/lentigo maligna melanoma (LMM) have been identified. However, no study compared the diagnostic accuracy of these techniques. Objective: We evaluated the diagnostic accuracy of dermoscopy and RCM for LM/LMM using a holistic assessment of the images. Methods: A total of 223 facial lesions were evaluated by 21 experts. Diagnostic accuracy of the clinical, dermoscopic and RCM examination was compared. Interinvestigator variability and confidence level in the diagnosis were also evaluated. Results: Overall diagnostic accuracy of the two imaging techniques was good (area under the curve of the sROC function: 0.89). RCM was more sensitive (80%, vs. 61%) and less specific (81% vs. 92%) than dermoscopy for LM/LMM. In particular, RCM showed a higher sensitivity for hypomelanotic and recurrent LM/LMM. RCM had a higher interinvestigator agreement and a higher confidence level in the diagnosis than dermoscopy. Conclusion: Reflectance confocal microscopy and dermoscopy are both useful techniques for the diagnosis of facial lesions and in particular LM/LMM. RCM is particularly suitable for the identification of hypomelanotic and recurrent LM/LMM.

2018 - Early Diagnosis of Skin Melanoma Metastasis by Means of Dermoscopy and Confocal Microscopy [Articolo su rivista]
Paganelli, A.; Longo, C.; Pampena, R.; Piana, S.; Borsari, S.
abstract

NA

2018 - Ex vivo fluorescence confocal microscopy for intraoperative, real-time diagnosis of cutaneous inflammatory diseases: A preliminary study [Articolo su rivista]
Bertoni, L; Azzoni, P; Reggiani, C; Pisciotta, A; Carnevale, G; Chester, J; Kaleci, S; Reggiani Bonetti, L; Cesinaro, Am; Longo, C; Pellacani, G.
abstract

Ex vivo fluorescence confocal microscopy (FCM) is an innovative imaging tool that can be used intraoperatively to obtain real-time images of untreated excised tissue with almost histologic resolution. As inflammatory diseases often share overlapping clinical features, histopathology evaluation is required for dubious cases, delaying definitive diagnoses, and therefore therapy. This study identifies key-features at ex vivo FCM for differential diagnoses of cutaneous inflammatory diseases, in particular, psoriasis, eczema, lichen planus and discoid lupus erythematosus. Retrospective ex vivo FCM and histological evaluations with relevant diagnoses were correlated with prospectively reported histopathologic diagnoses, to evaluate agreement and the level of expertise required for correct diagnoses. We demonstrated that ex vivo FCM enabled the distinction of the main inflammatory features in most cases, providing a substantial concordance to histopathologic diagnoses. Moreover, ex vivo FCM and histological evaluations reached a substantial agreement with histopathologic diagnoses both for all raters and for each operator. After a yet to be defined learning curve, these preliminary results suggest that dermatologists may be able to satisfactorily interpret ex vivo FCM images for correct real-time diagnoses. Despite some limitations mainly related to the equipment of FCM with a single objective lens, our study suggests that ex vivo FCM seems a promising tool in assisting diagnoses of cutaneous inflammatory lesions, with a level of accuracy quite close to that offered by histopathology. This is the first study to investigate ex vivo FCM application in cutaneous inflammatory lesions, and to evaluate the diagnostic capability of this technology.

2018 - Folliculotropism in pigmented facial macules: Differential diagnosis with reflectance confocal microscopy [Articolo su rivista]
Persechino, F.; De Carvalho, N.; Ciardo, S.; De Pace, B.; Casari, A.; Chester, J.; Kaleci, S.; Stanganelli, I.; Longo, C.; Farnetani, F.; Pellacani, G.
abstract

Pigmented facial macules are common on sun damage skin. The diagnosis of early stage lentigo maligna (LM) and lentigo maligna melanoma (LMM) is challenging. Reflectance confocal microscopy (RCM) has been proven to increase diagnostic accuracy of facial lesions. A total of 154 pigmented facial macules, retrospectively collected, were evaluated for the presence of already-described RCM features and new parameters depicting aspects of the follicle. Melanocytic nests, roundish pagetoid cells, follicular infiltration, bulgings from the follicles and many bright dendrites and infiltration of the hair follicle (ie, folliculotropism) were found to be indicative of LM/LMM compared to non-melanocytic skin neoplasms (NMSNs), with an overall sensitivity of 96% and specificity of 83%. Concerning NMSNs, solar lentigo and lichen planus-like keratosis resulted better distinguishable from LM/LMM because usually lacking malignant features and presenting characteristic diagnostic parameters, such as epidermal cobblestone pattern and polycyclic papillary contours. On the other hand, distinction of pigmented actinic keratosis (PAK) resulted more difficult, and needing evaluation of hair follicle infiltration and bulging structures, due to the frequent observation of few bright dendrites in the epidermis, but predominantly not infiltrating the hair follicle (estimated specificity for PAK 53%). A detailed evaluation of the components of the folliculotropism may help to improve the diagnostic accuracy. The classification of the type, distribution and amount of cells, and the presence of bulging around the follicles seem to represent important tools for the differentiation between PAK and LM/LMM at RCM analysis.

2018 - In vivo dermoscopic and confocal microscopy multi-step algorithm to detect in situ melanomas [Articolo su rivista]
Borsari, S; Pampena, R; Benati, E; Bombonato, C; Athanassios, K; Moscarella, E; Lallas, A; Argenziano, G; Pellacani, G; Longo, C
abstract

Although several dermoscopic features of in situ melanoma (MIS) have been identified, data on confocal features for MIS are still lacking.

2018 - Integration of dermoscopy and reflectance confocal microscopy for distinguishing melanomas from nevi of the breast area [Articolo su rivista]
Mandel, Victor Desmond; Bombonato, Caterina; Pampena, Riccardo; Kyrgidis, Athanassios; Borsari, Stefania; Benati, Elisa; Mirra, Marica; Piana, Simonetta; Pellacani, Giovanni; Longo, Caterina
abstract

Background: Nevi of special sites encompass a class of benign lesions characterized by the presence of atypical clinical and histopathological features that can be difficult to distinguish from melanoma. Dermoscopy and reflectance confocal microscopy may improve the clinical assessment of melanocytic lesions to avoid unnecessary excisions. Objectives: The aim of this study was to assess the value of specific dermoscopic and confocal criteria in distinguishing melanomas from nevi of the breast area. Methods: Dermoscopic and confocal images from consecutive patients with at least one clinically and/or dermoscopically equivocal melanocytic skin lesion of the breast area were retrospectively evaluated. In this case-control study, only histopathologically proven melanomas (cases) and nevi (controls) were included. Spearman's coefficients were first calculated to flag significant correlation; then univariate and multivariate logistic regression analyses were performed to assess which factors were independently associated with the histopathological diagnosis. Finally, a mixed dermoscopic/confocal score was created to distinguish nevi from melanomas on the breast area. Results: The study population included 55 skin lesions of the breast area, 34 (61.8%) nevi and 21 (38.2%) melanomas. Among dermoscopic criteria, atypical network and irregular pigmentation resulted independently associated with melanoma diagnosis (OR: 11.1; 95% CI 1.0-119.9; P:0.048 and OR: 6.5; 95% CI 1.1-37.5; P:0.037, respectively). Furthermore, on RCM examination, the presence of pagetoid cells was an independent positive predictor for melanoma (OR: 38.5; 95% CI 3.9-379.6; P:0.002). The mixed score showed high levels of sensitivity and specificity, 95.2% and 82.4%, respectively, which were higher than dermoscopic and confocal evaluations alone. Conclusion: The combined use of dermoscopy and confocal microscopy in the triage of pigmented lesions of the breast area may help in increasing the diagnostic accuracy and avoiding unnecessary excisions.

2018 - Merkel cell Carcinoma arising on a pre-existing Bowen's disease: Is it just by chance? [Articolo su rivista]
Longo, Caterina; Pellacani, Giovanni
abstract

Merkel cell Carcinoma (MCC) is a cutaneous Carcinoma with neuroendocrine differentiation. It arises typically on sun-exposed areas of elderly men as an asymptomatic, rapidly growing, red nodule. Although it is usually found as a solitary nodule, in almost one third of cases MCC may be associated with other malignancies such as basal cell or squamous cell carcinomas. Merkel cell Carcinoma should be considered as differential diagnosis every time we have a rapidly growing, red nodule, arising in an elderly patient with signs of sun-damage. We report a case of MCC developing in association with a pre-existing Bowen's disease. The association between MCC and Bowen's disease is quite common and their area of occurrence is usually a sun-exposed area. Ultraviolet radiation contributes to the etiology of both the malignancies.

2018 - Multiple granuloma faciale: A clinical finding from a dermoscopic point a view [Articolo su rivista]
Pampena, R.; Paolino, G.; Didona, D.; Longo, C.; Salvi, M.; Giona, F.; Santopietro, M.; Carbone, A.; Frascione, P.; Calvieri, S.; Donati, P.
abstract

2018 - Nevus-Associated Melanoma: Patient Phenotype and Potential Biological Implications [Articolo su rivista]
Pampena, R.; Pellacani, G.; Longo, C.
abstract

Pandeya et al. report that nevus-associated melanoma is associated with a specific phenotype, namely, young age, high number of nevi, non-brown eye color and slight dermal elastosis. Potential implications regarding differences between nevus-associated melanomas and de novo melanomas are discussed.

2018 - Reflectance confocal microscopy: a crucial role for actinic keratosis treatment monitoring [Articolo su rivista]
Pellacani, G.; Longo, C.
abstract

NA

2018 - Reinterpreting dermoscopic pigment network with reflectance confocal microscopy for identification of melanoma-specific features [Articolo su rivista]
De Pace, B.; Farnetani, F.; Losi, A.; Ciardo, S.; De Carvalho, N.; Cesinaro, A. M.; Reggiani Bonetti, L.; Chester, J.; Kaleci, S.; Del Duca, E.; Nisticò, S. P.; Longo, C.; Pellacani, G.
abstract

Background: Pigment network is an important dermoscopic feature for melanocytic lesions, but alterations in grid line thickness are also observed in melanomas. Objective: To investigate features of thick, thin and mixed pigment networks at dermoscopy and their respective features at reflectance confocal microscopy (RCM) for differential diagnosis, correlated with histology. Methods: All melanocytic lesions with histological diagnosis, evaluated between January 2010 and May 2014, were enrolled and classified according to dermoscopy evaluation of the pigment networks: thin, thick and mixed. Results: Thin network in melanoma was characterized by a honeycombed pattern (P < 0.001), dendritic cells (P < 0.001), atypical ringed pattern (P = 0.035) and structureless area (P = 0.012), whereas round cells (P < 0.001), dendritic cells (P < 0.001) and atypical meshwork pattern (<0.001) characterized thick network in melanoma. Mixed network type in melanoma shared honeycombed (P = 0.049) and typical ringed patterns (P = 0.045) in the thin area and round cells (P < 0.001) and atypical meshwork pattern (P < 0.001) in the thick area. Thin network in nevi was characterized by cobblestone (P < 0.001) and typical ringed patterns (P = 0.035), whereas thick network in nevi showed a typical meshwork pattern (P < 0.001). Mixed nevi shared the same features and patterns, but more frequently with inflammatory infiltrate (P = 0.047). Conclusion: Differential diagnosis between melanocytic lesions (nevi or melanoma) in thin, thick and mixed pigment networks observed at dermoscopy can be assisted by RCM to improve diagnostic accuracy.

2018 - Subcutaneous pigmented clear cell sarcoma as a challenging simulator of melanoma [Articolo su rivista]
Bombonato, C.; Moscarella, E.; Longo, C.; Castagnetti, F.; Nicoli, D.; Piana, S.
abstract

NA

2018 - The smart approach: feasibility of lentigo maligna superficial margin assessment with hand-held reflectance confocal microscopy technology [Articolo su rivista]
Pellacani, G.; De Carvalho, N.; Ciardo, S.; Ferrari, Beatrice; Cesinaro, A. M.; Farnetani, F.; Bassoli, S.; Guitera, P.; Star, P.; Rawson, R.; Rossi, E.; Magnoni, C.; Gualdi, G.; Longo, C.; Scope, A.
abstract

Background: Lentigo maligna may be challenging to clear surgically. Objective: To evaluate feasibility of using superficial skin cuts as RCM imaging anchors for attaining negative surgical margins in lentigo maligna. Methods: Included patients presented with lentigo maligna near cosmetically sensitive facial structures. We evaluated, with hand-held-RCM, microscopic clearance of melanoma beyond its dermoscopically detected edges. Evaluated margins were annotated using shallow skin cuts. If a margin was positive at ‘first-step’ RCM evaluation, we sequentially advanced the margin radially outward at that segment by 2-mm intervals until an RCM-negative margin was identified. Prior to final surgical excision, we placed sutures at the outmost skin cuts to allow comparison of RCM and histopathological margin assessments. Primary outcome measure was histopathological verification that RCM-negative margins were clear of melanoma. Results: The study included 126 first-step margin evaluations in 23 patients, median age 70 years (range: 43–91). Seventeen patients (74%) had primary in-situ melanoma and six (26%) invasive melanoma, mean thickness 0.3 mm (range 0.2–0.4 mm). Six cases (26%) showed complete negative RCM margins on ‘first-step’, 11 (48%) were negative at ‘second-step’, and four (17%) at ‘third-step’. In two additional cases (9%), margins clearance could not be determined via RCM due to widespread dendritic cells proliferation. The RCM-negative margins in all 21 cases proved clear of melanoma on histopathology. Of the 15 cases that returned at 1-year follow-up, none showed any residual melanoma on dermoscopic and RCM examinations. Interobserver reproducibility showed fair agreement between bedside RCM reader and blinded remote-site reader, with Spearman's rho of 0.48 and Cohen's kappa of 0.43; using bedside reader as reference, the remote reader's sensitivity was 92% and specificity 57% in positive margin detection. Conclusions: Margin mapping of lentigo maligna with hand-held-RCM, using superficial skin cuts, appears feasible. This approach needs validation by larger studies.

2018 - Tracking actinic keratosis of face and scalp treated with 0.015% ingenol mebutate to identify clinical and dermoscopic predictors of treatment response [Articolo su rivista]
Pampena, R.; Benati, E.; Borsari, S.; Bombonato, C.; Lombardi, M.; Raucci, M.; Mirra, M.; Lallas, A.; Apalla, Z.; Papadimitriou, I.; Moscarella, E.; Kyrgidis, A.; Argenziano, G.; Pellacani, G.; Longo, C.
abstract

Background: Ingenol mebutate (IngMeb) 0.015% gel is an approved field treatment option for non-hyperkeratotic non-hypertrophic actinic keratosis (AK) of face and scalp. Efficacy of IngMeb has been assessed only on a clinical ground, in the majority of studies. Dermoscopy is a pivotal tool for the diagnosis of AK, while its role in evaluating the response to non-surgical therapies for AK has not been fully defined. Objectives: Our study aims to determine whether some dermoscopic features of AK of the face and scalp areas may independently predict the response to IngMeb therapy. Methods: Clinical and dermoscopic responses, 1 month after 0.015% IngMeb therapy, were retrospectively evaluated using a per-patient and per-lesion approach. Safety was evaluated through local skin reaction composite score calculation. Demographic, clinical and dermoscopic factors were then evaluated via univariate and multivariate logistic regression analysis to assess independent predictors of response. Results: Fifty-five patients with 245 AKs were enrolled. Clinically, per-patient response evaluation identified 25 (45.4%) poor/partial and 30 (54.5%) complete responders, corresponding on a per-lesion approach to 66 (26.9%) and 179 (73.1%) AKs, respectively. Dermoscopy reclassified 14 patients in the per-patient and 48 AKs in the per-lesion analysis from complete to poor/partial responders. Multivariate logistic regression analysis showed that AKs dermoscopically characterized by red pseudonetwork and located on the face were independently associated with a complete dermoscopic response to 0.015% IngMeb therapy, while microerosions were negative predictors. Conclusion: Specific dermoscopic features of AK may predict the response to 0.015% IngMeb therapy, together with the location on the face.

2018 - Uncovering the diagnostic dermoscopic features of flat melanomas located on the lower limbs [Articolo su rivista]
Bassoli, S; Kyrgidis, A; Ciardo, S; Casari, Alice; Losi, A; De Pace, B; Babino, G; De Col, E; Marchetti Cautela, Jennifer; Ferrari, Federica; Moscarella, E; Lallas, A; Argenziano, G; Pellacani, G; Longo, C
abstract

a

2018 - Update of calcineurin inhibitors to treat inverse psoriasis: A systematic review [Articolo su rivista]
Dattola, A.; Silvestri, M.; Bennardo, L.; Del Duca, E.; Longo, C.; Bianchi, L.; Nistico, S.
abstract

Inverse psoriasis commonly involves skin fold areas including the axillae, perianal skin, intergluteal cleft, inframammary, genital/inguinal, abdominal, and retroauricular folds. Topical calcineurin inhibitors are indicated for the treatment of atopic dermatitis but have also been studied in the treatment of psoriasis. The object of the present study is to define the efficacy of topical calcineurin inhibitors in the treatment of psoriasis. We checked for English-vernacular articles conveyed since 1990 in PubMed, Ovid/Cochrane, and Embase using “tacrolimus,” “pimecrolimus,” or “topical calcineurin inhibitors,” and “psoriasis” as keywords. Eight double-blind studies and seven open studies displayed the ampleness of topical tacrolimus in psoriasis. Included studies demonstrated a considerable efficacy of topical administration of tacrolimus and pimecrolimus in the treatment of psoriasis, especially for facial, genital, and intertriginous areas. The role of topical tacrolimus and pimecrolimus in the treatment of psoriasis seems to be promising as shown by the results of double-blind and open studies. Because these agents do not cause cutaneous atrophy, they have a special role in facial, genital, and intertriginous psoriatic lesions. Both agents await additional investigation to determine their roles.

2018 - Wide skin markings pattern - melanoma descriptor or patient-related factor?: reply from authors [Articolo su rivista]
Longo, C; Lallas, A; Kyrgidis, A; Bassoli, S; Moscarella, E; Pellacani, G; Argenziano, G
abstract

We read with great interest the letter by Rishpon and Colleagues on our paper titled "Uncovering the diagnostic dermoscopic features of flat melanomas located on the lower limbs" (1). In the current letter, we investigated a series of 247 lesions, including 71 thin melanomas, located on lower limbs with the aim to identify diagnostic specific dermoscopic criteria for melanoma diagnosis. Furthermore, a new dermoscopic descriptor, namely wider skin markings was introduced. This article is protected by copyright. All rights reserved.

2017 - A meta-analysis of nevus-associated melanoma: Prevalence and practical implications [Articolo su rivista]
Pampena, Riccardo; Kyrgidis, Athanassios; Lallas, Aimilios; Moscarella, Elvira; Argenziano, Giuseppe; Longo, Caterina
abstract

The reported prevalence of nevus-associated melanoma varies substantially. We performed a systematic review and meta-analysis to determine the incidence and prevalence of this disease; we also performed subanalyses considering age, tumor thickness, and nevus-type classification. In 38 observational cohort and case-control studies, 29.1% of melanomas likely arose from a preexisting nevus and 70.9% de novo. Any given melanoma was 64% less likely to be nevus-associated than de novo (risk ratio 0.36, 95% confidence interval [CI] 0.29-0.44; P < .001; I2= 99%); nevus-associated melanomas had a lower mean Breslow thickness than de novo melanomas (mean difference -0.39 mm; 95% CI -0.60 to -0.18; P = .0003; I2= 66%). No significant differences were noted regarding the association of nevus-associated melanomas with nondysplastic nevi or dysplastic nevi (risk ratio 0.77, 95% CI 0.49-1.20; P = .24; I2= 98%).

2017 - A solitary pink lesion: dermoscopy and RCM features of lichen planus [Articolo su rivista]
Pezzini, Claudia; Piana, Simonetta; Longo, Caterina; Benati, Elisa; Borsari, Stefania; Specchio, Francesca; Moscarella, Elvira
abstract

We present an unusual onset of cutaneous lichen planus (LP) in a middle-aged patient. The initial presentation as solitary, indolent pink lesion required further investigations to rule out malignancy, especially amelanotic melanoma. Dermoscopy and reflectance confocal microscopy findings were found to be helpful in our case in addressing the correct diagnosis.

2017 - Acral melanoma [Articolo su rivista]
Persechino, Flavia; Longo, Caterina; Benati, Elisa; Borsari, Stefania; Lombardi, Mara; Piana, Simonetta; Argenziano, Giuseppe; Moscarella, Elvira
abstract

Aged, 80 and over; Foot Diseases; Humans; Male; Melanoma; Skin Neoplasms; 2708

2017 - Association between dermoscopic and reflectance confocal microscopy features of cutaneous melanoma with BRAF mutational status [Articolo su rivista]
Bombonato, Caterina; Ribero, S.; Pozzobon, F. C.; Puig Butille, J. A.; Badenas, C.; Carrera, C.; Malvehy, J.; Moscarella, Elvira; Lallas, A.; Piana, S.; Puig, S.; Argenziano, Giuseppe; Longo, Caterina
abstract

Background: Melanomas harbouring common genetic mutations might share certain morphological features detectable with dermoscopy and reflectance confocal microscopy. BRAF mutational status is crucial for the management of metastatic melanoma. Objectives: To correlate the dermoscopic characteristics of primary cutaneous melanomas with BRAF mutational status. Furthermore, a subset of tumours has also been analysed for the presence of possible confocal features that might be linked with BRAF status. Methods: Retrospectively acquired dermoscopic and confocal images of patients with melanoma in tertiary referral academic centres: Skin Cancer Unit in Reggio Emilia and at the Melanoma Unit in Barcelona. Kruskal–Wallis test, logistic regressions, univariate and multivariate analyses have been performed to find dermoscopic and confocal features significantly correlated with BRAF mutational status. Results: Dermoscopically, the presence of irregular peripheral streaks and ulceration were positive predictors of BRAF-mutated melanomas with a statistically significance value, while dotted vessels were more represented in wild-type melanomas. None of the evaluated reflectance confocal microscopy features were correlated with genetic profiling. Conclusions: Ulceration and irregular peripheral streaks represent dermoscopic feature indicative for BRAF-mutated melanoma, while dotted vessels are suggestive for wild-type melanoma.

2017 - Baldness and scalp melanoma [Articolo su rivista]
Benati, E.; Longo, C.; Bombonato, C.; Moscarella, E.; Alfano, R.; Argenziano, G.
abstract

J Eur Acad Dermatol Venereol. 2017 Dec;31(12):e528-e530. doi: 10.1111/jdv.14395. Epub 2017 Aug 4. No abstract available.

2017 - Both short-term and long-term dermoscopy monitoring is useful in detecting melanoma in patients with multiple atypical nevi [Articolo su rivista]
Moscarella, Elvira; Tion, I.; Zalaudek, I.; Lallas, A.; Kyrgidis, A.; Longo, Caterina; Lombardi, M.; Raucci, M.; Satta, R.; Alfano, R.; Argenziano, Giuseppe
abstract

Background: Digital dermoscopy monitoring (DDM) is an effective strategy for melanoma detection. Two methods are currently employed. Short-term follow-up (STFU) for the evaluation of single, atypical lesions to detect subtle changes over a short period of time (3–6 months). Long-term follow-up (LTFU) is recommended for patients with multiple nevi. Although a study demonstrated that STFU improves the patients’ compliance for DDM, little remains known about the impact and reliability of STFU in this setting. Objectives: The aim of this retrospective, observational study was to evaluate the impact and reliability of a schedule combining STFU and LTFU in patients with multiple atypical nevi. Methods: We searched our database for all cases of patients with multiple atypical nevi occurring between 2006 and 2014. Results: A total of 3823 lesions in 541 patients were dermoscopically monitored (mean number = 7 lesions per patient; median = 6 lesions; range, 2–51). In all, 264 (6.9%) lesions in 184 (34.4%) patients were excised (mean of 0.5 lesions per patient). In total, 197 (74.6%) lesions were excised at follow-up, with melanomas representing 30.5% of lesions excised after follow-up. A total of 30 (33.3%) melanomas were excised at baseline, 23 (25.6%) after STFU and 37 (41.1%) after LTFU. There was no difference in the number of in situ melanomas detected at baseline with those detected after follow-up. The mean Breslow thickness of melanomas detected at baseline was higher than those detected after STFU (P = 0.038) and LTFU (P = 0.055). Conclusions: Our study confirm that digital dermoscopy follow-up is a valid management strategy for patients with multiple atypical nevi, with short-term monitoring playing an effective role also in this setting of patients.

2017 - Can we improve melanoma detection methods? [Articolo su rivista]
Pampena, Riccardo; Longo, Caterina
abstract

NA

2017 - Clinical and dermoscopic clues to differentiate pigmented nail bands: an International Dermoscopy Society study [Articolo su rivista]
Benati, E.; Ribero, S.; Longo, Caterina; Piana, S.; Puig, S.; Carrera, C.; Cicero, F.; Kittler, H.; Deinlein, T.; Zalaudek, I.; Stolz, W.; Scope, Alon; Pellacani, Giovanni; Moscarella, Elvira; Piraccini, B. M.; Starace, M.; Argenziano, Giuseppe
abstract

Background: Longitudinal melanonychia might be difficult to differentiate and the use of dermoscopy can be useful for the preoperative evaluation and management decision. Objectives: The aim of our study was to investigate clinical and dermoscopic criteria of acquired longitudinal melanonychia in adults to identify the best predictors of melanoma using a multivariate analysis and to explore eventual new dermoscopic criteria for nail melanoma diagnosis. Methods: In this retrospective observational study, 82 histopathologically diagnosed, acquired nail pigmented bands were collected and examined. All variables were included in the analysis and examined as possible predictors of nail melanoma. Both univariate and multivariable analyses have been performed. Results: Among 82 cases, 25 were diagnosed as nail melanoma and 57 as benign lesions (including 32 melanocytic nevi and 25 benign melanocytic hyperplasia). Melanoma cases were significantly associated with a width of the pigmented band higher than 2/3 of the nail plate, grey and black colours, irregularly pigmented lines, Hutchinson and micro-Hutchinson signs, and nail dystrophy. Granular pigmentation, a newly defined dermoscopic criterion, was found in 40% of melanomas and only in 3.51% of benign lesions. Conclusions: Dermoscopic examination of longitudinal melanonychia provides useful information that could help clinicians to improve melanoma recognition.

2017 - Clinicodermoscopic features of Spitz naevi by age and anatomical site: a study of 378 Spitz naevi [Articolo su rivista]
de Mestier, Y.; Moscarella, E.; Marchetti Cautela, J.; Lallas, A.; Longo, C.; Zalaudek, I.; Hofmann-Wellenhof, R.; Argenziano, G.
abstract

a

2017 - Confocal and dermoscopic features of basal cell carcinoma in Gorlin–Goltz syndrome: A case report [Articolo su rivista]
Casari, A.; Argenziano, G.; Moscarella, E.; Lallas, A.; Longo, C.
abstract

Gorlin–Goltz (GS) syndrome is an autosomal dominant disease linked to a mutation in the PTCH gene. Major criteria include the onset of multiple basal cell carcinoma (BCC), keratocystic odontogenic tumours in the jaws and bifid ribs. Dermoscopy and reflectance confocal microscopy represent imaging tools that are able to increase the diagnostic accuracy of skin cancer in a totally noninvasive manner, without performing punch biopsies. Here we present a case of a young woman in whom the combined approach of dermoscopy and RCM led to the identification of multiple small inconspicuous lesions as BCC and thus to the diagnosis of GS syndrome.

2017 - Confocal microscopy and dermoscopy for the monitoring of BRAF inhibitor therapy of melanoma skin metastases [Articolo su rivista]
Ribero, S.; Marra, E.; Tomasini, C. F.; Fierro, M. T.; Bombonato, C.; Longo, C.
abstract

a

2017 - Cutaneous photoaging: Description and algorithms [Capitolo/Saggio]
Prow, T. W.; Raphael, A. P.; Wurm, E. M.; Longo, C.; Soyer, H. P.
abstract

Skin aging and photoaging are the result of long-term biological processes that are difficult to study but easily recognized clinically.1 Photoaging has both chronological and UV exposure components, for a recent review see Rittie and Fisher.2 Photoaging describes the earlier portion of the spectrum of disease that begins with healthy skin and ends with malignant disease. Along the path to malignant disease there are hallmarks of photoaging. These include visible pigmentation responses, wrinkling, skin sagging, and premalignant lesions called actinic keratoses. Both the epidermis and dermis are significantly altered during photoaging. This is due to cleaved collagen and accumulating elastin in the dermis, commonly called solar elastosis.

2017 - Dermoscopic and reflectance confocal microscopy features of cutaneous squamous cell carcinoma [Articolo su rivista]
Manfredini, M.; Longo, C.; Ferrari, B.; Piana, S.; Benati, E.; Casari, A.; Pellacani, G.; Moscarella, E.
abstract

Background: Squamous cell carcinoma (SCC) of the skin is a highly prevalent neoplasm. The management and the prognosis of this tumour are dependent on its invasiveness and its grade of differentiation. Objectives: To evaluate whether specific dermoscopic and reflectance confocal microscopy (RCM) criteria can predict the diagnosis of invasive SCC vs. in situ SCC and poorly differentiated compared with well- and moderately differentiated SCC. Methods: Dermoscopic and RCM images of SCC were retrospectively evaluated for the presence of predefined criteria. Results: Among 143 SCCs, 121 cases had a complete set of images and thus were included in the study set. The head and neck area was the most frequently involved body site (74/121; 61.1%) followed by extremities (36/121, 29.7%) and trunk (11/121, 9.1%). Seventy tumours were in situ (57.8%), while 51 were invasive (42.1%), of these 11 were poorly differentiated (21.5%), 16 were moderately differentiated (31.3%), and 24 were well differentiated (47.0%). Chi-squared analysis demonstrated that invasive SCCs were characterized by polymorphic vessels, erosion/ulceration, architectural disarrangement, speckled nucleated cells in the dermis, irregularly dilated vessels and absence of hyperkeratosis. Buttonhole vessels, white structureless areas and dotted or glomerular vessels were significantly associated with in situ lesions. Poorly differentiated SCCs were typified by red areas, erosion/ulceration and architectural disarrangement. Well- or moderately differentiated SCCs were associated with white areas and speckled nucleated cells in the epidermis. Conclusion: Clinical, dermoscopic and RCM images provide useful information that should be integrated in order to achieve the optimal therapeutic management for the patient.

2017 - Dermoscopic clues for diagnosing melanomas that resemble seborrheic keratosis [Articolo su rivista]
Carrera, Cristina; Segura, Sonia; Aguilera, Paula; Scalvenzi, Massimiliano; Longo, Caterina; Barreiro, Alicia; Broganelli, Paolo; Cavicchini, Stefano; Llambrich, Alex; Zaballos, Pedro; Thomas, Luc; Malvehy, Josep; Puig, Susana; Zalaudek, Iris
abstract

IMPORTANCE: Melanomas that clinically mimic seborrheic keratosis (SK) can delay diagnosis and adequate treatment. However, little is known about the value of dermoscopy in recognizing these difficult-to-diagnose melanomas. OBJECTIVE: To describe the dermoscopic features of SK-like melanomas to understand their clinical morphology. DESIGN, SETTING, AND PARTICIPANTS: This observational retrospective study used 134 clinical and dermoscopic images of histopathologically proven melanomas in 134 patients treated in 9 skin cancer centers in Spain, France, Italy, and Austria. Without knowledge that the definite diagnosis for all the lesions was melanoma, 2 dermoscopy-trained observers evaluated the clinical descriptions and 48 dermoscopic features (including all melanocytic and nonmelanocytic criteria) of all 134 images and classified each dermoscopically as SK or not SK. The total dermoscopy score and the 7-point checklist score were assessed. Images of the lesions and patient data were collected from July 15, 2013, through July 31, 2014. MAIN OUTCOMES AND MEASURES: Frequencies of specific morphologic patterns of (clinically and dermoscopically) SK-like melanomas, patient demographics, and interobserver agreement of criteria were evaluated. RESULTS: Of the 134 cases collected from 72 men and 61 women, all of whom were white and who had a mean (SD) age of 55.6 (17.5) years, 110 (82.1%) revealed dermoscopic features suggestive of melanoma, including pigment network (74 [55.2%]), blue-white veil (72 [53.7%]), globules and dots (68 [50.7%]), pseudopods or streaks (47 [35.1%]), and blue-black sign (43 [32.3%]). The remaining 24 cases (17.9%) were considered likely SKs, even by dermoscopy. Overall, lesions showed a scaly and hyperkeratotic surface (45 [33.6%]), yellowish keratin (42 [31.3%]), comedo-like openings (41 [30.5%]), and milia-like cysts (30 [22.4%]). The entire sample achieved a mean (SD) total dermoscopy score of 4.7 (1.6) and a 7-point checklist score of 4.4 (2.3), while dermoscopically SK-like melanomas achieved a total dermoscopy score of only 4.2 (1.3) and a 7-point checklist score of 2.0 (1.9), both in the range of benignity. The most helpful criteria in correctly diagnosing SK-like melanomas were the presence of blue-white veil, pseudopods or streaks, and pigment network. Multivariate analysis found only the blue-black sign to be significantly associated with a correct diagnosis, while hyperkeratosis and fissures and ridges were independent risk markers of dermoscopically SK-like melanomas. CONCLUSIONS AND RELEVANCE: Seborrheic keratosis-like melanomas can be dermoscopically challenging, but the presence of the blue-black sign, pigment network, pseudopods or streaks, and/or blue-white veil, despite the presence of other SK features, allows the correct diagnosis of most of the difficult melanoma cases.

2017 - Dermoscopic features of squamous cell carcinoma on the lips [Articolo su rivista]
Benati, E.; Persechino, F.; Piana, S.; Argenziano, G.; Lallas, A.; Moscarella, E.; Castagnetti, F.; Longo, C.
abstract

a

2017 - Dermoscopic features predicting the presence of mitoses in thin melanoma [Articolo su rivista]
Ribero, S.; Argenziano, G.; Lallas, A.; Moscarella, E.; Benati, E.; Raucci, M.; Piana, S.; Longo, C.
abstract

Background The latest AJCC classification has included the number of mitoses as a factor for upstaging thin melanomas. Meanwhile, while dermoscopy has often been used to predict melanoma thickness, its value in predicting number of mitoses remains unknown. Objective Our aim is to evaluate the correlation between dermoscopic features and the presence of mitoses in a consecutive cohort of thin melanomas. Methods A case control study has been performed to identify specific dermoscopic parameters that could differentiate thin melanomas with 1 or more mitoses per mm2 from those without mitoses. Results Of 177 melanomas equal to or thinner than 1Â&nbsp;mm, 131 (74%) lesions had no mitoses and 46 (36%) lesions had at least 1 mitosisÂ&nbsp;Ã Â&nbsp;mm2. Dermoscopic features associated with the presence of 1 or more mitoses were the following: peripheral streaks (OR 4.11; 95% CI 1.94â 8.71) and black colour (OR 4.70; 95% CI; 2.28â 9.68). In contrast, atypical pigment network (OR (0.30; 95% CI 0.15â 0.61)) and brown colour (OR 0.36; 95% CI 0.18â 0.75) were associated to melanomas without mitoses. The same variables were also associated to the increasing number of mitoses at linear regression. Conclusion Black colour and peripheral streaks can predict the presence of mitoses in thin melanoma, while atypical pigment network and brown colour are associated to thin melanoma without mitoses.

2017 - Dermoscopic ulceration is a predictor of basal cell carcinoma response to imiquimod: A retrospective study [Articolo su rivista]
Urech, M.; Kyrgidis, A.; Argenziano, G.; Reggiani, C.; Moscarella, E.; Longo, C.; Alfano, R.; Zalaudek, I.; Lallas, A.
abstract

NA

2017 - Dermoscopy of small-size basal cell carcinoma: a case–control study [Articolo su rivista]
Longo, Caterina; Specchio, F.; Ribero, S.; Coco, V.; Kyrgidis, A.; Moscarella, Elvira; Ragazzi, M.; Peris, K.; Argenziano, Giuseppe
abstract

ND

2017 - Dermoscopy pathology correlation in melanoma [Articolo su rivista]
Russo, Teresa; Piccolo, Vincenzo; Ferrara, Gerardo; Agozzino, Marina; Alfano, Roberto; Longo, Caterina; Argenziano, Giuseppe
abstract

Dermoscopy is a widely used technique whose role in the clinical (and preoperative) diagnosis of melanocytic and non-melanocytic skin lesions has been well established in recent years. The aim of this paper is to clarify the correlations between the â localâ dermoscopic findings in melanoma and the underlying histology, in order to help clinicians in routine practice.

2017 - Dermoscopy: Basic knowledge of an innovative imaging tool [Capitolo/Saggio]
Witkowski, A.; Pellacani, G.; Gonzalez, S.; Longo, C.
abstract

Dermoscopy: Basic knowledge of an innovative imaging tool

2017 - Diagnostic accuracy of confocal microscopy imaging vs. punch biopsy for diagnosing and subtyping basal cell carcinoma [Articolo su rivista]
Kadouch, D. J.; Leeflang, M. M.; Elshot, Y. S.; Longo, C.; Ulrich, M.; van der Wal, A. C.; Wolkerstorfer, A.; Bekkenk, M. W.; de Rie, M. A.
abstract

Background: In vivo reflectance confocal microscopy (RCM) is a promising non-invasive skin imaging technique that could facilitate early diagnosis of basal cell carcinoma (BCC) instead of routine punch biopsies. However, the clinical value and utility of RCM vs. a punch biopsy in diagnosing and subtyping BCC is unknown. Objective: To assess diagnostic accuracy of RCM vs. punch biopsy for diagnosing and subtyping clinically suspected primary BCC. Methods: A prospective, consecutive cohort of 100 patients with clinically suspected BCC were included at two tertiary hospitals in Amsterdam, the Netherlands, between 3 February 2015 and 2 October 2015. Patients were randomized between two test-treatment pathways: diagnosing and subtyping using RCM imaging followed by direct surgical excision (RCM one-stop-shop) or planned excision based upon the histological diagnosis and subtype of punch biopsy (standard care). The primary outcome was the agreement between the index tests (RCM vs. punch biopsy) and reference standard (excision specimen) in correctly diagnosing BCC. The secondary outcome was the agreement between the index tests and reference standard in correctly identifying the most aggressive BCC subtypes. Results: Sensitivity to detect BCC was similar for RCM and punch biopsy (100% vs. 93.94%), but a punch biopsy was more specific than RCM (79% vs. 38%). RCM expert evaluation for diagnosing BCC had a sensitivity of 100% and a specificity of 75%. The agreement between RCM and excision specimen in identifying the most aggressive BCC subtype ranged from 50% to 85% vs. 77% by a punch biopsy. Conclusion: Reflectance confocal microscopy and punch biopsy have comparable diagnostic accuracy to diagnose and subtype BCC depending on RCM experience. Although experienced RCM users could accurately diagnose BCC at a distance, we found an important difference in subtyping BCC. Future RCM studies need to focus on diagnostic accuracy, reliability and specific criteria to improve BCC subtype differentiation.

2017 - Does pregnancy influence melanoma prognosis? A meta-analysis [Articolo su rivista]
Kyrgidis, Athanassios; Lallas, Aimilios; Moscarella, Elvira; Longo, Caterina; Alfano, Roberto; Argenziano, Giuseppe
abstract

The literature has not been able to conclude whether pregnancy influences the prognosis of melanoma. The aim of this study was to explore the prognosis of melanoma diagnosed during pregnancy or post partum [pregnancy-associated melanoma (PAM)] compared with melanoma in female patients who were not pregnant. We systematically searched for studies of female patients with melanoma that reported outcomes related to survival. Fifteen eligible studies were found. Overall, PAM was associated with a 17% higher mortality compared with melanoma diagnosed in female patients who were not pregnant (hazard ratio=1.17, 95% confidence interval: 1.03-1.33, P=0.02). The heterogeneity associated with this test was moderate (P=0.07; I 2 =38%). PAM was also associated with a 50% higher recurrence rate compared with melanoma not associated with pregnancy (hazard ratio=1.50, 95% confidence interval: 1.19-1.90, P&lt;0.001). The heterogeneity associated with this test was low (P=0.69; I 2 =0%). A limitation of this meta-analysis is the definition of PAM, which is not unanimous among the studies included. Our results indicate that PAM is associated with a worse prognosis than melanoma not related to pregnancy, both in terms of overall survival and disease-free survival. On the basis of our data, we anticipate that the survival difference we report here will be further amplified with the addition of future well-carried out studies. We suggest that detection of PAM requires particular awareness by healthcare professionals.

2017 - Dysplastic nevi [Capitolo/Saggio]
Gill, M.; Jain, M.; Perino, F.; Malvehy, J.; Borsari, S.; Pellacani, G.; Longo, C.
abstract

dysplastic nevi

2017 - Evolution of Spitz naevi: a dermoscopic and confocal follow-up of 26 cases [Articolo su rivista]
Ferrari, C.; Longo, C.; Stanganelli, I.; Magi, S.; Mazzoni, L.; Pellacani, G.; Argenziano, G.; Ribero, S.; Moscarella, E.
abstract

A conservative management of Spitz nevi (SN) in children is currently adopted by many pediatric dermatologists in case of flat to slightly palpable lesions, clinically and dermoscopically diagnosed as SN (1-5). The aim of the current study was to analyze the dermoscopic and reflectance confocal microscopy (RCM) in vivo changes observed over time, during the sequential follow up of a series of SN. This article is protected by copyright. All rights reserved.

2017 - Ex vivo fluorescent confocal microscopy to guide micrographic mohs surgery [Capitolo/Saggio]
Longo, C.; Ragazzi, M.; Nehal, K.; Bennassar, A.; Malvehy, J.; Rajadhyaksha, M.
abstract

Standard surgery is generally considered the treatment of choice for basal cell carcinomas (BCCs). However, even with surgery, there are several tumor characteristics that are associated with higher recurrence rates. These include tumors located around the eyes, nose, lips, and ears; morpheic, infiltrative, micronodular, and basosquamous histopathological subtypes; BCCs with ill-defined margins; recurrent lesions; incompletely excised lesions; and perineural or perivascular involvement. Thus, in these instances, BCCs are preferably treated with Mohs micrographic surgery (MMS), which allows for complete examination of all residual tumor margins, minimizing the risk of recurrence and avoiding unnecessary removal of healthy tissue.

2017 - Glycaemic index, glycaemic load and risk of cutaneous melanoma in a population-based, case-control study [Articolo su rivista]
Malavolti, Marcella; Malagoli, Carlotta; Crespi, Cm; Brighenti, F; Agnoli, C; Sieri, S; Krogh, V; Fiorentini, Chiara; Farnetani, Francesca; Longo, Caterina; Ricci, C; Albertini, G; Lanzoni, A; Veneziano, L; Virgili, A; Pagliarello, C; Feliciani, C; Fanti, Pa; Dika, E; Pellacani, Giovanni; Vinceti, Marco
abstract

Glycaemic index (GI) and glycaemic load (GL) are indicators of dietary carbohydrate quantity and quality and have been associated with increased risk of certain cancers and type 2 diabetes. Insulin resistance has been associated with increased melanoma risk. However, GI and GL have not been investigated for melanoma. We present the first study to examine the possible association of GI and GL with melanoma risk. We carried out a population-based, case-control study involving 380 incident cases of cutaneous melanoma and 719 age- and sex-matched controls in a northern Italian region. Dietary GI and GL were computed for each subject using data from a self-administered, semi-quantitative food frequency questionnaire. We computed the odds ratio (OR) for melanoma according to quintiles of distribution of GL and GL among controls. A direct association between melanoma risk and GL emerged in females (OR 2·38; 95 % CI 1·25, 4·52 for the highest v. the lowest quintile of GL score, P for trend 0·070) but not in males. The association in females persisted in the multivariable analysis after adjusting for several potential confounders. There was no evidence of an association between GI and melanoma risk. GL might be associated with melanoma risk in females.

2017 - How genetic traits may influence the dermoscopic and confocal morphology of nevi [Capitolo/Saggio]
Bassoli, S.; Ribero, S.; Longo, C.; Ciardo, S.; Peris K., E; Carrera, C.
abstract

Currently nevi can be characterized in relation to their demographics, evolution, clinical and dermoscopic morphology, genetics, and associated risk of melanoma development. The recent introduction of reflectance confocal microscopy (RCM) has opened a new morphologic dimension of melanocytic nevi; this along with recent progresses in our understanding of the molecular pathways and genetic traits involved in nevogenesis opened new ways to classify nevi and link peculiar morphologic aspects with patient phenotype.

2017 - In vivo assessment of cytological changes by means of reflectance confocal microscopy – demonstration of the effect of topical vitamin E on skin irritation caused by sodium lauryl sulfate [Articolo su rivista]
Casari, Alice; Farnetani, Francesca; De Pace, Barbara; Losi, Amanda; Pittet, Jean Christophe; Pellacani, Giovanni; Longo, Caterina
abstract

Background: Irritant contact dermatitis is caused by skin barrier damage. Vitamin E is an antioxidant that is commonly used in cosmetics to prevent photo-damage. Objectives: To show the usefulness of reflectance confocal microscopy in the assessment of irritant skin damage caused by sodium lauryl sulfate (SLS) and of the protective action of vitamin E applied prior to skin irritation. Patients/materials/methods: Ten healthy volunteers were enrolled. Irritation was induced by the application of a patch test containing SLS 5% aq. for 24h. Three sites were compared: one site on which a product with vitamin E was applied before SLS treatment, one site on which the same product was applied after SLS treatment, and one control site (SLS only). Each site was evaluated with reflectance confocal microscopy, providing invivo tissue images at nearly histological resolution. We also performed a computerized analysis of the VivaStack® images. Results: Reflectance confocal microscopy is able to identify signs of skin irritation and the preventive effect of vitamin E application. Conclusion: Reflectance confocal microscopy is useful in the objective assessment of irritative skin damage.

2017 - In vivo confocal microscopy in clinical dermatology [Capitolo/Saggio]
Longo, C.; Pellacani, G.; Gonzalez, S.
abstract

In vivo confocal microscopy in clinical dermatology

2017 - Intralesional (incision) biopsy for melanoma diagnosis: The rules and the exception [Articolo su rivista]
Moscarella, Elvira; Argenziano, Giuseppe; Moreno, Claudia; Piana, Simonetta; Lallas, Aimilios; Lombardi, Mara; Longo, Caterina; Ferrara, Gerardo
abstract

Intralesional (incision) biopsy for melanoma diagnosis can be warranted for large lesions or for those lesions whose in-toto excision leads to cosmetic and/or functional impairment. However, this diagnostic approach carries a risk of underdiagnosis, if a clinicopathologic diagnostic approach is not implemented. As a rule, in large pigmented lesions from special body areas (scalp and acral skin), clinicodermoscopic differential diagnosis of melanoma includes non-melanocytic skin lesions, traumatic skin changes, and nevi. The unique indication to incision biopsy for the differential diagnosis between nevus and melanoma is a relatively small nodular proliferation developing within a medium-large congenital nevus.

2017 - Lesions revealing regressive structures [Capitolo/Saggio]
Moscarella, E.; Bombonato, C.; Piana, S.; Benati, E.; Borsari, S.; Longo, C.
abstract

Histological regression phenomena have been described in both benign and malignant lesions.1-5 Regression of benign nevi can occur spontaneously or after repeated trauma, and has an incidence of 1% in the general population.6,7 Spontaneous regression of melanomas occurs with an estimated prevalence of 10%–35%.1-5 The exact significance of regression phenomena is a matter of continuous debate.8,9 Recent studies analyzing cases of regressing melanoma suggest a favorable prognostic role of regression, possibly due to a host immunological response to the tumor.9 This phenomenon therefore could reflect the role of the immunologic system against the primary tumor; thus, its presence should be considered prognostically favorable. However, the prognostic value of extensive regression has been described by some authors as a worsening factor in melanoma.

2017 - Lymph nodes' capsular naevi are associated with high naevus count in melanoma patients: A case-control study [Articolo su rivista]
Ribero, Simone; Longo, Caterina; Specchio, Francesca; Piana, Simonetta; Castagnetti, Fabio; Moscarella, Elvira; Lallas, Aimilios; Alfano, Roberto; Argenziano, Giuseppe
abstract

Capsular naevi (CNs) in lymph nodes (LNs) are relatively common, occurring in 3-22% of patients who undergo LN surgery for melanoma. Naevus count is one of the principal risk factors for melanoma, as well as a prognostic factor in melanoma patients. However, little is known about the occurrence of CN in melanoma patients on the basis of their naevus count. A case-control study was performed, to look at the naevus count differences between CN-positive and CN-negative melanoma patients. Cases (CN positive) were matched for age, sex and Breslow thickness with controls (CN negative). Total naevus count was recorded at diagnosis and compared between the two groups. This study was conducted in a tertiary referral academic centre for skin cancer. Twenty-two positive CN patients were matched with 22 negative CN patients. The mean Breslow thickness was 2.66 mm (range: 0.6-9). Positive CN patients were significantly associated with an increasing naevus count on their skin (P=0.02). Patients with more than 100 naevi reported an odds ratio of 7.78 on having a CN compared with patients with fewer than 50 naevi on their skin (P=0.02). An increased melanocytic migration to LNs might be the reason for the association between CNs and a high number of melanocitic naevi on the skin. This could shed some light on the physiology of melanocytes and could be an easy way to predict patients at greater risk of having CNs.

2017 - Management of cancerization field with a medical device containing photolyase: a randomized, double-blind, parallel-group pilot study [Articolo su rivista]
Moscarella, E.; Argenziano, G.; Longo, C.; Aladren, S.
abstract

a

2017 - Mass spectrometry-based biomarker discovery [Capitolo/Saggio]
Zhou, W.; Petricoin, E. F.; Longo, C.
abstract

The discovery of candidate biomarkers within the entire proteome is one of the most important and challenging goals in proteomic research. Mass spectrometry-based proteomics is a modern and promising technology for semiquantitative and qualitative assessment of proteins, enabling protein sequencing and identification with exquisite accuracy and sensitivity. For mass spectrometry analysis, protein extractions from tissues or body fluids and subsequent protein fractionation represent an important and unavoidable step in the workflow for biomarker discovery. Following extraction of proteins, the protein mixture must be digested, reduced, alkylated, and cleaned up prior to mass spectrometry. The aim of our chapter is to provide comprehensible and practical lab procedures for sample digestion, protein fractionation, and subsequent mass spectrometry analysis.

2017 - Merkel cell carcinoma: morphologic aspects on reflectance confocal microscopy [Articolo su rivista]
Longo, C.; Benati, E.; Borsari, S.; Bombonato, C.; Pampena, R.; Moscarella, E.; Piana, S.; Pellacani, G.
abstract

a

2017 - New imaging tools for an old disease: Secondary syphilis [Articolo su rivista]
Guardoli, Davide; Reggiani, Camilla; Ciardo, Silvana; Coppini, Maurizio; Cesinaro, Anna Maria; Piana, Simonetta; Pellacani, Giovanni; Longo, Caterina
abstract

a

2017 - Performance of the "if in doubt, cut it out" rule for the management of nodular melanoma [Articolo su rivista]
Moscarella, Elvira; Lallas, Aimilios; Longo, Caterina; Zalaudek, Iris; Caccavale, Stefano; Gambardella, Alessio; Lupoli, Amalia; Alfano, Roberto; Argenziano, Giuseppe
abstract

The recognition of nodular melanoma is clinically challenging, and the diagnostic accuracy of dermoscopy and confocal microscopy is lower than for superficial spreading melanoma.

2017 - Permanent implants for lip augmentation: Results from a retrospective study and presentation of tips and tricks [Articolo su rivista]
Guida, Stefania; Mandel, Victor Desmond; Farnetani, Francesca; Manola, Carmelo Mirko; Rubino, Giuseppe; Ruzzu, Simonetta; Pellacani, Giovanni; Longo, Caterina; Urtis, Giacomo Giovanni
abstract

Background: Requests for lip augmentation are increasing because of expanding media exposure and consumer needs. Temporary effects can be obtained by several techniques, but a recent procedure consisting of lip prosthesis implantation, offering a permanent result, is emerging. Accordingly, the implantation of solid lip prosthesis represents an innovation in the field of esthetic medicine and surgery. Methods: A total of 100 women with atrophic or hypoplastic lips were treated with lip implants. The treatment was performed in a single session, and controls were scheduled at fixed time intervals. A standard digital photo was used for measurement and analysis. Data concerning patient satisfaction and complications of the technique were collected and analyzed. Variations to the original technique were also discussed. Results: Patient evaluation revealed that a permanent and natural result without discomfort for the patient and/or the partner was reached with the implantation of silicone prosthesis in the upper and/or lower lip. Swelling, bruising, and malpositions were the most frequent adverse events. A case of severe edema was reported. Practical tricks acquired through experience were discussed to prevent complications. Conclusions: One of the most widespreading methods for lip remodeling is hyaluronic acid injections. Nevertheless, hyaluronic acid has a variable duration, and it is not always the first choice. This context allowed for the development of other techniques such as the implantation of silicone prosthesis. The advantages of this prosthesis are as follows: safety, definitive result, and reversibility considering the possibility to remove the implanted prosthesis in the case of a request.

2017 - Pigmented nonmelanocytic skin lesions [Capitolo/Saggio]
Moscarella, E; Piana, S; Longo, C; Argenzioano, G
abstract

2017 - Pigmented actinic keratosis and porokeratosis [Capitolo/Saggio]
Moscarella, E.; Piana, S.; Benati, E.; Bombonato, C.; Borsari, S.; Longo, C.
abstract

Actinic keratoses (AKs) are the most common lesions within the spectrum of keratinocyte skin cancer.1-6 They typically arise on chronically sun-damaged skin of fair skin-type individuals, presenting as pink to red macules, with variably scaly surfaces. Less frequently, AKs may present a clinically visible pigmentation, pigmented AK (PAK) (Figure 32.1). PAK can be difficult to differentiate from other pigmented lesions such as melanoma and lentigo maligna melanoma, solar lentigo, early seborrheic keratosis, and lichen planus-like keratosis. In the context of actinically damaged skin, characterized by the presence of mottled pigmentation, discriminating between benign macules and pigmented tumors may be challenging; thus, histopathologic confirmation is frequently required in the diagnosis of PAK in order to exclude melanoma.

2017 - Pregnancy and melanoma: a European-wide survey to assess current management and a critical literature overview [Articolo su rivista]
Ribero, S.; Longo, C.; Dika, E.; Fortes, C.; Pasquali, S.; Nagore, E.; Glass, D.; Robert, C.; Eggermont, A. M.; Testori, A.; Quaglino, P.; Nathan, P.; Argenziano, G.; Puig, S.; Bataille, V.
abstract

Background: Management of melanoma during pregnancy can be extremely challenging. The reported incidence of melanoma in pregnancy ranges from 2.8 to 5.0 per 100 000 pregnancies. There are no guidelines for the management of melanoma during pregnancy. Methods: The survey was designed to investigate the opinions of melanoma physicians on decision making in relation to pregnancy and melanoma. A clinical scenario-based survey on management of pregnancy in melanoma was distributed all over Europe via the membership of the EORTC and other European melanoma societies. Results: A total of 290 questionnaires were returned with a larger participation from southern Europe. A large heterogeneity was found for the answers given in the different clinical scenarios with 50% of the answers showing discordance, especially regarding sentinel lymph node biopsy during pregnancy. Discordant answers were also found for the counselling of women about a potential delay in getting pregnant after a high-risk melanoma (35% for a 2 year wait minimum vs. 57% no waiting needed), while for thin melanomas, as expected, there was more concordance with 70% of the physicians recommending no delay. Fifteen per cent of physicians recommended an abortion in stage II melanoma during the third month of pregnancy. Twenty per cent of the responders advised against hormonal replacement therapy in melanoma patients. Conclusions: The management of melanoma during pregnancy varies widely in Europe. At present, there is a lack of consensus in Europe, which may lead to very important decisions in women with melanoma, and guidelines are needed.

2017 - Preliminary evaluation of reflectance confocal microscopy features of scalp melanoma [Articolo su rivista]
Benati, E.; Longo, C.; Piana, S.; Moscarella, E.
abstract

NA

2017 - Reflectance confocal microscopy [Capitolo/Saggio]
Longo, C.; Greco, M.; Ciardo, S.; Pellacani, G.
abstract

Reflectance confocal microscopy

2017 - Sebaceous hyperplasia and adenoma. Clear cell acanthoma and dermatofibroma [Capitolo/Saggio]
Pampín, A.; Longo, C.; Ulrich, M.; González, S.
abstract

Sebaceous hyperplasia (SH) is a common, benign condition of sebaceous glands in adults of middle age or older. Lesions can be single or multiple and manifest as yellowish, soft, small papules on the face (particularly nose, cheeks, and forehead). SH occasionally also occurs on the chest, areola, mouth, scrotum, foreskin, shaft of penis, and vulva. Lesions of SH are benign, with no known potential for malignant transformation, but may be associated with nonmelanoma skin cancer in transplantation patients.

2017 - Similar but Different: How Reflectance Confocal Microscopy May Help in the Diagnosis of Pink Lesions [Articolo su rivista]
Ferrari, Federica; Bassoli, Sara; Pellacani, Giovanni; Argenziano, Giuseppe; Cesinaro, Anna; Longo, Caterina
abstract

Background: Among skin neoplasms, solitary pink tumors represent challenging lesions in clinical practice since they can mimic melanocytic and nonmelanocytic lesions or even inflammatory ones. Objective: In this case series we described dermoscopic and confocal features of 2 couples of similar lesions in order to achieve the correct diagnosis and the best therapeutic approach. Methods: During clinical routine practice, 2 couples of clinically and dermoscopically similar lesions were examined by means of confocal microscopy. Results: All lesions revealed no clear-cut diagnostic features on dermoscopy. However, confocal microscopy revealed tumor islands with palisading cells and a dark clefting at the periphery in basal cell carcinomas. In the other “false twin” lesions, atypical cells and elongated junctional nests were observed and the diagnosis of amelanotic melanomas was rendered. Conclusions: In the current case series, the combined use of dermoscopy and reflectance confocal microscopy was an optimal workup for difficult-to-diagnose lesions such as pink tumors.

2017 - Spectrophotometry [Capitolo/Saggio]
Pampena, Riccardo; Longo, C
abstract

Darkening patches on the skin can result in great distress for the patient. However, definitive diagnosis between the many possible causes and effective treatment can be very hard for the medical practitioner to achieve. This is the first major professional reference with systematic coverage of diagnosis and the various treatment options, and it will be an indispensable clinical reference.

2017 - The value of reflectance confocal microscopy in diagnosis of flat pigmented facial lesions: a prospective study [Articolo su rivista]
Wurm, E.; Pellacani, G.; Longo, C.; Soyer, H. P.; Gonzalez, S.; Hofmann-Wellenhof, R.; Ahlgrimm-Siess, V.; Guitera, P.; Sinz, C.; Kittler, H.
abstract

Background: Flat pigmented facial lesions are difficult to diagnose even with dermatoscopy. It is controversial how additional information obtained by in vivo reflectance confocal microscopy (RCM) impacts the diagnosis and management. Objective: To examine what in vivo reflectance confocal microscopy of flat pigmented facial lesions adds to clinical examination using dermatoscopy including digital dermatoscopic monitoring. Methods: We prospectively collected 70 cases of flat pigmented facial lesions and recorded diagnoses and management decisions by experts based on direct clinical examination aided by dermatoscopy including digital dermatoscopic monitoring and by remote experts who reviewed the corresponding confocal images. The expert confocal readers were blinded to the clinical and dermatoscopic appearance of the lesion. Results: The sensitivity of dermatoscopy plus digital dermatoscopic monitoring was 95.0% (95% CI 75.13% to 99.87%) and the specificity was 84.0% (95% CI 70.89% to 92.83%). The sensitivity of RCM was 95.0% (95% CI 75.13% to 99.87%) and the specificity was 82.0% (95% CI 68.56% to 91.42%). Conclusion: Although most flat pigmented facial lesions can be managed by clinical examination and dermatoscopy alone, confocal microscopy is a useful adjunct in selected lesions. If RCM is not correlated with clinical and dermatoscopic information, there is risk of overdiagnosis of actinic keratosis, however.

2017 - Therapeutic potential of the metabolic modulator phenformin in targeting the stem cell compartment in melanoma [Articolo su rivista]
Petrachi, Tiziana; Romagnani, Alessandra; Albini, Adriana; Longo, Caterina; Argenziano, Giuseppe; Grisendi, Giulia; Dominici, Massimo; Ciarrocchi, Alessia; Dallaglio, Katiuscia
abstract

Melanoma is the most dangerous and treatment-resistant skin cancer. Tumor resistance and recurrence are due to the persistence in the patient of aggressive cells with stem cell features, the cancer stem cells (CSC). Recent evidences have shown that CSC display a distinct metabolic profile as compared to tumor bulk population: a promising anti-tumor strategy is therefore to target specific metabolic pathways driving CSC behavior. Biguanides (metformin and phenformin) are anti-diabetic drugs able to perturb cellular metabolism and displaying anti-cancer activity. However, their ability to target the CSC compartment in melanoma is not known. Here we show that phenformin, but not metformin, strongly reduces melanoma cell viability, growth and invasion in both 2D and 3D (spheroids) models. While phenformin decreases melanoma CSC markers expression and the levels of the pro-survival factor MITF, MITF overexpression fails to prevent phenformin effects. Phenformin significantly reduces cell viability in melanoma by targeting both CSC (ALDHhigh) and non-CSC cells and by significantly reducing the number of viable cells in ALDHhighand ALDHlowderived spheroids. Consistently, phenformin reduces melanoma cell viability and growth independently from SOX2 levels. Our results show that phenformin is able to affect both CSC and non-CSC melanoma cell viability and growth and suggests its potential use as anti-cancer therapy in melanoma.

2017 - Unknown Primary Melanoma: Worldwide Survey on Clinical Management [Articolo su rivista]
Ribero, S.; Pampena, R.; Bataille, V.; Moscarella, E.; Thomas, L.; Quaglino, P.; Potenza, C.; Van Akkooi, A. C. J.; Testori, A.; Nathan, P.; Puig, S.; Zalaudek, I.; Argenziano, G.; Longo, C.
abstract

Background: How to deal with melanoma of unknown primary (MUP) origin is a debated topic in the literature. Objective: We performed a worldwide survey to inquire what clinical and investigational workup is performed as well as the physicians' perception of this disease. Methods: A questionnaire was sent via mail to clinicians involved in melanoma care from December 2015 to April 2016 using the International Dermoscopy Society website. Results: 119 physicians from 47 different countries answered the questionnaire. The most reported examination was skin examination followed by CT and/or PET scans. All the participants declared asking about previous excisions of skin lesions with 81% of them asking for a histopathological slide review of previous biopsies. Half of the participants checked for a possible vitiligo phenomenon that may explain regression of the primary lesion. BRAF, cKIT, and GNAQ mutations were screened by 32% of participants. The majority of participants (76%) applied the same treatment protocols for MUP as patients with known primary melanomas of the same AJCC stage. Conclusion: Strong heterogeneity was found between physicians dealing with MUP. Thus, a consensus document should be strongly encouraged.

2017 - Vascular structures in dermal nevi: a reappraisal [Articolo su rivista]
Caccavale, Stefano; Lupoli, Amalia; Alfano, Roberto; Longo, Caterina; Argenziano, Giuseppe
abstract

NA

2017 - Wait time to seek skin cancer screening in Italy [Articolo su rivista]
Borsari, S.; Tschandl, P.; Longo, Caterina; Lallas, A.; Moscarella, Elvira; Alfano, R.; Argenziano, Giuseppe
abstract

NA

2016 - Basics of Confocal Microscopy and the Complexity of Diagnosing Skin Tumors: New Imaging Tools in Clinical Practice, Diagnostic Workflows, Cost-Estimate, and New Trends [Articolo su rivista]
Que, Syril Keena T; Grant Kels, Jane M.; Longo, Caterina; Pellacani, Giovanni
abstract

The use of reflectance confocal microscopy (RCM) and other noninvasive imaging devices can potentially streamline clinical care, leading to more precise and efficient management of skin cancer. This article explores the potential role of RCM in cutaneous oncology, as an adjunct to more established techniques of detecting and monitoring for skin cancer, such as dermoscopy and total body photography. Discussed are current barriers to the adoption of RCM, diagnostic workflows and standards of care in the United States and Europe, and medicolegal issues. The potential role of RCM and other similar technological innovations in the enhancement of dermatologic care is evaluated.

2016 - Brown globules in lentigo maligna (LM): A useful dermoscopic clue [Articolo su rivista]
Peris, Ketty; Maiorino, Alessia; Di Stefani, Alessandro; Longo, Caterina; Piana, Simonetta; Argenziano, Giuseppe
abstract

ND

2016 - Caractéristiques dermoscopiques et en microscopie confocale par réflectance dgune kératose séborrhéique clonale [Dermoscopic and reflectance confocal microscopic features of clonal seborrhoeic keratosis] [Articolo su rivista]
Persechino, Flavia; Longo, Caterina; Cesinaro, A. M.; Cinotti, E; Ciardo, Silvia; Pellacani, Giovanni; Bassoli, S.
abstract

ND

2016 - Clinical indications for use of reflectance confocal microscopy for skin cancer diagnosis [Articolo su rivista]
Borsari, Stefania; Pampena, Riccardo; Lallas, Aimilios; Kyrgidis, Athanassios; Moscarella, Elvira; Benati, Elisa; Raucci, Margherita; Pellacani, Giovanni; Zalaudek, Iris; Argenziano, Giuseppe; Longo, Caterina
abstract

Importance Reflectance confocal microscopy (RCM) improves diagnostic accuracy in skin cancer detection when combined with dermoscopy; however, little evidence has been gathered regarding its real impact on routine clinical workflow, and, to our knowledge, no studies have defined the terms for its optimal application. Objective To identify lesions on which RCM performs better in terms of diagnostic accuracy and consequently to outline the best indications for use of RCM. Design, Setting, and Participants Prospectively acquired and evaluated RCM images from consecutive patients with at least 1 clinically and/or dermoscopically equivocal skin lesion referred to RCM imaging, from January 2012 to October 2014, carried out in a tertiary referral academic center. Main Outcomes and Measures A total of 1279 equivocal skin lesions were sent for RCM imaging. Spearman correlation, univariate, and multivariate regression models were performed to find features significantly correlated with RCM outcome. Results In a total of 1279 lesions in 1147 patients, RCM sensitivity and specificity were 95.3% and 83.9%, respectively. The number of lesions needed to excise to rule out a melanoma was 2.4. After univariate and multivariate regression analysis, head and neck resulted as the most appropriate body location for confocal examination; RCM showed a high diagnostic accuracy for lesions located on sun-damaged skin (adjusted odds ratio [aOR], 2.13; 95% CI, 1.37-3.30; P=.001) and typified by dermoscopic regression (aOR, 2.13; 95% CI, 1.31-3.47; P=.002) or basal-cell carcinoma specific criteria (aOR, 9.35; 95% CI, 1.28-68.58; P=.03). Conclusions and Relevance Lesions located on the head and neck, damaged by chronic sun-exposure, and dermoscopically typified by regression represent best indications for the use of RCM.

2016 - Collision tumors: A diagnostic challenge [Articolo su rivista]
Bernardini, Maria Clara; Moscarella, Elvira; Borsari, Stefania; Lallas, Aimilios; Longo, Caterina; Piana, Simonetta; Argenziano, Giuseppe
abstract

ND

2016 - Comment to: 'Evidence and consensus based (S3) Guidelines for the Treatment of Actinic Keratosis' [Articolo su rivista]
Pellacani, Giovanni; Neri, L.; Longo, Caterina
abstract

Guidelines for the Treatment of Actinic Keratosis'

2016 - Confocal Microscopy [Curatela]
Grant-Kels, Jm; Pellacani, G.; Longo, C
abstract

Description This issue of Dermatologic Clinics, guest edited by Jane M. Grant-Kels, Giovanni Pellacani, and Caterina Longo, is devoted to Confocal Microscopy. Articles in this timely issue include: Basics of Confocal Microscopy and the Complexity of Diagnosing Skin Tumors: New Imaging Tools in Clinical Practice, Diagnostic Workflows, Cost-estimate and New Trends; Opening a Window Into Living Tissue: Histopathologic Features of Confocal Microscopic Findings in Skin Tumors; Addressing the Issue of Discriminating Nevi from Early Melanomas: Dues and Pitfalls; Melanoma Types and Melanoma Progression: The Different Faces; Lentigo Maligna, Macules of the Face and Lesions on Sun-damaged Skin: Confocal makes the Difference; Glowing in the dark: use of confocal microscopy in dark pigmented lesions; Enlightening the Pink: Use of Confocal Microscopy in Pink Lesions; Shining into the White: The Spectrum of Epithelial Tumors from Actinic Keratosis to SCC; Application of Wide-probe and Handy-probe for Skin Cancer Diagnosis: Pros and Cons; Confocal Microscopy for Special Sites and Special Uses; Confocal Algorithms for Inflammatory Skin Diseases and Hair Diseases; In Vivo and Ex Vivo Confocal Microscopy for Dermatologic and Mohs’ Surgeons; Telediagnosis with Confocal Microscopy: A Reality or a Dream?; “Well-aging": Early Detection of Skin Aging Signs; The Role of Confocal Microscopy in Clinical Trials for Treatment Monitoring; and Fluorescence (multiwave) Confocal Microscopy.

2016 - Confocal microscopy in the diagnosis and management of non-pigmented skin tumors (which, when, and when not) [Capitolo/Saggio]
Longo, C.; Moscarella, E.; Pellacani, G.
abstract

Reflectance confocal microscopy (RCM) features diagnosing a solitary pink lesion include the presence of melanocytic nesting, basaloid tumor islands, keratinocytic atypia, and vascular structures. RCM is a useful tool to classify a given solitary pink tumor lacking clear-cut clinical and dermoscopic diagnostic features. RCM is a novel imaging tool that provides in vivo detailed information on architecture and cytology similar to histopathology. The major source of contrast in RCM images is provided by melanin that appears very bright, even if present in very small quantities. When dealing with a solitary pink lesion, several differential diagnoses have to be taken into account, considering both melanocytic and nonmelanocytic neoplasms. The RCM analysis of a given lesion, which should include the imaging of three anatomic levels (epidermis, dermoepidermal junction, and dermis), can reveal the presence of junctional or dermal melanocytic nesting, thus allowing one to establish the melanocytic nature of the tumor.

2016 - Contemporary and potential future molecular diagnosis of melanoma [Articolo su rivista]
Gandolfi, G.; Dallaglio, Katiuscia; Longo, Caterina; Moscarella, Elvira; Lallas, A.; Alfano, R.; Argenziano, Giuseppe; Ciarrocchi, A.
abstract

Introduction: The increasing incidence of cutaneous melanoma and the still limited effective treatments available for this disease represent a major health problem and a great challenge for research. The raise of the “omics” era and the development of new techniques to explore phenotypic heterogeneity are helping to decipher the mechanisms at the basis of melanoma heterogeneity. Areas covered: We reviewed the most recent publications about the biology of cutaneous melanoma, to provide an overview of the most recent insights into the complexity of this tumor and their potential impact in the clinical settings. Expert commentary: Starting from the first attempts to provide a molecular classification of melanoma, it has been evident that this tumor represents a widely heterogeneous disease. This complexity and the multivariate nature of melanoma represent a major obstacle in developing the best management strategies for patients.

2016 - Cost-benefit of reflectance confocal microscopy in the diagnostic performance of melanoma [Articolo su rivista]
Pellacani, Giovanni; Witkowski, Alexander Michael; Cesinaro, A. M; Losi, A; Colombo, G. L; Campagna, A; Longo, Caterina; Piana, S; De Carvalho, N; Giusti, F; Farnetani, Francesca
abstract

The sub-optimal diagnostic accuracy for melanoma leads to excise a high number of benign lesions, with consequent costs. Reflectance confocal microscopy (RCM) improves diagnostic specificity, thus possibly inducing a reduction in unnecessary excisions and related costs.

2016 - Dabrafenib: A new opportunity for the treatment of BRAFV600-positive melanoma [Articolo su rivista]
Banzi, Maria; de Blasio, Simona; Lallas, Aimilios; Longo, Caterina; Moscarella, Elvira; Alfano, Roberto; Argenziano, Giuseppe
abstract

Prior to 2011, the 1-year survival rates for patients suffering from advanced or metastatic melanoma was as low as 33%, with a median overall survival of about 9 months. Several chemotherapeutic regimens have been applied, either as monochemotherapy or as poly-chemotherapy, overall not resulting in an improvement of progression-free or overall survival. Novel insights into the epidemiology and biology of melanoma allowed the development of newer therapies. The discovery of mutations in BRAF, a part of the mitogen-activated protein kinase, allowed the development of two BRAF inhibitors, vemurafenib and dabrafenib, which significantly improved the outcome of metastatic melanoma treatment. This article reviews the mechanism of action, efficacy, and safety profile of dabrafenib. An in-depth knowledge of this medication will encourage clinicians to select the appropriate therapeutic strategy for each patient, as well as to prevent or adequately manage side effects, optimizing, thus, the drug’s applicability.

2016 - Dermoscopic hemorrhagic dots: an early predictor of response of psoriasis to biologic agents [Articolo su rivista]
Lallas, Aimilios; Argenziano, Giuseppe; Zalaudek, Iris; Apalla, Zoe; Ardigo, Marco; Chellini, Patricia; Cordeiro, Natalia; Guimaraes, Mariana; Kyrgidis, Athanassios; Lazaridou, Elizabeth; Longo, Caterina; Moscarella, Elvira; Papadimitriou, Ilias; Pellacani, Giovanni; Sotiriou, Elena; Vakirlis, Efstratios; Ioannides, Dimitrios
abstract

Biologic agents are routinely used in the treatment of severe psoriasis. The evaluation of treatment response is mainly based on the physician's global clinical assessment.

2016 - Dermoscopy and Reflectance Confocal Microscopy for Monitoring the Treatment of Actinic Keratosis with Ingenol Mebutate Gel: Report of Two Cases [Articolo su rivista]
Longo, Caterina; Borsari, Stefania; Benati, Elisa; Moscarella, Elvira; Alfano, Roberto; Argenziano, Giuseppe
abstract

Introduction: A relatively novel application for dermoscopy and reflectance confocal microscopy (RCM) is their use in the monitoring of topical treatment response for non-melanoma skin cancer. Actinic keratosis (AK) is the early phase of a multistep biologic continuum leading to invasive squamous cell carcinoma. A number of topical therapies are now available for the treatment of AK but their disadvantages include long treatment duration and prolonged local reactions. Ingenol mebutate is a newer therapy for AK which is only applied for 2 or 3&nbsp;days. Case Report: Dermoscopy and RCM findings in two patients with AK treated with ingenol mebutate confirm that it induces rapid lesion necrosis and specific neutrophil-mediated, antibody-dependent cellular cytotoxicity. Necrosis occurs via mitochondrial membrane disruption, with subsequent eradication of residual tumor cells via transient inflammation. Local skin reactions to ingenol mebutate should be considered part of the drug’s mechanism of action rather than an adverse effect. Conclusion: Ingenol mebutate is a valuable therapy for the treatment of AK. This case report adds further evidence to the usefulness of dermoscopy and RCM in the assessment and monitoring of treatment outcome.

2016 - Dermoscopy and in vivo confocal microscopy are complementary techniques for diagnosis of difficult amelanotic and light-coloured skin lesions [Articolo su rivista]
Guitera, P.; Menzies, S. W.; Argenziano, G.; Longo, C.; Losi, A.; Drummond, M.; Scolyer, R. A.; Pellacani, G.
abstract

Background: Amelanotic melanomas are often difficult to diagnose. Objectives: To find and test the best methods of diagnosis using dermoscopy and reflectance confocal microscopy (RCM) tools. Methods: We selected consecutive, difficult-to-diagnose, light-coloured and amelanotic skin lesions from three centres (in Australia and Italy). Dermoscopy and RCM diagnostic utility were evaluated under blinded conditions utilizing 45 melanomas (16 in situ, 29 invasive), 68 naevi, 48 basal cell carcinomas (BCCs), 10 actinic keratoses, 10 squamous cell carcinomas (SCCs) and 13 other benign lesions. Results: Sensitivity and specificity for melanoma with dermoscopy pattern analysis by two blinded observers and their ‘confidence in diagnosis’ were low. The amelanotic dermoscopy method had the highest sensitivity (83%) for a diagnosis of malignancy (melanoma, BCC or SCC), but specificity was only 18%. Multivariate analysis confirmed the utility of RCM features previously identified for the diagnosis of BCC and melanoma (highest odds ratio for melanoma: epidermal disarray, dark and/or round pagetoid cells). RCM sensitivity was 67% and 73% for melanoma and BCC diagnosis, respectively, and its specificity for nonmalignant lesion diagnosis was 56%. RCM reader confidence was higher than for dermoscopy; 84% of melanomas would have been biopsied and biopsy avoided in 47% of benign lesions. All melanomas misclassified by either dermoscopy or RCM were detected by the other tool. Conclusions: Dermoscopy and RCM represent complementary/synergistic methods for diagnosis of amelanotic/light-coloured skin lesions.

2016 - Dermoscopy as an adjuvant tool for the diagnosis and management of basal cell carcinoma [Articolo su rivista]
Fabiano, Antonella; Argenziano, Giuseppe; Longo, Caterina; Moscarela, Elvira; Specchio, Francesca; Lalas, Aimilios
abstract

The list of dermoscopic criteria associated with basal cell carcinoma (BCC) have been several times updated and renewed. Up to date, dermoscopy has been shown to increase diagnostic and therapeutic accuracy, since provides valuable information about histopathologic subtype, a more accurate assessment of the true extension of tumor, the presence of pigmentation not visible to the naked eye and the treatment choice for BCC. In the current review, we provide an update of the traditional and latest knowledges on the value of dermatoscopy for the diagnosis and management of BCC.

2016 - Diagnostic accuracy of reflectance confocal microscopy for lesions typified by dermoscopic island [Articolo su rivista]
Figueroa Silva, O; Cinotti, E; de Almeida Silva, T; Moscarella, Elvira; Lallas, A; Ciardo, Silvia; Argenziano, Giuseppe; Pellacani, Giovanni; Piana, S; Longo, Caterina
abstract

Dermoscopic island (DI) is a dermoscopic clue for the diagnosis of thin melanoma (MM). However, its positive predictive value is about 50% and several naevi with DI are unnecessarily excised. Reflectance confocal microscopy (RCM) is a second level non-invasive imaging tool that increases diagnostic accuracy for MM.

2016 - Eccrine poroma: the great dermoscopic imitator [Articolo su rivista]
Lallas, A; Chellini, P. R.; Guimarães, M. G.; Cordeiro, N.; Apalla, Z.; Longo, Caterina; Moscarella, Elvira; Alfano, R.; Argenziano, Giuseppe
abstract

ND

2016 - Ex Vivo (fluorescence) confocal microscopy in surgical pathology: State of the art [Articolo su rivista]
Ragazzi, Moira; Longo, Caterina; Piana, Simonetta
abstract

First developed in 1957, confocal microscopy is a powerful imaging tool that can be used to obtain near real-time reflected light images of untreated human tissue with nearly histologic resolution. Besides its research applications, in the last decades, confocal microscopy technology has been proposed as a useful device to improve clinical diagnosis, especially in ophthalmology, dermatology, and endomicroscopy settings, thanks to advances in instrument development. Compared with the wider use of the in vivo tissue assessment, ex vivo applications of confocal microscopy are not fully explored. A comprehensive review of the current literature was performed here, focusing on the reliable applications of ex vivo confocal microscopy in surgical pathology and on some potential evolutions of this new technique from pathologists' viewpoint.

2016 - Ex Vivo Fluorescence Microscopy: Clinical Applications in Dermatology and Surgical Pathology [Capitolo/Saggio]
Longo, C.; Gardini, S.; Piana, S.; Castagnetti, F.; Argenziano, G.; Pellacani, G.; Ragazzi, M.
abstract

Ex Vivo Fluorescence Microscopy: Clinical Applications in Dermatology and Surgical Pathology

2016 - False-Negative Cases on Confocal Microscopy Examination: A Retrospective Evaluation and Critical Reappraisal [Articolo su rivista]
Coco, Valeria; Farnetani, Francesca; Cesinaro, Anna Maria; Ciardo, Silvana; Argenziano, Giuseppe; Peris, Ketty; Pellacani, Giovanni; Longo, Caterina
abstract

Confocal microscopy is a second-level examination for dermoscopically equivocal melanocytic lesions. However, the number of false-negative cases on confocal microscopy and the scenarios in which confocal microscopy may fail have not been fully elucidated.

2016 - Fibroepithelioma of Pinkus: Solitary tumor or sign of a complex gastrointestinal syndrome [Articolo su rivista]
Longo, Caterina; Pellacani, Giovanni; Tomasi, Aldo; Mandel, Victor Desmond; Ponti, Giovanni
abstract

Fibroepithelioma of Pinkus (FEP), which is considered to be an uncommon variant of basal cell carcinoma, has been described in association with other systemic diseases. However, no specific studies are currently available on this subject. The aim of our study was to evaluate the clinical and morphological characteristics of FEP and investigate whether this rare tumor is a single entity or seen in the context of a more complex syndrome. We retrospectively analyzed 49 cases of FEP diagnosed and excised in a single academic institution from 1995 to 2011. The tumors were mainly located on the trunk (77.55%), followed by the lower extremities (12.20%) and the head and neck (10.20%). In 9 of the 49 cases (18%), FEP was associated with gastrointestinal tumors. The abovementioned cases are presented in an attempt to make clinicians more aware of a possible association between FEP and gastrointestinal cancer. Although a possible underlying common genetic background between FEP and gastrointestinal tumors was not provided, our study suggests that patients with FEP should be screened for the occurrence of gastrointestinal tumors.

2016 - Fluorescence Confocal Microscopy for Ex Vivo Diagnosis of Conjunctival Tumors: A Pilot Study [Articolo su rivista]
Iovieno, Alfonso; Longo, Caterina; De Luca, Mariacarla; Piana, Simonetta; Fontana, Luigi; Ragazzi, Moira
abstract

Purpose To evaluate the potential use of fluorescence confocal microscopy (FCM) for ex vivo diagnosis and excision margin assessment of conjunctival neoplasms. Design Validity study. Methods setting: Single institution. participants: Consecutive patients with clinically suspicious conjunctival lesions. intervention: Conjunctival lesions were excised in toto using a standard "no-touch technique" by a single surgeon (A.I.). Collected specimens were examined with a commercially available laser scanning fluorescence confocal microscope after immersion in a 0.6 mM solution of acridine orange dye for 10-20 seconds. Specimens were subsequently processed with standard histologic analysis. main outcome measures: FCM diagnosis of the nature and extension of conjunctival lesions. Results Sixteen consecutive patients were included in the study (11 male, 5 female; mean age 58.1 ± 26.1 years, range 10-90 years). The median time needed to process and analyze a sample with FCM was 15 minutes. Eleven of 16 lesions were identified by FCM as squamous (2 benign papillomas, 2 grade 2 conjunctival intraepithelial neoplasias, 7 in situ squamous carcinomas) and 5 as nonsquamous (1 pingueculum, 1 dermolipoma, 2 melanocytic nevi, 1 melanoma). In all cases FCM was able to detect horizontal and vertical extension of the lesion. All FCM findings were confirmed by corresponding subsequent histologic examination. Conclusions FCM provides a fast ex vivo preliminary diagnosis of suspicious conjunctival lesions with good histologic details and margin assessment, and may represent a novel tool for intraoperative and postsurgical management of conjunctival tumors. This is the first study to investigate ex vivo FCM application in ophthalmology.

2016 - Follicular psoriasis: an under-recognized condition [Articolo su rivista]
Babino, G.; Moscarella, Elvira; Longo, Caterina; Lallas, A.; Ferrara, G.; Cusano, F.; Cinotti, E.; Argenziano, Giuseppe
abstract

ND

2016 - Fully regressive lesions: how dermoscopy can help us? [Articolo su rivista]
Pampena, R.; Piana, S.; Moscarella, Elvira; Longo, Caterina; Lallas, A.; Alfano, R.; Argenziano, Giuseppe
abstract

ND

2016 - Halo and pseudo-halo melanoma [Articolo su rivista]
Suzuki, Nathalie; Dalapicola, Monique; Argenziano, Giuseppe; Lallas, Aimilios; Longo, Caterina; Piana, Simonetta; Ferrara, Gerardo; Raucci, Margherita; Moscarella, Elvira
abstract

ND

2016 - Heritability of naevus pattern [Articolo su rivista]
Longo, Caterina; Ribero, Simone
abstract

ND

2016 - Image Gallery: Brain? no, melanoma [Articolo su rivista]
Piana, S.; Moscarella, Elvira; Longo, Caterina
abstract

ND

2016 - In Vivo Reflectance Confocal Microscopy in Dermatology [Capitolo/Saggio]
Alarcon, I.; Longo, C.; Gonzalez, S.
abstract

Imaging techniques capable of noninvasive, high-resolution, skin imaging in vivo have been the focus of recent attention in the dermatology field. These efforts are directed to improve the diagnostic accuracy of skin cancer, especially cutaneous melanoma. Reflectance confocal microscopy (RCM) is an innovative imaging tool that allows the analysis of the skin horizontally with a nearly histological resolution. Similar to dermoscopy images, real-time images obtained by RCM are oriented horizontal to the skin surface (optical transversal sections). Melanin provides strong contrast because of its high refractive index (1.7) relative to the surrounding epidermis. It has been applied in the clinical arena for the diagnosis of melanocytic and nonmelanocytic lesions where it has been proven to increase greatly the diagnostic accuracy when coupled with dermoscopy. Beyond its application in skin oncology, confocal microscopy can be useful to delineate the overall aspect of inflammatory skin disease and infectious ones. The main limitation of RCM is its relatively low penetration through the dermis; a maximum depth of 250-300. μm can currently be achieved, preventing imaging of structures located in the deep dermis and hypodermis. The main challenge is the interpretation of images. Specific photographic atlas, courses, and further development of teledermatology may solve this problem.

2016 - In Vivo and Ex Vivo Confocal Microscopy for Dermatologic and Mohs Surgeons [Articolo su rivista]
Longo, Caterina; Ragazzi, Moira; Rajadhyaksha, Milind; Nehal, Kishwer; Bennassar, Antoni; Pellacani, Giovanni; Malvehy Guilera, Josep
abstract

Confocal microscopy is a modern imaging device that has been extensively applied in skin oncology. More specifically, for tumor margin assessment, it has been used in two modalities: reflectance mode (in vivo on skin patient) and fluorescence mode (on freshly excised specimen). Although in vivo reflectance confocal microscopy is an add-on tool for lentigo maligna mapping, fluorescence confocal microscopy is far superior for basal cell carcinoma and squamous cell carcinoma margin assessment in the Mohs setting. This article provides a comprehensive overview of the use of confocal microscopy for skin cancer margin evaluation.

2016 - Increased mortality for pregnancy-associated melanoma: different outcomes pooled together, selection and publication biases [Articolo su rivista]
Kyrgidis, A; Argenziano, Giuseppe; Moscarella, Elvira; Longo, Caterina; Alfano, R.; Lallas, A.
abstract

ND

2016 - Management of local skin reactions after the application of ingenol mebutate gel for the treatment of actinic keratosis: Four illustrative cases [Articolo su rivista]
Longo, Caterina; Neri, L.; Argenziano, Giuseppe; Calvieri, S.; Calzavara Pinton, P. G.; Cantisani, C.; Catricalà, C.; Peris, K.; Peserico, A.; Pimpinelli, N.; Pellacani, Giovanni
abstract

ND

2016 - Medical consultation the year before melanoma diagnosis: could we detect melanoma earlier? [Articolo su rivista]
Urech, M.; Moscarella, Elvira; Lallas, A.; Ricci, C.; Longo, Caterina; Argenziano, Giuseppe
abstract

ND

2016 - Melanomas [Articolo su rivista]
Longo, Caterina; Pellacani, Giovanni
abstract

Melanomas are a wide range of tumors that differ in their epidemiology, morphology, genetic profile, and biological behavior. They can be grouped as superficial spreading melanoma, lentigo maligna, and nodular melanoma. Reflectance confocal microscopy is useful for the evaluation of skin lesions that are dermoscopically doubtful by increasing diagnostic accuracy and specificity. This article provides a comprehensive overview of the different confocal main morphologies of distinct melanoma types as a function of the anatomic location of the tumor.

2016 - Multicentre study on inflammatory skin diseases from The International Confocal Working Group: specific confocal microscopy features and an algorithmic method of diagnosis [Articolo su rivista]
Ardigo, M; Longo, Caterina; Gonzalez, S.; Agozzino, Marina; Debarbieux, Sebastien; Di Stefani, Alessandro; Gerittsen, Marie Jeanne; Gill, Melissa; Hofmann Wellenhof, Rainer; Kline, Mitchell; Malvehy, Joseph; Menezes, Nuno; Moscarella, Elvira; Pellacani, Giovanni; Puig, Susanna; Rao, Babar; Rao, Babar; Segura, Sonia; Soyer, Peter; Stanganelli, Ignazio; Ulrich, Martina; Venturini, Marina
abstract

Background: The real value of reflectance confocal microscopy (RCM) for the evaluation of inflammatory skin conditions remains unclear. A project on RCM for inflammatory skin diseases involving international centres was designed by a coordinating centre and executed under the supervision of the International Confocal Working Group. Objectives: To identify specific confocal features useful for distinction between the three main groups of superficial inflammatory skin diseases. Methods: Nineteen different RCM features were evaluated in a total of 155 lesions, diagnosed as spongiotic (45), interface (52) or psoriasiform (58) dermatitis, collected by a consortium of 19 different centres. Results: Univariate and multivariate analysis identified RCM descriptors for the three main superficial inflammatory disease groups. Later, a multivariate method was employed to define a scoring system to be applied on an algorithmic method of analysis for fast clinical application. Conclusions: Our preliminary evaluation supports the use of RCM for the identification of confocal patterns consistent with the major features of the diagnostic groups of inflammatory skin diseases. Moreover, an efficient multivariate method for clinical in vivo RCM diagnosis using a tree decision diagram has been established.

2016 - Multiple Spitz naevi: the randomly distributed variant [Articolo su rivista]
Moscarella, Elvira; Gandolfi, G.; Piana, S.; Ciarrocchi, A.; Ferrara, G.; Lallas, A.; Longo, Caterina; Rosato, S.; Argenziano, Giuseppe
abstract

ND

2016 - Multiple angiomatous nodules: a novel skin tumor in Birt–Hogg–Dubé syndrome [Articolo su rivista]
Nikolaidou, C.; Moscarella, Elvira; Longo, Caterina; Rosato, S.; Cavazza, A.; Piana, S.
abstract

Birt–Hogg–Dubé syndrome (BHDS), first described in 1977, is a rare autosomal dominant disorder, linked to germline mutations in the FLCN (folliculin) gene. Patients may present with different skin tumors, pulmonary cysts with recurrent spontaneous pneumothorax, and renal cancers, but it has also been estimated that about 25% of carriers older than 20 years do not show skin involvement. So far, besides the triad of skin lesions of the original description (fibrofolliculomas, trichodischomas and acrochordons), a wide range of neoplastic and non-neoplastic skin conditions have been reported, i.e. melanomas, trichoblastoma, neural- and connective tissue tumors, lipomas, angiolipomas and focal cutaneous mucinosis. We describe a patient with BHDS developing multiple skin angiomatous lesions with prominent signet-ring features, an association never reported so far. As renal carcinomas represent the most threatening complication in BHDS and the identification of the patients with BHDS is mainly based on the clinical and histopathologic identification of the diagnostic skin lesions, the role of the dermatologist can be crucial in the prevention and early detection of a potentially aggressive renal cancer.

2016 - Non-invasive diagnosis of pink basal cell carcinoma: how much can we rely on dermoscopy and reflectance confocal microscopy? [Articolo su rivista]
Witkowski, A. M; Łudzik, J; TEIXEIRA DE CARVALHO, Nathalie; Ciardo, S; Longo, Caterina; DI NARDO, Antonio; Pellacani, Giovanni
abstract

Background: Non-pigmented 'pink' cutaneous lesions in differential diagnosis with basal cell carcinoma may present a challenge for clinicians. Our objective was to determine the potential improvement of diagnostic accuracy using combined dermoscopy-reflectance confocal microscopy (RCM) image evaluation. Methods: Two hundred and sixty clinically equivocal 'pink' cutaneous lesions were evaluated retrospectively. Reader accuracy was tested with dermoscopy images only vs. RCM and combined dermoscopy-RCM images. Results: Out of 260 equivocal 'pink' cutaneous lesions, there were 114 basal cell carcinomas within a total of 140 malignancies that included 12 melanomas, 13 squamous cell carcinomas, and 1 other malignancy type. Dermoscopy only evaluation resulted in an overall sensitivity of 85.1% and specificity of 92.4%, resulting in a positive predictive value (PPV) of 89.8%, with 1 of 12 melanomas misdiagnosed. RCM evaluation resulted in an overall sensitivity of 85.1% and specificity of 93.8%, resulting in a PPV of 91.5%, with no melanomas misdiagnosed. Combined dermoscopy-RCM evaluation resulted in an overall sensitivity of 77.2% and specificity of 96.6%, resulting in a PPV of 94.6%. Conclusion: The combination of dermoscopy-RCM evaluation significantly improves the accuracy and safety threshold in equivocal 'pink' cutaneous lesions in the differential diagnosis of basal cell carcinoma.

2016 - Omics Landscape in Disease Biomarkers Discovery [Articolo su rivista]
Neagu, Monica; Longo, Caterina; Ribero, Simone
abstract

ND

2016 - Orthovoltage radiotherapy for nonmelanoma skin cancer (NMSC): Comparison between 2 different schedules [Articolo su rivista]
Pampena, Riccardo; Palmieri, Tamara; Kyrgidis, Athanassios; Ramundo, Dafne; Iotti, Cinzia; Lallas, Aimilios; Moscarella, Elvira; Borsari, Stefania; Argenziano, Giuseppe; Longo, Caterina
abstract

Background Radiotherapy is an established treatment for some types of patients with nonmelanoma skin cancer. A hypofractionated schedule has been proposed as a valuable option for elderly disabled patients to minimize the number of hospital visits. Objective We sought to compare a weekly hypofractionated orthovoltage radiotherapy regimen with a standard daily one for the treatment of nonmelanoma skin cancer. Methods A retrospective cohort study was performed on 436 tumors. Overall survival, disease-free survival, and cosmetic outcome were measured. Life-table analysis, Kaplan-Meier survival analysis, and multivariate Cox regression model were performed. Results The hypofractionated regimen was not associated with increased recurrence rates and mortality, or with a poorer cosmetic outcome, when compared with the daily schedule. Limitations Absence of complete information about acute treatment toxicity and a shorter follow-up time for patients receiving the weekly schedule are limitations of this study. Conclusions A weekly hypofractionated regimen of orthovoltage radiotherapy seems to be the most appropriate approach in elderly disabled patients with nonmelanoma skin cancers.

2016 - Paradigmatic cases of pigmented lesions: How to not miss melanoma [Articolo su rivista]
Farnetani, Francesca; Scope, Alon; Coco, Valeria; Guida, Stefania; Cesinaro, Anna Maria; Piana, Simonetta; Peris, Ketty; Pellacani, Giovanni; Longo, Caterina
abstract

A large number of cases of melanoma exhibit clinical and dermoscopic clues leading to the correct diagnosis; however, sometimes melanoma can mimic benign melanocytic and non-melanocytic lesions. We present a small series of melanomas in which additional clues provided by confocal microscopy increased the index of suspicion and prompted us to perform an excisional biopsy. Practical rules that are useful in difficult-to-diagnose melanomas are discussed.

2016 - Pigmented epithelioid melanocytoma: Clinical, dermoscopic and histopathological features [Articolo su rivista]
Moscarella, Elvira; Ricci, R.; Argenziano, Giuseppe; Lallas, A.; Longo, Caterina; Lombardi, M.; Alfano, R.; Ferrara, G.
abstract

ND

2016 - Pigmented globules in dermoscopy as a clue for lentigomaligna mimicking non-melanocytic skin neoplasms: A lesson from reflectance confocal microscopy [Articolo su rivista]
De Carvalho, N.; Guida, Stefania; Cesinaro, A. M.; Abraham, L. S.; Ciardo, Silvia; Longo, Caterina; Farnetani, Francesca; Pellacani, Giovanni
abstract

Pigmented globules in dermoscopy as a clue for lentigomaligna mimicking non-melanocytic skin neoplasms: a lesson from reflectance confocal microscopy.

2016 - Precise Longitudinal Tracking of Microscopic Structures in Melanocytic Nevi Using Reflectance Confocal Microscopy: A Feasibility Study [Articolo su rivista]
Scope, Alon; Selinger, Limor; Oliviero, Margaret; Farnetani, Francesca; Moscarella, Elvira; Longo, Caterina; Rabinovitz, Harold S; Pellacani, Giovanni
abstract

Reflectance confocal microscopy (RCM), a cellular-level, in vivo imaging technique, may be potentially used for monitoring melanocytic neoplasms for microscopic stability vs changes over time.

2016 - Reflectance Confocal Microscopy Clinical Applications: The Skin from Inside [Articolo su rivista]
Grant Kels, Jane M.; Pellacani, Giovanni; Longo, Caterina
abstract

ND

2016 - Regression in cutaneous melanoma: a comprehensive review from diagnosis to prognosis [Articolo su rivista]
Ribero, S.; Moscarella, Elvira; Ferrara, G.; Piana, S.; Argenziano, Giuseppe; Longo, Caterina
abstract

Histological regression in primary cutaneous melanoma occurs in 10–35% of cases. Although a large body of literature exists to suggest that histological regression serves very little purpose in predicting biologic behaviour with melanoma, recognizing the presence of regression at clinical and histological ground may still retain some value in grading melanoma aggressiveness. In the current review, a comprehensive overview of the main aspects of regression will be provided. Histologically, many classifications have been reported so far, but all of them only agreed on the presence of an infiltrate of lymphocytes admixed with pigment-laden macrophages underlying an atrophic epidermis with flattened rete ridges. Upon dermoscopy, regression is also named Blue White Scar-like areas and could be variably admixed with granularity or peppering. Almost fully regressed lesions represent a main diagnostic issue in dermoscopy, and thus, confocal microscopy can be of help to identify whether the tumour is melanocytic or not. The clinical utility of regression as a prognostic factor has been challenged recently. Nowadays, evidences showed that it is less likely associated to SLN metastases.

2016 - Sebaceous hyperplasia [Capitolo/Saggio]
Longo, C.
abstract

Crown vessels are typically seen in sebaceous hyperplasia and are characterized by elongated, blurred telangiectases that embrace centrally located white to yellow lobular structureless areas. The vessels do not usually cross over the central portions of the lesion, and they reveal a radial arrangement. The main differential diagnosis of sebaceous hyperplasia is basal cell carcinoma. The different vascular patterns and vessels arrangements are important clues that help in the distinction between these two entities. More specifically, the branching or arborizing vessels of nodular basal cell carcinoma are bright red, are sharply focused, and often course over the central part of the lesion. Conversely, sebaceous hyperplasia is typified by the presence of crown-like vessels located around the periphery of the lesion that are less bright red and are blurred compared to the vessels observed in basal cell carcinoma.

2016 - Spitz naevi and melanomas with similar dermoscopic pattern: can confocal microscopy differentiate? [Articolo su rivista]
Guida, Stefania; Pellacani, Giovanni; Cesinaro, A. M; Moscarella, Elvira; Argenziano, Giuseppe; Farnetani, Francesca; Bonamonte, Domenico; Longo, Caterina
abstract

Background Differentiating Spitz naevi from melanomas can be difficult both clinically and dermoscopically. Previous studies have reported the potential role of in vivo reflectance confocal microscopy (RCM) in increasing diagnostic accuracy. Objectives To define RCM criteria that can differentiate 'false twins', namely Spitz naevi and melanomas sharing similar dermoscopic appearance. Methods Lesions histopathologically diagnosed as Spitz naevi or melanomas were retrospectively retrieved. They were selected to cover all dermoscopic types and were put into couples sharing similar aspects. Lesions were classified into three main dermoscopic categories: globular and starburst pattern, spitzoid with dotted vessels, and multicomponent or aspecific pattern. Results RCM findings revealed that striking cell pleomorphism within the epidermis, widespread atypical cells at the dermoepidermal junction and marked pleomorphism within nests were significantly associated with the diagnosis of melanoma, while spindled cells and peripheral clefting were found exclusively with and pathognomonic of Spitz naevi. Furthermore, the analysis of a dermoscopic subgroup highlights the importance of striking pleomorphism and spindled cells as clues to differentiate 'false twins' with globular or starburst patterns. Conclusions The current study highlights the role of RCM in discriminating 'false twins' of Spitz naevi and melanomas for lesions showing starburst and globular patterns on dermoscopy, whereas RCM is not useful in the other dermoscopic subgroups.

2016 - The extent of whole-genome copy number alterations predicts aggressive features in primary melanomas [Articolo su rivista]
Gandolfi, Greta; Longo, Caterina; Moscarella, Elvira; Zalaudek, Iris; Sancisi, Valentina; Raucci, Margherita; Manzotti, Gloria; Gugnoni, Mila; Piana, Simonetta; Argenziano, Giuseppe; Ciarrocchi, Alessia
abstract

Recent evidence indicates that melanoma comprises distinct types of tumors and suggests that specific morphological features may help predict its clinical behavior. Using a SNP-array approach, we quantified chromosomal copy number alterations (CNA) across the whole genome in 41 primary melanomas and found a high degree of heterogeneity in their genomic asset. Association analysis correlating the number and relative length of CNA with clinical, morphological, and dermoscopic attributes of melanoma revealed that features of aggressiveness were strongly linked to the overall amount of genomic damage. Furthermore, we observed that melanoma progression and survival were mainly affected by a low number of large chromosome losses and a high number of small gains. We identified the alterations most frequently associated with aggressive melanoma, and by integrating our data with publicly available gene expression profiles, we identified five genes which expression was found to be necessary for melanoma cells proliferation. In conclusion, this work provides new evidence that the phenotypic heterogeneity of melanoma reflects a parallel genetic diversity and lays the basis to define novel strategies for a more precise prognostic stratification of patients.

2016 - Unusual Dermoscopic Patterns of Seborrheic Keratosis [Articolo su rivista]
Squillace, Lorenzo; Cappello, Milena; Longo, Caterina; Moscarella, Elvira; Alfano, Roberto; Argenziano, Giuseppe
abstract

Background: Seborrheic keratoses (SKs) may sometimes mimic benign and malignant skin tumors, and a biopsy can be necessary in order to rule out malignancy. Methods: From the database of our pigmented lesion clinic, we evaluated the dermoscopic features of difficult-to-diagnose SKs that were biopsied between January 2010 and December 2014. Results: SKs represented 3.8% of all excised lesions (161/ 4,182). Specifically, 91 (56.5%) were excised to rule out melanoma, 63 (39.1%) to rule out squamous cell carcinoma and 7 (4.4%) to rule out basal cell carcinoma. The following 10 global dermoscopic patterns were identified: multicomponent (32; 19.9%); reticular (24; 14.9%), characterized by an irregular pigment network; bowenoid (21; 13.0%); hairpin (19; 11.8%); keratoacanthoma-like (16; 9.9%); blue-nevus-like (15; 9.3%); lichenoid (6; 3.7%); hyperkeratotic (6; 3.7%); clonal (5; 3.1%); spitzoid (5; 3.1%). Furthermore, 12 SKs (7.5%) were not included in any of such patterns (not classified). Conclusion: Our results are in line with previous studies highlighting the dermoscopic variability of SKs. Although excised SKs may be classified into 1 of 10 repetitive dermoscopic patterns, a biopsy remains mandatory for those that cannot be clearly differentiated from common skin malignancies.

2016 - Well-aging: Early Detection of Skin Aging Signs [Articolo su rivista]
Longo, Caterina
abstract

The aim of the current review is to provide an overview of the use of reflectance confocal microscopy to detect early skin aging signs. This new imaging tool holds the promise to morphologically explore the epidermis and upper dermis at nearly histologic resolution and over time. The main confocal findings of aged skin include the presence of irregular honeycombed pattern, linear skin furrows, mottled pigmentation, and distinct collagen types (coarse and huddled).

2016 - What is New in Melanoma Genetics and Treatment? [Articolo su rivista]
Ribero, Simone; Longo, Caterina; Glass, Dan; Nathan, Paul; Bataille, Veronique
abstract

New therapies for advanced melanoma have led to major advances, which, for the first time, showed improved survival for patients with this very challenging neoplasm. These new treatments are based on gene-targeted therapies or stimulation of immune responses. However, these treatments are not without challenges in terms of resistance and toxicity. Physicians should be aware of these side effects as prompt treatment may save lives. Melanoma genetics is also unravelling new genetic risk factors involving telomere genes as well as new gene pathways at the somatic level which may soon become therapeutic targets. It is also shedding new light onto the pathology of this tumour with links to neural diseases and longevity.

2016 - When dermoscopy is supported by Tzanck smear [Articolo su rivista]
Piccolo, V; Russo, T.; Mascolo, M.; Longo, Caterina; Alfano, R.; Ruocco, E.; Argenziano, Giuseppe
abstract

ND

2015 - A novel BRAF mutation in association with primary amelanotic melanoma with oral metastases [Articolo su rivista]
Zalaudek, I.; Ciarrocchi, A.; Piana, S.; Argenziano, Giuseppe; Torricelli, Federica; Sancisi, Valentina; Gandolfi, G.; Longo, Caterina; Moscarella, Elvira; Banzi, C.; Nicoli, D.
abstract

Background: In the context of amelanotic melanoma, little is known on the genetic or molecular background that determines the onset of this peculiar phenotype of melanoma and its sites of metastatic spread. However, it appears that amelanotic melanomas frequently lack BRAF mutations. Objective: To report the genetical analysis of one case amelanotic melanoma developing oral metastasis. Methods: The BRAF mutational status of the primary lesion was assessed by both Sanger sequencing and pyrosequencing. Results: Both methodologies showed changes in three nucleotides: C1796T; G1798A and T1799A. These mutations should result in a rare double aminoacid substitution in codons 599 and 600 of the BRAF protein (BRAF T599I/V600K). Conclusion: This unusual mutation was associated with an uncommon clinical phenotype of the primary tumour and with an unusual site of metastatic spread. In the lack of comparable data, a potential association between the unusual mutation and clinical findings remains a matter of further studies.

2015 - A novel CYLD germline mutation in Brooke-Spiegler syndrome. [Articolo su rivista]
Guardoli, D; Argenziano, G; Ponti, Giovanni; Nasti, S; Zalaudek, I; Moscarella, E; Lallas, A; Piana, S; Specchio, F; Martinuzzi, C; Raucci, M; Pellacani, Giovanni; Longo, Caterina
abstract

BACKGROUND: Brooke-Spiegler syndrome (BSS) is a rare, inherited, autosomal dominant disorder characterized by the development of multiple adnexal neoplasms including spiradenomas, cylindromas, trichoepitheliomas and major and minor salivary glands neoplasms. This syndrome encompasses a wide variability of clinical phenotypes depending on the variable number of tumours present in the given patient. OBJECTIVE: Somatic mutations in adjunct to CYLD germline mutations may play a central role in the development of the tumour phenotype and in the genotype-phenotype correlations. METHODS: Blood sample and paraffin embedded tissue biopsied from three cylindromas, one trichoepithelioma and one spiradenomas were collected after obtaining informed consent from our patient and genomic DNA was isolated. RESULTS: We found out a novel germline mutation in the CYLD gene in exon 15 that resulted in the deletion of one nucleotide. This gives rise to a premature translational termination codon at amino acid position 693 prior to four Cys-X-X-Cys pairs and one of the two catalytic domains of ubiquitin carboxy-terminal hydrolases. In only one cylindroma we detected the same germline mutation (c.2070delT/p.F690FfsX3) in addition to two somatic events (I645V and R936X). The presence of this unique mutation could be linked to the peculiar phenotype of our patient who presented an attenuated form of BSS, an autosomal dominant inheritance with low penetrance and no additional visceral tumours. CONCLUSIONS: The overall phenotype of our patient may support the hypothesis that somatic mutations in adjunct to CYLD germline mutations may play a central role in the development of the tumour phenotype and in the genotype-phenotype correlations.

2015 - Acne: in vivo morphologic study of lesions and surrounding skin by means of reflectance confocal microscopy [Articolo su rivista]
Manfredini, Marco; Mazzaglia, Giovanna; Ciardo, Silvana; Farnetani, Francesca; Mandel, Victor Desmond; Longo, Caterina; Zauli, Stefania; Bettoli, Vincenzo; Virgili, Anna; Pellacani, Giovanni
abstract

Background: Acne vulgaris is a common disease of the pilosebaceous unit, clinically showing alteration of the keratinization process leading to comedos formation and subsequent inflammatory process. Objective: To characterize the morphology of acne lesions and pilosebaceous units by means of in vivo reflectance confocal microscopy, in order to non-invasively define the microscopic alterations occurring during the acne process. Methods: A set of standardized clinical pictures and a set of reflectance confocal images were acquired from 25 volunteers, presenting mild-to-moderate acne, and 10 healthy volunteers, using Vivascope 3000, and 10 mosaics on apparently normal skin were acquired by 5 acne patients and 5 healthy volunteers by Vivascope 1500, and evaluated by experts. Results: Confocal microscopy enabled to identify morphological aspects characterizing different types of acne lesions. Apparently normal skin of acne patients, compared with healthy skin of patients with no history of acne, revealed peculiar confocal features, such as bright rings around hair follicle that may represent the early events in acne lesion formation. Conclusion: The fast and reliable characterization of acne lesions and identification of subclinical alterations in acne-prone skin through confocal examination, corresponding to infundibular hyper-keratinization, may have important clinical consequences in the assessment of acne severity, therapeutic decisions and treatment efficacy monitoring.

2015 - Age, gender, and topography influence the clinical and dermoscopic appearance of lentigo maligna [Articolo su rivista]
Tiodorovic Zivkovic, Danica; Argenziano, Giuseppe; Lallas, Aimilios; Thomas, Luc; Ignjatovic, Aleksandra; Rabinovitz, Harold; Moscarella, Elvira; Longo, Caterina; Hofmann Wellenhof, Rainer; Zalaudek, Iris
abstract

Background Little is known about the frequency of clinical and dermoscopic patterns of lentigo maligna (LM) in relation to specific anatomic subsites and patients characteristics. Objective We sought to assess the frequency of clinical and dermoscopic features of LM and to correlate them to specific anatomic subsites, and patients' age and gender. Methods This was a retrospective analysis of clinical and dermoscopic images of a series of consecutive, histopathologically diagnosed, facial and extrafacial LM. Results A total of 201 cases from 200 patients (mean age 69.51 ± 12.26 years) including 120 women were collected. Most cases were located on the face (n = 192, 95.5%). In 102 cases, LM presented as clinically solitary facial macule (s/LM), whereas it was associated with multiple surrounding freckles in the remaining cases. s/LM were significantly smaller (&lt;10 vs &gt;10 mm; P =.020) and associated with younger age compared with LM associated with multiple surrounding freckles (mean age 67.73 ± 12.68 years vs 71.34 ± 11.59 years, respectively; P =.036). Dermoscopically, gray color irrespective of a specific pattern was the most prevalent finding seen in 178 (88.6%) cases. Limitations This was a retrospective study. Conclusions The knowledge about patient age, patient gender, and site-related clinical features of LM associated with gray color upon dermoscopy may enhance the clinical recognition of LM.

2015 - Age-related prevalence and morphological appearance of facial skin tumours: A prospective, cross-sectional, observational, multicentre study with special emphasis on melanocytic tumours [Articolo su rivista]
Moscarella, Elvira; Kyrgidis, A.; Sperduti, I.; Abramavicus, A.; Argenziano, Giuseppe; Cota, C.; Eibenschutz, L.; De Simone, P.; Longo, Caterina; Hofmann Wellenhof, R.; Zalaudek, I.
abstract

Background The clinical and histopathological diagnosis of skin tumours arising on the face may be challenging. Objective An improved knowledge about the age-related patterns of facial skin tumours may aid the correct diagnosis and management. Methods We conducted a prospective, cross-sectional morphological study to investigate the age-related frequency and morphological variability in facial skin tumours in a cohort of consecutive subjects attending two skin lesion clinics in Italy between June and September 2011. A total of 454 consecutive subjects (249 women; 55.5%) presenting with a total of 1866 facial tumours were enrolled in the study. Of the entire cohort, 54 (11.9%) subjects had no facial lesion. Results Total body naevus count correlated significantly with the mean number of facial lesions (ρ = 0.289, P &lt; 0.001). The majority of flat lesions were pigmented (1056; 75.70%), compared to palpable (233; 17.40%) and raised lesions (93; 6.90%), the association being statistically significant (Pearson's chi square, P &lt; 0.001. Considering melanocytic tumours only, the frequency of flat lesions significantly decreased with increasing age, while the number of palpable and raised lesions increased with increasing age (chi-square, P &lt; 0.001). This trend was mainly due to naevi, whereby pigmented melanocytic naevi decreased with increasing age. Conversely, the percentage of non- pigmented naevi increased with increasing age (chi-square, P &lt; 0.001). Limitations The study was conducted in skin lesion clinics in Italy, thus any general conclusions with respect to common traits or features based on the phenotypic and genetic diversity within the European population cannot be stated. Conclusions and relevance Our study suggests that a high number of facial naevi could predict a high total naevus count. Moreover, naevi present a different morphological appearance during lifetime being initially flat, small and pigmented and becoming later raised, large and hypopigmented. Instead, lentigo maligna is an intraepidermal proliferation that typically presents as flat, large pigmented macule. A given histopathological diagnosis of a junctional naevus of a flat, facial pigmented macule of an elderly should be critically reviewed and treated with caution.

2015 - Agminated blue nevus combined with nevus spilus: An uncommon association [Articolo su rivista]
Simonetti, Vito; Grenzi, Laura; Piana, Simonetta; Albertini, Giuseppe; Longo, Caterina
abstract

ND

2015 - Are glycemic index and glycemic load associated with risk of cutaneous melanoma? A case-control study in an Italian population. [Abstract in Atti di Convegno]
Malavolti, Marcella; Malagoli, Carlotta; Furio, Brighenti; Sabina, Sieri; Vittorio, Krogh; Farnetani, Francesca; Longo, Caterina; Pellacani, Giovanni
abstract

Are glycemic index and glycemic load associated with risk of cutaneous melanoma? A case-control study in an Italian population.

2015 - Association between genetic factors, naevus count and dermoscopic pattern [Articolo su rivista]
Longo, Caterina; Pellacani, Giovanni
abstract

ND

2015 - CD271 is expressed in melanomas with more aggressive behaviour, with correlation of characteristic morphology by in vivo reflectance confocal microscopy [Articolo su rivista]
Beretti, F.; Manni, P.; Longo, C.; Argenziano, G.; Farnetani, F.; Cesinaro, A. M.; Witkowski, A. M.; De Pol, A.; Pellacani, G.
abstract

Background Melanoma is the most highly aggressive type of skin cancer. Its resistance to existing treatments and the rapid rise in incidence underscore the importance of acquiring a better understanding of melanomagenesis. Objectives To assess the impact of reflectance confocal microscopy (RCM) on the description of cell morphology, which may influence the growth pattern and changes with increasing tumour severity, correlating with biological aspects. Methods A retrospective analysis of 30 primary melanomas in vivo, evaluated by RCM, to correlate cell morphology and cellular arrangement with a marker of melanoma progression (CD271) using immunohistochemical evaluations. Results Typical cells organized in dermal nests with peculiar in vivo confocal morphology result in melanoma with high malignancy and positivity to CD271. This architecture might be due to the presence of a type of cells, intrinsically predisposed to invasion, as a result of dedifferentiation programming, revealed by expression of the neural crest marker CD271. Conclusions With the hypothesis that dedifferentiated cells would be strongly responsible for initiation of tumour development and progression, we propose that CD271 detection could be associated with RCM evaluation in order to detect more aggressive melanoma subtypes.

2015 - Chemokines in the melanoma metastasis biomarkers portrait [Articolo su rivista]
Neagu, Monica; Constantin, Carolina; Longo, Caterina
abstract

Skin tumorigenesis is linked to inflammatory chemokines accumulation that can induce cancer-associated immune-suppression. Deregulation of the CXCR4/CXCL12 axis was reported in melanoma tumorigenesis while also linked to BRAF mutation. Some chemokine-receptor patterns can direct the organ-specific metastasis. CXCL10 can help to prognosticate high-risk patients as it is a chemokine that differentiated patients with vs. metastasis free ones. Besides serum/plasma, chemokine identification in the cerebrospinal fluid of melanoma patients can indicate brain metastasis. Interplay between suppressed and elevated chemokines in cerebrospinal fluid can pinpoint an aggressive melanoma brain metastasis. Chemokines are gaining rapid momentum in the biomarker discovery domain aiding melanoma prognosis and high-risk patients stratification.

2015 - Clinical and dermoscopic features of atypical Spitz tumors: A multicenter, retrospective, case-control study [Articolo su rivista]
Moscarella, Elvira; Lallas, Aimilios; Kyrgidis, Athanassios; Ferrara, Gerardo; Longo, Caterina; Scalvenzi, Massimiliano; Staibano, Stefania; Carrera, Cristina; Díaz, M. Alba; Broganelli, Paolo; Tomasini, Carlo Francesco; Cavicchini, Stefano; Gianotti, Raffaele; Puig, Susana; Malvehy, Josep; Zaballos, Pedro; Pellacani, Giovanni; Argenziano, Giuseppe
abstract

Background Few studies have described the clinical and dermoscopic features of atypical Spitz tumors. Objective We sought to describe the clinical and dermoscopic features of a series of atypical Spitz tumors as compared with those of conventional Spitz nevi. Methods This was a multicenter, retrospective, case-control study, analyzing the clinical and dermoscopic characteristics of 55 atypical Spitz tumors and 110 Spitz nevi that were excised and diagnosed histopathologically. Results The majority of atypical Spitz tumors presented clinically as a plaque or nodule, dermoscopically typified by a multicomponent or nonspecific pattern. A proportion of lesions (16.4%) exhibited the typical nonpigmented Spitzoid pattern of dotted vessels and white lines under dermoscopy. Nodularity, ulceration, linear vessels, polymorphic vessels, white lines, and blue-white veil were associated with atypical Spitz tumors by univariate analysis, but only nodularity and white lines remained significant after multivariate analysis. In contrast, a pigmented typical Spitzoid pattern was a potent predictor of Spitz nevi, associated with 6.5-fold increased probability. Limitations Differentiation from Spitzoid melanoma and other nonmelanocytic lesions was not investigated. Conclusion Atypical Spitz tumors are polymorphic melanocytic proliferations with a nodular clinical appearance. Dermoscopically they demonstrate a multicomponent and nonspecific pattern. A typical nonpigmented Spitzoid pattern on dermoscopy (with dotted vessels and white lines) does not exclude atypical Spitz tumors.

2015 - Cutaneous metastasis of renal carcinoma [Articolo su rivista]
Soares, Gabriela Hertz; Lallas, Aimilios; Lombardi, Mara; Longo, Caterina; Moscarella, Elvira; Raucci, Margherita; Argenziano, Giuseppe
abstract

ND

2015 - Dermoscopic difficult lesions: an objective evaluation of reflectance confocal microscopy impact for accurate diagnosis [Articolo su rivista]
Ferrari, Barbara; Pupelli, Gaia; Farnetani, Francesca; Teixeira De Carvalho, Nathalie; Longo, Caterina; Reggiani, Camilla; Argenziano, Giuseppe; Pellacani, Giovanni
abstract

Background Early detection of melanoma is the main objective to ensure a high survival rate. In some cases melanoma diagnosis still remain difficult and this leads to unnecessary excisions. Objective The aim of this study was to detect the most relevant Reflectance confocal microscopy (RCM) features for the detection of dermoscopic difficult melanomas. Method A total of 322 lesions were selected from database and were evaluated on dermoscopy according to the 7-point checklist score, in blind from histological diagnosis. We classified the lesions into three categories: (i) 'featureless' lesions with score ranging between 0 and 2; (ii) 'positive-borderline' moles with score between 3 and 4 and (iii) 'positive-clear cut' lesions with score from 5 to 10. We evaluated confocal features of the 'featureless' lesions and of the 'positive-borderline' lesions. Evaluated confocal features were as follows: presence of pagetoid cells, cell shape (roundish or dendritic) and number (&lt; 5 or &gt;5 cells per mm2), overall architecture (ringed, meshwork, clods and non-specific pattern); architectural disorder, presence of cytological atypia (&gt;5 cells per mm2) and cells arranged in nests. Results Among 322 lesions 70 were melanomas and 252 were nevi. According to the classification based on the 7-point checklist score, 130 'featureless lesions' (score 0-2) including six melanomas, and 102 'positive-borderline' moles (score 3-4) including 17 melanomas, were identified. Round pagetoid cells &gt;5 cells per mm2 and/or architectural disorder on RCM were found in all of six melanomas with featureless dermoscopy. Round pagetoid infiltration and five or more atypical cells at the DEJ were found in 16 positive 'borderline melanomas'. Conclusions RCM represents a rapid non-invasive technique that can aid early diagnosis of dermoscopic difficult melanomas. Use of RCM on lesions with clinical and/or dermoscopic suspect of malignancy may reduce the number of unnecessary excision increasing the rate of accurate diagnoses.

2015 - Dermoscopic pattern of radiation-induced angiosarcoma (RIA) [Articolo su rivista]
Figueroa Silva, Olalla; Argenziano, Giuseppe; Lallas, Aimilios; Longo, Caterina; Piana, Simonetta; Moscarella, Elvira
abstract

ND

2015 - Dermoscopy and reflectance confocal microscopy of pigmented actinic keratoses: A morphological study [Articolo su rivista]
Moscarella, E.; Rabinovitz, H.; Zalaudek, I.; Piana, S.; Stanganelli, I.; Oliviero, M. C.; Lallas, A.; Ardigo, M.; Cota, C.; Catricala, C.; Mazzoni, L.; Pellacani, G.; Argenziano, G.; Longo, C.
abstract

BackgroundActinic keratoses (AKs) are very common lesions on sun damaged skin and, when pigmented, represent a challenge in the differential diagnosis with early melanoma. Non-invasive diagnostic methods, such as dermoscopy and reflectance confocal microscopy (RCM) have been shown to improve the diagnostic accuracy of melanoma and non-melanoma skin cancer, however, only one case report described confocal findings of pigmented AKs up to now.ObjectivesThe aim of our retrospective morphological study was to analyse dermoscopic and confocal images of a series of histopathologically proven pigmented AKs, located on the face and other body sites, to define peculiar features of these difficult to diagnose lesions.MethodsClinical, dermoscopic and RCM images of 17 histopathologically confirmed pigmented AKs were retrospectively collected from the databases of four skin lesion clinics in Italy and USA. Dermoscopic and RCM images were analysed for prevalent morphological features.ResultsThe majority of the lesions were located on the face (n=8); followed by scalp (n=4) and trunk (n=4); and one lesion was located on the lower limbs. On dermoscopy the majority of lesions were characterized by grey dots/globules/granularity and structureless brown pigmentation. The main RCM feature of pigmented AKs was as follows: (i) the presence of epidermal changes (atypical keratinocytes, parakeratosis, scaling); (ii) increased epidermal thickness; (iii) bright, small, dermal papillae with enlarged interpapillary space; and (iv) intraepidermal dendritic cells referrable to Langherans cells. Features suggestive of melanocytic lesions, such as nesting, meshwork pattern or atypical cells infiltrating the junction, were never detected in our case series at the dermal epidermal junction (DEJ) level.ConclusionLarger case series with adequate control population are warranted to validate these findings and to test their value in clinical setting.

2015 - Dermoscopy in the diagnosis and management of basal cell carcinoma [Articolo su rivista]
Lallas, Aimilios; Apalla, Zoe; Ioannides, Dimitrios; Argenziano, Giuseppe; Castagnetti, Fabio; Moscarella, Elvira; Longo, Caterina; Palmieri, Tamara; Ramundo, Dafne; Zalaudek, Iris
abstract

The dermoscopic findings of basal cell carcinoma (BCC) were first described more than a decade ago and the list of BCC-related criteria has been several times updated and enriched. Today, the dermatoscope is considered the key tool for the diagnosis of BCC, since it allows its early detection and enables its discrimination from other pigmented and nonpigmented skin tumors. The dermoscopic pattern of BCC results from several combinations of well-known BCC criteria, depending on several factors, including histopathologic subtype, location, gender, age and pigmentary trait. In addition, recent evidence highlighted that dermoscopy is also useful in the management of BCC, since it provides information on the tumor subtype, the presence of pigmentation or ulceration and the response to nonablative treatments.

2015 - Dermoscopy of clear cell acanthoma [Articolo su rivista]
Tiodorovic Zivkovic, Danica; Lallas, Aimilios; Longo, Caterina; Moscarella, Elvira; Zalaudek, Iris; Argenziano, Giuseppe
abstract

ND

2015 - Dermoscopy of melanoma and non-melanoma skin cancer [Articolo su rivista]
Babino, G.; Lallas, A.; Longo, Caterina; Moscarella, Elvira; Alfano, R.; Argenziano, Giuseppe
abstract

Skin cancer is a major health problem because of its high incidence in white populations, as well as its related potential morbidity and mortality. Dermoscopy is a noninvasive tool that allows the identification of specific morphological features in different skin tumors, improving significantly the early diagnosis of melanoma and non-melanoma skin cancer (NMSC). This tool has also gained increased interest in the management of NMSC therapy and in the post-treatment follow-up. In this article, we provide a review of the dermoscopic patterns and criteria for the diagnosis of melanoma and NMSC described until now in the literature.

2015 - Diet Quality and Risk of Melanoma in an Italian Population [Articolo su rivista]
Malagoli, Carlotta; Malavolti, Marcella; Agnoli, Claudia; Crespi, Catherine M; Fiorentini, Chiara; Farnetani, Francesca; Longo, Caterina; Ricci, Cinzia; Albertini, Giuseppe; Lanzoni, Anna; Veneziano, Leonardo; Virgili, Annarosa; Pagliarello, Calogero; Santini, Marcello; Fanti, Pier Alessandro; Dika, Emi; Sieri, Sabina; Krogh, Vittorio; Pellacani, Giovanni; Vinceti, Marco
abstract

Background: Some results from laboratory and epidemiologic studies suggest that diet may influence the risk of melanoma, but convincing evidence for a role of single nutrients or food items is lacking. Diet quality, which considers the combined effect of multiple food items, may be superior for examining this relation. Objective: We sought to assess whether diet quality, evaluated with the use of 4 different dietary indexes, is associated with melanoma risk. Methods: In this population-based case-control study, we analyzed the relation between 4 diet quality indexes, the Healthy Eating Index 2010 (HEI-2010), Dietary Approaches to Stop Hypertension (DASH) index, Greek Mediterranean Index (GMI), and Italian Mediterranean Index (IMI), and melanoma risk in a northern Italian community, with the use of data from 380 cases and 719 matched controls who completed a semiquantitative food frequency questionnaire. Results: In the overall sample, we found an inverse association between disease risk and the HEI-2010 and DASH index, but not the Mediterranean indexes, adjusting for potential confounders (skin phototype, body mass index, energy intake, sunburn history, skin sun reaction, and education). However, in sex stratified analyses, the association appeared only in women (P-trend: 0.10 and 0.04 for the HEI-2010 and DASH index, respectively). The inverse relations were stronger in women younger than age 50 y than in older women, for whom the GMI and IMI scores also showed an inverse association with disease risk (P-trend: 0.05 and 0.02, respectively). Conclusions: These results suggest that diet quality may play a role in cutaneous melanoma etiology among women.

2015 - Digital dermoscopy monitoring in patients with multiple nevi: How many lesions should we monitor per patient? [Articolo su rivista]
Moscarella, Elvira; Pampena, Riccardo; Kyrgidis, Athanassios; Tion, Isolina; Longo, Caterina; Lallas, Aimilios; Argenziano, Giuseppe
abstract

ND

2015 - Ex vivo fluorescence confocal microscopy in conjunction with Mohs micrographic surgery for cutaneous squamous cell carcinoma [Articolo su rivista]
Longo, Caterina; Ragazzi, Moira; Gardini, Stefano; Piana, Simonetta; Moscarella, Elvira; Lallas, Aimilios; Raucci, Margherita; Argenziano, Giuseppe; Pellacani, Giovanni
abstract

ND

2015 - Ex vivo fluorescence confocal microscopy of eccrine syringomatous carcinoma: A report of 2 cases [Articolo su rivista]
Longo, Caterina; Ragazzi, Moira; Gardini, Stefano; Moscarella, Elvira; Argenziano, Giuseppe
abstract

ND

2015 - Fordyce granules and hyperplastic mucosal sebaceous glands as distinctive stigmata in Muir-Torre syndrome patients: characterization with reflectance confocal microscopy [Articolo su rivista]
Ponti, Giovanni; Meschieri, Andrea; Pollio, Annamaria; Ruini, Cristel; Manfredini, Marco; Longo, Caterina; Mandel, Victor Desmond; Ciardo, Silvana; Tomasi, Aldo; Giannetti, Luca; Pellacani, Giovanni
abstract

Background: The Muir-Torre syndrome (MTS), a variant of Lynch syndrome (LS), is characterized by the presence of sebaceous skin adenomas and/or carcinomas and keratoacanthomas associated with visceral malignancies. Fordyce granules (FGs) are oral mucosal lesions previously found in association with LS. The aim of this study was to analyze the specific frequency of FGs in sporadic individuals and gene carriers patients with MTS of known mismatch repair genes mutations. The secondary aim was to characterize FGs by means of reflectance confocal microscopy (RCM). Methods: A total of 13 patients belonging to nine different genetically unrelated MTS kindreds (MLH1 gene mutation n = 2; MSH2 gene mutation n = 11) and 140 genetically unrelated healthy controls were examined. Depending on the clinical examination of the oral mucosa surface, subjects were categorized as either FGs positive or FGs negative. Results: FGs were diagnosed in 13 of 13 (100%) of MMR gene carriers patients with MTS vs. 9 of 140 (6.4%) controls. The most common site for FGs in MTS was the vestibular oral mucosa, compared with the gingival mandibular and retromandibular pad in controls. RCM examination found multiple sebaceous acinar cells that appear as round or oval hyper-refractive globules and that create a lobular aspects of the sebaceous glands defined as 'moruliform' or 'berry-like' structures. Conclusions: Clinical and RCM evidences of our study suggest that an activation of the sebaceous glands system occurs in patients with MTS. Fordyce granules and intra-oral sebaceous hyperplasia may constitute an additional clinical parameter, which may be adopted to distinguish individuals with highest likelihood of being affected from MTS.

2015 - Grading keratinocyte atypia in actinic keratosis: A correlation of reflectance confocal microscopy and histopathology [Articolo su rivista]
Pellacani, Giovanni; Ulrich, M.; Casari, A.; Prow, T. W.; Cannillo, F.; Benati, Elisa; Losi, A.; Cesinaro, A. M.; Longo, Caterina; Argenziano, Giuseppe; Soyer, H. P.
abstract

Grading keratinocyte atypia in actinic keratosis: A correlation of reflectance confocal microscopy and histopathology

2015 - Hypoxia-Inducible Factor-1α and CD271 inversely correlate with melanoma invasiveness [Articolo su rivista]
Marconi, Alessandra; Borroni, Riccardo Giovanni; Truzzi, Francesca; Longo, Caterina; Pistoni, Francesca; Pellacani, Giovanni; Pincelli, Carlo
abstract

Melanoma is characterized, among other features, by microenvironmental factors and by an altered apoptotic machinery. Melanoma cell response to a hypoxic environment is transcriptionally regulated by the Hypoxia-Inducible Factor (HIF)-1α. p75 neurotrophin receptor (p75(NTR) ), also called CD271, mediates apoptosis in several cell systems. The purpose of this study was to analyze the expression of HIF-1α and CD271 in melanomas at different phases of progression, as evaluated by histology and reflectance confocal microscopy (RCM). By RCM, 41.67% tumors were characterized by the presence of a population of dendritic and pleomorphic cells (D+P), corresponding to in situ melanoma; 25% exhibited a predominantly round-cell (RN) proliferation with histologic features of superficial melanoma, and 33.33% showed the presence of cells aggregated in nests (DN), typical of invasive melanoma. HIF-1α was scarcely detected in D+P and in RN melanomas, while it was highly expressed in DN tumors. By contrast, CD271 positive cells were mostly detected in D+P population, and barely observed in the other subtypes. This work demonstrates that CD271 expression inversely correlates with hypoxia in melanoma, and that the two markers may be used in the future as diagnostic/prognostic tools for this neoplasm.

2015 - In vivo confocal microscopic substrate of grey colour in melanosis [Articolo su rivista]
Cinotti, E; Couzan, C.; Perrot, J. L.; Habougit, C.; Labeille, B.; Cambazard, F.; Moscarella, E.; Kyrgidis, A.; Argenziano, Giuseppe; Pellacani, Giovanni; Longo, Caterina
abstract

confocal microscopy

2015 - In vivo detection of peripheral clefting in melanocytic lesions [Articolo su rivista]
Benati, E.; Zalaudek, I.; Piana, S.; Argenziano, Giuseppe; Moscarella, Elvira; Lallas, A.; Pellacani, Giovanni; Longo, Caterina
abstract

ND

2015 - Indice Glicemico e Carico Glicemico e rischio di melanoma in una popolazione della Emilia-Romagna. [Abstract in Atti di Convegno]
Malavolti, Marcella; Malagoli, Carlotta; Brighenti, F; Sieri, S; Krogh, V; Farnetani, Francesca; Longo, Caterina; Pellacani, Giovanni; Vinceti, Marco
abstract

.

2015 - Integration of reflectance confocal microscopy in sequential dermoscopy follow-up improves melanoma detection accuracy [Articolo su rivista]
Stanganelli, I.; Longo, Caterina; Mazzoni, Laura; Magi, S.; Medri, M.; Lanzanova, G.; Farnetani, Francesca; Pellacani, Giovanni
abstract

Background Successful treatment of melanoma depends on early diagnosis, but its varied clinical presentation means that no single noninvasive method or criterion can provide reliable detection in all cases. Objectives To determine whether combining sequential dermoscopy imaging with reflectance confocal microscopy (RCM) can improve melanoma detection and reduce the burden of unnecessary excisions. Methods We conducted a retrospective study with median follow-up of 25 months. We included equivocal pigmented lesions that lacked clear dermoscopy criteria for melanoma at baseline but were excised subsequently because of changes during digital monitoring. RCM imaging was performed before excision. Main melanoma dermoscopy features, seven-point checklist score at baseline, and changes in structure and/or colour, and development of new melanoma-specific criteria at follow-up (scored as major, moderate or minor) were considered. Main melanoma RCM criteria were evaluated and diagnosis was made. Histopathological diagnosis was the reference standard for defining parameter frequency and diagnostic accuracy. Results Seventy lesions were included. Major changes were more frequently correlated with melanoma diagnosis, although one-third (four of 12) of melanomas showed moderate or minor changes. Cytological atypia and architectural disarrangement on RCM were correlated with melanoma diagnosis. A correct melanoma diagnosis was achieved with RCM in almost all cases (11 of 12, 92%). Referring for excision only those lesions with RCM-positive features and/or presenting major changes at digital dermoscopy follow-up, theoretically 27 of 58 naevi could be saved from surgery. Conclusions Integration of RCM in the clinical and instrumental strategy for managing difficult pigmented lesions provided additional diagnostic information useful in the decision-making process.

2015 - Lichen planopilaris after imiquimod 5% cream for multiple BCC in basal cell naevus syndrome [Articolo su rivista]
Drummond, Alessandra; Pichler, Janine; Argenziano, Giuseppe; Zalaudek, Iris; Longo, Caterina; Lallas, Aimilios; Piana, Simonetta; Moscarella, Elvira
abstract

Basal cell naevus syndrome is an inherited autosomal dominant genetic disorder characterised by multiple basal cell carcinomas (BCC), skeletal, neurological and opthalmological abnormalities. The treatment of choice of the often multiple and large BCC consists of a combined approach including surgery, liquid nitrogen and other topical treatment modalities. Imiquimod 5% cream is an immune-response-modifying drug with antiviral and anti-tumour activity. Recent reports have associated the immune-stimulant properties of imiquimod with the exacerbation of several autoimmune skin diseases, such as eczema, psoriasis, vitiligo and lichenoid dermatitis. Here we report a patient with basal cell naevus syndrome who developed a lichen planopilaris on the same site of the scalp, which had been previously treated with two cycles of imiquimod for multiple BCC.

2015 - Likelihood of finding melanoma when removing a Spitzoid-looking lesion in patients aged 12 years or older [Articolo su rivista]
Lallas, Aimilios; Moscarella, Elvira; Longo, Caterina; Kyrgidis, Athanassios; de Mestier, Yuka; Vale, Gabrielle; Guida, Stefania; Pellacani, Giovanni; Argenziano, Giuseppe
abstract

Dermoscopy improves the recognition of melanoma and Spitz nevus but occasionally melanoma may exhibit a symmetric pattern mimicking Spitz nevus.

2015 - Melanoma and naevi with a globular pattern: confocal microscopy as an aid for diagnostic differentiation [Articolo su rivista]
Benati, Elisa; Argenziano, G.; Kyrgidis, A.; Moscarella, Elvira; Ciardo, S.; Bassoli, Sara; Farnetani, Francesca; Piana, S.; Cesinaro, A. M.; Lallas, A.; Borsari, Stefania; Pellacani, Giovanni; Longo, Caterina
abstract

Background Dermoscopically, one of the most common findings in melanocytic lesions is a globular pattern. A regular globular pattern is a common finding in naevi. Melanoma can also show a globular pattern, with globules typically irregular in size, colour and distribution. Objectives To investigate the likelihood of diagnosing melanoma according to distinct dermoscopic and confocal aspects. Methods Dermoscopic and confocal aspects of 83 excised melanocytic lesions dermoscopically showing globules were analysed. Results Our study population included 39 acquired melanocytic naevi, 16 Spitz naevi and 28 melanomas. Univariate analysis showed that regular distribution of globules on dermoscopy is associated with a ninefold lower risk for melanoma, whereas an irregular distribution is associated with an almost 10-fold increased risk for melanoma. Concerning confocal features, dense nests are associated with a fivefold lower risk for melanoma, whereas loosely arranged nests are associated with an almost sixfold risk for melanoma; moreover, the presence of round cells is associated with a 17-fold lower risk for melanoma, whereas pleomorphic cells are associated with an almost 16-fold risk for melanoma. Conclusions So that melanoma is not missed, clinicians should carefully analyse globular lesions in adults, focusing, in particular, on the distribution of globules and on the presence of confocal cytological atypia.

2015 - Morphological features of naevoid melanoma: Results of a multicentre study of the International Dermoscopy Society [Articolo su rivista]
Longo, Caterina; Piana, S.; Marghoob, A.; Cavicchini, S.; Rubegni, P.; Cota, C.; Ferrara, G.; Cesinaro, A. M.; Baade, A.; Bencini, P. L.; Mantoux, F.; Mijuskovic, Z. P.; Pizzichetta, M. A.; Stanganelli, I.; Carrera, C.; Giovene, G. L.; Ranasinghe, S.; Zalaudek, I.; Lallas, A.; Moscarella, Elvira; Specchio, F.; Pepe, Patrizia; Pellacani, Giovanni; Argenziano, Giuseppe
abstract

Background Naevoid melanoma (NeM), a rare variant of melanoma, can be difficult to detect as its clinical and histopathological morphology can simulate a naevus. Objectives To describe the clinical and dermoscopic features associated with NeM. Methods Lesions with a histopathological diagnosis of NeM were collected via an e-mail request sent to all members of the International Dermoscopy Society. All lesions were histopathologically reviewed and only lesions fulfilling a set of predefined histopathological criteria were included in the study and analysed for their clinical and dermoscopic features. Results Twenty-seven of 58 cases (47%) fulfilled the predefined histopathological criteria for NeM and were included in the study. Clinically, 16 of the 27 NeMs presented as a nodular lesion (59%), eight (30%) as plaque type and three (11%) as papular. Analysis of the global dermoscopic pattern identified three types of NeM. The first were naevus-like tumours (n = 13, 48%), typified by a papillomatous surface resembling a dermal naevus. In these lesions local dermoscopic features included irregular dots/globules (46%), multiple milia-like cysts (38%) and atypical vascular structures (46%). The second type were amelanotic tumours (n = 8, 30%), typified by an atypical vascular pattern (75%). The third type consisted of tumours displaying a multicomponent pattern (n = 4, 15%), characterized by classical local melanoma-specific criteria. Two lesions (7%) were classified as mixed-pattern tumours as they did not manifest any of the aforementioned patterns. Conclusions While NeMs may be clinically difficult to differentiate from naevi, any papillomatous lesion displaying dermoscopically atypical vessels and/or irregular dots/globules should prompt consideration for the possible diagnosis of NeM. What's already known about this topic? Naevoid melanoma is a rare variant of melanoma, and can be difficult to detect as its clinical and histopathological morphology can simulate a naevus. What does this study add? This study provides new insights into the clinical and dermoscopic morphology of naevoid melanoma, facilitating its clinical recognition.

2015 - Non-invasive, investigative methods in skin aging [Articolo su rivista]
Longo, Caterina; Ciardo, S.; Pellacani, Giovanni
abstract

A precise and noninvasive quantiication of aging is of outmost importance for in vivo assessment of the skin aging "stage", and thus acts to minimize it. Several bioengineering methods have been proposed to objectively, precisely, and non-invasively measure skin aging, and to detect early skin damage, that is sub-clinically observable. In this review we have described the most relevant methods that have emerged from recently introduced technologies, aiming at quantitatively assessing the effects of aging on the skin.

2015 - Orange color: A dermoscopic clue for the diagnosis of granulomatous skin diseases [Articolo su rivista]
Bombonato, Caterina; Argenziano, Giuseppe; Lallas, Aimilios; Moscarella, Elvira; Ragazzi, Moira; Longo, Caterina
abstract

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2015 - Practical Clues to recognize Melanoma incognito [Poster]
Farnetani, Francesca; Coco, Valeria; Manfredini, Marco; Mandel, Victor Desmond; Guida, Stefania; Peris, Ketty; Pellacani, Giovanni; Longo, Caterina
abstract

Introduction &amp; Objectives: To avoid missing melanoma, the current practice is to biopsy all lesions that are suspicious based on clinical and dermoscopic ground. Although most cases of melanoma exhibit clinical clues leading to the correct diagnosis, melanoma can mimic benign melanocytic and non-melanocytic lesions. Confocal microscopy has been shown to increase the diagnostic accuracy for melanoma diagnosis, but little is known about its ability to detect melanoma in the context of lesions that appear dermoscopically benign. Materials &amp; Methods: We present 10 difficult-to-diagnose melanomas, in which additional clues provided by confocal microscopy increased the index of suspicion and prompt us to perform an excisional biopsy. Results: Our cases highlight the following 3 management rules. Confocal microscopy should be used: 1) in newly appearing lesions in high-risk patients; 2) lesions referred by the patient himself as growing lesions even if they are clinically banal 3) Biopsy lesions with unspecific confocal pattern that does not permit to classify the lesion as clear-cut benign. Conclusions: Our case series highlight that melanoma diagnosis is a complex process in which several factors such as patient-related information, clinical history, dermoscopic and confocal features along with “gut” feelings may influence patient’s management. Confocal microscopy in conjunction with dermoscopy can increase the index of suggestion to perform biopsy in difficult-to-diagnose melanomas.

2015 - Reasons for excision of skin tumors: A one-year prospective study in a tertiary skin cancer unit [Articolo su rivista]
Lallas, Aimilios; Longo, Caterina; Moscarella, Elvira; Lombardi, Mara; Specchio, Francesca; Raucci, Margherita; Zalaudek, Iris; Argenziano, Giuseppe
abstract

Background: Biopsies and surgical excisions represent routine procedures in clinical settings dealing with skin cancer. Objective: To evaluate the impact of clinical examination, dermoscopy, reflectance confocal microscopy and digital monitoring on the decision to excise or biopsy a lesion in routine practice. Methods: Patients scheduled for biopsy or excision of a skin lesion were prospectively enrolled. The expert dermatologist was asked to select the main factor that prompted him/her to excise or biopsy the lesion. Results: The most common reason for melanoma excision was clinical and dermoscopic morphology (70.3%), followed by dermoscopy (11.4%), monitoring (8.9%) and clinical context (8.2%). Most basal and squamous cell carcinomas were recognized both clinically and dermoscopically, while 18.6 and 15.0%, respectively, could only be detected with dermoscopic examination. Conclusion: Each part of the clinical examination has a contributory role in the diagnosis of melanoma and other skin cancers.

2015 - Reflectance confocal microscopy [Capitolo/Saggio]
Longo, Caterina; Pellacani, Giovanni
abstract

Reflectance confocal microscopy

2015 - Reflectance confocal microscopy correlates of dermoscopic patterns of facial lesions help to discriminate lentigo maligna from pigmented nonmelanocytic macules [Articolo su rivista]
De Carvalho, N.; Farnetani, Francesca; Ciardo, S.; Ruini, Cristel; Witkowski, Alexander Michael; Longo, Caterina; Argenziano, Giuseppe; Pellacani, Giovanni
abstract

Background The clinical recognition of lentigo maligna (LM) and LM melanoma can be very challenging due to the overlapping features it shares with other pigmented macules of the skin. Noninvasive diagnostic techniques can assist in the differential diagnosis. Objectives To identify reflectance confocal microscopy (RCM) indicators for LM through the identification of in vivo microscopic substrates of the main dermoscopic features seen in flat pigmented lesions of the face. Methods Retrospective analysis of 60 pigmented lesions (LM, invasive melanoma, solar lentigo/flat seborrhoeic keratosis, lichen planus-like keratosis, pigmented actinic keratosis) was carried out. The main dermoscopic patterns and RCM features were described. A new method for correlating RCM with dermoscopic patterns was developed. Results Pseudonetwork (37 of 60 lesions) and annular granular structures (37 of 60 lesions) were the most frequent dermoscopic patterns, followed by pigmented blotches (27 of 60 lesions). Upon RCM examination, pseudonetwork and blotches differed in melanomas and other nonmelanocytic lesions. These differences included the intraepidermal proliferation of atypical cells (predominantly dendritic-shaped with adnexal tropism) and the presence of a meshwork pattern at the junction. Also, annular granular structures exhibited dendritic cells almost exclusively in melanoma, with no difference between melanomas and nonmelanocytic lesions for the junctional and upper dermal pattern (characterized by dermal inflammation). Fingerprinting was mostly present in nonmelanocytic lesions or corresponded to an overlap with solar lentigo in melanomas. Conclusions RCM is useful for identifying the histological substrate of dermoscopic features in pigmented lesions of the face. It can provide a better definition of the lesion areas, enabling an improved diagnostic approach. What's already known about this topic? The clinical diagnosis of facial pigmented lesions can be challenging because of the overlapping features of benign and malignant entities. Dermoscopy and reflectance confocal microscopy (RCM) can assist in the diagnostic process. What does this study add? This article provides an original perspective regarding the role of dermoscopy and RCM in the diagnosis of facial malignant lesions. RCM can be used to assess appropriate treatment options and follow-up protocols for facial lesions.

2015 - Reflectance confocal microscopy for plaque psoriasis therapeutic follow-up during an anti-TNF-α monoclonal antibody: An observational multicenter study [Articolo su rivista]
Ardigò, M; Agozzino, M.; Longo, Caterina; Lallas, A.; Di Lernia, V.; Fabiano, A.; Conti, A.; Sperduti, I.; Argenziano, Giuseppe; Berardesca, E.; Pellacani, Giovanni
abstract

ND

2015 - Reflectance confocal microscopy in the diagnosis of solitary pink skin tumours: Review of diagnostic clues [Articolo su rivista]
Longo, Caterina; Moscarella, Elvira; Argenziano, Giuseppe; Lallas, A.; Raucci, M.; Pellacani, Giovanni; Scope, Alon
abstract

Reflectance confocal microscopy (RCM) is a noninvasive tool that can be helpful in the diagnosis of nonpigmented skin tumours. As RCM enables visualization of architectural and cytological structures at near-histological resolution, it can improve the diagnostic accuracy of dermoscopically equivocal solitary pink neoplasms. For management decisions, it is important to identify specific morphological clues that allow bedside classification of nonpigmented skin neoplasms into benign vs. malignant and melanocytic vs. nonmelanocytic. More specifically, the presence of a nested melanocytic proliferation at the dermoepidermal junction or dermis level permits the clinician to ascribe a given lesion as melanocytic; the identification of basaloid bright tumour islands is a key RCM feature for the diagnosis of basal cell carcinoma; and the presence of disarrayed epidermis along with small demarcated papillae is suggestive for the diagnosis of squamous cell carcinoma. The present review offers a comprehensive description of the main RCM diagnostic clues for solitary pink neoplasms that direct clinicians to the correct diagnosis and that may serve as groundwork for future prospective studies. What's already known about this topic? Solitary pink tumours represent a diagnostic challenge for clinicians as they often reveal subtle clinical and dermoscopic features. Reflectance confocal microscopy (RCM) has been shown to improve the accuracy of diagnosis of amelanotic melanoma and basal cell carcinoma. What does this study add? This review describes the criteria for RCM diagnosis of neoplasms that present as solitary pink lesions. This descriptive information may facilitate the formulation of prospective studies testing RCM-based diagnosis of amelanotic neoplasms.

2015 - Regressive scalp lesions: Dermoscopic and confocal clues [Articolo su rivista]
Buçard, Alice Mota; Marques Da Costa, Juliana; Argenziano, Giuseppe; Moscarella, Elvira; Specchio, Francesca; Longo, Caterina
abstract

ND

2015 - Routine clinical-pathologic correlation of pigmented skin tumors can influence patient management [Articolo su rivista]
Longo, Caterina; Piana, Simonetta; Lallas, Aimilios; Moscarella, Elvira; Lombardi, Mara; Raucci, Margherita; Pellacani, Giovanni; Argenziano, Giuseppe
abstract

Routine clinical-pathologic correlation of pigmented skin tumors can influence patient management

2015 - Skin Cancer Diagnosis With Reflectance Confocal Microscopy: Reproducibility of Feature Recognition and Accuracy of Diagnosis [Articolo su rivista]
Farnetani, Francesca; Scope, Alon; Braun, Ralph P; Gonzalez, Salvador; Guitera, Pascale; Malvehy, Josep; Manfredini, Marco; Marghoob, Ashfaq A; Moscarella, Elvira; Oliviero, Margaret; Puig, Susana; Rabinovitz, Harold S; Stanganelli, Ignazio; Longo, Caterina; Malagoli, Carlotta; Vinceti, Marco; Pellacani, Giovanni
abstract

IMPORTANCE: Reflectance confocal microscopy (RCM) studies have been performed to identify criteria for diagnosis of skin neoplasms. However, RCM-based diagnosis is operator dependent. Hence, reproducibility of RCM criteria needs to be tested. OBJECTIVE: To test interobserver reproducibility of recognition of previously published RCM descriptors and accuracy of RCM-based skin cancer diagnosis. DESIGN, SETTING, AND PARTICIPANTS: Observational retrospectiveweb-based study of a set of RCM images collected at a tertiary academic medical center. Nine dermatologists (6 of whom had ≥3 years of RCM experience) from 6 countries evaluated an RCM study set from 100 biopsy-proven lesions, including 55 melanocytic nevi, 20 melanomas, 15 basal cell carcinomas, 7 solar lentigines or seborrheic keratoses, and 3 actinic keratoses. Between June 15, 2010, and October 21, 2010, participanting dermatologists, blinded to histopathological diagnosis, evaluated 3 RCM mosaic images per lesion for the presence of predefined RCM descriptors. MAIN OUTCOMES AND MEASURES: The main outcomewas identification of RCM descriptors with fair to good interrater agreement (κ statistic ≥0.3) and independent correlation with malignant vs benign diagnosis on discriminant analysis. Additional measures included sensitivity and specificity for diagnosis of malignant vs benign for each evaluator, for majority diagnosis (rendered by ≥5 of 9 evaluators), and for experienced vs recent RCM users. RESULTS: Eight RCM descriptors showed fair to good reproducibility and were independently associated with a specific diagnosis. Of these, the presence of pagetoid cells, atypical cells at the dermal-epidermal junction, and irregular epidermal architecture were associated with melanoma. Aspecific junctional pattern, basaloid cords, and ulceration were associated with basal cell carcinomas. Ringed junctional pattern and dermal nests were associated with nevi. The mean sensitivity for the group of evaluators was 88.9% (range, 82.9%-100%), and the mean specificity was 79.3%(range, 69.2%-90.8%). Majority diagnosis showed sensitivity of 100% and specificity of 80.0%. Sensitivity was higher for experienced vs recent RCM users (91.0% vs 84.8%), but specificity was similar (80.0%vs 77.9%). CONCLUSIONS AND RELEVANCE: The study highlights key RCM diagnostic criteria for melanoma and basal cell carcinoma that are reproducibly recognized among RCM users. Diagnostic accuracy increases with experience. The higher accuracy of majority diagnosis suggests that there is intrinsically more diagnostic information in RCM images than is currently used by individual evaluators.

2015 - Tape stripping: A very short-term follow-up procedure for suspicious black lesions [Articolo su rivista]
Babino, Graziella; Specchio, Francesca; Lallas, Aimilios; Longo, Caterina; Moscarella, Elvira; Argenziano, Giuseppe
abstract

ND

2015 - The BRAAFF checklist: A new dermoscopic algorithm for diagnosing acral melanoma [Articolo su rivista]
Lallas, A; Kyrgidis, A.; Koga, H.; Moscarella, Elvira; Tschandl, P.; Apalla, Z.; Di Stefani, A.; Ioannides, D.; Kittler, H.; Kobayashi, K.; Lazaridou, E.; Longo, Caterina; Phan, A.; Saida, T.; Tanaka, M.; Thomas, L.; Zalaudek, I.; Argenziano, Giuseppe
abstract

Background The parallel ridge pattern (PRP) is considered the dermoscopic hallmark of acral melanoma (AM). However, it was recently shown that approximately one-third of AMs do not display a PRP dermoscopically, rendering their detection more troublesome. Objectives To investigate the diagnostic accuracy of dermoscopic criteria for the diagnosis of AM. Methods Dermoscopic images of consecutive cases of histopathologically diagnosed AMs and acral naevi with histopathological diagnosis or with at least 1 year of follow-up were evaluated by three independent investigators for the presence of predefined criteria. Crude and adjusted odds ratios and their corresponding 95% confidence intervals were calculated by univariate and multivariate logistic regression, respectively. Receiver operating characteristic curves were used to choose among competing classification schemes. Results In total 603 lesions (472 naevi and 131 AMs) were included in the study. A scoring system (named BRAAFF) composed of six variables was associated with optimal area under the curve and sensitivity for the diagnosis of AM. This method includes four positive (irregular blotches, ridge pattern, asymmetry of structures and asymmetry of colours) and two negative predictors (furrow pattern and fibrillar pattern). Conclusions The BRAAFF checklist significantly improves the diagnostic accuracy of dermoscopy for the diagnosis of AM.

2015 - The clinical and dermoscopic features of invasive cutaneous squamous cell carcinoma depend on the histopathological grade of differentiation [Articolo su rivista]
Lallas, A; Pyne, J.; Kyrgidis, A.; Andreani, S.; Argenziano, Giuseppe; Cavaller, A.; Giacomel, J.; Longo, Caterina; Malvestiti, A.; Moscarella, Elvira; Piana, S.; Specchio, F.; Hofmann Wellenhof, R.; Zalaudek, I.
abstract

Background Little is known about the variability of the dermoscopic criteria of squamous cell carcinoma (SCC) according to the histopathological differentiation grade. Objectives To evaluate whether specific dermoscopic criteria can predict the diagnosis of poorly differentiated SCC compared with well- and moderately differentiated SCC. Methods Clinical and dermoscopic images of SCCs were retrospectively evaluated for the presence of predefined criteria. Univariate and adjusted odds ratios were calculated. Discriminant functions were used to plot receiver-operator characteristic curves. Results Of 143 SCCs included, 48 (33·5%) were well differentiated, 45 (31·5%) were moderately differentiated and 50 (35·0%) were poorly differentiated. Flat tumours had a fourfold increased probability of being poorly differentiated. Dermoscopically, the presence of a predominantly red colour posed a 13-fold possibility of poor differentiation, whereas a predominantly white and white-yellow colour decreased the odds of poorly differentiated SCC by 97% each. The presence of vessels in more than 50% of the tumour's surface, a diffuse distribution of vessels and bleeding were significantly associated with poor differentiation, while scale/keratin was a potent predictor of well- or moderately differentiated tumours. Conclusions Dermoscopy may be regarded as a reliable preoperative tool to distinguish poorly from well- and moderately differentiated SCC. Given that poor differentiation of SCC represents an independent risk factor for recurrence, metastasis and disease-specific death, identifying poorly differentiated tumours in vivo may enhance their appropriate management. What's already known about this topic? While the dermoscopic criteria of squamous cell carcinoma (SCC) have been well described, little is currently known about the variability of these criteria with respect to the histopathological grade of differentiation in SCC. What does this study add? Poorly differentiated SCC is dermoscopically typified by a predominantly red colour, attributed to the presence of bleeding and/or dense vascularity. Identifying poorly differentiated tumours in vivo may enhance their appropriate management.

2015 - The dermoscopic variability of dermatofibromas [Articolo su rivista]
Espasandín Arias, Martina; Moscarella, Elvira; Mota Buçard, Alice; Moreno Moreno, Claudia; Lallas, Aimilios; Longo, Caterina; Argenziano, Giuseppe
abstract

ND

2015 - The stars within the melanocytic garden: Unusual variants of Spitz naevi [Articolo su rivista]
Moscarella, Elvira; AL JALBOUT, Samer; Piana, S.; Argenziano, Giuseppe; Lallas, A.; Longo, Caterina; Hofmann Wellenhof, R.; Zalaudek, I.
abstract

Background Spitz naevi may present a wide spectrum of morphologies. Histopathologically, many variants, including desmoplastic, angiomatoid, verrucous/polypoid, plexiform, pagetoid, halo, myxoid, granulomatous and tubular Spitz naevi have been described. Clinical and dermoscopic features of these unusual variants of Spitz naevi have been reported only rarely. Objectives The aim of this study is to describe clinical, dermoscopic and histopathological features of uncommon morphological variants of Spitz naevi in order to raise awareness among clinicians about their peculiar patterns of presentation. Methods We searched our image database retrospectively from 2004 to 2014 for images of excised tumours using Spitz/Reed naevus as a keyword. Results A total of 307 excised skin lesions with a histopathological diagnosis of Spitz/Reed naevus were found. Among those we identified 13 uncommon variants of Spitz naevi including six cases of desmoplastic Spitz naevus, five cases of angiomatoid Spitz naevus and two cases of verrucous Spitz naevus. These lesions did not fulfil the already described dermoscopic criteria of Spitz naevi, with the exception of angiomatoid Spitz naevi, exhibiting a pinkish background and dotted vessels in dermoscopy. Desmoplastic Spitz naevi may be difficult to differentiate from dermatofibroma clinically, and from melanoma under dermoscopic examination. Verrucous Spitz naevi, despite their relatively unusual clinical features, show reassuring morphological clues histologically, which allows the differential diagnosis from an atypical spitzoid tumour. Conclusions In all cases an atypical melanocytic lesion could not be excluded under dermoscopy, thus warranting excision and histopathological examination. What's already known about this topic? Spitz naevi may present a wide spectrum of morphologies. Clinical and dermoscopic features of unusual variants of Spitz naevi have been reported only rarely. What does this study add? We describe clinical, dermoscopic and histopathological features of uncommon morphological variants of Spitz naevi, in order to raise awareness among clinicians about their peculiar patterns of presentation.

2015 - Twin melanomas [Articolo su rivista]
Marchetti Cautela, Jennifer; Moscarella, Elvira; Lallas, Aimilios; Longo, Caterina; Piana, Simonetta; Argenziano, Giuseppe
abstract

ND

2015 - Update on non-invasive imaging techniques in early diagnosis of non-melanoma skin cancer [Articolo su rivista]
Reggiani, Camilla; Manfredini, Marco; Mandel, Victor Desmond; Farnetani, Francesca; Ciardo, Silvana; Bassoli, Sara; Casari, Alice; Guida, Stefania; Argenziano, Giuseppe; Lallas, Aimilios; Ulrich, Martina; Pellacani, Giovanni; Longo, Caterina
abstract

Non-melanoma skin cancer (NMSC) is the most common malignancy in fair skinned populations. Dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) are non-invasive imaging techniques that play an important role in diagnosis of skin tumors. The aim of this study was to provide new insights into the role of non-invasive tecniques in the diagnosis of non-melanoma skin cancers, concentrating especially on dermoscopy, RCM and OCT. The analysis of the studies obtained from the most recent literature, taking into account previous essential reported information in this field. A search concerning the role of dermoscopy, RCM and OCT in the diagnosis of NMSC was performed on PubMed. Exclusion criteria: duplicated studies, single case report, and papers with language other than English New and old literature about early diagnosis of NMSC through non-invasive imaging techniques were analyzed. The role and the diagnostic accuracy of dermoscopy, RCM and OCT for the diagnosis of NMSC were reported according to the data given by literature. The development of non-invasive diagnostic devices (especially dermoscopy, RCM and OCT) allows tissue imaging in-vivo contributing to a more accurate diagnosis of skin cancer, sparing time for the patient and costs for the public health system.

2015 - Update on the use of confocal microscopy in Melanoma and non-Melanoma skin cancer [Articolo su rivista]
Guida, Stefania; Longo, Caterina; Casari, Alice; Ciardo, Silvia; Manfredini, Marco; Reggiani, Camilla; Pellacani, Giovanni; Farnetani, Francesca
abstract

Reflectance confocal microscopy (RCM) is a new technique enabling the visualization of the skin at a quasi-histological resolution, allowing the identification of clues for the diagnosis of skin diseases. The aim of this analysis was to provide new insights into the role of RCM in the diagnosis of skin cancers. Data comes from the most recent literature, taking into account previous essential reported information in this field. The study eligibility criteria were: studies providing update information, focusing on RCM findings in melanoma and non-melanoma skin cancers (NMSC), without restrictions for age, sex, ethnicity. Duplicated studies and single case report were excluded from this study. A search concerning the role of RCM in melanoma and NMSC was performed on the Medline. RCM clues were analyzed for different skin cancers, in particular melanoma and NMSC, in association with clinical, dermoscopic and histopathologic findings. Diagnostic accuracy, sensibility and specificity of the technique were reviewed. Furthermore, some new findings have been described and recent applications have been discussed. The selection of articles was limited in order to provide an up-to-date revision. In conclusion, several RCM features were implemented for the diagnosis of melanoma and NMSC, leading to a confocal-based classification in most cases.

2015 - When a clinical-dermoscopic correlation is warranted [Articolo su rivista]
Marques Da Costa, Juliana; Buçard, Alice Mota; Piana, Simonetta; Moscarella, Elvira; Argenziano, Giuseppe; Longo, Caterina
abstract

ND

2015 - When the 'Ugly Duckling' Loses Brothers, It Becomes the 'Only Son of a Widowed Mother' [Articolo su rivista]
Borsari, Stefania; Longo, Caterina; Piana, Simonetta; Moscarella, Elvira; Lallas, Aimilios; Alfano, Roberto; Argenziano, Giuseppe
abstract

ND

2014 - A worrisome sudden change: Targetoid hemosiderotic nevus [Articolo su rivista]
Raucci, Margherita; Argenziano, Giuseppe; Zalaudek, Iris; Lallas, Aimilios; Longo, Caterina; Moscarella, Elvira
abstract

ND

2014 - Accuracy of dermoscopic criteria for discriminating superficial from other subtypes of basal cell carcinoma [Articolo su rivista]
Lallas, Aimilios; Tzellos, Thrassivoulos; Kyrgidis, Athanasios; Apalla, Zoe; Zalaudek, Iris; Karatolias, Athanasios; Ferrara, Gerardo; Piana, Simonetta; Longo, Caterina; Moscarella, Elvira; Stratigos, Alexander; Argenziano, Giuseppe
abstract

Background The management of basal cell carcinoma (BCC) depends, among other factors, on its histopathologic subtype. Although dermoscopic criteria of BCC have been investigated, the possible role of dermoscopy in predicting the tumor subtype remains unclear. Objectives We sought to assess the diagnostic accuracy of dermoscopic criteria for differentiating superficial BCC (sBCC) from other BCC subtypes. Methods Dermoscopic images of histopathologically confirmed BCCs were retrospectively evaluated for the presence of predefined criteria. Univariate and adjusted odds ratios were calculated. Discriminant functions were used to plot receiver operating characteristic curves. Results In all, 77 sBCCs and 258 non-sBCCs were included. Maple leaf-like areas, short fine superficial telangiectasia, multiple small erosions, and shiny white-red structureless areas were potent predictors of sBCC, each making its diagnosis over 5-fold more likely. Conversely, the presence of arborizing vessels, blue-gray ovoid nests, and ulceration gave 11-fold, 15-fold, and 3-fold increased possibility for the diagnosis of non-sBCCs, respectively. Based on the results of the multivariate analysis, we propose a diagnostic algorithm that can predict the diagnosis of sBCC with a sensitivity of 81.9% and a specificity of 81.8%. Limitations The retrospective design and the inclusion of only Caucasian patients are limitations. Conclusion Dermoscopy is reliable in differentiating sBCC from other BCC subtypes. © 2013 by the American Academy of Dermatology, Inc.

2014 - Aspect en dermatoscopie et en microscopie confocale par réflectance d'un mélanome en thèques du sujet âgé [Articolo su rivista]
Casari, Alice; Cinotti, E.; Cesinaro, A. M.; Pellacani, Giovanni; Longo, Caterina
abstract

Background.-We report a case of a nested melanoma of the elderly, a recently describedentity, and we describe its aspect under confocal reflectance microscopy.Patients and methods.-A 70-year-old woman presented a pigmented lesion of the left legmeasuring 2 × 2.5 cm in diameter which was increasing in size. Dermatoscopic examinationshowed a predominantly globular pattern, with globules of irregular color and distribution.Reflectance confocal microscopy revealed the presence of dense nests at the dermo-epidermaljunction with cytologic atypia and pagetoid cells. The histological appearance was overlappingand a diagnosis of nested melanoma of the elderly was made.Comments.-The presence in an older subject of a large pigmented lesion with an irregularglobular pattern should be suspected of nested melanoma of the elderly. Reflectance confocalmicroscopy may be useful in the case of such difficult lesions to proceed with more confidenceto surgical excision.

2014 - Assessment of SIAscopy in the triage of suspicious skin tumours [Articolo su rivista]
Sgouros, D; Lallas, A.; Julian, Y.; Rigopoulos, D.; Zalaudek, I.; Longo, Caterina; Moscarella, Elvira; Simonetti, V.; Argenziano, Giuseppe
abstract

Background/purpose: Spectrophotometric Intracutaneous Analysis (SIAscopy) is a non-invasive, computerized technique for the diagnosis of pigmented skin tumours. The analysis is based on the evaluation of skin chromophores, i.e. melanin, haemoglobin and collagen within the epidermis and papillary dermis. Our aim was to assess the diagnostic validity of SIAscopy in the detection of melanoma and non-melanoma skin cancers compared to the clinical-dermoscopic diagnosis and the histopathologic results of the excised lesions. Methods: In total, 188 lesions of 180 patients were examined by dermoscopy and SIAscopy. A SIAscopy scoring system was first compared with the clinical-dermoscopic diagnosis and then with the histopathologic diagnosis of the excised lesions. Results: With respect to the clinical-dermoscopic evaluation, SIAscopy had sensitivity and specificity values of 85.7% and 65.4% respectively. Of the 188 evaluated lesions, 44 were excised with histopathologic examination revealing 31 malignant tumours, including 18 melanomas. With respect to histopathology SIAscopy had a sensitivity of 83.9%. Seven of the 13 benign excised lesions were scored as malignant by SIAscopy resulting in a specificity of 46.1%. Conclusion: SIAscopy cannot replace the standard of care in skin cancer diagnosis, which includes clinical and dermoscopic examination. However, considering that the technique does not require specific training and expertise, it might represent an additional, relatively cost-effective tool to select lesions for referral.

2014 - Atypical Spitz tumours and sentinel lymph node biopsy: A systematic review [Articolo su rivista]
Lallas, Aimilios; Kyrgidis, Athanassios; Ferrara, Gerardo; Kittler, Harald; Apalla, Zoe; Castagnetti, Fabio; Longo, Caterina; Moscarella, Elvira; Piana, Simonetta; Zalaudek, Iris; Argenziano, Giuseppe
abstract

Sentinel lymph node biopsy has been proposed as a diagnostic method for estimation of the malignant potential of atypical Spitz tumours. However, although cell deposits are commonly detected in the sentinel lymph nodes of patients with atypical Spitz tumours, their prognosis is substantially better than that of patients with melanoma and positive sentinel lymph node biopsies. We did a systematic review of published reports to assess the role of sentinel lymph node biopsy as a prognostic method in the management of atypical Spitz tumours. The results of our analysis did not show any prognostic benefit of sentinel lymph node biopsy; having a positive sentinel lymph node does not seem to predict a poorer outcome for patients with atypical Spitz tumours. These findings indicate that, especially in the paediatric population, it might be prudent initially to use complete excision with clear margins and careful clinical follow-up in patients with atypical Spitz tumours. © 2014 Elsevier Ltd.

2014 - Classifying distinct basal cell carcinoma subtype by means of dermatoscopy and reflectance confocal microscopy [Articolo su rivista]
Longo, Caterina; Lallas, Aimilios; Kyrgidis, Athanassios; Rabinovitz, Harold; Moscarella, Elvira; Ciardo, Silvana; Zalaudek, Iris; Oliviero, Margaret; Losi, Amanda; Gonzalez, Salvador; Guitera, Pascale; Piana, Simonetta; Argenziano, Giuseppe; Pellacani, Giovanni
abstract

Background: The current guidelines for the management of basal cell carcinoma (BCC) suggest a different therapeutic approach according to histopathologic subtype. Although dermatoscopic and confocal criteria of BCC have been investigated, no specific studies were performed to evaluate the distinct reflectance confocal microscopy (RCM) aspects of BCC subtypes. Objectives: To define the specific dermatoscopic and confocal criteria for delineating differentBCCsubtypes. Methods: Dermatoscopic and confocal images of histopathologically confirmed BCCs were retrospectively evaluated for the presence of predefined criteria. Frequencies of dermatoscopic and confocal parameters are provided. Univariate and adjusted odds ratios were calculated. Discriminant analyses were performed to define the independent confocal criteria for distinct BCC subtypes. Results: Eighty-eight BCCs were included. Dermatoscopically, superficial BCCs (n = 44) were primarily typified by the presence of fine telangiectasia, multiple erosions, leaf-like structures, and revealed cords connected to the epidermis and epidermal streaming upon RCM. Nodular BCCs (n = 22) featured the classic dermatoscopic features and well outlined large basaloid islands upon RCM. Infiltrative BCCs (n = 22) featured structureless, shiny red areas, fine telangiectasia, and arborizing vessels on dermatoscopy and dark silhouettes upon RCM. Limitations: The retrospective design. Conclusion: Dermatoscopy and confocal microscopy can reliably classify different BCC subtypes. ( JAmAcad Dermatol 2014;71:716-24.).

2014 - Clonal seborrheic keratosis: Dermoscopic and confocal microscopy characterization [Articolo su rivista]
Longo, C.; Zalaudek, I.; Moscarella, E.; Lallas, A.; Piana, S.; Pellacani, G.; Argenziano, G.
abstract

Background The diagnosis of clonal seborrheic keratosis may be challenging clinically and histologically.Objective In our study, we describe the common aspects of this benign entity that show peculiar dermoscopic and confocal findings.Methods A total of nine clonal seborrheic keratosis were analyzed. Results Upon dermoscopy, it reveals the presence of globular-like structures and sharply demarcated borders whereas confocal microscopy displays the typical intraepidermal nesting of pigmented keratinocytes that permits to have a reliable in vivo diagnosis.Conclusions Dermoscopy and confocal microscopy permit to in vivo diagnose this variant of seborrheic keratosis.

2014 - Collision tumor of melanoma and atypical fibroxanthoma of the scalp [Articolo su rivista]
Specchio, Francesca; Argenziano, Giuseppe; Zalaudek, Iris; Guardoli, Davide Vincenzo; Longo, Caterina; Moscarella, Elvira; Piana, Simonetta; Lallas, Aimilios
abstract

Several combinations of different skin tumors occuring one adjacent to the other or even in a single lesion have been described up to date. Collision tumors involving atypical fibroxanthoma and melanoma are extremely uncommon. Herein we present a case of melanoma associated with AFX and discuss on the usefulness of dermoscopy in the clinical diagnosis of collision tumors.

2014 - Confocal microscopy: A new era in understanding the pathophysiologic background of inflammatory skin diseases [Articolo su rivista]
Moscarella, E.; Argenziano, G.; Lallas, A.; Pellacani, G.; Longo, C.
abstract

One of the emerging and intriguing applications of reflectance confocal microscopy is the evaluation of 'dynamic' processes of the skin that cannot be otherwise analysed using histopathology that offers a picture of the tissue at one time point. This is nicely illustrated by recent article by Wolberink et al. in the current issue of Exp Dermatol, in which the Authors evaluated patterns and time interval of polymorphonuclear neutrophil (PMN) migration in psoriatic plaques by means of reflectance confocal microscopy (RCM). This example underscores that a new era of confocal microscopy is starting, which promises to reveal a dynamic in vivo understanding of the pathophysiology of human skin diseases. © 2014 John Wiley &amp; Sons A/S. Published by John Wiley &amp; Sons Ltd.

2014 - Dermoscopic nevus patterns in skin of colour: a prospective, cross-sectional, morphological study in individuals with skin type V and VI [Articolo su rivista]
Lallas, A.; Reggiani, C.; ARGENZIANO, GIUSEPPE; Kyrgidis, A.; Bakos, R.; Masiero, N. C. M. S.; Scheibe, A. B.; Cabo, H.; Ozdemir, F.; Sortino Rachou, A. M.; Turk, B. Gerceker; MOSCARELLA, ELVIRA; LONGO, Caterina; Zalaudek, I.
abstract

Background: Most of the knowledge on the prevailing dermoscopic patterns of acquired melanocytic nevi (AMV) is based on studies in Caucasians, while little research focuses on the dermoscopic variability in nevi in skin of colour. Objective: To analyse the prevalent dermoscopic nevus patterns in subjects with a skin type (ST) V and VI. Methods: Prospective, cross-sectional, morphological study was conducted in six clinics with enrolment of consecutive individuals with a ST V or VI. Digital dermoscopic images of selected representative AMN were assessed for dermoscopic colours, morphological patterns and pigment distribution. Results: Analysis of 300 nevi from subjects with ST V and VI revealed significant differences in the nevus pattern between these two groups. The majority of nevi in ST V revealed a reticular pattern, whereas persons with ST VI more frequently exhibited a structureless pattern. Black, blue and grey were more frequent in ST VI, whereas the vast majority of nevi in ST V individuals showed dark brown colour. Conclusions: Our study provides new insights into the nevus pattern in individuals with a dark pigmentary trait, which may aid the diagnosis and management of nevi in this patients group.

2014 - Dermoscopic pattern of psoriatic lesions on specific body sites [Articolo su rivista]
Lallas, Aimilios; Apalla, Zoe; Argenziano, Giuseppe; Sotiriou, Eleni; Di Lernia, Vito; Moscarella, Elvira; Longo, Caterina; Sidiropoulos, Theodoros; Zalaudek, Iris
abstract

Background: Scarce evidence exists on the dermoscopic pattern of psoriasis on specific body sites. Objective: To describe the dermoscopic characteristics of psoriatic plaques located on the scalp, face, folds, palms, soles and genitalia. Methods: Dermoscopic images of psoriatic lesions located on the aforementioned body sites were retrospectively evaluated for the presence of predefined criteria. Results: A total of 139 lesions from 85 patients were included in the study. Dotted vessels were the commonest dermoscopic criterion (97.1%) followed by white scales (64.7%), while vessel distribution was regular in 87.7% of cases. Regularly distributed dotted vessels represented a constant finding in all locations, while the frequency of white scales varied significantly among different body sites. Conclusion: The well-known dermoscopic criteria of psoriasis can also be seen in lesions located on the scalp, face, palms, soles, folds and genitalia, with the frequency of white scales varying among different body sites. © 2014 S. Karger AG, Basel.

2014 - Dermoscopic patterns of common facial inflammatory skin diseases [Articolo su rivista]
Lallas, A; Argenziano, Giuseppe; Apalla, Z.; Gourhant, J. Y.; Zaballos, P.; Di Lernia, V.; Moscarella, Elvira; Longo, Caterina; Zalaudek, I.
abstract

Background Several common inflammatory dermatoses, such as rosacea, seborrheic dermatitis (SD), discoid lupus erythematosus (DLE) and granulomatous skin diseases manifest as erythematous macules or plaques on the facial skin. Although clinical examination represents the cornerstone of diagnosis, the broad variety of clinical features and uncommon presentations of these diseases may cause at times diagnostic and therapeutic uncertainty. Dermoscopy, in addition to its well-documented value in evaluation of skin tumours, is continuously gaining appreciation also in the field of general dermatology. Objective To describe and compare the dermoscopic patterns of common facial inflammatory skin diseases including SD, erythematotelangiectatic rosacea (ER), sarcoidosis, lupus vulgaris (LV), DLE and granuloma faciale (GF). Methods Dermoscopic images of lesions from patients with histopathologically confirmed diagnosis of SD, ER, sarcoidosis, LV, DLE or GF were retrospectively evaluated for the presence of several criteria. Selection of the dermoscopic variables included in the evaluation process was based on the data available in the literature and on our preliminary observations. Results One hundred and fifteen dermoscopic images were included in the study. SD was dermoscopically characterized by dotted vessels and yellow scales, whereas ER was typified by a characteristic pattern of vascular polygons. Sarcoidosis and LV very commonly exhibited orange-yellowish areas and linear branching vessels. Features related to follicle abnormalities and linear branching vessels were the most common dermoscopic criteria of DLE and GF. Conclusions This study provides new insights into the dermoscopic variability in common facial inflammatory dermatoses. © 2013 European Academy of Dermatology and Venereology.

2014 - Dermoscopy of uncommon skin tumours [Articolo su rivista]
Lallas, Aimilios; Moscarella, Elvira; Argenziano, Giuseppe; Longo, Caterina; Apalla, Zoe; Ferrara, Gerardo; Piana, Simonetta; Rosato, Simonetta; Zalaudek, Iris
abstract

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2014 - Dermoscopy uncovers clinically undetectable pigmentation in basal cell carcinoma [Articolo su rivista]
Lallas, A; Argenziano, Giuseppe; Kyrgidis, A.; Apalla, Z.; Moscarella, Elvira; Longo, Caterina; Ferrara, G.; Piana, S.; Benati, Elisa; Zendri, E.; Sotiriou, E.; Zalaudek, I.
abstract

Background The presence of pigmentation might influence the management of basal cell carcinoma (BCC), with pigmented BCC responding poorly to certain treatments. Clinical studies report on a generally lower frequency of pigmentation compared with dermoscopic and histopathological studies, but the true frequency at which pigmentation occurs in clinically nonpigmented BCC has not been studied in detail. Objectives To compare the clinical and dermoscopic frequency of pigmentation in a series of histopathologically diagnosed BCCs and to correlate it with patient demographics, tumour location and histopathological subtype. Methods Clinical and dermoscopic images of histopathologically confirmed BCCs were retrospectively evaluated for the presence of pigmentation. Dichotomous outcome variables were clinically pigmented and dermoscopically pigmented BCC. All separate dermoscopic variables were included in the analysis. Differences in proportions were evaluated using Pearson's chi-square test. Results Five hundred and seven BCCs from 507 patients with a mean age of 67 years and a male-to-female ratio of 1·35: 1 were included in the study. Clinically, 295 tumours were judged as nonpigmented. Of those, dermoscopy disclosed pigmentation in 88 cases (29·8%). Overall, blue-grey ovoid nests were the most frequent dermoscopic pattern (n = 184, 36·3%), followed by multiple blue-grey dots/globules (n = 147, 29%) and maple-leaf-like areas (n = 70, 13·8%). Superficial tumours exhibited mainly maple-leaf-like areas, spoke-wheel areas and brown dots, whereas pigmented nodular BCC was most frequently typified by the presence of blue-grey ovoid nests. Conclusions Dermoscopy allows detection of pigmentation in about 30% of clinically nonpigmented BCCs, providing additional information that may aid the clinical choice of adequate treatment modalities. What's already known about this topic? Dermoscopy is useful in the pre-operative diagnosis of basal cell carcinoma (BCC). Management of BCC depends mainly on the histopathological subtype, but is also influenced by the presence of pigmentation, as pigmented BCC is known to respond poorly to certain treatment modalities. What does this study add? Dermoscopy has the potential to reveal clinically undetectable pigmentation in BCC, providing additional information that is potentially useful for tumour management. © 2013 British Association of Dermatologists.

2014 - Diagnosis and management of facial pigmented macules [Articolo su rivista]
Lallas, Aimilios; Argenziano, Giuseppe; Moscarella, Elvira; Longo, Caterina; Simonetti, Vito; Zalaudek, Iris
abstract

The differential diagnosis of pigmented macules on the mottled chronic sun-damaged skin of the face is challenging and includes lentigo maligna (LM), pigmented actinic (solar) keratosis, solar lentigo, and lichen-planus-like keratosis. Although dermatoscopy improves the diagnostic accuracy of the unaided eye, the accurate diagnosis and management of pigmented facial macules remains one of the most challenging scenarios in daily practice. This is related to the fact that pigmented actinic (solar) keratosis, lichen-planus-like keratosis, and LM may reveal overlapping criteria, making their differential diagnosis clinically difficult. For this reason, practical rules have been introduced, which should help to minimize the risk for inappropriate diagnosis and management of LM. © 2014.

2014 - Distinct melanoma types based on reflectance confocal microscopy [Articolo su rivista]
Pellacani, Giovanni; De Pace, Barbara; Reggiani, Camilla; Cesinaro, Anna Maria; Argenziano, Giuseppe; Zalaudek, Iris; Soyer, H. Peter; Longo, Caterina
abstract

Distinct melanoma types exist in relation to patient characteristics, tumor morphology, histopathologic aspects and genetic background. A new diagnostic imaging tool, reflectance confocal microscopy (RCM), allows in vivo analysis of a given lesion with nearly histologic resolution while offering a dynamic view of the tissue in its 'natural' environment. The aim of this study was to analyse cell morphology of consecutive melanomas as they appear on RCM and to correlate morphology with tumor and patient characteristics. One hundred melanomas were visualized by RCM before excision. Clinical data, confocal features and histologic criteria were analysed. Four types of melanomas were identified as follows: (i) Melanomas with a predominantly dendritic cell population ('dendritic-cell melanomas') typically were thin by Breslow index; (ii) Melanomas typified by roundish melanocytes were smaller in size than dendritic cell MMs, but thicker by Breslow index, and predominantly occurred in patients with a high nevus count; (iii) Melanomas characterized by dermal nesting proliferation usually were thick by Breslow index at the time of diagnosis, although frequently smaller in size compared with the other types; and (iv) combined type melanomas may represent an evolution of dendritic cell and/or round cell types. Integration of confocal microscopy with clinical and histologic aspects may help in identifying and managing distinct tumors. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

2014 - Dormant melanomas or changing nevi? [Articolo su rivista]
Argenziano, Giuseppe; Lallas, Aimilios; Longo, Caterina; Moscarella, Elvira; Raucci, Margherita; Zalaudek, Iris
abstract

The development of new primary melanomas in patients treated with vemurafenib has been reported recently in a study by Perier-Muzet et al. The primary outcome of the study was to describe the dermoscopic changes that prompted excision of those melanomas. However, the crucial point raised by the study is the large number of melanomas that were detected.

2014 - Erratum: Molecular targeted approaches for advanced BRAF V600, N-RAS, c-KIT, and GNAQ melanoma (Disease Markers) [Articolo su rivista]
Ponti, Giovanni; Pellacani, Giovanni; Tomasi, Aldo; Loschi, Pietro; Luppi, Gabriele; Gelsomino, Fabio; Longo, Caterina
abstract

ND

2014 - Evaluating ex vivo fluorescence confocal microscopy images of basal cell carcinomas in Mohs excised tissue [Articolo su rivista]
Longo, C.; Rajadhyaksha, M.; Ragazzi, M.; Nehal, K.; Gardini, S.; Moscarella, E.; Lallas, A.; Zalaudek, I.; Piana, S.; Argenziano, G.; Pellacani, G.
abstract

Summary Background Fluorescence confocal microscopy (FCM) is an emerging technology for rapid imaging of excised tissue, without the need for frozen- or fixed-section processing. Basal cell carcinomas (BCCs) can be detected in Mohs excisions although few studies have described the major BCC findings as seen on FCM. Objectives To describe the major BCC findings of excised tissue during Mohs surgery and to correlate them with histopathology. Methods Freshly excised tumours and frozen-thawed discarded tissue of BCC during Mohs surgery were analysed by means of FCM. A side-by-side correlation between FCM images and histological sections was performed. The FCM features of overlying skin and adnexal structures were also described. Results Sixty-four BCC cases were analysed. Distinct BCC types appeared unique in terms of shape and size of tumour islands [bigger in nodular (18/25), smaller and rounded in micronodular (7/7) and tiny cords for infiltrative ones (24/30)] and for the presence of clefting, palisading and increased nucleus/cytoplasm ratio. An excellent correlation was found between FCM and histological findings (Cohen's κ statistics = 0·9). In six cases, the presence of sebaceous glands and intense stroma reaction represented possible confounders. Conclusions Fluorescence confocal microscopy is a fast and new imaging technique that allows an excellent visualization of skin structures and BCC findings during Mohs surgery. What's already known about this topic? Fluorescence confocal microscopy (FCM) permits the analysis of freshly excised skin tissue to detect residual tumours during Mohs surgery. However, few studies have been performed to describe the major morphological features of basal cell carcinoma (BCC) as seen on FCM. What does this study add? FCM allowed obtaining an excellent correlation of BCC findings with the corresponding histopathology. Additionally, it was possible to distinguish distinct BCC and to highlight possible confounders.

2014 - Flat pigmented macules on sun-damaged skin of the head/neck: Junctional nevus, atypical lentiginous nevus, or melanoma in situ? [Articolo su rivista]
Zalaudek, Iris; Cota, Carlo; Ferrara, Gerardo; Moscarella, Elvira; Guitera, Pascale; Longo, Caterina; Piana, Simonetta; Argenziano, Giuseppe
abstract

The clinical recognition of lentigo maligna (LM) in the mottled chronic sun-damaged skin can be challenging, because it shares many clinical features with other pigmented macules that commonly arise on sun-damaged skin. These include solar lentigo, flat seborrheic keratosis, and pigmented actinic keratosis, but almost never "nevus." The reason nevus is not included in the differential diagnosis of LM can be explained by the fact that the stereotypical appearance of a facial nevus differs remarkably from that of an LM. Facial nevi in adults are usually nodular, dome-shaped, well-defined, and hypopigmented (ie, intradermal nevus of the Miescher type), whereas LM typically appears as a flat, ill-defined, and pigmented macule. Although this concept based on clinical observations sounds reasonable, clinicians apply it often only unconsciously and accept a given histopathologic diagnosis of a "junctional or lentiginous nevus" of a flat pigmented facial macule without the necessary criticism about its clinicopathologic validity. © 2014.

2014 - Fluorescence confocal microscopy for pathologists [Articolo su rivista]
Ragazzi, M.; Piana, S.; Longo, C.; Castagnetti, F.; Foroni, M.; Ferrari, G.; Gardini, G.; Pellacani, G.
abstract

Confocal microscopy is a non-invasive method of optical imaging that may provide microscopic images of untreated tissue that correspond almost perfectly to hematoxylin- and eosin-stained slides. Nowadays, following two confocal imaging systems are available: (1) reflectance confocal microscopy, based on the natural differences in refractive indices of subcellular structures within the tissues; (2) fluorescence confocal microscopy, based on the use of fluorochromes, such as acridine orange, to increase the contrast epithelium-stroma. In clinical practice to date, confocal microscopy has been used with the goal of obviating the need for excision biopsies, thereby reducing the need for pathological examination. The aim of our study was to test fluorescence confocal microscopy on different types of surgical specimens, specifically breast, lymph node, thyroid, and colon. The confocal images were correlated to the corresponding histological sections in order to provide a morphologic parallel and to highlight current limitations and possible applications of this technology for surgical pathology practice. As a result, neoplastic tissues were easily distinguishable from normal structures and reactive processes such as fibrosis; the use of fluorescence enhanced contrast and image quality in confocal microscopy without compromising final histologic evaluation. Finally, the fluorescence confocal microscopy images of the adipose tissue were as accurate as those of conventional histology and were devoid of the frozen-section-related artefacts that can compromise intraoperative evaluation. Despite some limitations mainly related to black/white images, which require training in imaging interpretation, this study confirms that fluorescence confocal microscopy may represent an alternative to frozen sections in the assessment of margin status in selected settings or when the conservation of the specimen is crucial. This is the first study to employ fluorescent confocal microscopy on surgical specimens other than the skin and to evaluate the diagnostic capability of this technology from pathologists' viewpoint. © 2014 USCAP, Inc All rights reserved.

2014 - Hyporeflective pagetoid cells: A new clue for amelanotic melanoma diagnosis by reflectance confocal microscopy [Articolo su rivista]
Losi, A.; Longo, C.; Cesinaro, A. M.; Benati, E.; Witkowski, A.; Guitera, P.; Pellacani, G.
abstract

Background Amelanotic melanoma represents a diagnostic challenge both clinically and dermoscopically. Few studies based on case series have explored the possibility of using reflectance confocal microscopy (RCM) to diagnose amelanotic melanoma. Objectives To validate a new confocal feature, named hyporeflective pagetoid cells (HPCs), for the diagnosis of amelanotic melanoma. Methods A group of 20 amelanotic melanomas and a control population of nonpigmented melanocytic naevi (10), hypo/nonpigmented nonmelanocytic lesions (20) and pigmented melanomas (20), imaged by RCM, were retrospectively evaluated. The presence of HPCs and other diagnosis-specific confocal features was assessed and correlated with histopathology. Results HPCs were present, and usually abundant, in the majority of amelanotic melanomas (85%). As expected, they were also observed in Spitz naevi. On histopathology, they were correlated with pagetoid infiltration of hypomelanotic melanocytes in all melanocytic lesions. Few nonmelanocytic lesions (three squamous cell carcinomas, two seborrhoeic keratoses and one basal cell carcinoma) showed the presence of HPCs. In these cases, they corresponded to enlarged or dyskeratotic keratinocytes by histopathology. Conclusions The identification of HPCs in the epidermis is a new parameter that is frequently found in amelanotic melanoma. Possible confounders are represented by atypical keratinocytes that can be present in nonmelanocytic lesions. However, the whole architecture and the presence of additional diagnostic criteria should be considered in order to obtain a correct diagnosis. What's already known about this topic? Amelanotic and hypopigmented lesions can be readily evaluated by means of confocal microscopy. Few reports have explored the characteristic confocal aspects of amelanotic melanoma as seen by confocal microscopy. What does this study add? We define a new descriptor, named hypomelanotic pagetoid cells, as a clue for differentiating amelanotic melanoma from other benign and malignant nonpigmented lesions. © 2013 British Association of Dermatologists.

2014 - In vivo confocal microscopy in skin oncology [Capitolo/Saggio]
Longo, Caterina; De Pace, Barbara; Piana, Simonetta; Pellacani, Giovanni
abstract

In vivo reflectance confocal microscopy is a novel technique which enables the visualization of the skin at quasi-histologic resolution up to the papillary dermis. Since the melanin and small organelles are a strong source of contrast, this technique revealed to be useful in skin cancer diagnosis. Through confocal microscopy it is possible to in vivo visualize the architecture and the cytology of a skin tumor. In melanocytic lesion, it is possible to detect aggregates of melanocytes at the junction and in superficial dermis and to distinguish between a regular benign proliferation and malignant cells in the epidermis and superficial dermis. It is also useful for the diagnosis of epithelial tumors, such as basal cell carcinoma and squamous cell carcinoma, and in the identification of benign epithelial proliferation, like seborrheic keratosis and solar lentigo.

2014 - Melanocytic nevi with special features: Clinical-dermoscopic and reflectance confocal microscopic-findings [Articolo su rivista]
Larre Borges, A.; Zalaudek, I.; Longo, Caterina; Dufrechou, L.; Argenziano, Giuseppe; Lallas, A.; Piana, S.; Moscarella, Elvira
abstract

Histopathology is considered the 'gold' standard for the diagnosis and classification of melanocytic nevi, but the widespread use of in vivo diagnostic technologies such as dermoscopy and reflectance confocal microscopy (RCM), has enriched profoundly the knowledge regarding the morphological variability in nevi. This is because most morphological observations made via these in vivo tools are closely correlated with features seen in histopathology. Dermoscopy has allowed for a more detailed classification of nevi. As such, dermoscopy identifies four main morphologic groups (i.e. globular, reticular, starburst and structureless blue nevi), one group of nevi located at special body sites (i.e. face, acral, nail) and one group of nevi with special features. This latter category consists of nevi of the former categories, which are typified by peculiar clinical-histopathological findings. They can be subdivided into 'melanoma simulators' including combined nevi, recurrent nevi and sclerosing nevus with pseudomelanomatous features, 'targetoid' nevi (i.e. halo, cockade, irritated targetoid haemosiderotic and eczematous nevus) and uncommon histopathological variants such as desmoplastic, white dysplastic or ballon cell nevus. While the dermoscopic and RCM patterns of the former categories have been studied in detail, little is currently known about the clinical morphology of the heterogeneous group of 'special' nevi. In this article, we describe the clinical, dermoscopic and RCM features of 'special' nevi and review the current literature on this group of melanocytic proliferations. © 2013 European Academy of Dermatology and Venereology.

2014 - Melasma and low-energy Q-switched laser: Treatment assessment by means of in vivo confocal microscopy [Articolo su rivista]
Longo, Caterina; Pellacani, Giovanni; Tourlaki, Athanasia; Galimberti, Michela; Bencini, Pier Luca
abstract

Melasma is an acquired disorder of pigmentation for which several therapeutical options are currently available. Among them, low-energy Q-switched Nd:YAG laser (1,064 nm) has been successfully applied in case series although its long-term efficacy has yet to be proven. In vivo confocal microscopy is a novel imaging technique that permits to explore the skin tissue at a nearly histologic resolution. The aim of our study was to evaluate the laser treatment efficacy by means of confocal microscopy at different time points to elucidate the mechanism of action of the laser and its possible drawbacks. Eight women who presented with melasma on the face were subjected to low-energy Q-switched Nd:YAG laser treatment and then analyzed by means of confocal microscopy. An overall improvement of melasma was noticed clinically and microscopically by means of confocal microscopy. Four cases revealed the presence of dendritic-shaped cells upon confocal microscopy and those patients were the ones presenting with a relapse of the disease. The interpretation of these cells is that they could represent reasonably activated melanocytes. This opens the question whether laser treatment should be modulated to avoid side-effects associated with its use. Confocal microscopy has emerged as an excellent tool for a better understanding of the changes occurring during laser treatment.

2014 - Molecular Targeted Approaches for Advanced BRAF V600, N-RAS, c-KIT, and GNAQ Melanomas [Articolo su rivista]
Ponti, Giovanni; Pellacani, Giovanni; Tomasi, Aldo; Loschi, Pietro; Luppi, Gabriele; Gelsomino, Fabio; Longo, Caterina
abstract

The introduction of a newly developed target therapy for metastatic melanomas poses the challenge to have a good molecular stratification of those patients who may benefit from this therapeutic option. Practically, BRAF mutation status (V600E) is commonly screened although other non-V600E mutations (i.e., K-R-M-D) could be found in some patients who respond to therapy equally to the patients harboring V600E mutations. Furthermore, other mutations, namely, N-RAS, KIT, and GNAQ, should be sequenced according to distinct melanoma specific subtypes and clinical aspects. In our report, a practical flow chart is described along with our experience in this field.

2014 - Morphologic grading and treatment of facial actinic keratosis [Articolo su rivista]
Zalaudek, Iris; Piana, Simonetta; Moscarella, Elvira; Longo, Caterina; Zendri, Enrico; Castagnetti, Fabio; Pellacani, Giovanni; Lallas, Aimilios; Argenziano, Giuseppe
abstract

Actinic keratoses (AKs) represent the earliest stage in the development of squamous cell carcinoma (SCC) and represent important biomarkers for individuals at risk for development of invasive SCC. Based on clinical morphology, AK can be subdivided into three different grades, which correspond to specific dermatoscopic, reflectance confocal microscopic, and histopathologic substrates. Given the risk for potential progression toward invasive SCC, AK should be treated at the earliest stage. A wide range of minimal destructive or topical therapies is available for the treatment of AK. The choice of treatment depends on the number, size, clinical grading, duration, and location of lesions, patient's compliance, general health conditions, and cosmetic outcome. Treatment can be divided into lesion-directed and field-directed therapies. Lesion-directed treatment focuses on the treatment of single lesions, whereas field-directed treatment aims to eliminate both clinically visible and subclinical lesions within the field of actinic damage (concept of field cancerization). Noninvasive techniques such as dermoscopy and reflectance confocal microscopy can be helpful in identifying AK potentially progressing toward SCC, as well as in the selection of the adequate treatment and monitoring of the treatment outcome.

2014 - Muir-Torre syndrome or phenocopy? The value of the immunohistochemical expression of mismatch repair proteins in sebaceous tumors of immunocompromised patients [Articolo su rivista]
Ponti, Giovanni; Pellacani, Giovanni; Ruini, Cristel; Percesepe, Antonio; Longo, Caterina; Mandel, Victor Desmond; Crucianelli, Francesca; Gorelli, Greta; Tomasi, Aldo
abstract

Primary and secondary immunodepressive conditions are associated with an increased incidence of sebaceous tumors. Microsatellite instability (MSI) and lack of expression of mismatch repair (MMR) proteins, typical markers of Muir-Torre/Lynch heredo-familial settings, can be recognized also in immunocompromised patients. We aimed to carry on a systematic examination of clinical, immunohistochemical, biomolecular features of sebaceous tumors arising in immunocompromised and immunocompetent patients between 1986 and 2012. Microsatellite screening, immunohistochemical analysis and genetic testing were performed for hMLH1, hMSH2 and hMSH6. Methylation status of MMR genes was checked in cases with immunohistochemistry (IHC) loss of MMR proteins expression and no germline mutations. Fifteen patients had a personal history of visceral carcinomas fulfilling diagnostic criteria for Muir-Torre syndrome. In this cohort, IHC analysis, MSI status and genetic testing were in agreement, showing eight MSH2 and two MLH1 germline mutations. Five patients were immunosuppressed and their sebaceous tumors showed a lack of MSH2/MSH6 expression, although just one case with positive family history for visceral cancer harbored a germline mutation. In immunosuppressed patients, loss of IHC for MMR proteins is not necessarily secondary to MMR germline mutations. IHC false positives are probably due to epigenetic alterations. MSI and lack of expression of MMR proteins can be recognized also in immunocompromised patients without MMR germline mutations.

2014 - Non-invasive in vivo dermatopathology: identification of reflectance confocal microscopic correlates to specific [Articolo su rivista]
Gill, M; Longo, Caterina; Farnetani, Francesca; Cesinaro, Am; González, S; Pellacani, Giovanni
abstract

Background Reflectance confocal microscopy (RCM) allows for non-invasive, in vivo evaluation of skin lesions and it has been extensively applied in skin oncology although systematic studies on nevi characterization are still lacking. Objective The aim of this study was to determine whether reliable RCM correlates to histological features used to diagnose melanocytic neoplasms exist. Methods We blindly evaluated the RCM and histological features of 64 melanocytic neoplasms (19 non-dysplastic nevi, 27 dysplastic nevi, 14 melanomas) and analysed the data using Spearman's rho calculation. Results Many histological features can be identified using RCM. Elongated rete ridges corresponded on RCM to edge papillae, whereas flattened rete ridges to several features which involve dermal–epidermal junction disruption. Bridging of junctional nesting (JN) corresponded on RCM to both JN with irregular size/shape and JN with short interconnections. While we could reliably identify dermal melanocytes, the RCM features did not reliably distinguish between benign and concerning dermal melanocytic arrangements, suggesting further refinement of dermal melanocytic RCM features is needed. Conclusion Reliable correlates for epidermal and junctional histological features used to diagnose melanocytic neoplasms are identifiable on RCM, suggesting harnessing histological criteria may be a reasonable method to move beyond the algorithmic approach.

2014 - Not all lesions with a verrucous surface are seborrheic keratoses [Articolo su rivista]
Longo, C.; Moscarella, E.; Piana, S.; Lallas, A.; Carrera, C.; Pellacani, G.; Zalaudek, I.; Argenziano, G.
abstract

2014 - Palmar and plantar melanomas differ for sex prevalence and tumor thickness but not for dermoscopic patterns [Articolo su rivista]
Lallas, Aimilios; Sgouros, Dimitrios; Zalaudek, Iris; Tanaka, Masaru; Saida, Toshiaki; Thomas, Luc; Kittler, Harald; Kobayashi, Ken; Koga, Hiroshi; Phan, Alice; Longo, Caterina; Moscarella, Elvira; Katoulis, Alexandros; Argenziano, Giuseppe
abstract

The specific anatomy of the glabrous skin, characterized by marked orthokeratosis and the presence of furrows and ridges, results in peculiar dermoscopic patterns of acral melanocytic lesions. Most frequently, acral nevi are typified by a parallel furrow pattern and acral melanoma (AM) by a parallel ridge pattern (PRP). Although the dermoscopic patterns of AM have been extensively investigated, little attention has been paid to site-related differences between palmar and plantar AM. The current study aimed to compare patients' characteristics, melanoma thickness, and the morphologic variability of AM depending on the localization on palms or soles. Patients demographics and dermoscopic images of 118 AM, including 99 (83.9%) plantar and 19 (16.1%) palmar lesions (mean thickness, 2.1 mm), were extracted from the databases of seven pigmented skin lesion clinics and were evaluated for the presence of predefined criteria. Palmar melanomas were remarkably more frequent in women (male-to-female ratio, 1/3.8) and thinner than plantar melanomas (1.3 vs. 2.2 mm). Dermoscopically, no significant differences were found between plantar and palmar melanomas, with PRP scored in 64.6 and 68.4% of plantar and palmar lesions, respectively. Non-site-specific melanoma criteria were detected in 83.9% of lesions and, among melanomas not exhibiting a PRP, 95.1% showed at least one non-site-specific melanoma criterion. In conclusion, plantar and palmar AMs show sex-related and thickness-related differences, but do not differ with respect to their dermoscopic features. For cases lacking the PRP, non-site-specific melanoma criteria may be considered as helpful additional clues for the correct diagnosis. © 2014 Wolters Kluwer Health | Lippincott Williams &amp; Wilkins.

2014 - Pattern alimentari e rischio di melanoma cutaneo: studio epidemiologico multicentrico in una popolazione del nord-Italia. [Abstract in Atti di Convegno]
Malavolti, Marcella; Malagoli, Carlotta; Agnoli, C; Fiorentini, Chiara; Longo, Caterina; Farnetani, Francesca; Sieri, S; Krogh, V; Pellacani, Giovanni; Vinceti, Marco
abstract

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2014 - Polygonal vessels of rosacea are highlighted by dermoscopy [Articolo su rivista]
Lallas, Aimilios; Argenziano, Giuseppe; Longo, Caterina; Moscarella, Elvira; Apalla, Zoe; Koteli, Christina; Zalaudek, Iris
abstract

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2014 - Prediction of survival in patients with thin melanoma: Results from a multi-institution study [Articolo su rivista]
Maurichi, Andrea; Miceli, Rosalba; Camerini, Tiziana; Mariani, Luigi; Patuzzo, Roberto; Ruggeri, Roberta; Gallino, Gianfranco; Tolomio, Elena; Tragni, Gabrina; Valeri, Barbara; Anichini, Andrea; Mortarini, Roberta; Moglia, Daniele; Pellacani, Giovanni; Bassoli, Sara; Longo, Caterina; Quaglino, Pietro; Pimpinelli, Nicola; Borgognoni, Lorenzo; Bergamaschi, Daniele; Harwood, Catherine; Zoras, Odysseas; Santinami, Mario
abstract

Purpose: Cutaneous melanoma incidence is increasing. Most new cases are thin (≤ 1 mm) with favorable prognoses, but survival is nonetheless variable. Our aim was to investigate new prognostic factors and construct a nomogram for predicting survival in individual patients. Patients and Methods: Data from 2,243 patients with thin melanoma were retrieved from prospectively maintained databases at six centers. Kaplan-Meier survival and crude cumulative incidences of recurrence were estimated, and competing risks were taken into account. Multivariable Cox regression was used to investigate survival predictors. Results: Median follow-up was 124 months (interquartile range, 106 to 157 months); 12-year overall survival was 85.3% (95% CI, 83.4% to 87.2%). Median times to local, regional, and distant recurrence were 79, 78, and 107 months, respectively. Relapse was significantly related to age, Breslow thickness, mitotic rate (MR), ulceration, lymphovascular invasion (LVI), and regression; incidence was lower and subgroup differences were less marked for distant metastasis than for regional relapse. The worst prognosis categories were age older than 60 years, Breslow thickness more than 0.75 mm, MR ≥ 1, presence of ulceration, presence of LVI, and regression ≥ 50%. Breslow thickness more than 0.75 mm, MR ≥ 1, presence of ulceration, and LVI (all P = .001) were significantly associated with sentinel node positivity. Age, MR, ulceration, LVI, regression, and sentinel node status were independent predictors of survival and were used to construct a nomogram to predict 12-year overall survival. The nomogram was well calibrated and had good discriminative ability (adjusted Harrell C statistic, 0.88). Conclusion: Our findings suggest including LVI and regression as new prognostic factors in the melanoma staging system. The nomogram appears useful for risk stratification in clinical management and for recruiting patients to clinical trials. © 2014 by American Society of Clinical Oncology.

2014 - Reflectance confocal microscopy as a second-level examination in skin oncology improves diagnostic accuracy and saves unnecessary excisions: A longitudinal prospective study [Articolo su rivista]
Pellacani, Giovanni; Pepe, Patrizia; Casari, Alice; Longo, Caterina
abstract

Summary Background Dermatoscopy increases both the sensitivity and specificity of melanoma diagnosis. Reflectance confocal microscopy (RCM) is a noninvasive technique that complements dermatoscopy in the evaluation of equivocal lesions at cellular resolution.Objectives To determine prospectively the potential impact of confocal microscopy when implemented in a routine melanoma diagnosis workflow.Methods Patients referred to a single melanoma clinic were consecutively enrolled. At dermatoscopy, patients were referred to one of the following pathways: (i) no further examination or (ii) RCM examination. On examination atypical lesion(s) were referred for either (a) RCM documentation (lesions with consistent suspicious clinical/dermatoscopic criteria, already qualified and scheduled for surgical excision) or (b) RCM consultation for equivocal lesions, where RCM diagnosis would determine lesion definite outcome (excision or digital follow-up).Results Reflectance confocal microscopy examination was performed for 41% of 1005 patients enrolled. In two-thirds of these cases RCM influenced the lesion outcome. The systematic application of RCM for equivocal lesions saved over 50% of benign lesions from unnecessary excision. The number needed to excise a melanoma was 6·8 with RCM examination, compared with a hypothetical 14·6 without RCM evaluation.Conclusions Reflectance confocal microscopy as a second-level examination to dermatoscopy proved to be highly accurate in diagnosis and reduced the number of unnecessary excisions. Improved accuracy, considering that RCM enabled the detection of the six melanomas (2%) in the group of 308 lesions eligible for follow-up, also minimizes the risk of referring a melanoma to digital dermatoscopy monitoring, and potentially losing the patient to follow-up. What's already known about this topic? Reflectance confocal microscopy is an add-on tool to dermatoscopy that can increase specificity and improve diagnostic accuracy. What does this study add? We demonstrated that the systematic use of confocal microscopy can reduce the number of benign lesions excised to rule out a melanoma and minimize the risk to refer a melanoma to digital dermatoscopy monitoring.

2014 - Stem cell properties in cell cultures from different stage of melanoma progression. [Articolo su rivista]
Magnoni, Cristina; S., Guidice; Pellacani, Giovanni; G., Bertazzoni; Longo, Caterina; E., Veratti; D., Morini; L., Benassi; S., Al Jalbout; C., Vaschieri; P., Azzoni; DE POL, Anto; S., Seidenari; Tomasi, Aldo; Ponti, Giovanni
abstract

Cutaneous Melanoma is an extremely heterogeneous human cancer. The most aggressive melanoma may contain deregulated cells with undifferentiated/stem cell-like phenotype. A critical mechanism by which melanoma cells enhance their invasive capacity is the dissolution of the intercellular adhesions and the acquisition of mesenchymal features as a part of an epithelial-to-mesenchimal transition (EMT). The aim of this study was to clarify the role of stem cell-like population in human melanomas through the in vitro analysis of melanocytic cell cultures, obtained from distinct histotypes of primary and metastatic malignant melanoma. Patients with advanced melanoma larger than 2cm diameter and/or wider than 300mm2 surface were enrolled. The melanoma cells were isolated from skin biopsies of lentigo melanoma (LM), superficial spreading (SS), nodular melanoma (NM) and metastatic melanoma (MM) and maintained in different media in order to evaluate the colony-forming unit assay, alkaline phosphatase and toluidine blue stain and the cell ability to differentiate into osteogenic and adipogenic lineages. Immunohistochemistry and flow cytometry analysis were performed in order to evaluate antigenic markers CD90, CD73, CD105, CD146, CD20, CD166 and nestin. This study confirms that melanoma can include an heterogeneous cell population with both abilities to self-renew and to give rise to differentiated progeny. Melanoma cells displayed the intra-tumoral heterogeneity and dynamic antigen phenotypes. Histologically, the transitions from normal skin to DN to LM to NM to MM was associated with a gradual increase in the expression of CD146, CD20, CD133, Nestin and CD73 by melanoma cells. These molecular evidences could be a milestone for the development of novel biomolecular targeted-therapy approaches.

2014 - Towards an in vivo morphologic classification of melanocytic nevi [Articolo su rivista]
Pellacani, Giovanni; Scope, A.; Farnetani, Francesca; Casaretta, Giovanni; Zalaudek, Z; Moscarella, Elvira; Casari, Alice; Cesinaro, Am; Argenziano, Giuseppe; Longo, Caterina
abstract

BACKGROUND: Nevi are common benign neoplasms and the main diagnostic entity in the differential diagnosis of melanoma. Reflectance confocal microscopy (RCM), a novel technique for skin imaging at cellular-level magnification, has been shown to be useful for differentiating nevi from melanoma. However, systematic studies of the specific RCM features of nevi are still lacking. OBJECTIVE: To describe the characteristic RCM features of common melanocytic nevi and to correlate them with histopathology. METHODS: A total of 180 biopsy-proven nevi were imaged with RCM prior to excision. RCM images were evaluated for the overall nevus pattern and presence of specific RCM criteria. Upon histopathology, nevi were analysed for thickness using adapted Breslow depth and Clark's level grading. RESULTS: Observed RCM patterns varied according to anatomic depth of nevi. Junctional nevi were mainly characterized on RCM by a Ringed pattern, indicating a predominantly single cell proliferation of melanocytes; in contrast, the junctional component of compound nevi appeared on RCM as a Meshwork pattern, indicating a predominantly nested-proliferation. In compound nevi, the size of dermal nests was related to the thickness of nevi. Moreover, nevi extending deeper into the dermis were more likely to display a junctional component that extended laterally beyond the dermal component and appeared on RCM as either Ringed or Meshwork pattern. Intradermal nevi showed on RCM, in almost all cases, large clods. CONCLUSIONS: The possibility for in vivo histopathological classification of nevi may help in attaining a better understanding of the origin of nevi and of nevus-related melanoma risk.

2014 - Twenty nevi on the arms: A simple rule to identify patients younger than 50 years of age at higher risk for melanoma [Articolo su rivista]
Argenziano, Giuseppe; Giacomel, Jason; Zalaudek, Iris; Apalla, Zoe; Blum, Andreas; De Simone, Paola; Lallas, Aimilios; Longo, Caterina; Moscarella, Elvira; Tiodorovic Zivkovic, Danica; Tiodorovic, Jelica; Jovanovic, Dragan L.; Kittler, Harald
abstract

Patients with a high total nevus count (TNC) merit a total-body examination, but a simple strategy to identify these high-risk individuals is essentially missing. The aim of this study was to investigate the correlation between the number of melanocytic nevi on both arms and the TNC, and to evaluate patient variables that may have an effect on this association. In this multicenter, cross-sectional study, 2175 patients were examined and the mean number of arm nevi in relation to TNC was calculated. A mean value of fewer than 10 arm nevi was found in patients with TNC lower than 51 and a mean value of greater than 19 arm nevi was scored in patients with TNC greater than 50. These values remained unchanged after adjustment for various patient variables. In relation to TNC greater than 50, the presence of 20 or more arm nevi had specificity and negative predictive values of 95.2 and 89.6%, respectively. The sensitivity was 65.5% in patients younger than 50 years of age and 37.5% in the older age group. The number of arm nevi was significantly higher in individuals with a history of melanoma and in those with a melanoma detected during the study period. The presence of 20 or more nevi on the arms is an independent predictor of a high TNC and risk of melanoma. This sign thus represents a simple and rapid screening tool for either the primary care physician or the dermatologist to help identify high-risk patients. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

2014 - Uncovering a hidden basal cell carcinoma [Articolo su rivista]
Stefanello, Betina; Rezende, Patricia Makino; Argenziano, Giuseppe; Piana, Simonetta; Moscarella, Elvira; Longo, Caterina; Zalaudek, Iris; Lallas, Aimilios
abstract

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2013 - "White" network in Spitz nevi and early melanomas lacking significant pigmentation [Articolo su rivista]
Zalaudek, Iris; Kittler, Harald; Hofmann Wellenhof, Rainer; Kreusch, Juergen; Longo, Caterina; Malvehy, Joseph; Puig, Susana; Moscarella, Elvira; Piana, Simonetta; Massone, Cesare; Cota, Carlo; Ferrara, Gerardo; Fleischer, Mariella; Argenziano, Giuseppe
abstract

Background: Spitz nevi and early melanomas lacking significant pigmentation exhibit overlapping dermoscopic patterns of regularly arranged dotted vessels over a pink background. Although white network has been described in both tumors, little is known about the frequency of this pattern in both tumors. Objective: We sought to compare the frequency of white network in Spitz nevi and early melanomas lacking significant pigmentation and to correlate this feature with histopathology. Methods: Two independent dermoscopists scored the presence of white network in a series of retrospectively collected images of histopathologically diagnosed cases of Spitz nevi and melanomas, dermoscopically typified by dotted vessels. Results: A total of 65 cases including 39 melanomas (median thickness 0.4 mm) and 26 Spitz nevi were analyzed. Patients with Spitz nevi were significantly younger compared to patients with melanoma (mean age: 26.8 vs 51.2 years, respectively; P <.001). The 2 observers scored white network being present in 23 (88.5%) and 24 (92.3%) Spitz nevi compared with 10 (25.6%) and 8 (20.5%) cases of 39 melanomas, respectively (P <.001). Interobserver agreement for white network was good (kappa = 0.67; 95% confidence interval 0.44-0.90). Histopathologically, elongated rete ridges were observed in 22 (88.5%) Spitz nevi and 11 (36.7%) melanomas (P <.001). Limitations: We did not evaluate other dermoscopic-histopathologic correlates commonly seen in Spitz nevi and melanomas in our study. Conclusion: Although white network occurs at significantly higher frequency among hypopigmented/amelanotic Spitz nevi compared with early melanoma, it is not exclusively seen in Spitz nevi. Thus, excision of melanocytic tumors showing this pattern is mandatory. © 2012 by the American Academy of Dermatology, Inc.

2013 - 'Eruptive' amelanotic compound nevi in children with facial freckles and pale skin colour: More than an occasion? [Articolo su rivista]
Zalaudek, I; Moscarella, Elvira; Sturm, R. A.; Argenziano, Giuseppe; Longo, Caterina; Misciali, C.; Patrizi, A.; Neri, I.
abstract

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2013 - Association between dietary vitamin C and risk of cutaneous melanoma in a population of Northern Italy [Articolo su rivista]
Malavolti, Marcella; Malagoli, Carlotta; Fiorentini, Chiara; Longo, Caterina; Farnetani, Francesca; Ricci, Cinzia; Albertini, Giuseppe; Lanzoni, Anna; Reggiani, Camilla; Virgili, Annarosa; Pagliarello, Calogero; Santini, Marcello; Fanti, Pier A; Dika, Emi; Sieri, Sabina; Krogh, Vittorio; Pellacani, Giovanni; Vinceti, Marco
abstract

Cutaneous melanoma incidence has been increasing during the last few years, and diet has been suggested as one of the lifestyle factors responsible for this increase. Since antioxidant nutrients such as ascorbic acid might prevent skin carcinogenesis, we investigated the risk of cutaneous melanoma related to vitamin C intake in a population-based case-control study in Northern Italy based on 380 melanoma patients and 719 matched controls, to whom we administered a semiquantitative food-frequency questionnaire. After adjusting for potential confounders, odds ratio of melanoma were 0.86 (95 % confidence interval 0.65 - 1.15) and 0.59 (95 % confidence interval 0.37 - 0.94) in the intermediate and highest categories of vitamin C dietary intake respectively, compared with the bottom one. The association between vitamin C and decreased risk persisted after adjustment for some potential confounders. In age- and gender-stratified analyses, this association was seen in young females (< 60 years old), and was found to be enhanced in subjects with phototypes II and III. These results suggest a possible protective activity of vitamin C intake against cutaneous melanoma in specific subgroups of this population of Northern Italy.

2013 - Blue Lesions [Articolo su rivista]
Longo, Caterina; Scope, Alon; Lallas, Aimilios; Zalaudek, Iris; Moscarella, Elvira; Gardini, Stefano; Argenziano, Giuseppe; Pellacani, Giovanni
abstract

Blue color is found in a wide range of malignant and benign melanocytic and nonmelanocytic lesions and in lesions that result from penetration of exogenous materials, such as radiation or amalgam tattoo or traumatic penetration of particles. Discriminating between different diagnostic entities that display blue color relies on careful patient examination and lesion assessment. Dermoscopically, the extent, distribution, and patterns created by blue color can help diagnose lesions with specificity and differentiate between benign and malignant entities. This article provides an overview of the main diagnoses whereby blue color can be found, providing simple management rules for these lesions. © 2013 Elsevier Inc.

2013 - Can noninvasive imaging tools potentially predict the risk of ulceration in invasive melanomas showing blue and black colors? [Articolo su rivista]
Longo, Caterina; F., Farnetani; E., Moscarella; B., de Pace; S., Ciardo; Ponti, Giovanni; S., Piana; Am, Cesinaro; C., Cota; G., Argenziano; C., Rosendahl; Pellacani, Giovanni; I., Zalaudek
abstract

The aim of this study was to evaluate the reflectance microscopy and histopathologic correlates of dermoscopic blue and black color (BB) in a series of melanomas. We searched our database for dermoscopic images of histopathologically diagnosed pigmented nodular melanomas (pNM), superficial spreading melanomas with a nodular component (SSM+Nod), and melanoma metastasis (METs). All cases were assessed for the presence of dermoscopic BB. Confocal microscopy findings were then compared with those of histopathology. A total of 17 BB-positive tumors including eight pNMs, five SSM+Nod, and four METs were included in the study. We identified two different dermoscopic patterns associated with black color, namely, large black blotches and irregular black dots/globules, which corresponded to two different confocal and histopathologic findings. Black blotches resulted from a total filling of the epidermis by an upward migration of melanocyte nests and pagetoid melanocytes as single cells and clusters, whereas black dots/globules also corresponded to the upward migration of melanocyte nests in the epidermis and pagetoid spread, but with sparing of intervening areas of epidermis. Interestingly, two pNM and two METs showing black color lacked any epidermal involvement and, instead, they were characterized by upward-bulging dermal masses of atypical melanocytes covered by an highly attenuated epidermis. In both cases, black color corresponded to pigment-containing melanocytes in close proximity to the surface of the skin. Our study suggests that black color results not only from epidermal melanin but also from a dense dermal proliferation of pigmented melanocytes under a thinned epidermis. It seems reasonable to suggest that a bulging proliferation of dermal melanocytes beneath a thin epidermal layer could precede ulceration. As ulceration is a very significant prognostic factor, speculation arising from this study that dermoscopic black color may in some cases indicate incipient ulceration is worthy of further study.

2013 - Clinical, dermoscopic and histopathological features of eccrine poroid neoplasms [Articolo su rivista]
Sgouros, Dimitris; Piana, Simonetta; Argenziano, Giuseppe; Longo, Caterina; Moscarella, Elvira; Karaarslan, Isil Kilinc; Akalin, Taner; Özdemir, Fezal; Zalaudek, Iris
abstract

Background: Eccrine poroma (EP) belongs to the group of benign adnexal tumors, but cases of eccrine porocarcinoma (EPC) arising on long-standing and untreated EP suggest a certain risk of malignant transformation. Objectives: To describe the clinical, dermoscopic and histopathologic features associated with different extremes in the spectrum of eccrine poroid neoplasms and to review the according literature. Methods: A retrospective analysis of patient characteristics and morphologic features associated with EP, EPC in situ and invasive porocarcinoma patients who attended two skin lesion clinics in Italy and Turkey between 2010 and 2011. Results: A total of 4 cases including 1 EP, 1 EPC in situ and 2 cases of invasive EPC in 4 patients were analyzed. Recent changes including bleeding, ulceration and sudden enlargement of a pre-existing lesion were associated with malignant transformation. Dermoscopically, polymorphous vessels consisting of coiled, hairpin and linear vessels were seen at all stages of progression. Histopathological findings of EPC in situ were limited to the epidermal component and were evident only at higher magnification. Conclusions: Clinicians and pathologists should carefully evaluate EPs with a recent history of change and erosion in order to avoid overlooking the potential development of EPC. © 2013 S. Karger AG, Basel.

2013 - Clinical, dermoscopic and reflectance confocal microscopy features of sebaceous neoplasms in Muir-Torre syndrome [Articolo su rivista]
Moscarella, Elvira; Argenziano, Giuseppe; Longo, Caterina; Cota, C.; Ardigò, M.; Stigliano, V.; Mete, L. S.; Donati, P.; Piana, S.; Silipo, V.; Catricalà, C.; Albertini, G.; Zalaudek, I.
abstract

Background Muir-Torre syndrome (MTS) is an autosomal-dominant disorder characterized by the association of sebaceous tumors or keratoacanthomas with an early onset visceral cancer in the spectrum of Lynch syndrome. Observations A total of 20 sebaceous tumors including 18 sebaceous adenoma and two sebaceomas of six patients with MTS were analysed. Two main clinico-dermoscopic features were observed: (1) clinically pink to white papules/nodules with a central crater, dermoscopically characterized by radially arranged, elongated crown vessels surrounding opaque structureless yellow areas at times covered by blood crusts (n = 13) and (2), clinically pink to yellow papules/nodules without a central crater, dermoscopically exhibiting a few, loosely arranged yellow comedo-like globules and branching arborizing vessels (n = 7). Confocal microscopy was available in three sebaceous adenomas and revealed a good histopathologic correlation; sebaceous lobules were composed by clusters of ovoid cells with dark nuclei and bright, highly refractile glistening cytoplasm. They were delimited by a rim of epithelial cells, corresponding to basaloid cells. Conclusions A better characterization of clinical, dermoscopic and confocal microscopy features of sebaceous tumors may improve their recognition and consequently, aid to rise the suspect for MTS. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

2013 - Clues for differentiating discoid lupus erythematosus from actinic keratosis [Articolo su rivista]
Lallas, Aimilios; Apalla, Zoe; Argenziano, Giuseppe; Moscarella, Elvira; Longo, Caterina; Zalaudek, Iris
abstract

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2013 - Confocal microscopy insights into the treatment and cellular immune response of Basal cell carcinoma to photodynamic therapy [Articolo su rivista]
Longo, Caterina; Casari, A; Pepe, P; Moscarella, E; Zalaudek, I; Argenziano, G; Pellacani, Giovanni
abstract

Background: Photodynamic therapy (PDT) represents an optimal treatment for basal cell carcinoma (BCC). Reflectance confocal microscopy (RCM) is a noninvasive imaging tool that has been applied in skin oncology and for BCC diagnosis. Moreover, RCM is a useful tool to determine noninvasive treatment efficacy of nonmelanoma skin cancer. Objective: We aimed to investigate the role of RCM in assessing the efficacy of PDT in the treatment of BCC and to evaluate the skin changes following the PDT. Methods: Ten patients with 12 BCCs were treated with PDT. Dermoscopy and RCM imaging were performed at baseline as well as 7 days (T1), 30 days and 18 months after PDT. Cytological examination was taken at baseline and in case of BCC persistence. Results: At T1, RCM showed the presence of several dendritic-shaped cells within the epidermis, corresponding to activated Langerhans cells. After 1 month, RCM showed the persistence of 2 BCCs, which escaped the clinical and dermoscopic diagnosis. At the long-term follow-up, none of the tumors revealed signs of persistence or recurrence. Conclusion: RCM is a valuable noninvasive tool for the diagnosis and treatment monitoring of BCC using PDT.

2013 - Dermoscopic patterns of granuloma annulare and necrobiosis lipoidica [Articolo su rivista]
Lallas, A; Zaballos, P.; Zalaudek, I.; Apalla, Z.; Gourhant, J. Y.; Longo, Caterina; Moscarella, Elvira; Tiodorovic Zivkovic, D.; Argenziano, Giuseppe
abstract

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2013 - Dermoscopy and confocal microscopy clues in the diagnosis of psoriasis and porokeratosis [Articolo su rivista]
Moscarella, Elvira; Longo, Caterina; Zalaudek, Iris; Argenziano, Giuseppe; Piana, Simonetta; Lallas, Aimilios
abstract

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2013 - Dermoscopy and confocal microscopy of nested melanoma of the elderly recognizing a newly defined entity [Articolo su rivista]
Longo, C.; Zalaudek, I.; Piana, S.; Pellacani, G.; Lallas, A.; Reggiani, C.; Argenziano, G.
abstract

IMPORTANCE Nested melanoma of the elderly is a newly identified histopathologic variant of superficial spreading melanoma, characterized by intraepidermal large nests. However, the clinical, dermoscopic, and confocal aspects have been depicted only partially. OBSERVATIONS In our cases series, nested melanoma was a flat, irregularly shaped lesion with variably pigmented and irregularly distributed globules on dermoscopic examination. Confocal microscopy revealed the presence of a "clod" pattern made of large compact nests with variable atypia. These findings correlated well with histopathologic features. CONCLUSIONS AND RELEVANCE Nested melanoma of the elderly should be included in the differential diagnosis when a flat pigmented lesion, showing dermoscopically an irregular globular pattern, is seen in a patient older than 60 years.

2013 - Dermoscopy in General Dermatology [Articolo su rivista]
Lallas, Aimilios; Zalaudek, Iris; Argenziano, Giuseppe; Longo, Caterina; Moscarella, Elvira; Di Lernia, Vito; AL JALBOUT, Samer; Apalla, Zoe
abstract

In addition to its traditional use for the evaluation of skin tumors, dermoscopy continuously gains appreciation in other fields of dermatology. The patterns of several inflammatory and infectious skin diseases have already been described, and dermoscopy has been shown to improve the clinical diagnostic performance in the daily practice. The increasing use of dermoscopy was significantly enhanced by the development of the new generation hand-held dermatoscopes that can be easily placed in every dermatologist's pocket and do not require the use of immersion fluid. In this article, we provide an up-to-date summary of data on dermoscopy in general dermatology. © 2013 Elsevier Inc.

2013 - Dermoscopy of basosquamous carcinoma [Articolo su rivista]
Giacomel, J.; Lallas, A; Argenziano, Giuseppe; Reggiani, C.; Piana, S.; Apalla, Z.; Ferrara, G.; Moscarella, Elvira; Longo, Caterina; Zalaudek, I.
abstract

Background Basosquamous carcinoma (BSC) is a rare and potentially aggressive tumour, characterized by clinical and pathological features of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). It is reported to have a nonspecific clinical presentation, which makes naked-eye diagnosis a challenge. Objectives To describe the dermoscopic patterns of BSC, which may facilitate early diagnosis and accurate management. Methods This was a retrospective evaluation of clinical and dermoscopic images of histopathologically proven BSC, collected from skin cancer centres in Australia (Perth), Greece (Thessaloniki) and Italy (Naples, Reggio Emilia). Results Twenty-two tumours were included in the study. Our analysis revealed that the dermoscopic pattern of BSC comprises BCC-related criteria, as well as features that are known to characterize invasive SCC. The most frequently detected criteria were: unfocused (peripheral) arborizing vessels (73%), keratin masses (73%), white structureless areas (73%), superficial scale (68%), ulceration or blood crusts (68%), white structures (64%), blue-grey blotches (59%) and blood spots in keratin masses (55%). Notably, all but one of the tumours exhibited at least one BCC-related plus one SCC-related dermoscopic feature. Conclusions BSC appears to have overlapping dermoscopic features of BCC and invasive SCC, and detection of at least one dermoscopic criterion of both BCC and SCC should raise suspicion for the tumour. Appreciation of the dermoscopic patterns of BSC might assist in the timely and accurate diagnosis and subsequent optimal management of this unusual and potentially metastatic skin tumour. What's already known about this topic? Basosquamous carcinoma (BSC) is a rare and potentially aggressive tumour, characterized by clinical and pathological features of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Although dermoscopic characteristics of BCC and SCC have been extensively investigated, those of BSC remain unknown. What does this study add? BSC appears to have overlapping dermoscopic features of BCC and invasive SCC, and detection of at least one dermoscopic criterion of both BCC and SCC should raise suspicion for the tumour. © 2013 British Association of Dermatologists.

2013 - Dermoscopy should always be performed.even in clear-cut cases! [Articolo su rivista]
AL JALBOUT, Samer; Moscarella, Elvira; Longo, Caterina; Argenziano, Giuseppe; Piana, Simonetta; Zalaudek, Iris
abstract

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2013 - Does skin hydration influence keratinocyte biology? In vivo evaluation of microscpic skin changes induced by moisturizers by means of reflectance confocal microscopy [Articolo su rivista]
Manfredini, Marco; Mazzaglia, Giovanna; Ciardo, Silvia; Simonazzi, Silvia; Farnetani, Francesca; Longo, Caterina; Pellacani, Giovanni
abstract

Background Skin hydration is defined as the water content of the epidermis and the dermis. In vivo reflectance confocal microscopy offers the opportunity to determine in vivo the kinetics of the skin after the application of topical products. Objective To define confocal features associated with dry skin and assess the microscopic effects of different moisturizers. Methods Ten healthy volunteers were enrolled for the study. Two different formulations were tested: petrolatum and a commercially available emulsion. Measurements were performed from baseline to 3 h after removal of the occlusion at regular time points. Nine confocal features were assessed: furrows' size, overall interkeratinocyte reflectance, furrows' morphology, scales, skin surface irregularity, non-rimmed dermal papillae, exocytosis, dermal inflammation and collagen type. Furrows' size and interkeratinocyte reflectance were also quantitated using a digital analysis. Stratum corneum capacitance was recorded. Results At baseline, RCM showed the presence of micro-scales and high skin surface irregularity score. After the application of topical products, the scale score decreased significantly; Furrow's size and Digital Furrow's Size had a marked and directly correlated decrement. Furrow's morphology and Epidermal Irregularity scores decreased from baseline to 30 min, the latter reaching a plateau in product application areas. Interestingly, interkeratinocyte reflectance progressively increased with the application of the topical products, while remained stable in the control area, confirmed by Digital Interkeratinocytes reflectance quantitation. Conclusion RCM revealed that the changes involve the skin surface by reducing the micro-scales and epidermal irregularity. Even more interestingly, RCM showed that higher interkeratinocytes' brightness is seen for moisturizer, but not for the control area. This RCM finding could be linked to keratinocyte membrane protein exposure and/or substance release in the interkeratinocytic space.

2013 - Fibroepithelioma of pinkus: Case reports and review of the literature [Articolo su rivista]
Reggiani, Camilla; Zalaudek, Iris; Piana, Simonetta; Longo, Caterina; Argenziano, Giuseppe; Lallas, Aimilios; Pellacani, Giovanni; Moscarella, Elvira
abstract

Fibroepithelioma of Pinkus (FeP) is an unusual foof basal cell carcinoma, which may clinically mimic a range of benign skin tumors that are not routinely excised. Preliminary observations on a total of 20 published cases of FeP suggest that dermoscopy and reflectance confocal microscopy may aid the clinical diagnosis and management of FeP. Herein we report the clinical, dermoscopic and confocal microscopic features of 3 additional cases of FeP, which were clinically misclassified as benign skin tumors, and discuss the role of dermoscopy and confocal microscopy in the clinical diagnosis of this condition. Copyright © 2013 S. Karger AG, Basel.

2013 - Focal dermal hypoplasia (goltz-gorlin syndrome): A new case with a novel variant in the PORCN gene (c.1250T>C:p.F417S) and unusual spinal anomaly [Articolo su rivista]
Garavelli, Livia; Simonte, Graziella; Rosato, Simonetta; Wischmeijer, Anita; Albertini, Enrico; Guareschi, Elisa; Longo, Caterina; Albertini, Giuseppe; Gelmini, Chiara; Greco, Chiara; Errico, Stefania; Savino, Gustavo; Pavanello, Marco; Happle, Rudolf; Unger, Sheila; Superti Furga, Andrea; Grzeschik, Karl Heinz
abstract

Focal dermal hypoplasia (FDH; Goltz-Gorlin syndrome; OMIM 305600) is a disorder that features involvement of the skin, skeletal system, and eyes. It is caused by loss-of-function mutations in the PORCN gene. We report a young girl with FDH, microphthalmos associated with colobomatous orbital cyst, dural ectasia and cystic malformation of the spinal cord, and a de novo variant in PORCN. This association has not been previously reported, and based on these observations the phenotypic spectrum of FDH might be broader than previously appreciated. It would be prudent to alter the suggested surveillance for this rare disorder. © 2013 Wiley Periodicals, Inc.

2013 - Inserting ex vivo fluorescence confocal microscopy perioperatively in mohs micrographic surgery expedites bedside assessment of excision margins in recurrent basal cell carcinoma [Articolo su rivista]
Longo, C.; Ragazzi, M.; Castagnetti, F.; Gardini, S.; Palmieri, T.; Lallas, A.; Moscarella, E.; Piana, S.; Pellacani, G.; Zalaudek, I.; Argenziano, G.
abstract

Mohs micrographic surgery can be employed in recurrent basal cell carcinoma, although it is a time-consuming technique. Recently, ex vivo fluorescence confocal microscopy (FCM) has been employed to obtain a fast assessment of tumor margins at the bedside. In our case we successfully employed ex vivo FCM to assess the tumor margins and we treated the persistent tumor with intensity-modulated radiation therapy. Our case demonstrates that a multidisciplinary approach is very efficient in managing complex and recurrent tumors and highlights the benefits of FCM as a new technique that can be used in the surgical theater to speed up the entire procedure. © 2013 S. Karger AG, Basel.

2013 - Is confocal microscopy a valuable tool in diagnosing nodular lesions? A study on 140 cases. [Articolo su rivista]
Longo, Caterina; Farnetani, Francesca; S., Ciardo; Cesinaro, A. M.; E., Moscarella; Ponti, Giovanni; I., Zalaudek; G., Argenziano; Pellacani, Giovanni
abstract

BACKGROUND: Nodular lesions poses diagnostic challenge since nodular melanoma may simulate all kind of melanocytic and non-melanocytic lesions. Reflectance confocal microscopy is a novel technique that allows the visualization of skin at nearly histologic resolution although limited laser depth penetration hamper the visualization of deep dermis. METHODS: 140 nodules were retrospectively evaluated by means of confocal microscopy in blind from histopathologic diagnosis. At the end of the study the patients' codes were broken and the evaluations were matched with histopathologic diagnosis before performing statistical analysis. OBJECTIVE: We sought to assess whether the diagnostic accuracy of confocal microscopy compared to histopathology for the diagnosis of nodular lesions, and to identify possible limitations of this technique RESULTS: The study consisted of 140 nodular lesions (23 "pure" nodular melanomas, 9 melanoma metastasis, 28 BCCs, 6 invasive SCC, 32 naevi, 14 Seborrheic keratosis, 17 dermatofibroma, 5 vascular lesions and 6 other lesions). Confocal microscopy correctly diagnosed 121 out of 140 lesions (86,4%); eight out of 140 (5,7%) lesions revealed discordance between histopathology and confocal microscopy. Eight out of 140 (5,7%) cases were not evaluable by means of confocal microscopy due to the presence of ulceration or hyperkeratosis and three cases showed a non specific pattern. Interestingly, confocal microscopy reached a 96.5% sensitivity and 94.1% specificity (AUC: 0.970) (CI95%: 0.924-1.015) (p<0.001) for the diagnosis of melanoma. LIMITATIONS: The study is retrospective and lesions were not included on the basis of their diagnostic difficulty CONCLUSIONS: Despite the limited laser depth penetration of confocal microscopy, this imaging tool represents an effective instruments in diagnosing nodular lesions; however, fully ulcerated lesions or when a marked hyperkeratosis is present, biopsy should be always performed. Prospective studies on difficult to diagnose nodules should be performed to further analyze the pros and contra of RCM in skin cancer diagnosis.

2013 - Laser skin rejuvenation: epidermal changes and collagen remodeling evaluated by in vivo confocal microscopy [Articolo su rivista]
Longo, C; Galimberti, M; De Pace, B; Pellacani, G; Bencini, Pl.
abstract

Fractionated carbon dioxide (CO2) laser resurfacing is an effective treatment of skin aging. Several studies investigated the morphologic changes due to this laser treatment by using skin biopsies or animal model. Recently, reflectance confocal microscopy (RCM) has emerged as a new tool that can "optically" scan the skin in vivo with a nearly histologic resolution and in a totally noninvasive modality. Our study aims to analyze the skin changes following the ablative fractional CO2 laser sessions by using RCM. Ten patients were subjected to ablative fractional CO2 laser sessions for skin aging. Confocal microscopic images were acquired at baseline (w0), 3 weeks (w3), 6 weeks (w6), and 12 weeks (w12) after laser session. Previously identified confocal parameters were used to assess the skin aging at baseline and after treatment. At w3, the epidermis showed a complete disappearance of the mottled pigmentation upon RCM along with the presence of few Langherans' cells. The collagen type as seen upon RCM observed at baseline was replaced by a newly formed collagen type of long, bright and straight fibers (collagen remodeling). These fibers were parallel arranged and observed throughout the entire RCM mosaic. At w6 and w12 the confocal aspects of the skin was unchanged compared to w3. RCM confirmed the presence of an intense collagen remodeling following laser resurfacing. In line with previous studies, this collagen showed a peculiar arrangement and distribution. The collagen remodeling was still present after 3 months and confirms the long-term effect of the treatment. This is the first time that the skin can be analyzed in vivo at patient's bedside. In the near future, RCM can be an essential adjunct for Clinicians to measure the effects of laser treatment and possibly to gain new insights into the development of side effects.

2013 - Management rules to detect melanoma [Articolo su rivista]
Lallas, Aimilios; Zalaudek, Iris; Apalla, Zoe; Longo, Caterina; Moscarella, Elvira; Piana, Simonetta; Reggiani, Camilla; Argenziano, Giuseppe
abstract

Most melanomas are easy to be diagnosed clinically and dermoscopically. The question remains open concerning the correct strategies to detect those melanomas that look morphologically inconspicuous from a clinical and/or dermoscopic point of view. In our estimation, when morphology is not enough to recognize melanoma, one has to use specific management strategies. Herein we summarize the following 7 simple and practical rules that outline the need for a more general approach integrating clinical information with dermoscopic examination: (1) Look basically at all lesions. (2) Undress high-risk patients. (3) Use the 10 seconds rule in single lesions. (4) Compare and monitor multiple moles. (5) Excise doubtful nodular lesions. (6) Combine clinical and dermoscopic criteria. (7) Combine clinical and histopathologic criteria. © 2013 S. Karger AG, Basel.

2013 - Meeting of the american academy of dermatology [Articolo su rivista]
Moscarella, Elvira; Zalaudek, Iris; Albertini, Giuseppe; Lallas, Aimilios; Longo, Caterina; Argenziano, Giuseppe
abstract

71st Meeting of the American Academy of Dermatology Miami Beach, FL, USA, 1-5 March 2013 The 71st meeting of the American Academy of Dermatology took place in Miami Beach from 1st to 5th March 2013. The meeting was a big success in terms of scientific output and number of participants, being the most attended meeting in the history of the Academy up to now. The scientific sessions covered basically all the fields of dermatology, encompassing the newest updates from oncologic to cosmetic dermatology. Herein, we focus on cutaneous oncology sessions, including melanoma and non-melanoma skin cancer, resuming both diagnostic and therapeutic updates with special attention to skin cancer prevention and the fascinating frontiers of the new available treatments. © 2013 Informa UK Ltd.

2013 - Microsatellite Instability and Mismatch Repair protein expression in Sebaceous tumors, Keratocanthoma and Basal Cell Carcinomas with sebaceous differentiation in Muir-Torre Syndrome. [Articolo su rivista]
Ponti, Giovanni; Longo, Caterina
abstract

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2013 - Multiple primary melanomas: do they look the same ? [Articolo su rivista]
E., Moscarella; H., Rabinovitz; S., Puig; I., Zalaudek; Oliviero, M. C.; L., Brown; I., Alarcon; J., Malvehy; Longo, Caterina; D., Formisano; C., Carrera; C., Badenas; S., Piana; G., Albertini; Pellacani, Giovanni; G., Argenziano
abstract

BACKGROUND: A series of studies have investigated epidemiological, clinical and genetic characteristics of multiple primary melanoma (MPM) patients. However, a comparison of the clinical and dermoscopic features of MPM within a given individual have been described only in case reports. OBJECTIVE: To describe the dermoscopic features of MPM for each given patient, and to evaluate the characteristics eventually associated with the similar or dissimilar appearance. METHODS: From the databases of three skin lesion clinics in US, Italy, and Spain we collected the dermoscopic images of melanomas in patients diagnosed with MPM. RESULTS: Among 58 patients with MPM, we found 53.5% of patients having dermoscopically similar melanomas and 46.5% of patients having dermoscopically different melanomas. In older patients 59.1% of melanomas were dermoscopically similar vs 46.9% in younger patients (p=0.377). Similar thickness was associated with the occurrence of dermoscopically similar melanomas (19 cases; 63.3%) (p=0.039). Most (65.4%) of the synchronous lesions were similar, compared to 35.7% of non-synchronous lesions (p=0.029), and most (69%) of the melanomas on sun-damaged skin were similar, vs 36.7% of melanomas on non sun-damaged skin (p=0.015; OR=3.88; CI 95%, 1.11-13.98). The percentage of dermoscopically different melanomas was higher in patients with a family history of melanoma (66.7% vs 47.7%). LIMITATIONS: Thin and superficial spreading melanomas were predominant in our study population, this may have restricted variation in dermoscopic features according to tumour type. Information about positive family history for melanoma and mutation in CDKN2A gene were only partially documented in our series. CONCLUSION: MPM in a given patient have almost the same chance to look dermoscopically similar or different. However, a subset of elderly patients with sun-damaged skin may present multiple, similar, thin melanomas characterized by pigment network and regression structures.

2013 - Pigmentation in a scar: Use of dermoscopy in the management decision [Articolo su rivista]
Moscarella, Elvira; Argenziano, Giuseppe; Lallas, Aimilios; Longo, Caterina; AL JALBOUT, Samer; Zalaudek, Iris
abstract

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2013 - Problematic Lesions in Children [Articolo su rivista]
Moscarella, Elvira; Piccolo, Vincenzo; Argenziano, Giuseppe; Lallas, Aimilios; Longo, Caterina; Castagnetti, Fabio; Pizzigoni, Stefania; Zalaudek, Iris
abstract

Melanoma in childhood is rare, and appears more commonly either in association with a preexisting (congenital) nevus, or with spitzoid features than de novo. Thus, problematic melanocytic lesions in children are essentially represented by congenital nevi and Spitz nevi that can be regarded as melanoma precursors and melanoma simulators, respectively. As a consequence, clinical and dermoscopic features of melanoma in children differ from those in an adult population. Herein we describe common clinical and dermoscopic features of problematic lesions in children, focusing on congenital and Spitz/Reed nevi, and including other problematic lesions, such as atypical, blue, acral, and scalp nevi. © 2013 Elsevier Inc.

2013 - Problematic Lesions in the Elderly [Articolo su rivista]
Zalaudek, Iris; Lallas, Aimilios; Longo, Caterina; Moscarella, Elvira; Tiodorovic Zivkovic, Danica; Ricci, Cinzia; Albertini, Giuseppe; Argenziano, Giuseppe
abstract

As the population continues to age, clinicians and dermatologists are increasingly faced with geriatric patients presenting with a range of dermatologic manifestations, including benign and malignant skin tumors. Knowledge of epidemiologic and morphologic features, including dermoscopy of common and benign melanocytic and nonmelanocytic skin tumors, provides the basis for a better understanding and management of problematic skin tumors in this age group. This article provides an overview of common and problematic skin lesions in elderly patients and addresses epidemiologic, clinical, and dermoscopic clues that aid the differential diagnosis and management of challenging skin lesions. © 2013 Elsevier Inc.

2013 - Proposal for an in vivo histopathologic scoring system for skin aging by means of confocal microscopy [Articolo su rivista]
Longo, Caterina; Casari, Alice; De Pace, Barbara; Simonazzi, Silvia; Mazzaglia, Giovanna; Pellacani, Giovanni
abstract

BACKGROUND: Many instrumental devices have been testing in analysing and quantifying the skin aging signs. However, histopathology still remains the only methods that allow a microscopic assessment of the skin. However, a skin biopsy is not feasible in aesthetically critical areas such as the face. Recently, confocal microscopy has been discovered as a noninvasive tool with a nearly histologic resolution. Distinct morphologic confocal aspects on facial skin have been described and correlated with the histopathologic counterparts. OBJECTIVES: In our study we aim to develop an easy to use confocal aging score to quantify the skin aging related signs. METHODS: A sample of facial skin of fifty volunteers has been subjected to confocal imaging. Combining the previously identified confocal features, three different semi-quantitative scores were calculated: - epidermal disarray score (irregular honeycombed pattern + epidermal thickness + furrow pattern); - epidermal hyperplasia score (mottled pigmentation + extent of polycyclic papillary + epidermal thickness; - collagen score (curled fibers, 2 for huddles of collagen, 1 for coarse collagen structures, and 0 for thin reticulated collagen) RESULTS: The epidermal disarray score showed a stable trend up to 65 years and a dramatic increase in the elderly subjects epidermal. Hyperplasia score was characterized by an ascending trend from younger subjects to middle age. The total collagen score showed a progressive trend with age with a different proportion of distinct collagen type. CONCLUSIONS: RCM is a powerful, noninvasive technique that could permit to microscopically quantify the aging signs and to test cosmetic efficacy.

2013 - Psoriasis plaque test with confocal microscopy: Evaluation of different microscopic response pathways in NSAID and steroid treated lesions [Articolo su rivista]
Ardigo, M.; Agozzino, M.; Longo, C.; Conti, A.; Di Lernia, V.; Berardesca, E.; Pellacani, G.
abstract

Background: Pathophysiology of psoriasis is complex and characterized by microscopic, specific changes. In vivo reflectance confocal microscopy (RCM) provides tissue and cell morphology information in non-invasive way, generating quasi-histologic resolution. Concerning plaque psoriasis, confocal criteria have been described disclosing high agreement between RCM and conventional histology. Objective: We sought to evaluate the in vivo microscopic changes in plaque psoriasis occurring during treatment with two distinct actives (aceclofenac and betamethason). Methods: A total of 32 patients with psoriasis were recruited. Two lesions from the same body area or symmetrical were evaluated at baseline and after 3-6 weeks by RCM. Results: Aceclofenac induced clinical improvement in 32% of patients after 3 weeks and in 76% after 6 weeks. With betamethason, at the end of the 3rd week, the 45% of patients showed improvement that increased to 81% at the end of the study. Single confocal criteria was evaluated and results underwent to statistical analysis considering the modification of the microscopical changes during the two treatments. Conclusion: RCM followed the microscopic changes during treatment and enabled to differentiate effects of different actives. Although data are preliminary and based on a limited sample, aceclofenac seems to be effective in the treatment for psoriasis. © 2013 John Wiley &amp; Sons A/S.

2013 - Reflectance confocal microscopy for diagnosis of mammary and extramammary Paget's disease [Articolo su rivista]
Guitera, P; Scolyer, R. A.; Gill, M.; Akita, H.; Arima, M.; Yokoyama, Y.; Matsunaga, K.; Longo, Caterina; Bassoli, S.; Bencini, P. L.; Giannotti, R.; Pellacani, Giovanni; Alessi Fox, C.; Dalrymple, C.
abstract

Background Paget's disease is an intraepidermal adenocarcinoma that is difficult to diagnose clinically as it mimics inflammatory or infectious diseases. As a consequence, it may be clinically misdiagnosed resulting in a delay in appropriate management. Reflectance confocal microscopy allows the visualization of the upper layers of the skin and mucosa at cellular resolution. Paget's disease is characterized histologically by the presence of neoplastic cells scattered throughout all layers of the epidermis in a pattern similar to that also observed in melanoma (and termed Pagetoid spread). Objective In vivo confocal microscopy is an excellent diagnostic tool for detecting Pagetoid spread and for diagnosing melanoma. We therefore hypothesized that it may also assist in the diagnosis of Paget's disease. Methods In this study, we describe the confocal features of nine cases of extramammary Paget's disease and one case of mammary one. Results Large atypical Pagetoid cells were present singly and in clusters in all 10 cases and were readily visualized on ex vivo and in vivo confocal microscopy. The presence of Pagetoid spread and other confocal features, in the appropriate clinical context, is suggestive Paget's disease and should allow distinction from other inflammatory diseases that may appear similar clinically. Conclusion The use of confocal microscopy is likely to facilitate earlier diagnosis of Paget's disease and the instigation of appropriate management with concomitant improvement in clinical outcomes. © 2012 European Academy of Dermatology and Venereology.

2013 - Reflectance confocal microscopy: A new tool in skin oncology [Articolo su rivista]
Meschieri, Andrea; Pupelli, Gaia; Pellacani, Giovanni; Rajadhyaksha, Milind; Longo, Caterina
abstract

Nowadays in the contest of skin diseases the most important goals are the decrease of mortality through an early diagnosis and the reduction of unnecessary excisions of benign entities. Reflectance confocal microscopy (RCM) is a modern imaging technique that has been introduced in main dermatological-referral centers and applied mostly in skin oncology. Currently, RCM may be considered very useful for accurate and early diagnosis of skin cancers (such as melanoma, basal cell carcinoma, squamous cell carcinoma), enabling a specific study of epidermal structures, dermo-epidermal junction and upper dermis. RCM, as second level diagnosis tool, is helpful in several cases, in particular for challenging lesions. © 2013 Walter de Gruyter GmbH, Berlin/Boston.

2013 - Skin aging: in vivo microscopic assessment of epidermal and dermal changes by means of confocal microscopy [Articolo su rivista]
Longo, Caterina; Casari, Alice; Beretti, Francesca; Cesinaro, Anna Maria; Pellacani, Giovanni
abstract

BACKGROUND: Skin aging is thought to be a complex biological process that is traditionally classified as intrinsic and extrinsic aging. Several clinical score and instrumental devices have been applied to obtain a precise assessment of skin aging. Among them, confocal microscopy has emerged as a new technique capable of assessing cytoarchitectural changes with a nearly histopathologic resolution. OBJECTIVE: We sought to determine the microscopic skin changes occurring on the face in different age groups by means of confocal microscopy. METHODS: The skin of the cheek in 63 volunteers belonging to distinct age groups was analyzed by confocal microscopy. In 4 cases, routine histopathology was performed on site-matched surplus areas from routine excisions for obtaining a better comparison with confocal findings. RESULTS: Young skin was characterized by regular polygonal keratinocytes and thin reticulated collagen fibers. With aging, more irregularly shaped keratinocytes and areas with unevenly distributed pigmentation and increased compactness of collagen fibers were observed. In the elderly, thinning of the epidermis, marked keratinocyte alterations, and huddles of collagen and curled fibers, corresponding to elastosis, were present. A side-by-side correlation between confocal descriptors and histopathologic aspects has been provided in a few cases. LIMITATIONS: Reticular dermal changes cannot be assessed because of the limited depth laser penetration. CONCLUSIONS: Confocal microscopy was successfully applied to identify in vivo skin changes occurring in aged skin at both the epidermal and dermal levels at histopathologic resolution. This offers the possibility to test cosmetic product efficacy and to identify early signs of sun damage.

2013 - Small diameter melanocytic lesions: morphological analysis by means of in vivo confocal microscopy [Articolo su rivista]
Pupelli, G; Longo, Caterina; Veneziano, L; Cesinaro, Am; Ferrara, G; Piana, S; Moscarella, E; Ricci, C; Zalaudek, I; Seidenari, S; Argenziano, G; Pellacani, Giovanni
abstract

BACKGROUND: small diameter melanocytic lesions represent a diagnostic challenge for clinicians since they do not follow the ABCD rule and do not always display reliable histopathologic criteria OBJECTIVES: The aim of the study was to analyze the confocal features of small diameter lesions (naevi and melanomas with diameter ≤ 5 mm) to determine whether they show specific morphologic criteria PATIENTS AND METHODS: 24 melanomas and 72 naevi were subjected to dermoscopic and confocal evaluation along with histopathology. Significant dermoscopic and confocal differences between melanomas and naevi were evaluated by means of Pearson's Chi-square. Odds ratios and 95% confidence interval were calculated for each parameter. Binary logistic regression was calculated to identify the RCM independently significant features for melanoma diagnosis. RESULTS: The 7-point checklist dermoscopic score was ≥ 3 in 22 melanomas and in 33 naevi. The combination of cells' pleomorphism and architectural disorder (i.e. non specific pattern or irregular junctional nests upon confocal examination) are the most striking criteria for consistent small melanoma diagnosis. Presence of atypical cells, >5 atypical cells per mm(2) and roundish atypical cells at DEJ showed the highest odds ratios values. From logistic regression presence of > 5 pagetoid cells per mm(2) , tangled lines within the epidermis, atypical roundish cells at DEJ resulted to be the three independent confocal parameters that characterized small melanomas. CONCLUSIONS: small melanomas frequently reveal specific dermoscopic and confocal features. Moreover the combination of dermoscopy and RCM can lead to a correct diagnosis of a quote of naevi that share some morphologic aspects with melanomas.

2013 - The Role of Reflectance Confocal Microscopy as an Aid in the Diagnosis of Collision Tumors [Articolo su rivista]
Moscarella, Elvira; Rabinovitz, H; Oliviero, Mc; Brown, L; Longo, Caterina; Zalaudek, I; Piana, S; Farnetani, Francesca; Lallas, A; Argenziano, Giuseppe; Pellacani, Giovanni
abstract

BACKGROUND: The term 'collision tumor' refers to the association of 2 or more different neoplasms within the same lesion. The association of a benign neoplasm with a malignant neoplasm is of particular significance and warrants diagnostic accuracy. OBJECTIVE: The purpose of our study was to see if reflectance confocal microscopy (RCM) was a valuable tool when dealing with collision tumors. METHODS: We retrospectively evaluated 24 histologically confirmed cases of collision tumors, which were initially assessed using dermoscopy and RCM. RESULTS: The malignancy most commonly detected in association with collision tumors was basal cell carcinoma (BCC) (n = 13), followed by melanoma (n = 5, of which 2 collided with BCC) and squamous cell carcinoma in situ (n = 4). Seborrheic keratoses were the most common benign neoplasms found in association with collision tumors (n = 18), followed by nevi (n = 7). Dermoscopy revealed the malignant component in 14 out of 20 lesions compared to RCM, which revealed a malignant component in 19 out of 20 neoplasms. There was excellent concordance between RCM and histopathology with regard to the identification of a malignant component within a tumor (kappa value >0.9). CONCLUSION: The dermatoscope and the reflectance confocal microscope, when used in conjunction, are valuable tools aiding in the diagnosis of collision tumors.

2013 - The light and the dark of dermatoscopy in the early diagnosis of melanoma: Facts and controversies [Articolo su rivista]
Apalla, Zoe; Lallas, Aimilios; Argenziano, Giuseppe; Ricci, Cinzia; Piana, Simonetta; Moscarella, Elvira; Longo, Caterina; Zalaudek, Iris
abstract

Early diagnosis remains the best method to reduce melanoma and non-melanoma skin cancer- related mortality and morbidity. Dermatoscopy was first introduced at the end of the last century, and besides the strict criticism that it initially received, the majority of the scientific community presently considers it revolutionary in the field of melanocytic lesion diagnostics. Cumulative evidence provides definite data that dermatoscopy improves the clinicians' diagnostic accuracy for melanoma compared with other clinical diagnostic approaches. There remain some barriers for its use such as lack of training, lack of time, and lack of reimbursement, as well as persisting skepticism about its true utility. In the current contribution, we focus on false beliefs and facts concerning dermatoscopy in the early diagnosis of melanoma and shed some light on some of the remaining "dark sides" of this issue. © 2013.

2013 - Update on non-melanoma skin cancer and the value of dermoscopy in its diagnosis and treatment monitoring [Articolo su rivista]
Lallas, A.; Argenziano, G.; Zendri, E.; Moscarella, E.; Longo, C.; Grenzi, L.; Pellacani, G.; Zalaudek, I.
abstract

Dermoscopy has become an integrative part of the clinical examination of skin tumors. This is because it significantly improves the early diagnosis of melanoma and non-melanoma skin cancer (NMSC) including basal cell carcinoma and keratinocyte skin cancer compared with the unaided eye. Besides its value in the noninvasive diagnosis of skin cancer, dermoscopy has also gained increased interest in the management of NMSC. Dermoscopy has been used in the preoperative evaluation of tumor margins, monitoring of the outcomes of topical treatments and post-treatment follow-up. This article provides an update on NMSC with special emphasis on dermoscopy in the diagnosis and management of basal cell carcinoma, actinic keratosis, Bowens' disease and squamous cell carcinoma. © 2013 2013 Expert Reviews Ltd.

2012 - Ameloblastoma: a neglected criterion for nevoid basal cell carcinoma (Gorlin) syndrome. [Articolo su rivista]
Ponti, Giovanni; L., Pastorino; A., Pollio; S., Nasti; Pellacani, Giovanni; M. D., Mignogna; Tomasi, Aldo; C. D., Forno; Longo, Caterina; G., Bianchi Scarrà; G., Ficarra; Seidenari, Stefania
abstract

Ameloblastomas are considered to be aggressive and locally invasive neoplasms derived from odontogenic epithelium with a tendency for recurrence and bone destruction. Although the relationship between nevoid basal cell carcinoma syndrome (NBCCS) and ameloblastoma is less frequent, it might constitute a peculiar stigmata of this hereditary disorder. The objective of the current study was to evaluate whether a combined clinical and biomolecular approach could be useful for the identification of NBCCS among patients with a diagnosis of ameloblastoma. The authors collected ameloblastoma tumors recorded in the databases of the Pathology Departments of the University of Modena during the period 1991-2011. Family trees were drawn for all 41 patients affected by these specific odontogenic tumors. Two patients with ameloblastoma were also affected by multiple basal cell carcinomas and odontogenic keratocysts tumors (OKCTs) achieving the requested clinical criteria for the diagnosis of NBCCS. The clinical diagnoses were confirmed by the identification of two different novel PTCH1 germline mutations (c.2186A > T [p.K729 M]; c.931insA) in those unrelated patients. Clinical ameloblastoma findings can be used as screening for the identification of families at risk of NBCCS. Ameloblastomas diagnosis warrants the search for associated cutaneous basal cell carcinomas and other benign and malignant tumors related to NBCCS. Thus, we propose the inclusion of ameloblasoma as criterion for the identification of NBCCS.

2012 - Application of photodynamic therapy combined with pre-illumination microneedling in the treatment of actinic keratosis in organ transplant recipients [Articolo su rivista]
Bencini, P. L; Galimberti, M. G.; Pellacani, Giovanni; Longo, Caterina
abstract

ND

2012 - Atypical/dysplastic nevi [Capitolo/Saggio]
Pellacani, Giovanni; Farnetani, Francesca; Argenziano, Giuseppe; Zalaudek, Iris; Longo, Caterina; Gill, Melissa
abstract

Atypical nevi, also referred as dysplastic nevi, are characterized by intermediate aspects in between to common nevi and melanomas. From a clinical point of view, they usually show up as larger and more irregular and nonhomogenously pigmented lesions than common nevi. In dermatopathology, they are classically characterized by lentiginous melanocytic hyperplasia, epithelioid melanocytic atypia, lamellar fibroplasias and perivascular lymphocytic infiltrate [1]. From these observations a pathogenetic model for stepwise development of a MM from a nevus has been proposed. However, this model remains controversial due to nonclear and reproducible clinical definition of dysplastic nevus, limitations in recognition of early melanoma and dysplastic nevus, and weak correlation between histologic dysplasia and clinical atypia [2].

2012 - Classifying melanocytic nevi [Capitolo/Saggio]
Zalaudek, Iris; Longo, Caterina; Ricci, Cinzia; Albertini, Giuseppe; Argenziano, Giuseppe
abstract

Different types of melanocytic nevi do exist in relation to their epidemiology, evolution, morphology, genetics, and their associated melanoma risk. The introduction of dermoscopy has opened a new morphologic dimension of melanocytic nevi; this along with recent progresses in our understanding of the molecular pathways involved in the formation of nevi opened new ways to classify nevi.

2012 - Confocal features of equivocal facial lesions on severely sun-damaged skin: four case studies with dermatoscopic, confocal, and histopathologic correlation [Articolo su rivista]
Wurm, Elisabeth M. T; Curchin, Claudia E. S; Lambie, Duncan; Longo, Caterina; Pellacani, Giovanni; Soyer, H. Peter
abstract

Facial skin has a distinct histologic architecture and reveals specific dermatoscopic features. Diagnosis of lentigo maligna on the face is often challenging because of the overlap of clinical and morphologic features with other lesions.

2012 - Confocal microscopy: Improving our understanding of nevogenesis [Capitolo/Saggio]
De Pace, B; Ferrari, B; Predieri, Barbara; Iughetti, Lorenzo; Veneziano, L; Zalaudek, I; Argenziano, G; Longo, Caterina; Pellacani, Giovanni
abstract

n.a.

2012 - Dermoscopic and histopathologic correlations [Capitolo/Saggio]
Pupelli, Gaia; Veneziano, Leonardo; Longo, Caterina; Rezze, Gisele Gargantini; Soyer, Hans Peter; Pellacani, Giovanni
abstract

Dermoscopy is a widely diffused technique that offers the possibility to analyze subsurface structures not otherwise visible by naked eye. It has been proved that dermoscopy is an essential clinical tool in the hands of experts for diagnostic definition of melanocytic and non-melanocytic skin lesions, while improving diagnostic accuracy [1]. In addition to dermoscopy, reflectance-mode confocal microscopy (RCM) holds the great advantage to explore histological details of skin tissue, in vivo and in real time. Similarly to dermoscopy RCM produces images corresponding to horizontal section of the skin from the epidermis surface to the papillary dermis but offering a cellular level resolution, similarly to histopathology. Thus, it seems to be the natural link between dermoscopy and histopathology.

2012 - Dermoscopy of scalp tumours: A multi-centre study conducted by the international dermoscopy society [Articolo su rivista]
Stanganelli, I.; Argenziano, Giuseppe; Sera, F.; Blum, A.; Ozdemir, F.; Karaarslan, I. K.; Piccolo, D.; Peris, K.; Kirchesch, H.; Bono, R.; Pizzichetta, M. A.; Gasparini, S.; Braun, R. P.; Correia, O.; Thomas, L.; Zaballos, P.; Puig, S.; Malvehy, J.; Scalvenzi, M.; Rabinovitz, H.; Bergamo, A.; Pellacani, Giovanni; Longo, Caterina; Pavlovic, M.; Rosendahl, C.; Hofmann Wellenhof, R.; Cabo, H.; Marghoob, A. A.; Langford, D.; Astorino, S.; Manganoni, A. M.; Gourhant, J. Y.; Keir, J.; Grichnik, J. M.; Fumo, G.; Dong, H.; Sortino Rachou, A. M.; Ferrara, G.; Zalaudek, I.
abstract

Background Little is known about the dermoscopic features of scalp tumours. Objective To determine the dermoscopic features of scalp tumours. Methods Retrospective analysis of dermoscopic images of histopathologically diagnosed scalp tumours from International Dermoscopy Society members. Results A total of 323 tumours of the scalp from 315 patients (mean age: 52 years; range 3-88 years) were analysed. Scalp nevi were significantly associated with young age (<30 years) and exhibited a globular or network pattern with central or perifollicular hypopigmentation. Melanoma and non-melanoma skin cancer were associated with male gender, androgenetic alopecia, age >65 years and sun damage. Atypical network and regression were predictive for thin (1 mm) melanomas, whereas advanced melanomas (tumour thickness > 1 mm) revealed blue white veil, unspecific patterns and irregular black blotches or dots. Conclusions The data collected provide a new knowledge regarding the clinical and dermoscopy features of pigmented scalp tumours. © 2011 European Academy of Dermatology and Venereology.

2012 - Early diagnosis of melanoma: What is the impact of dermoscopy? [Articolo su rivista]
Argenziano, Giuseppe; Albertini, Giuseppe; Castagnetti, Fabio; De Pace, Barbara; Di Lernia, Vito; Longo, Caterina; Pellacani, Giovanni; Piana, Simonetta; Ricci, Cinzia; Zalaudek, Iris
abstract

There are three possible explanations for the improved melanoma recognition when a clinician uses dermoscopy: first, the presence of early dermoscopy signs that become visible in melanoma much before the appearance of the classical clinical features; second, an increased attitude of clinicians to check more closely clinically banal-looking lesions; and third, an improved attitude of clinicians to monitor their patients. In this review, the light and the dark sides of melanoma screening are briefly discussed, including the need to find better strategies to decrease the number of unnecessary excision of benign lesions on one hand, and to finally decrease melanoma mortality rates on the other. © 2012 Wiley Periodicals, Inc.

2012 - Evaluation of allergic vesicular reaction to patch test using in vivo confocal microscopy [Articolo su rivista]
Ardigò, M; Longo, Caterina; Cristaudo, A; Berardesca, E; Pellacani, Giovanni
abstract

Background: Confocal microscopy has been successfully applied both in oncologic and inflammatory diseases. In particular, it has been proved as a useful tool for the in vivo detection of microscopical changes occurring in allergic reactions. Aims of the study: To evaluate microscopic changes occurring in positive patch test reactions. Methods: Eight patients with history of allergic dermatitis and positive patch test reaction were analysed by means of confocal microscopy. Results: Confocal microscopy showed the presence of spongiotic vesicle preferentially localized around the adnexal ducts that appeared to be in the middle of the spongiotic phenomena. Conclusion: Confocal microscopy offered for the first time new insight into vesicle formation and development, showing that adnexal ducts can play a role in allergic reaction. © 2011 John Wiley & Sons A/S.

2012 - Feasibility of in vivo confocal microscopy in diagnosing nodular lesions. [Abstract in Rivista]
Longo, Caterina; Ciardo, S.; Farnetani, F.; Cesinaro, A.; Ponti, Giovanni; Pellacani, Giovanni
abstract

abstract

2012 - Functional protein pathway activation mapping of the progression of normal skin to squamous cell carcinoma [Articolo su rivista]
Einspahr, Janine G; Calvert, Valerie; Alberts, David S; Curiel Lewandrowski, Clara; Warneke, James; Krouse, Robert; Stratton, Steven P; Liotta, Lance; Longo, Caterina; Pellacani, Giovanni; Pellicani, Giovanni; Prasad, Anil; Sagerman, Paul; Bermudez, Yira; Deng, Jianghong; Bowden, G. Timothy; Petricoin, Emanuel F.
abstract

Reverse phase protein microarray analysis was used to identify cell signaling derangements in squamous cell carcinoma (SCC) compared with actinic keratosis (AK) and upper inner arm (UIA). We analyzed two independent tissue sets with isolation and enrichment of epithelial cells by laser capture microdissection. Set 1 served as a pilot and a means to identify protein pathway activation alterations that could be further validated in a second independent set. Set 1 was comprised of 4 AK, 13 SCC, and 20 UIA. Set 2 included 15 AK, 9 SCCs, and 20 UIAs. Activation of 51 signaling proteins, known to be involved in tumorigenesis, were assessed for set 1 and showed that the MEK-ERK [mitogen-activated protein (MAP)/extracellular signal-regulated (ERK; MEK)] pathway was activated in SCC compared with AK and UIA, and that epidermal growth factor receptor (EGFR) and mTOR pathways were aberrantly activated in SCC. Unsupervised two-way hierarchical clustering revealed that AK and UIA shared a common signaling network activation architecture while SCC was dramatically different. Statistical analysis found that prosurvival signaling through phosphorylation of ASK and 4EBP1 as well as increased Bax and Bak expression was higher in AK compared with UIA. We expanded pathway network activation mapping in set 2 to 101 key signaling proteins, which corroborated activation of MEK-ERK, EGFR, and mTOR pathways through discovery of a number of upstream and downstream signaling molecules within these pathways to conclude that SCC is indeed a pathway activation-driven disease. Pathway activation mapping of SCC compared with AK revealed several interconnected networks that could be targeted with drug therapy for potential chemoprevention and therapeutic applications.

2012 - Improving triage and management of patients with skin cancer: challenges and considerations for the future [Articolo su rivista]
Argenziano, G; Giacomel, J; Abramavicus, A; Pellacani, Giovanni; Longo, Caterina; De Pace, B; Albertini, G; Cristofolini, M; Zalaudek, I.
abstract

Skin cancer is the most common malignancy in humans, thus representing a major health concern. Because of the increasing attention to skin cancer prevention, there has been a growing workload for dermatology clinics, with patients referred from primary care requiring assessment of suspicious skin tumors. This places a strain on limited specialist resources and can create a paradoxical situation wherein an early diagnosis becomes increasingly difficult for those patients who actually do suffer from skin cancer. The aim of these recommendations is to propose an updated, rational system of triage, involving improved accuracy of diagnosis and more timely management of skin cancer by both general practitioners and dermatologists.

2012 - In vivo assessment of chronological ageing and photoageing in forearm skin using reflectance confocal microscopy [Articolo su rivista]
Wurm, E. M. T.; Longo, Caterina; Curchin, C.; Soyer, H. P.; Prow, T. W; Pellacani, Giovanni
abstract

Background Skin ageing is a complex process due to intrinsic chronological factors (chronoageing) and extrinsic environmental factors. The primary extrinsic factor is cumulative ultraviolet (UV) exposure, and is therefore termed photoageing. The current standards for measuring cumulative sun damage are biopsy histology and skin microtopography. However, skin biopsies are too invasive for population studies and skin replicas render only superficial skin architecture data. Reflectance confocal microscopy (RCM) is a noninvasive imaging tool that allows for in vivo imaging of the skin at quasihistological resolution. Objectives To define and identify RCM features associated with chronological ageing and photoageing on the forearm in two age groups with different skin phototypes and to assess whether these results agree with previous findings. Methods We obtained RCM images of dorsal and volar nonlesional skin of the lower forearm of 75 individuals with skin Fitzpatrick phototypes I-III in two age groups (20-30 years and 50-60 years). From each participant and body site, 21 RCM features were assessed and statistically significant differences between the two age groups and different forearm sites determined. Results RCM enabled identification of changes in architecture, cell morphology and extracellular matrix (collagen) at the level of the epidermis, dermoepidermal junction and papillary dermis. Changes that were correlated with chronological ageing and which were aggravated on the UV-exposed dorsal forearm were: loss of small skin furrows resulting in wider and less intersecting furrows; irregularity of the epidermal honeycomb pattern; irregularly distributed (mottled) pigmented keratinocytes/melanocytes; irregularity of the papillary rings and/or effacement of the rete ridges; and loss of thin collagen fibres and presence of collagen clods. Conclusion We have tested previously reported and new parameters for skin ageing evaluation by RCM, and identified 15 statistically significant RCM features that can be used to quantify ageing and photoageing in forearm skin noninvasively. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

2012 - In vivo confocal microscopic pattern of fibroepithelioma of pinkus [Articolo su rivista]
Longo, Caterina; Soyer, Hp; Pepe, P; Casari, Alice; Wurm, Em; Guitera, P; Pellacani, Giovanni
abstract

2012 - In vivo confocal microscopy for detection and grading of dysplastic nevi: a pilot study [Articolo su rivista]
Pellacani, Giovanni; Farnetani, Francesca; Gonzalez, G; Longo, Caterina; Cesinaro, Am; Casari, Alice; Beretti, Francesca; Seidenari, Stefania; Gill, M.
abstract

.

2012 - In vivo confocal microscopy for diagnosis of melanoma and basal cell carcinoma using a 2-step method: analysis of 710 consecutive clinically equivocal cases [Articolo su rivista]
P., Guitera; S. W., Menzies; Longo, Caterina; A. M., Cesinaro; R. A., Scolyer; Pellacani, Giovanni
abstract

We describe two algorithms to diagnose basal cell carcinomas (BCCs) and melanomas (MMs) using in vivo reflectance confocal microscopy (RCM). A total of 710 consecutive cutaneous lesions excised to exclude malignancy (216 MMs, 266 nevi, 119 BCCs, 67 pigmented facial macules, and 42 other skin tumors) were imaged by RCM. RCM features were correlated with pathology diagnosis to develop diagnostic algorithms. The diagnostic accuracy of the BCC algorithm defined on multivariate analysis of the training set (50%) and tested on the remaining cases was 100% sensitivity, 88.5% specificity. Positive features were polarized elongated features, telangiectasia and convoluted vessels, basaloid nodules, and epidermal shadowing corresponding to horizontal clefting. Negative features were non-visible papillae, disarrangement of the epidermal layer, and cerebriform nests. Multivariate discriminant analysis on the training set (excluding the BCCs) identified seven independently significant features for MM diagnosis. The diagnostic accuracy of the MM algorithm on the test set was 87.6% sensitivity, 70.8% specificity. The four invasive MMs that were misdiagnosed by RCM were all of nevoid subtype. RCM is a highly accurate non-invasive technique for BCC diagnosis. Good diagnostic accuracy was achieved also for MM diagnosis, although rare variants of melanocytic tumors may limit the strict application of the algorithm.Journal of Investigative Dermatology advance online publication, 21 June 2012

2012 - Mass spectrometry-based biomarker discovery [Capitolo/Saggio]
Zhou, Weidong; Petricoin III, Emanuel F.; Longo, Caterina
abstract

Discovery of candidate biomarkers within the entire proteome is one of the most important and challenging goals in proteomic research. Mass spectrometry-based proteomic is a modern and promising technology for semiquantitative and qualitative assessment of proteins, enabling protein sequencing and identification with exquisite accuracy and sensitivity. For mass spectrometry analysis, protein extractions from tissues of interest or body fluids with subsequent protein fractionation represent an important and unavoidable step in the workflow for biomarker discovery. The aim of our chapter is to provide practical lab procedures for sample digestion and protein fractionation for subsequent mass spectrometry analysis.

2012 - Melanoma progression [Capitolo/Saggio]
Longo, Caterina; Casari, Alice; Argenziano, Giuseppe; Zalaudek, Iris; Pellacani, Giovanni
abstract

Melanoma arises by a process of stepwise progression in which the transition from melanocytes to metastatic melanoma involves several histologic intermediates. According to the “three-step tumor progression model”, these intermediates include radial growth phase melanoma (RGP), microinvasive radial growth phase and vertical growth phase melanoma (VGP) [1, 2].

2012 - New directions in dermatopathology: in vivo confocal microscopy in clinical practice [Articolo su rivista]
Longo, Caterina; Zalaudek, Iris; Argenziano, Giuseppe; Pellacani, Giovanni
abstract

In vivo confocal microscopy represents a new device that generates a virtual skin biopsy at cytologic resolution. This article describes the most relevant confocal findings and their histopathologic correlates in skin oncology and inflammatory diseases. The light and dark of confocal microscopy are briefly discussed in relation with its clinical applications.

2012 - Nonablative fractional photothermolysis for acne scars: clinical and in vivo microscopic documentation of treatment efficacy [Articolo su rivista]
Bencini, Pier Luca; Tourlaki, Athanasia; Galimberti, Michela; Longo, Caterina; Pellacani, Giovanni; De Giorgi, Vincenzo; Guerriero, Giuseppe
abstract

Fractional photothermolysis has been shown to improve various types of scarring, including atrophic acne scars. The aim of the present authors was to assess the efficacy and safety of the nonablative fractional photothermolysis in the treatment of moderate and severe acne scars. Eighty-seven patients with moderate or severe acne scarring were treated with six sessions with a 1540-nm Erbium glass fiber laser at 3-week intervals. Six months after the final session, 7/87 (8%) patients showed a moderate improvement, whereas 80/87 (92%) patients had a marked improvement. In a subset of patients, the present authors also applied in vivo reflectance confocal microscopy to highlight the relevant microscopic changes. Hence, early and late posttreatment findings, most importantly the replacement of a coarser collagen with a new one, similar to the collagen seen in healthy skin, were observed. In accordance to previous studies, the present authors conclude that nonablative fractional photothermolysis is a safe and effective treatment for moderate or severe acne scarring.

2012 - Novel PTCH1 Mutations in Patients with Keratocystic Odontogenic Tumors Screened for Nevoid Basal Cell Carcinoma (NBCC) Syndrome. [Articolo su rivista]
L., Pastorino; A., Pollio; PELLACANI, Giovanni; C., Guarneri; P., Ghiorzo; LONGO, Caterina; W., Bruno; F., Giusti; S., Bassoli; G., Bianchi Scarrà; C., Ruini; S., Seidenari; TOMASI, Aldo; PONTI, Giovanni
abstract

Keratocystic odontogenic tumors (KCOTs) are cystic tumors that arise sporadically or associated with nevoid basal cell carcinoma syndrome (NBCCS). NBCCS is a rare autosomal dominantly inherited disease mainly characterized by multiple basal cell carcinomas, KCOTs of the jaws and a variety of other tumors. PTCH1 mutation can be found both in sporadic or NBCCS associated KCOTs. The aim of the current study was to assess whether a combined clinical and bio-molecular approach could be suitable for the detection of NBCCS among patients with a diagnosis of keratocystic odontogenic tumors (KCOTs). The authors collected keratocystic odontogenic tumors recorded in the database of the Pathology Department of the University of Modena and Reggio Emilia during the period 1991-2011. Through interviews and examinations, family pedigrees were drawn for all patients affected by these odontogenic lesions. We found out that 18 of the 70 patients with KCOTs and/or multiple basal cell carcinomas actually met the clinical criteria for the diagnosis of NBCCS. A wide inter- and intra-familial phenotypic variability was evident in the families. Ameloblastomas (AMLs) were reported in two probands that are also carriers of the PCTH1 germline mutations. Nine germline mutations in the PTCH1 gene, 5 of them novel, were evident in 14 tested probands. The clinical evaluation of the keratocystic odontogenic tumors can be used as screening for the detection of families at risk of NBCCS. Keratocystic odontogenic lesions are uncommon, and their discovery deserves the search for associated cutaneous basal cell carcinomas and other benign and malignant tumors related to NBCCS.

2012 - Novel PTCH1 mutations in patients with keratocysic odontogenic umors as first hint to NBCC (Gorlin) detection [Poster]
Fabiano, Antonella; Ponti, Giovanni; Pastrino, L; Pellacani, Giovanni; Longo, Caterina; Bassoli, S; Bianchi Scarrà, G; Seidenari, S.
abstract

Keratocystic odontogenic tumors (KCOTs) are cystic tumors that arise sporadically or associated with nevoid basal cell carcinoma syndrome (NBCCS). NBCCS is a rare autosomal dominantly inherited disease mainly characterized by multiple basal cell carcinomas, KCOTs of the jaws and a variety of other tumors. PTCH1 mutation can be found both in sporadic or NBCCS associated KCOTs. The aim of the current study was to assess whether a combined clinical and bio-molecular approach could be suitable for the detection of NBCCS among patients with a diagnosis of keratocystic odontogenic tumors (KCOTs). The authors collected keratocystic odontogenic tumors recorded in the database of the Pathology Department of the University of Modena and Reggio Emilia during the period 1991-2011. Through interviews and examinations, family pedigrees were drawn for all patients affected by these odontogenic lesions.We found out that 18 of the 70 patients with KCOTs and/or multiple basal cell carcinomas actually met the clinical criteria for the diagnosis of NBCCS. A wide inter- and intra-familial phenotypic variability was evident in the families. Ameloblastomas (AMLs) were reported in two probands that are also carriers of the PCTH1 germline mutations. Nine germline mutations in the PTCH1 gene, 5 of them novel, were evident in 14 tested probands.The clinical evaluation of the keratocystic odontogenic tumors can be used as screening for the detection of families at risk of NBCCS. Keratocystic odontogenic lesions are uncommon, and their discovery deserves the search for associated cutaneous basal cell carcinomas and other benign and malignant tumors related to NBCCS.

2012 - Novel PTCH1 mutations in patients with keratocystic odontogenic tumors as first hint to Gorlin-Goltz syndrome detection [Abstract in Rivista]
A., Fabiano; Ponti, Giovanni; L., Pastorino; Longo, Caterina; G., Bianchi Scarrà; S., Seidenari; Pellacani, Giovanni
abstract

abstract

2012 - Peripheral stellate telangiectasias: A clinical-dermoscopic clue for diganosing cutaneous melanoma metastases [Articolo su rivista]
Julian, Yamina; Argenziano, Giuseppe; Moscarella, Elvira; de Paula Ramos Castro, Raquel; Longo, Caterina; Abeldaño, Alejandra; Zalaudek, Iris
abstract

Background: The clinical and dermoscopic diagnosis of cutaneous melanoma meta-stases may be challenging especially in patients with unknown primary melanoma. Main observations: We observed repetitive dermoscopic patterns of peripheral stel-late telangiectasias in cutaneous melanoma metastases from 3 patients, of whom 2 had an unknown primary melanoma. Conclusions: Stellate telangiectasias surrounding bluish to purple or red nodules with recent onset may represent a clue for cutaneous melanoma metastases.

2012 - Reflectance confocal microscopy applications in cosmetology [Capitolo/Saggio]
Pellacani, Giovanni; Longo, Caterina; Ardigò, Marco
abstract

Skin is a multi-functional organ that present distinct aspects in physiological and pathological conditions. The two main structural layers of the skin, the epidermis and the dermis, can be either affected by many pathologic processes. An inevitable skin change occurs with the passage of time (skin aging) that can be dramatically accelerated by environmental factors. Since the epidermis is the outer layer of skin, which serves as a physical and chemical barrier to the environment, several damage can affect this compartment, mainly due to irritants or medical treatments such as peelings. Another pathologic phenomenon regards the skin pigmentation that can be located exclusively in the epidermis and at dermo-epidermal junction or deeper into the dermis. The skin comprises also adnexal structures such as hairs that are part of distinct cutaneous entities belonging from the spectrum of inflammatory or degenerative diseases.

2012 - Spitz nevi [Capitolo/Saggio]
Bassoli, Sara; Longo, Caterina; Pellacani, Giovanni
abstract

The Spitz–Reed nevi family includes benign melanocytic tumors, generally acquired, characterized by a wide variety of clinical presentations, dermoscopic pattern and histopathologic features. The clinical differential diagnosis with melanoma is often considered due to its alarming clinical presentation. Spitz nevi are often described as pinkish-red papule suddenly arising in very young people, whereas Reed ones are commonly seen on the legs of adult patients. In both cases, patients often refer that the lesion suddenly appeared and is quickly growing. In this chapter, and often in the daily clinical experience, these two entities are joined in the same group, showing common histopathologic findings. © Springer-Verlag Berlin Heidelberg 2012.

2012 - Successful treatment of two invasive squamous cell carcinomas with topical 5% imiquimod cream in elderly patients [Articolo su rivista]
Tiodorovic Zivkovic, Danica; Zalaudek, Iris; Longo, Caterina; De Pace, Barbara; Albertini, Giuseppe; Argenziano, Giuseppe
abstract

ND

2012 - Superficial spreading melanoma [Capitolo/Saggio]
Longo, Caterina; Casari, Alice; Pellacani, Giovanni
abstract

Superficial spreading melanoma (SSM) is the most common type of melanoma in Caucasian, accounting for about 70% of all diagnosed melanoma cases [1]. This type of melanoma can strike at any age and occurs slightly more often in females than males. SSM has two growth phases: the radial growth phase and the vertical ones [2]. The radial phase involves expansion of the lesion through the epidermis (upper skin layer). In the early radial phase, the lesion is thin, and it can remain in this phase for months or years. This is the less life threatening of the two phases because once the melanoma enters into the vertical growth stage, the prognosis worsens.

2012 - Tele-reflectance confocal microscopy [Capitolo/Saggio]
Wurm, Elisabeth M. T; Longo, Caterina; Hemmer, Paul; Pellacani, Giovanni
abstract

Evaluation of RCM images requires specialized training that is not universally available, despite a growing number of publications in this field and this present work being the second book published in this area. Application of teledermatology in RCM (Tele-RCM) aims to overcome this shortage of distribution of experts and to improve distribution of knowledge by e-learning.

2012 - Tele-reflectance confocal microscopy [Capitolo/Saggio]
Longo, Caterina; Hemmer, P.; Pellacani, Giovanni
abstract

Reflectance confocal microscopy (RCM) is a revolutionary diagnostic tool that enables rapid non-invasive imaging of skin tissue at nearly histologic resolution without biopsy. In the field of dermato-oncology, RCM has been successfully applied on melanoma and non-melanoma skin cancers for diagnostic purposes, even in equivocal dermoscopic lesions where subtle cyto-architectural atypia is present. RCM provides the clinicians with a combination of clinical, dermoscopic and in vivo pathologic information that greatly increase the diagnostic confidence. RCM application in clinical centers dealing with challenging skin cancers, could be of great value for both clinicians and patients. However, the need of intense confocal training and expertise could represent an impediment for its successful application. Tele-RCM has been created to solve the issue of personnel training (e-learning) and also to offer a tele-consult among scientific community while improving diagnostic knowledge.

2012 - The "signature" pattern of multiple basal cell carcinomas [Articolo su rivista]
Zalaudek, Iris; Moscarella, Elvira; Longo, Caterina; De Pace, Barbara; Argenziano, Giuseppe
abstract

ND

2012 - The dual pathway of nevogenesis [Capitolo/Saggio]
Zalaudek, Iris; Scope, Alon; Argenziano, Giuseppe; Longo, Caterina; Piana, Simonetta; Carticalà, Caterina; Marghoob, Ashfaq A.
abstract

The evolution of melanocytic nevi is a complex, multifactorial process involving both constitutional and environmental factors. While histopathology remains the gold standard for diagnosis of melanocytic lesions, it is a mere cross-sectional view of nevus evolution at one point in time. Dermoscopy and more recently, reflectance confocal microscopy (RCM) are in vivo diagnostic techniques for the assessment of morphologic features of nevi; the fact that most dermoscopic features are well correlated with histopathologic criteria makes these methods valuable for observing gross tissue changes of nevi over time without need to biopsy (Table 4.1). Thus, dermoscopy and RCM have enriched profoundly our knowledge about the morphological variability of nevi and offered new insights into their evolution.

2012 - p16 immunohistochemistry of multiple primary melanomas as screening to identify Familial Melanoma Syndrome [Articolo su rivista]
Ponti, Giovanni; G., Luppi; Losi, Lorena; A. M., Cesinaro; Sartori, Giuliana; Maiorana, Antonino; Pellacani, Giovanni; Longo, Caterina; E., Boni; P., Pepe; Giannetti, Alberto; Seidenari, Stefania; M. T., Landi
abstract

The Authors describe the use of p16 immunohistochemistry in multiple primary melanomas as screening to identify Familial Melanoma Syndrome.

2011 - A novel biomarker harvesting nanotechnology identifies Bak as a candidate melanoma biomarker in serum. [Articolo su rivista]
Longo, Caterina; G., Gambara; V., Espina; A., Luchini; B., Bishop; A. S., Patanarut; E. F., Petricoin; Beretti, Francesca; B., Ferrari; E., Garaci; DE POL, Anto; Pellacani, Giovanni; L. A., Liotta
abstract

Melanoma represents only 4\% of all skin cancers, but nearly 80\% of skin cancer deaths. This manuscript applies several new measurement technologies with the purpose of elucidating molecular signatures of melanoma aggressiveness.We sought to determine whether low-abundant serum proteins related to apoptotic pathways could be measured and correlated with defined melanoma subtypes. Hydrogel core shell nanoparticles, a new technology capable of selectively entrapping low molecular weight proteins and protecting them from enzymatic degradation, were used to capture candidate serum biomarkers. Biomarker levels were correlated with confocal microscopy, thereby representing a combination of new technologies for in vivo histologic documentation.Among a panel of analyzed serum proteins, Bak was differentially expressed between nevi and melanomas. Melanomas with higher Bak serum levels exhibited more pronounced junctional activity on confocal imaging, whereas lesions with 'sparse' dermal nests had weak Bak expression.Our study links serum proteome analysis with confocal microscopic clinical in vivo histologic classification of melanomas. Bak has not been previously measured in serum. Bak differential expression among melanoma subtypes confirms the importance of the apoptotic pathway as a contributor to melanoma aggressiveness.

2011 - Blue-black rule: A simple dermoscopic clue to recognize pigmented nodular melanoma [Articolo su rivista]
Argenziano, Giuseppe; Longo, Caterina; Cameron, A.; Cavicchini, S.; Gourhant, J. Y.; Lallas, A.; Mccoll, I.; Rosendahl, C.; Thomas, L.; Tiodorovic Zivkovic, D.; Zaballos, P.; Zalaudek, I.
abstract

Background Dermoscopy improves melanoma recognition, but most criteria were described in the context of superficial spreading melanoma. Objectives To test whether pigmented nodular melanoma could be recognized dermoscopically by the presence of a combination of blue and black colour within the lesion. Methods Dermoscopic images of histopathologically diagnosed pigmented nodular tumours with no (or only minimal) flat component were evaluated for the presence of standard melanoma criteria and for the presence of a new feature named blue-black (BB) colour. Sensitivity, specificity, positive predictive value and negative predictive value were calculated for standard criteria and BB feature in relation to the diagnosis of melanoma and to diagnosis of malignancy. Results Of 283 lesions, 160 were malignant, including 78 (27·6%) melanomas, and 123 were benign. The BB feature and the standard criteria had 78·2% and 43·6% sensitivity for melanoma, respectively, whereas a combined method based on the presence of either the BB feature or one (or more) of the standard criteria reached 84·6% sensitivity, with 80·5% specificity and 93·2% negative predictive value. Sensitivity values for malignant lesions were only 24·4%, 56·9% and 60% for standard criteria, BB feature and the combined method, respectively. However, the combined method gave 91·9% specificity and 90·6% positive predictive value for malignancy. Conclusions Using a method based on the BB feature or one of the standard melanoma criteria, only 9·4% of positive pigmented nodular lesions were found to be benign and only 6·8% of negative lesions were found to be melanoma histopathologically. © 2011 British Association of Dermatologists.

2011 - Confocal microscopy of recurrent naevi and recurrent melanomas: A retrospective morphological study [Articolo su rivista]
Longo, Caterina; Moscarella, Elvira; Pepe, P; Cesinaro, Am; Casari, Alice; Manfredini, M; Stanganelli, I; Gardini, S; Cota, C; Argenziano, G; Pellacani, Giovanni; Zalaudek, I.
abstract

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2011 - De novo melanoma and melanoma arising from pre-existing nevus: In vivo morphologic differences as evaluated by confocal microscopy [Articolo su rivista]
Longo, Caterina; Rito, Cintia; Beretti, Francesca; Cesinaro, Anna Maria; Piñeiro Maceira, Juan; Seidenari, Stefania; Pellacani, Giovanni
abstract

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2011 - Effectiveness and limitations of reflectance confocal microscopy in detecting persistence of basal cell carcinomas: A preliminary study [Articolo su rivista]
Webber, Sa; Wurm, Emt; Douglas, Nc; Lambiec, D; Longo, Caterina; Pellacani, Giovanni; Soyer, Hp
abstract

Background/Objectives: Reflectance confocal microscopy (RCM) can accurately and non-invasively diagnose basal cell carcinoma (BCC). The use of RCM in assessing responses to saucerization or curettage and cautery of BCC has not been established. The aim of the present study was to expound the usefulness of RCM in assessing treatment responses of BCC to saucerization or curettage and cautery 8-12 weeks after treatment. Methods: Eight sequential patients, with 11 superficial BCCs, were recruited. Lesions were evaluated clinically and dermoscopically. Three operators performed RCM imaging for each BCC at baseline and 8-12 weeks after treatment. Diagnostic criteria for RCM diagnosis included streaming of basal cells and the presence of cord-like structures and horizontal vessels. Results were compared against histopathology. Difficulties in establishing tumour clearance were identified and the effectiveness of RCM in assessing the response to treatment was explored. Results: At baseline, all lesions were consistent with superficial BCC. At 8-12 weeks after treatment, RCM correctly diagnosed 10 of 11 lesions as tumour free. Furthermore, RCM was reliable across operators of variable experience and the findings were confirmed histopathologically. Limitations were identified, but appeared to be related to operator experience. Conclusion: The diagnosis of BCC was straightforward and reliable in the present study. Thus, RCM appears useful in assessing the early treatment response of superficial BCC treated with saucerization or curettage and cautery despite operator-dependant limitations. © 2011 The Authors. Australasian Journal of Dermatology © 2011 The Australasian College of Dermatologists.

2011 - First experiences using Reflectance Confocal Microscopy on equivocal skin lesions in Queensland [Articolo su rivista]
Curchin, Ces; Wurm, Emt; Lambie, D; Longo, Caterina; Pellacani, Giovanni; Soyer, Hp
abstract

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2011 - Inverse association between dietary vitamin D and risk of cutaneous melanoma in a Northern Italy population [Articolo su rivista]
Vinceti, Marco; Malagoli, Carlotta; Fiorentini, Chiara; Longo, Caterina; Crespi, Cm; Albertini, G; Ricci, C; Lanzoni, A; Reggiani, M; Virgili, A; Osti, F; Lombardi, M; Santini, M; Fanti, Pa; Dika, E; Sieri, S; Krogh, V; Seidenari, Stefania; Pellacani, Giovanni
abstract

The possibility of an inverse association between vitamin D and risk of cancer and, in particular, of cutaneous malignant melanoma has been suggested, but results of epidemiologic studies are still conflicting. We examined the relation between dietary vitamin D intake and melanoma risk through a population-based case-control study (380 cases, 719 controls) in a northern region of Italy, a country with an average vitamin D intake lower than that in northern Europe or the United States. We assessed average daily intake of vitamin D from foodstuffs using the European Prospective Investigation into Cancer and Nutrition (EPIC) semiquantitative food frequency questionnaire. In this population, levels of vitamin D intake were considerably lower than those observed in recent U.S. studies. We found an inverse relation between dietary vitamin D and melanoma risk in the sample as a whole, in both crude and adjusted analyses. In sex- and age-specific analyses, this association appeared to be stronger among males and among older subjects. These findings suggest that, at the relatively low levels of intake observed in this sample, an inverse relation between dietary vitamin D and risk of cutaneous malignant melanoma may exist.

2011 - Pigmented nodular Basal cell carcinomas in differential diagnosis with nodular melanomas: confocal microscopy as a reliable tool for in vivo histologic diagnosis. [Articolo su rivista]
Casari, Alice; Pellacani, Giovanni; Seidenari, Stefania; A. M., Cesinaro; Beretti, Francesca; P., Pepe; Longo, Caterina
abstract

Nodular basal cell carcinoma, especially when pigmented, can be in differential diagnosis with nodular melanomas, clinically and dermoscopically. Reflectance confocal microscopy is a relatively new imaging technique that permits to evaluate in vivo skin tumors with a nearly histological resolution. Here, we present four cases of challenging nodular lesions where confocal microscopy was able to clarify the diagnosis.

2011 - The dermoscopic and histopathologic pattern of nevi correlate with the frequency of BRAF mutations [Articolo su rivista]
I., Zalaudek; C., Guelly; R., Hofmann Wellenhof; S., Trajanoski; H., Kittler; B., Leinweber; Pellacani, Giovanni; A., Scope; A., Marghoob; Longo, Caterina; G., Ferrara; T., Saida; J. M., Gricknick; G., Argenziano; J. C., Becker
abstract

ND

2011 - in vivo detectionof Demodex folliculorum by means of confocal microscopy [Articolo su rivista]
Longo, Caterina; Pellacani, Giovanni; Argenziano, G; De Pace, B; Zalaudek, I.
abstract

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2010 - Dermoscopic island: A new descriptor for thin melanoma [Articolo su rivista]
Borsari, Stefania; Longo, Caterina; Ferrari, Chiara; Benati, Elisa; Bassoli, Sara; Schianchi, Simona; Giusti, Francesca; A. M., Cesinaro; Pellacani, Giovanni; Seidenari, Stefania
abstract

Objectives: To determine the frequency and the features of the dermoscopic island (DI) in melanocytic lesions and to assess its specificity for the diagnosis of melanoma. Dermoscopy improves the diagnostic accuracy of melanoma, but only a few dermoscopic descriptors specific for thin melanomas have been identified. We defined a new descriptor, the dermoscopic island, a well-circumscribed area showing a uniform dermoscopic pattern that differs from the rest of the pigmented lesion. Design: Dermoscopic images of 96 in situ melanomas, 266 invasive melanomas, and 612 dermoscopic atypical nevi were evaluated to establish the presence and the main pattern of the DI. Also, clinical and histologic characteristics were analyzed. Setting: Dermoscopic images were collected from lesions excised between 2003 and 2008 at the Department of Dermatology, University of Modena and Reggio Emilia. Main Outcome Measures: Specificity and odds ratio for melanoma; dermoscopic and histologic characteristics of lesions with a DI. Results: The DI was present in 10.4% of in situ melanomas, 4.1% of invasive melanomas, and 3.1% of dermoscopic atypical nevi. The odds ratio for melanoma was 1.922, and specificity was 96.9%. Invasive melanomas with a DI were thinner than those lacking this descriptor. In addition, more than half of the melanomas with a DI arose on a nevus. The DI appeared mainly reticular on a reticular background. Conclusion: The DI is characteristic of thin melanoma arising in a nevus; thus, it can be considered a potential early sign of transformation of a nevus into a melanoma. ©2010 American Medical Association. All rights reserved.

2010 - In vivo histologic diagnosis of basal cell carcinoma by means of confocal microscopy [Abstract in Atti di Convegno]
Longo, C.; Manfredini, M.; Casari, A.; Pepe, P.; Pellacani, G.
abstract

In vivo histologic diagnosis of basal cell carcinoma by means of confocal microscopy

2010 - Reflectance confocal microscopy as an aid to dermoscopy to improve diagnosis on equivocal lesions: evaluation of three bluish nodules. [Articolo su rivista]
Bassoli, Sara; Seidenari, Stefania; Pellacani, Giovanni; Longo, Caterina; A. M., Cesinaro
abstract

Nodular lesions can be difficult to diagnose under dermoscopy alone, since they often lack specific diagnostic features. Confocal microscopy can be used as an aid to dermoscopy, to increase the diagnostic accuracy on equivocal skin lesions. We report three cases of bluish nodular lesions, difficult to diagnose under dermoscopy alone. Confocal features were very useful in these cases to lead us to the correct diagnosis, recognizing benign versus malignant entities. Histopathology is also reported, with high correspondence compared to the confocal imaging.

2010 - Synthesis and characterization of hydrogel particles containing Cibacron Blue F3G-A [Articolo su rivista]
Patanarut, Alexis; Luchini, Alessandra; Botterell, Palma J.; Mohan, Anirudh; Longo, Caterina; Vorster, Paul; Petricoin, Emanuel F.; Liotta, Lance A.; Bishop, Barney
abstract

The analysis of low abundance and low molecular weight biomolecules is challenging due to their labile nature and the presence of high abundance, high molecular weight species such as serum albumin, which can hinder their detection. Functionalized hydrogel particles have proven to be ideally suited for this application. We here report the synthesis of hydrogel core and core-shell particles with incorporated Cibacron Blue F3G-A, and analysis of their harvesting properties. Hydrogel particle scaffolds consisting of cross-linked N-isopropylacrylamide and allylamine copolymers were synthesized via surfactant-free precipitation polymerization, with the blue dye subsequently affixed via a nucleophilic substitution reaction. The dye-functionalized core and core-shell particles were found to efficiently harvest and sequester dilute low molecular weight peptides and proteins from solution, with the core-shell particles more effectively excluding larger proteins. Moreover, proteins bound by core and core-shell particles containing blue dye were protected from tryptic degradation. These findings suggest that core and core-shell hydrogel particles containing Cibacron Blue F3G-A constitute promising new tools for peptide/protein biomarker harvesting applications. © 2010 Elsevier B.V.

2010 - The different psychological profiles of subjects attending melanoma screening campaigns and those delaying diagnosis: an aid for designing preventive campaigns? [Articolo su rivista]
Forghieri, Matilde; Longo, Caterina; Galeazzi, Gian Maria; Rigatelli, Marco; Seidenari, Stefania; Pellacani, Giovanni
abstract

Patient delay in seeking medical attention for melanoma (MM) constitutes one of the main challenges in designing prevention campaigns. No conclusive studies exploring psychological aspects of those patients, using standardized psychometric instruments, are currently available. We hypothesized that the attitude toward illness of subjects attending the melanoma screening day (EMD) would differ from patients diagnosed with MM following the usual clinical pathways. Five psychometric tests, assessing attitude toward illness, were administered both to EMD and MM groups, this latter further divided into two subgroups (good and bad detectors, GD and BD) considering the histo-clinical characteristics of the lesion. The Mann-Whitney U Test and Pearson Chi Square test were used to compare EMD patients with the other groups and to compare psychometric scores between GD and BD. BD and GD groups showed significant differences. Interestingly, the BD group was characterized by higher scores in Temperament and Character Inventory Fearful subscale, Multidimensional Health Locus of Control Powerful Others scale and Illness Behaviour Questionnaire General Hypochondriasis, Affective Disturbance and Irritability subscales. BD patients tend to react in a phobic manner to medical recommendations and they appear to favour external and more assertive help, which would suggest choosing a more direct approach in proposing a prevention campaign. Although this is a pilot study and further studies are needed, it gives new insight to build up more effective prevention campaigns for those patients.

2010 - The impact of in vivo reflectance confocal microscopy on the diagnostic accuracy of lentigo maligna and equivocal pigmented and nonpigmented macules of the face [Articolo su rivista]
Guitera, P; Pellacani, Giovanni; Crotty, Ka; Scolyer, Ra; Li, Lx; Bassoli, Sara; Vinceti, Marco; Rabinovitz, H; Longo, Caterina; Menzies, S. W.
abstract

Limited studies have reported the in vivo reflectance confocal microscopy (RCM) features of lentigo maligna (LM). A total of 64 RCM features were scored retrospectively and blinded to diagnosis in a consecutive series of RCM sampled, clinically equivocal, macules of the face (n=81 LM, n=203 benign macules (BMs)). In addition to describing RCM diagnostic features for LM (univariate), an algorithm was developed (LM score) to distinguish LM from BM. This comprised two major features each scoring +2 points (nonedged papillae and round large pagetoid cells >20 mum), and four minor features; three scored +1 point each (three or more atypical cells at the dermoepidermal junction in five 0.5 x 0.5 mm(2) fields, follicular localization of atypical cells, and nucleated cells within the dermal papillae), and one (negative) feature scored -1 point (a broadened honeycomb pattern). A LM score of >/=2 resulted in a sensitivity of 85% and specificity of 76% for the diagnosis of LM (odds ratio (OR) for LM 18.6; 95% confidence interval: 9.3-37.1). The algorithm was equally effective in the diagnosis of amelanotic lesions and showed good interobserver reproducibility (87%). In a test set of 29 LMs and 44 BMs, the OR for LM was 60.7 (confidence interval: 11.9-309) (93% sensitivity, 82% specificity).Journal of Investigative Dermatology advance online publication, 15 April 2010; doi:10.1038/jid.2010.84.

2009 - Core-Shell Hydrogel Particles Harvest, Concentrate and Preserve Labile Low Abundance Biomarkers [Articolo su rivista]
Longo, Caterina; A., Patanarut; T., George; B., Bishop; W., Zhou; C., Fredolini; M. M., Ross; V., Espina; Pellacani, Giovanni; E. F., Petricoin III; L. A., Liotta; A., Luchini
abstract

Background: The blood proteome is thought to represent a rich source of biomarkers for early stage disease detection. Nevertheless, three major challenges have hindered biomarker discovery: a) candidate biomarkers exist at extremely low concentrations in blood; b) high abundance resident proteins such as albumin mask the rare biomarkers; c) biomarkers are rapidly degraded by endogenous and exogenous proteinases. Methodology and Principal Findings: Hydrogel nanoparticles created with a N-isopropylacrylamide based core (365 nm)-shell (167 nm) and functionalized with a charged based bait (acrylic acid) were studied as a technology for addressing all these biomarker discovery problems, in one step, in solution. These harvesting core-shell nanoparticles are designed to simultaneously conduct size exclusion and affinity chromatography in solution. Platelet derived growth factor (PDGF), a clinically relevant, highly labile, and very low abundance biomarker, was chosen as a model. PDGF, spiked in human serum, was completely sequestered from its carrier protein albumin, concentrated, and fully preserved, within minutes by the particles. Particle sequestered PDGF was fully protected from exogenously added tryptic degradation. When the nanoparticles were added to a 1 mL dilute solution of PDGF at non detectable levels (less than 20 picograms per mL) the concentration of the PDGF released from the polymeric matrix of the particles increased within the detection range of ELISA and mass spectrometry. Beyond PDGF, the sequestration and protection from degradation for a series of additional very low abundance and very labile cytokines were verified. Conclusions and Significance: We envision the application of harvesting core-shell nanoparticles to whole blood for concentration and immediate preservation of low abundance and labile analytes at the time of venipuncture. © 2009 Longo et al.

2009 - Nanoparticle technology: Addressing the fundamental roadblocks to protein biomarker discovery [Articolo su rivista]
Luchini, Alessandra; Longo, Caterina; Espina, Virginia; Petricoin Iii, Emanuel F.; Liotta, Lance A.
abstract

The incorporation of affinity baits into N-isopropylacrylamide-hydrogel- based nanoparticles offers a novel technology that addresses the major analytical challenges of disease biomarker discovery. In solution in complex biologic fluids (e.g. blood or urine), core-shell bait-containing nanoparticles can perform three functions in one step: (a) sieve molecules according to size, (b) sequestrate and concentrate target analytes, and (c) protect analytes from degradation. © 2009 The Royal Society of Chemistry 2009.

2009 - New insights into nevogenesis: in vivo characterization and follow-up of melanocytic nevi by reflectance confocal microscopy [Articolo su rivista]
Pellacani, Giovanni; A., Scope; Ferrari, Barbara; Pupelli, Gaia; Bassoli, Sara; Longo, Caterina; A. M., Cesinaro; G., Argenziano; R., Hofmann Wellenhof; J., Malvehy; A. A., Marghoob; S., Puig; Seidenari, Stefania; H. P., Soyer; I., Zalaudek
abstract

BACKGROUND: Development of melanocytic nevi is a complex process.OBJECTIVE: The aim of the study was to characterize the in vivo confocal microscopy patterns and histopathologic correlates of melanocytic nevi. In addition, for the first time, confocal follow-up of characteristic nevi was performed documenting histologic changes in nevi.METHODS: For the correlation study, 33 melanocytic nevi showing characteristic dermatoscopic patterns were studied by confocal microscopy. For the follow-up study 20 nevi were monitored for 12 to 18 months.RESULTS: Reticular nevi showed two different confocal patterns, ringed and meshwork, mostly corresponding to lentiginous and nested junctional patterns, respectively. Globular nevi presented large junctional clusters, whereas cobblestone nevi were constituted by dermal dense melanocytic clusters. Homogeneous nevi did not show distinctive confocal and histopathologic findings. Nevi with a rim of globules presented a meshwork pattern with junctional clusters at the periphery. At the confocal follow-up study all lesions showed limited dynamic changes resulting in stable dermatoscopic and confocal patterns, but 3 globular nevi with junctional nests at baseline evolved into reticular-meshwork pattern nevi with peripheral rim of globules-junctional nests.LIMITATIONS: Longer confocal follow-up of more melanocytic nevi is required to confirm this theory and to validate our preliminary findings.CONCLUSIONS: A model explaining the nevus classification and patterns of evolution of nevi observed in the study was proposed.

2009 - Reflectance confocal microscopy and features of melanocytic lesions: An internet-based study of the reproducibility of terminology [Articolo su rivista]
Pellacani, Giovanni; Vinceti, Marco; Bassoli, Sara; R., Braun; S., Gonzalez; P., Guitera; Longo, Caterina; A. A., Marghoob; S. W., Menzies; S., Puig; A., Scope; Seidenari, Stefania; J., Malvehy
abstract

Objective: To test the interobserver and intraobserver reproducibility of the standard terminology for description and diagnosis of melanocytic lesions in in vivo confocal microscopy. Design: A dedicated Web platform was developed to train the participants and to allow independent distant evaluations of confocal images via the Internet. Setting: Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy. Participants: The study population was composed of 15 melanomas, 30 nevi, and 5 Spitz/Reed nevi. Six expert centers were invited to participate at the study. Intervention: Evaluation of 36 features in 345 confocal microscopic images from melanocytic lesions. Main Outcome Measure: Interobserved and intraobserved agreement, by calculating the Cohen κ statistics measure for each descriptor. Results: High overall levels of reproducibility were shown for most of the evaluated features. In both the training and test sets there was a parallel trend of decreasing κ values as deeper anatomic skin levels were evaluated. All of the features, except 1, used for melanoma diagnosis, including roundish pagetoid cells, nonedged papillae, atypical cells in basal layer, cerebriform clusters, and nucleated cells infiltrating dermal papillae, showed high overall levels of reproducibility. However, less-than-ideal reproducibility was obtained for some descriptors, such as grainy appearance of the epidermis, junctional thickening, mild atypia in basal layer, plump bright cells, small bright cells, and reticulated fibers in the dermis. Conclusion: The standard consensus confocal terminology useful for the evaluation of melanocytic lesions was reproducibly recognized by independent observers. ©2009 American Medical Association. All rights reserved.

2009 - Spitz nevi: In vivo confocal microscopic features, dermatoscopic aspects, histopathologic correlates, and diagnostic significance [Articolo su rivista]
Pellacani, Giovanni; Longo, Caterina; G., Ferrara; A. M., Cesinaro; Bassoli, Sara; P., Guitera; S. W., Menzies; Seidenari, Stefania
abstract

Spitz nevi are benign melanocytic tumors, sometimes misdiagnosed as malignant melanoma (MM). OBJECTIVE: We sought identification of characteristic in vivo microscopic features of Spitz nevi, their histopathologic correlates, and diagnostic usefulness. METHODS: Forty Spitz nevi were studied by in vivo confocal microscopy and dermatoscopy, evaluating histopathologic correlates, and compared with 40 MMs and 40 Clark nevi. RESULTS: Some histologic aspects characteristic for Spitz nevus diagnosis were correlated with confocal features, comprising some that can be useful for atypical Spitz nevus classification. The most striking features for differentiating Spitz nevi from MMs were the presence of sharp border cut-off, junctional nests, and melanophages. LIMITATIONS: No correlates were found for other aspects, such as Kamino bodies, hyperkeratosis, acanthosis, mitoses, and maturation with depth. The impossibility of exploring deeper aspects hampered an accurate distinction from MMs in some cases. CONCLUSION: Confocal and dermatoscopic examination enabled the identification of different Spitz categories with different histologic substrates.

2009 - Vitamina D e melanoma cutaneo: studio epidemiologico multicentrico nella regione Emilia-Romagna [Abstract in Rivista]
Vinceti, Marco; Pellacani, Giovanni; Seidenari, Stefania; V., Krogh; S., Sieri; A., Lanzoni; M., Reggiani; G., Albertini; C., Ricci; A., Virgili; F., Osti; Fiorentini, Chiara; Longo, Caterina; P., Fanti; G., De Panfilis; M., Santini; Malagoli, Carlotta
abstract

1.OBIETTIVIAlcuni studi epidemiologici hanno suggerito un ruolo della vitamina D nella riduzione dell’incidenza di alcuni tumori (colon-retto, mammella, melanoma). Essendo la dieta una importante fonte di questa vitamina, abbiamo realizzato uno studio caso-controllo di popolazione multicentrico in alcune province della regione Emilia-Romagna per approfondire la relazione tra il rischio di melanoma cutaneo e la quantità di vitamina D assunta tramite la dieta abituale, ed in generale, con le abitudini alimentari.2.METODIPresso Unità di Dermatologia del territorio emiliano-romagnolo abbiamo reclutato i pazienti con diagnosi di melanoma cutaneo effettuata nel periodo 2005/06. Abbiamo poi tratto dalla popolazione generale quattro controlli per ogni caso (di medesimo sesso, età e provincia di residenza) mediante estrazione casuale dall’anagrafe regionale del Servizio Sanitario Nazionale. Ad ogni soggetto incluso nello studio è stato consegnato un questionario, il Food Frequency Questionnaire di derivazione “EPIC”, composto da 248 items, atto ad analizzare in modo estremamente accurato la dieta abituale. Abbiamo inoltre raccolto informazioni anagrafiche, fisico-costituzionali ed alcuni dati di interesse dermatologico.3.RISULTATILa lettura dei 1099 questionari alimentari autocompilati dai 380 pazienti e dai 719 controlli che hanno aderito allo studio ci ha fornito informazioni sulla quantità e la frequenza di assunzione di numerosi nutrienti ed alimenti presenti nella dieta dei singoli individui.Le analisi multivariate aggiustate per i principali fattori confondenti (introito calorico, body mass index e fototipo) hanno rilevato un effetto protettivo della vitamina D nei confronti del melanoma cutaneo (odds ratio del quintile superiore vs. quintile inferiore 0,55; intervalli di confidenza al 95% 0,33-0,93; P trend: 0,019). L’analisi disaggregata nei due sessi ha evidenziato come questo apparente effetto protettivo della vitamina D sia presente soprattutto nel sesso maschile (odds ratio del quintile superiore vs. quintile inferiore 0,34; intervalli di confidenza al 95% 0,15-0,78; P trend 0,008). 4.CONCLUSIONIPur con la cautela dovuta alle limitazioni degli studi osservazionali ed al possibile effetto confondente dell’esposizione solare, questi risultati sembrano suggerire che la vitamina D assunta con la dieta influenzi in modo significativo il rischio di melanoma cutaneo.

2009 - in vivo reflectance confocal microscopy enhances secondary evaluation of melanocytic lesions [Articolo su rivista]
P., Guitera; Pellacani, Giovanni; Longo, Caterina; Seidenari, Stefania; M., Avradamis; S. W., Menzies
abstract

We recently described an in vivo reflectance confocal microscopy (RCM) method and our aim was to evaluate a possible additive value of this type of analysis in the management of melanocytic lesions. In two referral centers (Sydney and Modena), lesions (203 nevi and 123 melanomas (MMs) with a median Breslow thickness of 0.54 mm) were excised on the basis of clinical suspicion (history, dermoscopy examination, and/or digital monitoring). The RCM method was also trialed on a non-biopsied population of 100 lesions, which were clinically and dermoscopically diagnosed as benign nevi. All RCM and dermoscopy diagnoses were performed blinded to the histopathological diagnosis. Firstly, in the study population, a high interobserver agreement (on a subset of 90 lesions) was seen with the RCM method, which had superior specificity (68%, 95% confidence interval (95% CI): 61.1-74.3) for the diagnosis of MM compared with dermoscopy (32%, 95% CI: 25.9-38.7), while showing no difference in sensitivity (91%, 95% CI: 84.6-95.5, RCM; 88%, 95% CI: 80.7-92.6 dermoscopy). The two techniques had a weak correlation, resulting in only 2.4% of MMs being misclassified by both techniques. Diagnosis of light-colored lesions is improved by RCM (specificity 84%, 95% CI: 66.3-94.5) compared with dermoscopy (specificity 39%, 95% CI: 23.7-56.2). Secondly, the RCM method classified 100% of the non-biopsied control nevi population as benign.

2008 - Five years of Consultation Liaison Psychiatry in a Dermatological ward: An Italian experience [Abstract in Rivista]
Pingani, L; Forghieri, M; Po, S; Mazzi, F; Longo, Caterina; Pellacani, Giovanni; Rigatelli, Marco
abstract

Not available

2008 - In vivo confocal microscopic and histopathologic correlations of dermoscopic features in 202 melanocytic lesions [Articolo su rivista]
Pellacani, Giovanni; Longo, Caterina; J., Malvehy; S., Puig; C., Carrera; S., Segura; Bassoli, Sara; Seidenari, Stefania
abstract

Objectives: To identify in vivo microscopic substrates of the dermoscopic patterns of melanocytic lesions and to correlate them with histopathologic features. Design: Before excision, lesion areas that showed characteristic dermoscopic patterns were imaged by dermoscopy and confocal microscopy and directly correlated with histopathologic features. Setting: Departments of Dermatology of the University of Modena and Reggio Emilia and Hospital Clínico of Barcelona, between July 2006 and March 2007. Patients: Patients with 202 melanocytic lesions, corresponding to 76 melanomas, 114 nevi, and 12 Spitz or Reed nevi. Main Outcome Measures: Correlation of dermoscopic patterns in melanocytic lesions with confocal microscopic findings and conventional histopathologic findings. Results: Characteristic architectural and cytologic substrates were identified in vivo with the use of confocal microscopy and correlated with histopathologic features. Pigment network atypia was evidenced through confocal microscopy as a disarrangement of dermoepidermal junction architecture and cellular atypia. Pigmented globules consisted of cell clusters, corresponding to melanocytic nests identified on histopathologic analysis. Black dots correlated with intraepidermal reflective spots or with large pagetoid cells in nevi and melanoma, respectively. Blue structures usually consisted of numerous pleomorphic cells, corresponding to malignant melanocytes and inflammatory cells in melanomas, whereas plump bright cells, corresponding to melanophages on histopathologic analysis, characterized benign lesions. Within regression, a retiform distribution of collagen fibers, which sometimes intermingled with melanophages and rarely with nucleated cells, was observable. Conclusions: The knowledge of the cytologic and architectural aspects of the different dermoscopic patterns, as they appear by in vivo confocal microscopy, may guide the user to the identification of specific substrates in melanocytic lesions and consequently the interpretation of the dermoscopic features. ©2008 American Medical Association. All rights reserved.

2008 - In vivo microscopic features of nodular melanomas: Dermoscopy, confocal microscopy, and histopathologic correlates [Articolo su rivista]
S., Segura; Pellacani, Giovanni; S., Puig; Longo, Caterina; Bassoli, Sara; P., Guitera; J., Palou; S., Menzies; Seidenari, Stefania; J., Malvehy
abstract

Objective: To characterize nodular melanoma (NM) using dermoscopy, in vivo reflectance-mode confocal microscopy, and histopathologic analysis. Design: Consecutive pure NMs and superficial spreading melanomas (SSMs) with nodular or blue areas were studied using dermoscopy and confocal microscopy, and a correlation with histopathologic findings was performed. Materials: Ten NMs, 10 SSMs with a nodular area, and 10 SSMs with a blue palpable but not yet nodular area. Main Outcome Measure: Confocal differences within the nodular component between pure NMs and SSMs with a nodular area, hypothesizing different biological behaviors. Results: Whereas NMs had predominantly nonspecific global dermoscopic patterns, SSMs exhibited a multicomponent pattern and higher dermoscopic scores. Globules, blue-white veil, atypical vessels, and structureless areas were frequent in NMs and in nodular areas from SSMs. At confocal microscopy, NMs exhibited few pagetoid cells within a typical epidermal architecture in the superficial layers in most cases, differing from SSMs frequently characterized by epidermal disarrangement and pagetoid infiltration. At the dermoepidermal junction, dermal papillae were rarely seen in nodular areas both from NMs and from SSMs, frequently substituted by nonaggregated atypical cells distributed in sheetlike structures. In the upper dermis, all groups exhibited plump bright cells, dense dishomogeneous cell clusters, and atypical nucleated cells, whereas cerebriform clusters were characteristic of NMs. Conclusion: Distinctive dermoscopic and confocal features seen in NMs compared with SSMs are helpful in making the diagnosis and suggest different biological behavior. Arch Dermatol. 2008; 144(10): 1311-1320.

2008 - Reflectance confocal microscopy for in vivo skin imaging [Articolo su rivista]
CALZAVARA PINTON, Pg; Longo, Caterina; Venturini, M; Sala, R; Pellacani, Giovanni
abstract

Reflectance confocal microscopy (RCM) is a novel noninvasive technique for "in vivo" examination of the skin. In a confocal microscope, near- infrared light from a diode laser is focused on a microscopic skin target. As this light passes between cellular structures having different refraction indexes, it is naturally reflected, and this reflected light is then captured and recomposed into a two-dimensional gray scale image by computer software. Focusing the microscope (adjusting the focal point on the z-axis) allows images to be obtained of different levels within the skin. Commercially available microscope systems of this type can create images with enough detail for use in histological analysis. The first investigations using these microscopes served to identify the appearance of the various cell populations living in the different layers of normal skin. Today, the main interest has become focused on the use of these microscopes as a diagnostic tool: a means of investigating benign and malignant tumors of melanocytes and keratinocytes, and, more importantly, the findings of this field of study can be used to develop a diagnostic algorithm which would be not only highly sensitive but specific as well. The aim of the paper is to provide an updated literature review and an in-depth critique of the state-of-the-art of RCM for skin cancer imaging with a critical discussion of the possibilities and limitations for clinical use.

2008 - Reflectance confocal microscopy for melanoma and melanocytic lesions assessment [Articolo su rivista]
Longo, Caterina; Pellacani, Giovanni; Bassoli, Sara; Farnetani, Francesca; Ferrari, Barbara; Pupelli, Gaia; Seidenari, Stefania Pellacani
abstract

Reflectance confocal microscopy (RCM) is an emerging noninvasive diagnostic tool that provides in vivo tissue images at nearly cellular histological resolution. Peculiar confocal findings of melanocytic lesions have been evaluated and applied in real clinical settings to elucidate the impact of RCM in improving diagnostic accuracy. This review aims to clearly update the relevant confocal findings and to critically analyze their role in the clinical scenario

2007 - An atypical Meyerson's naevus: a dermoscopic, confocal microscopic and immunohistochemical description of one case [Articolo su rivista]
Longo, Caterina; S., Segura; A. M., Cesinaro; Bassoli, Sara; Seidenari, Stefania; Pellacani, Giovanni
abstract

An eczematous halo around a melanocytic naevus is an uncommon clinical and histological variation of the melanocytic naevus first described by Meyerson1 and later reported by other authors,2 which clears spontaneously or resolves under topical steroids.

2007 - BRAF mutations in multiple sebaceous hyperplasias of patients belonging to MYH-asociated polyposis pedigrees [Articolo su rivista]
Ponti, Giovanni; T., Venesio; Losi, Lorena; Pellacani, Giovanni; L., Bertario; P., Sala; Pedroni, Monica; C., Petti; S., Maffei; L., Varesco; E., Lerch; A., Baggio; Bassoli, Sara; Longo, Caterina; Seidenari, Stefania
abstract

The characteristics of sebaceous gland hyperplasia (SGH) consist of yellowish or skin-colored papules and nodules. Chronic sun exposure and immunosuppressed conditions are the main environmental risk factors, whereas chronological aging regulated by hormones and molecular changes are the intrinsic risk factors. We have evaluated the contribution of BRAF, K-Ras, and N-Ras mutations to the pathogenesis of SGHs in four patients belonging to three MYH-associated polyposis (MAP) pedigrees. MAP is an autosomal-recessive disease characterized by multiple colorectal adenomas and cancer. Immunohistochemistry of mismatch repair and APC proteins was performed. DNA isolated from blood lymphocytes and formalin-fixed or paraffin-em bedded SGHs was PCR amplified and sequenced. In the SGH patients, we detected T1796A heterozygous substitution (V600E) in the BRAF gene. Compound biallelic germline MYH mutations (Y165C/G382D, R168H/379delC, and Y90X/ delGGA464) were detected in the MAP patients. In contrast to the majority of melanocytic lesions, activating hotspot mutations in BRAF have not been involved so far in the pathogenesis of SGH. BRAF mutation is not a specific marker of melanocytic cancerogenesis, and it can also be involved in SGHs. In both melanocytic and non-melanocytic skin tumors, BRAF mutation is linked to early tumorigenesis events.

2007 - Diving into the blue: In vivo microscopic characterization of the dermoscopic blue hue [Articolo su rivista]
Pellacani, Giovanni; Bassoli, Sara; Longo, Caterina; Cesinaro, Am; Seidenari, Stefania
abstract

BACKGROUND: In dermoscopy the presence of a blue hue is a clue for malignancy, although a blue tint is sometimes observable in benign lesions. OBJECTIVE: To identify the in vivo confocal microscopy correlates of the blue hue for improving diagnostic accuracy for melanoma. METHODS: Fifty-seven melanomas, 41 junctional, 88 compound, and 27 Spitz nevi were studied by dermoscopy, confocal microscopy, and histopathology. RESULTS: Confocal microscopy enabled the distinction between blue areas and blue veil, the former characterized by plump cells corresponding to melanophages and inflammatory infiltrate at histology, the latter by the contemporary presence of epidermal and dermal features consistent with diagnosis of melanoma, such as disarranged pattern, pagetoid cells, cytologic and architectural atypias, nonhomogeneous and cerebriform clusters, and dermal nucleated cells. LIMITATIONS: Confocal microscopy failed to accurately distinguish Spitz nevi, because of the presence of cytoarchitectural disarray in the epidermis and the upper dermis. CONCLUSION: Confocal microscopy enabled the in vivo identification of characteristic cytological substrates correlated with the blue features in dermoscopy.

2007 - In vivo microscopic characterization of the dermoscopic blue hue by laser confocal microscopy. [Abstract in Rivista]
Bassoli, Sara; Longo, Caterina; Seidenari, Stefania; Pellacani, Giovanni
abstract

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2007 - In vivo microscopic features of nodular melanomas: dermoscopy, confocal microscopy and histopathologic correlates. [Abstract in Rivista]
S., Segura; Pellacani, Giovanni; S., Puig; Longo, Caterina; P., Guitera; J., Palou; S., Menzies; Seidenari, Stefania; J., Malvehy
abstract

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2007 - Pigmented mammary Paget disease - Dermoscopic, in vivo reflectance-mode confocal microscopic, and immunohistochemical study of a case [Articolo su rivista]
Longo, Caterina; Fantini, Fabrizio; Cesinaro, Anna Maria; Bassoli, Sara; Seidenari, Stefania; Pellacani, Giovanni
abstract

Background: Pigmented mammary Paget disease represents a rare variant of mammary Paget disease that clinically and dermoscopically simulates a melanoma. We report a case of pigmented mammary Paget disease mimicking a melanoma and describe the dermoscopic, reflectance-mode confocal microscopic, histological, and immunohistochemical features. Observations: A 70-year-old woman had a 5.5 X 4-cm pigmented plaque with a thin, scaly surface on her left breast; the plaque had slowly but progressively grown during the preceding 10 years. Dermoscopic examination showed a diffuse, light brown pigmentation with irregular black dots, small gray-blue structures, and irregular vessels. Confocal microscopic features, such as large reflecting cells with dark nuclei spreading upward in pagetoid fashion, were suggestive of melanoma. Histological evaluation integrated with immunohistochemical staining showed pigmented mammary Paget disease. Conclusions: This case demonstrates that the diagnosis of pigmented mammary Paget disease cannot be determined by clinical examination and dermoscopy alone. Therefore, immunohistochemical staining should be performed in growing lesions with equivocal clinical and dermoscopic aspects that are characterized by abundant pagetoid infiltration in hematoxylin-eosin-stained sections to avoid overlooking pigmented mammary Paget disease.

2007 - Prospective evaluation of a four-year period of application of a follow-up protocol for melanoma patient management. [Abstract in Rivista]
Miglietta, Roberta; Longo, Caterina; Bassoli, Sara; Seidenari, Stefania; Pellacani, Giovanni
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2007 - The impact of in vivo reflectance confocal microscopy for the diagnosis of melanoma. [Abstract in Rivista]
Longo, Caterina; Pellacani, Giovanni; P., Guitera; M., Avramidis; Seidenari, Stefania; S., Menzies
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2007 - The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions [Articolo su rivista]
Pellacani, Giovanni; P., Guitera; Longo, Caterina; M., Avramidis; Seidenari, Stefania; S., Menzies
abstract

In vivo confocal reflectance microscopy recently showed promising results for melanoma ( MM) diagnosis on a limited series. The aim of the study was to evaluate the sensitivity and specificity of confocal features for the diagnosis of MM 351 equivocal melanocytic lesions (136 MMs and 215 nevi) were evaluated for 37 confocal features by two blinded expert observers. chi(2) test, multivariate discriminant analysis and binary logistic regression were performed for the identification of the significant features and for testing newly created diagnostic models. Melanomas were mostly characterized by epidermal disarray and pagetoid cells in the epidermis, non-edged papillae, and cellular atypia at the junction, and atypical nests and bright nucleated cells in the upper dermis. On the other hand, regular dermal-epidermal architecture, and absence of pagetoid infiltration and atypical cells were suggestive of benign lesions. Five out of 136 melanomas, with mildly atypical melanocytes and occasional pagetoid cells at histopathology, were not diagnosed by confocal microscopy. Nevertheless, new diagnostic models showed no significant improvement compared with the previously proposed confocal microscopy algorithm. Owing to the visualization of cellular aspects, confocal microscopy seems useful for second level examination of clinically and dermoscopically equivocal lesions.

2007 - confocal microscopy assistance in the recognition of a difficult lesion of the face [Abstract in Rivista]
Bassoli, Sara; I., Stanganelli; Longo, Caterina; Pupelli, Gaia; Seidenari, Stefania; Pellacani, Giovanni
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2006 - Clinical selection of melanocytic lesions for dermoscopy decreases the identification of suspicious lesions in comparison with dermoscopy without clinical preselection [Articolo su rivista]
Seidenari, Stefania; Longo, Caterina; Giusti, Francesca; Pellacani, Giovanni
abstract

Background In most cases dermoscopy is performed only on lesions selected by clinical inspection which present worrying clinical features or appear to deviate from the patient's average type of naevus. Thus, possible early malignant melanomas (MMs) or MM precursors, lacking typical clinical characteristics, may elude the dermoscopic examination. Objectives To perform a comparison between two different approaches to the patient's examination, one based on a clinical preselection of lesions to be examined by dermoscopy, and the other consisting of the dermoscopic scrutiny of all melanocytic lesions with a diameter >= 2 mm (total dermoscopy). Methods Sixty-three consecutive patients with MM, undergoing periodic dermoscopic examinations of their naevi, were enrolled in the study. The patients first underwent an assessment of the entire skin with the unaided eye for the identification of lesions for dermoscopy. Subsequently, the patients underwent dermoscopic examination of all melanocytic lesions. Images of naevi identified by clinical examination or by total dermoscopy as having dermoscopic aspects characteristic of a suspicious lesion, i.e. necessitating either surgical excision or follow-up examinations, were separately recorded, classified and described employing the ABCD rule of dermoscopy and the seven-point checklist. Results Five hundred and fifty-one lesions were chosen by clinical inspection for subsequent dermoscopic examination; among these, 117 were considered for excision or follow-up. Ninety-two further lesions were identified for excision or follow-up by employing only total dermoscopy. Dermoscopy scores of lesions selected by clinical inspection plus dermoscopy were similar to those identified by dermoscopy alone. In the former group, 13 lesions showed either an ABCD or a seven-point score corresponding to a suspicious lesion, whereas eight such lesions were identified only by total dermoscopy. Thus, by clinical selection plus dermoscopy we were able to identify only 62% of dermoscopically suspicious lesions. Conclusions Clinical selection of melanocytic lesions for dermoscopic examination is associated with the 'loss' of a conspicuous number of lesions which deserve surgical excision or follow-up examinations. Total dermoscopy, enabling the detection of suspicious lesions, together with storage, retrieval and sequential comparison of their images, could enhance MM diagnosis by follow-up, in comparison with clinical preselection for dermoscopy.

2006 - Perspective evaluation of a four-year period of application of a follow-up protocol for melanoma patient management [Articolo su rivista]
Pellacani, Giovanni; P., Giannelli; Longo, Caterina; Bassoli, Sara; Seidenari, Stefania
abstract

Aim. Although numerous follow-up protocols have been proposed, there are no widely accepted guidelines for melanoma (MM) follow-up. In 2000, the Emilia-Romagna Melanoma Group agreed upon guidelines for the MM follow-up, considering histological thickness and disease stage. The purpose of this study was the perspective evaluation of this follow-up protocol, in order to verify the efficacy to identify metastases and the effectiveness of the therapeutic approaches. Methods. During a 4-year period (2001-2004), 176 MM patients were supervised according to our follow-up protocol. Results. Thirty-nine patients underwent disease progression, showing in transit metastases in 15 cases, lymph node metastases in 11 cases, and distant metastases in 13 cases. At the end of the study 11 patients were dead for the complications of the disease. Disease progression was related with MM thickness, tumour stage and presence of ulceration, with a significant proportion of visceral localization in ulcerated MMs. A low rate of metastases was observed for MMs of the upper limbs, chest and abdomen. Concerning the metastasis identification, the majority of the recurrences were diagnosed by the physician, by means of instrumental examination or during clinical examination. A great part of the first recurrences underwent surgery, with a significant proportion of complete responses for locoregional ones, whereas distant metastases, although frequently diagnosed before becaming symptomatic, showed a poor response to the treatments. Conclusion. This study represents a critical intermediate analysis of the application of the Emilia-Romagna protocol after 4 years of methodical application.

2006 - Total assessment of nevi in at risk patients [Abstract in Rivista]
Seidenari, Stefania; Longo, Caterina; Bassoli, Sara; Pellacani, Giovanni
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2005 - In Vivo Confocal Microscopy of Melanocytic Lesions Improves Diagnostic Accuracy for Melanoma [Abstract in Rivista]
Pellacani, Giovanni; A. M., Cesinaro; Longo, Caterina; Bassoli, Sara; Grana, Costantino; Seidenari, Stefania
abstract

In vivo reflectance-mode confocal laser microscopy enables the visualization of the skin at quasi- histopathologic resolution. The aim of our study was to describe confocal features in melanocytic lesions, to evaluate their diagnostic significance for melanoma identification, to develop a simple algorithm useful for diagnostic purposes. A total of 102 consecutive melanocytic lesions (37 melanomas, 49 acquired nevi and 16 Spitz nevi), corresponding to lesions with equivocal aspects at clinical and dermoscopic inspection and excised in order to rule out a melanoma, were investigated by means of confocal microscopy (Vivascope 1000). In superficial layers the general pattern and the presence and aspects of pagetoid cells were evaluated. At basal cell layer dermal papilla features and cytological aspects, suggesting the presence of cellular atypia, were described. In dermal papilla, the presence and morphology of melanocytic nests and the presence and aspect of solitary cells were evaluated. Some features were more frequently observed in melanomas. In multivariate analysis 6 features appeared independently correlated with melanoma diagnosis. The presence of non edged dermal papillae, atypical cells in basal layers and isolated nucleated cells within dermal papilla were strongly correlated with melanoma diagnosis and were considered as major criteria (scored 2 points), whereas the presence of pagetoid cells, a widespread pagetoid infiltration in superficial layers and cerebriform nests in upper dermis were considered ‘‘minor’’ criteria (scored 1 point). A total score, ranging between 0 to 9, was obtained for each lesion and a ROC curve with an area under the curve of 0.951 was obtained on our dataset. In conclusion, characterization of confocal microscopy features of melanomas and nevi seems to improve diagnostic accuracy for difficult to diagnose melanocytic lesions.

2005 - Microscopic in vivo description of cellular architecture of dermoscopic pigment network in nevi and melanomas [Articolo su rivista]
Pellacani, Giovanni; Am, Cesinaro; Longo, Caterina; Grana, Costantino; Seidenari, Stefania
abstract

Objective: To characterize the microscopic aspects of the dermoscopic pigment network in vivo, by means of confocal scanning laser microscopy. Design: Confocal imaging was performed on melanocytic lesions characterized by pigment network at dermoscopy. Some confocal architectural and cytologic features, as observed at the dermoepidermal junction, were morphologically described and quantified by means of a dedicated program. Setting: University medical department. Study Population: We studied confocal images of 15 melanomas, 15 dermoscopic atypical nevi, and 15 common nevi. Main Outcome Measures: Features referring to aspect, size, regularity, homogeneity, and infiltration of dermal papillae and to cellular size, regularity, and atypia were described by 2 observers on confocal images. Mean dermal papillary diameter, mean cell area, and shape irregularity were quantified by drawing papillae and cell contours on confocal images and measured with the use of a computer program. Results: Pigment network in melanomas consisted of large basal cells that circumscribed small to medium-sized dermal papillae with marked cellular atypia, sometimes infiltrating dermal papillae. On the other hand, common acquired nevi were characterized by lack of atypical cells and edged dermal papillae. Atypical nevi presented intermediate characteristics between clearly benign and malignant lesions. Conclusion: Cellular atypia was the most sensitive feature for melanoma diagnosis, whereas the presence of nucleated cells infiltrating dermal papillae was the most specific one.

2005 - Reflectance-mode confocal microscopy for the in vivo detection of Sarcoptes scabiei [Articolo su rivista]
Longo, Caterina; Bassoli, Sara; Monari, Paola; Seidenari, Stefania; Pellacani, Giovanni
abstract

2004 - Differential diagnosis between spitz nevi and melanomas by means of in-vivo confocal microscopy [Abstract in Rivista]
Pellacani, Giovanni; A. M., Cesinaro; Longo, Caterina; Grana, Costantino; Seidenari, Stefania
abstract

Spitz nevi may be often confused with malignant melanoma, because of its rapid growth and alarming clinical features. In vivo confocal reflectance microscopy (CRM) is a novel technique enabling the noninvasive imaging of the skin at a cellular level resolution. Twelve Spitz and 25 melanomas (MMs) were studied by means of CRM (Vivascope 1000, Lucid Inc., USA) and digital dermoscopy (Videocap 200, DS-Mediroup, Italy) for in vivo characterization of cytological and architectural features at CRM, and correlation with dermoscopy and histology. Although large cells with bright cytoplasm and dark eccentric nucleus, sometimes spreading upwards in a pagetoid fashion, were observed both in Spitz nevi and MMs, in the latter case they were more numerous and irregularly shaped. Dermoscopic globules corresponded to cell clusters at CRM and melanocytic nests at histopathology. Spitz nevi frequently presented a peripheral rim of medium sized peripheral clusters, constituted by compact aggregates of large polygonal cells, sometimes observable also on the whole lesion area. In MMs cell clusters were frequently constituted by sparse cells intercalated with thin fibrils giving a multi-lobate appearance or by large confluent aggregates of low reflecting polygonal or elongated cells, resulting in a cerebriform appearance. Although CRM appeared useful for distinction between melanocytic lesions, Spitz nevi presenting numerous atypical cells and dermal-epidermal architecture disarrangement can not be always distinguished from MMs, owing to the limited penetration of the near-infrared laser light, not enabling the evaluation of ‘cell maturation’ with increasing depth.

2004 - Improving melanoma diagnosis by means of in vivo confocal laser microscopy [Abstract in Rivista]
Pellacani, Giovanni; A. M., Cesinaro; Longo, Caterina; Grana, Costantino; Seidenari, Stefania
abstract

Confocal reflectance microscopy (CRM) enables the in-vivo observation of the skin at a nearly histologic resolution. Since melanin represents a strong source of contrast, this technique appeared particularly indicated for the study of melanocytic lesions. Cytological and architectural features of melanocytic skin lesions were studied on 25 melanomas and 50 atypical melanocytic nevi employing CRM (Vivascope 1000, Lucid Inc., USA) and digital dermoscopy (Videocap 200, DS-Mediroup, Italy). All lesions were excised for diagnostic confirmation. Some differences in CRM features were observed between benign and malignant lesions: in melanocytic nevi, cells were usually round to oval, mainly located in the basal layers or clustered into nests within the papillary dermis. Melanomas were characterized by numerous large cells within the superficial layers of the epidermis, suggesting a pagetoid fashion, and by cells polymorphic in size and shape mainly located in the basal layer, sometimes interrupted by small dermal papillae irregularly distributed throughout the lesion, owing to disarrangement of the normal architecture of the rete ridges. Moreover, large irregular cells with refractive cytoplasm and eccentric dark nucleus infiltrating dermal papilla and cell clusters with a multilobulated feature constituted by sparse cells or with a cerebriform aspect were specifically observed in melanomas. Although preliminary and based on a limited number of cases, these findings show the potential of this technique for the noninvasive diagnosis of clinically difficult lesions.