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Francesca FARNETANI

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

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Pubblicazioni

2024 - Combined Carbon Dioxide Laser with Photodynamic Therapy for Nodular Basal Cell Carcinoma Monitored by Reflectance Confocal Microscopy [Articolo su rivista]
Alma, A.; Pongetti, L.; Clementi, A.; Chester, J.; Toccaceli, M.; Ciardo, S.; Zappia, E.; Manfredini, M.; Pellacani, G.; Greco, M.; Bennardo, L.; Farnetani, F.
abstract

Introduction: Basal cell carcinoma (BCC) represents around 80% of all malignant skin cancers worldwide, constituting a substantial burden on healthcare systems. Due to excellent clearance rates (around 95%), surgery is the current gold-standard treatment. However, surgery is not always possible or preferred by patients. Numerous non-surgical therapies, sometimes combined, have been associated with promising tumor free survival rates (80-90%) in non-melanoma skin cancers (NMSCs). Most research has enrolled superficial basal cell carcinomas (sBCCs), with limited recent studies also involving low-risk nodular BCCs (nBCCs). Given lower efficacy rates compared to surgery, close monitoring during the follow-up period is essential for patients treated with non-surgical therapies. Monitoring with dermoscopy is constrained by low sensitivity rates. Reflectance confocal microscopy (RCM) is more sensitive in monitoring non-surgically treated NMSCs. Case presentation: A 41-year-old woman with a single nBCC relapse following photodynamic therapy (PDT) located on the dorsum of the nose presented to our center. Given the aesthetically sensitive location of the lesion and the patient's preference for a non-surgical approach, a combined treatment of CO2 laser and PDT was prescribed. A superpulsed CO2 laser (power: 0.5-3 W, frequency: 10 Hz, spot size 2 mm) with two PDT sessions (2 weeks apart) were conducted. At 6 weeks follow-up, monitoring performed with RCM revealed a reduction but not eradication of basaloid tumor islands. Another 2 sessions of PDT were recommended. At 3, 12 and 30 months of follow-up, the nasal dorsum area of the previous nBBC lesion was noted to be slightly hypopigmented (observed clinically), with a mild erythematous background (observed by dermoscopy). RCM evaluation confirmed the absence of RCM BCC criteria. The cosmetic outcome was very much improved. Conclusions: Combined CO2 laser and PDT for the treatment of a localized nBCC on the dorsum of the nose of a 41-year-old proved to offer tumor free survival at 30-month follow-up, as monitored with RCM. RCM is useful for the evaluation of non-surgical therapies as it has comparably higher sensitivity than dermoscopy and is especially useful in cases of suspected late recurrence. Further studies are needed to validate ongoing tumor free survival following this combined nonsurgical approach in the treatment of nBCC.

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.

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 - 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 - 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 - 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 - 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.

2022 - A Challenging Nodular Lesion of the Ear [Articolo su rivista]
Tammaro, A.; Cantisani, C.; Chello, C.; Adebanjo, G. A. R.; Lilli, L.; Farnetani, F.; Filippi, C.; Covelli, E.; Rogges, E.; Pellacani, G.
abstract

Skin nodular lesion are really frequent, but rapidly growing ones needs to be quickly removed since they can hide really aggressive skin tumor. Among malignant lesion Merkel cell carcinoma arise. It is a rare neuroendocrine skin tumor highly aggressive, not easy to diagnose at first stage, since at first diagnosis it is already widespreading all over the body. In order to renew interest in this letal skin tumori is mandatory to remind high risk population which include elderly people, white skin, chronically exposed to UV immunocompromised. Our unhappy case was described to increase awareness on this kind of skin tumor, since new drug appeared in the market can give an hope to these patients.

2022 - Ablative Fractional Erbium:YAG Laser Resurfacing: A Treatment Option for Acne [Articolo su rivista]
Guida, S.; Lippolis, N.; Giovani, M.; Pedroni, G.; Urtis, G. G.; Pellacani, G.; Farnetani, F.; Manfredini, M.
abstract

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 - De Novo Skin Neoplasms in Liver-Transplanted Patients: Single-Center Prospective Evaluation of 105 Cases [Articolo su rivista]
Paganelli, Alessia; Magistri, Paolo; Kaleci, Shaniko; Chester, Johanna; Pezzini, Claudia; Catellani, Barbara; Ciardo, Silvana; Casari, Alice; Giusti, Francesca; Bassoli, Sara; Di Sandro, Stefano; Pellacani, Giovanni; Farnetani, Francesca; Di Benedetto, Fabrizio
abstract

Background and Objectives: Solid-organ transplant recipients (SOTRs) are notably considered at risk for developing cutaneous malignancies. However, most of the existing literature is focused on kidney transplant-related non-melanoma skin cancers (NMSCs). Conflicting data have been published so far on NMSC incidence among liver transplant recipients (LTRs), and whether LTRs really should be considered at lower risk remains controversial. The aim of the present study was to prospectively collect data on the incidence of cutaneous neoplasms in an LTR cohort. Materials and Methods: All LTRs transplanted at the Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit of Modena University Hospital from October 2015 to June 2021 underwent a post-transplant periodic skin check at the Dermatology Unit according to our institutional integrated care pathway. Data on the presence of cutaneous malignant and premalignant lesions were collected at every timepoint. Results: A total of 105 patients were enrolled in the present study. Nearly 15% of the patients developed cutaneous cancerous and/or precancerous lesions during the follow-up period. Almost half of the skin cancerous lesions were basal cell carcinomas. Actinic keratoses (AKs) were observed in six patients. Four patients developed in situ squamous cell carcinomas, and one patient was diagnosed with stage I malignant melanoma. Otherwise, well-established risk factors for the occurrence of skin tumors, such as skin phototype, cumulative sun exposure, and familial history of cutaneous neoplasms, seemed to have no direct impact on skin cancer occurrence in our cohort, as well as an immunosuppressive regimen and the occurrence of non-cutaneous neoplasms. Conclusions: Close dermatological follow-up is crucial for LTRs, and shared protocols of regular skin checks in this particular subset of patients are needed in transplant centers.

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 - 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 - 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, Reflectance Confocal Microscopy and Optical Coherence Tomography Features of Acne: A Systematic Review [Articolo su rivista]
Alma, A.; Sticchi, A.; Chello, C.; Guida, S.; Farnetani, F.; Chester, J.; Bettoli, V.; Pellacani, G.; Manfredini, M.
abstract

Noninvasive imaging techniques have recently outlined precise microscopic features of acne elementary lesions and accurate quantifications for disease severity staging and therapeutical efficacy follow-up. The aim of this review is to systematically describe current applications of dermoscopy, reflectance confocal microscopy (RCM), and optical coherence tomography (OCT) in acne vulgaris assessment and management. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We included studies conducted on human subjects with elementary lesions of acne vulgaris, reporting assessment of the lesions with dermoscopy, RCM, and/or OCT. At present there are few large studies regarding acne and noninvasive imaging techniques, representing the main limitation of this review. Clinical examination represents the first line in acne diagnosis and treatment. However, dermoscopy, RCM, and OCT are further tools that can improve acne classification, monitoring of treatment, and pathophysiologic characterization. In the near future, dermoscopy, RCM, and OCT could become routinely used for the evaluation of acne vulgaris to provide a deeper knowledge of the disease and to guide the clinician in the prescription of tailored treatment protocols based on each patient’s characteristics.

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 - Hidradenitis suppurativa: Morphologic and vascular study of nodular inflammatory lesions by means of optical coherence tomography [Articolo su rivista]
Manfredini, M.; Chello, C.; Ciardo, S.; Guida, S.; Chester, J.; Lasagni, C.; Bigi, L.; Farnetani, F.; Bettoli, V.; Pellacani, G.
abstract

Hidradenitis suppurativa (HS) is an inflammatory disease characterized by a recurrent-remission trend and clinical lesions that range from asymptomatic to inflamed, deep-seated nodules with scarring and suppuration. The aim of our study was to identify morphologic and vascular features of HS nodules by means of dynamic optical coherence tomography (D-OCT) and to define if they are correlated to patient endotype and risk of disease progression. A set of standardized clinical pictures and D-OCT images were acquired from 57 inflammatory nodules of 40 patients affected by HS. A set of 20 clinical and D-OCT images were acquired from 20 healthy volunteers as a control group. The comparison of D-OCT features among HS and control group was analysed. The correlation between HS patient endotype and D-OCT features of the lesions was calculated. D-OCT enabled to identify vascular and morphological aspects characterizing HS nodular inflammatory lesions. In addition, several D-OCT features were significantly different among distinct disease endotypes. The characterization of HS nodular inflammatory lesions through D-OCT, corresponding to blood vessel dilation and inflammatory associated hyper-vascularization, may have important clinical consequences in the assessment of HS risk of progression, therapeutic decisions and treatment efficacy monitoring.

2022 - In Vivo Melanoma Cell Morphology Reflects Molecular Signature and Tumor Aggressiveness [Articolo su rivista]
Marconi, Alessandra; Quadri, Marika; Farnetani, Francesca; Ciardo, Silvana; Palazzo, Elisabetta; Lotti, Roberta; Cesinaro, Anna Maria; Fabbiani, Luca; Vaschieri, Cristina; Puviani, Mario; Magnoni, Cristina; Kaleci, Shaniko; Pincelli, Carlo; Pellacani, Giovanni
abstract

Melanoma is the deadliest type of skin cancer, characterized by high cellular heterogeneity which contributes to therapy resistance and unpredictable disease outcome. Recently, by correlating Reflectance-Confocal-Microscopy (RCM) morphology with histopathological type, we identified four distinct melanoma-subtypes: dendritic-cell (DC), round-cell (RC), dermal-nest (DN), and combined-type (CT) melanomas. In the present study, each RCM-melanoma subtype expressed a specific biomolecular profile and biological behavior in vitro. Markers of tumor aggressiveness, including Ki67, MERTK, nestin and stemness markers, were highest in the most invasive CT and DN melanomas, as compared to DC and RC. This was also confirmed in multicellular tumor spheroids. Transcriptomic analysis showed a modulation of cancer progression-associated genes from DC to CT melanomas. The switch from E- to N-cadherin expression proved the epithelial-to-mesenchymal transition from DC to CT subtypes. The DN melanoma was predominantly located in the dermis, as also shown in skin reconstructs. It displayed a unique behavior and a molecular profile associated with a high degree of aggressiveness. Altogether, our results demonstrate that each RCM-melanoma subtype has a distinct biological and gene expression profile, related to tumor aggressiveness, confirming that RCM can be a dependable tool for in vivo detecting different types of melanoma and for early diagnostic screening.

2022 - Leg-type cutaneous B-cell lymphoma: The description of a rare and aggressive skin tumor with D-OCT imaging [Articolo su rivista]
Chello, C.; Caramaschi, S.; Sticchi, A.; Naselli, A.; Pezzini, C.; Farnetani, F.; Reggiani Bonetti, L.; Ciardo, S.; Di Matteo, E.; Pellacani, G.; Manfredini, M.
abstract

2022 - Long-term vemurafenib therapy in advanced melanoma patients: cutaneous toxicity and prognostic implications [Articolo su rivista]
Mandel, Victor Desmond; Medri, Matelda; Manganoni, Ausilia Maria; Pavoni, Laura; DE ROSA, Francesco; Ribero, Simone; Foca, Flavia; Andreis, Daniele; Mazzoni, Laura; Magi, Serena; Farnetani, Francesca; Palla, Marco; Ulivi, Paola; Stanganelli, Ignazio
abstract

Background: The introduction of targeted therapies for the treatment of BRAF-mutated metastatic melanoma was associated with different cutaneous adverse events (AEs). Objectives: To describe the type, frequency and severity of cutaneous AEs related to vemurafenib; to understand the association between AEs and vemurafenib efficacy in terms of median overall survival (OS) and median progression-free survival (PFS); to identify molecular characteristics of long-term responders. Methods: This observational, retrospective, monocentric study included all consecutive patients with unresectable stage III or stage IV melanoma and BRAF V600E mutation that started treatment with vemurafenib between May 2012 and May 2014. Results: 62 patients with a median age of 56 years (range 26–82) were enrolled and received vemurafenib for a median period of 7.9 months (range 0.8–63.7). Among them, 45 patients presented at least one skin AE, 12 reduced the dosage due to cutaneous toxicity, and only one firstly reduced and after stopped the therapy. No specific molecular biomarkers were detected in long-term survivors. Conclusions: Among long-term survivors, skin AEs seem to be less frequent and less severe. Results on multivariable analysis revealed that the presence of at least one G2 toxicity is a protective factor considering PFS, but not in terms of OS.

2022 - Malignant lesions of the ear [Articolo su rivista]
Tammaro, A.; Adebanjo, G. A. R.; Chello, C.; Parisella, F. R.; Cantisani, C.; Farnetani, F.; Pellacani, G.
abstract

The dermatologic lesions of the external ear are quite protean and they encompass pre-malignant, malignant and inflammatory entities. The ear is endowed with functional and cosmetic importance and it is part of the “H-zone”, which is the area of the head that generally presents tumors that can be considered high risk regardless of their size. As a matter of fact, skin malignancies of the ear tend to have a less benign course compared to the ones located on other areas of the body and complete excision has proven to be challenging. This mini-review provides an overview on the malignant cutaneous lesions of the external ear with a focus on their dermoscopic and reflectance confocal microscopy features. The most prevalent neoplasms of the auricle are squamous cell carcinoma and basal cell carcinoma followed by melanoma. These malignant lesions appear to be more common in men and to have a worse prognosis compared to when they arise from other body districts. There is a relative dearth of large studies centered on the clinical, dermoscopic and reflectance confocal microscopy features of skin cancers of the ear. Hence, further research inquiring into the specific dermoscopic and reflectance confocal microscopy characteristics of the cutaneous malignant lesions of the external ear, if any, are warranted for the future.

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 - 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 - 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 - A Validated Photonumeric Scale for the Evaluation of Neck Skin Laxity [Articolo su rivista]
Guida, S.; Spadafora, M.; Longhitano, S.; Pellacani, G.; Farnetani, F.
abstract

BACKGROUND: Neck aging is usually evaluated together with the lower face. To date, a skin laxity scale for the neck as an independent anatomical district is lacking. OBJECTIVE: To create and validate a proposed photonumeric neck skin laxity (NSL) scale. MATERIALS AND METHODS: Frontal neck photographic images of 110 subjects were collected. Each standardized neck image was evaluated twice by 3 independent doctors, 1 week apart. A 4-point photonumeric NSL scale was developed (0 = absence of skin laxity and 4 = severe skin laxity) and validated in terms of intraobserver and interobserver correlation and internal consistency. RESULTS: The intraobserver reliability analysis of the 2 assessments performed by each observer revealed excellent correlation and consistency of the severity grading, independently of the time of evaluation (from 0.96 to 0.99, p < .01). Furthermore, the interobserver reliability analysis revealed an excellent agreement between the evaluators and an internal consistency independent of the evaluator (0.97, p < .01). CONCLUSION: The newly developed NSL scale is a reliable and reproducible scoring system for the aesthetic evaluation of skin laxity of the neck.

2021 - Acquired white oral lesions with specific patterns: Oral lichen planus and lupus erythematosus [Articolo su rivista]
Manfredini, M.; Pedroni, G.; Bigi, L.; Apponi, R.; dello Diago, A. M.; Dattola, A.; Farnetani, F.; Pellacani, G.
abstract

Background: Diagnosis of oral white lesions might be challenging. These lesions represent a wide spectrum of diseases with different etiology and prognosis. Oral white lesions can be categorized into two major groups, congenital and acquired, according to their development, and in four subgroups: lesions which can be scraped off or not and lesions with special pattern or not. Objectives: The aim of this manuscript is to review, from diagnosis to treatment, the current knowledge on oral white lesions with specific pattern. Methods: A review on oral white lesions with specific pattern was conducted on PubMed and Scopus from inception to January 2021. Results: Among acquired lesions with specific pattern two clinical entities are mostly represented: Oral lichenoid reactions and Lupus erythematosus. The etiology of both diseases is still not known but their pathogenesis is mainly immunological. At present the mucoscopic features of those disease have been described only in few case reports or case series. Immunomodulatory therapies are often the agents of choice for their treatment. Conclusions: The collaboration of dermatologists and dentists as a team is important for early diagnoses and effective treatments. Mucoscopy is a promising technique which may reveal important features for the differentiation of OLP and LE oral white lesions.

2021 - Atrophic and hypertrophic skin photoaging and melanocortin-1 receptor (MC1R): the missing link [Articolo su rivista]
Guida, S.; Ciardo, S.; De Pace, B.; De Carvalho, N.; Farnetani, F.; Pezzini, C.; Chester, J.; Shaniko, K.; Manganelli, M.; Guida, G.; Pellacani, G.
abstract

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 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 - Daylight photodynamic therapy with 5-aminolevulinic acid 5% gel for the treatment of mild-to-moderate inflammatory acne [Articolo su rivista]
Duca, E. D.; Manfredini, M.; Petrini, N.; Farnetani, F.; Chester, J.; Bennardo, L.; Schipani, G.; Tamburi, F.; Sannino, M.; Cannarozzo, G.; Pellacani, G.; Nistico, S. P.
abstract

BACKGROUND: Acne vulgaris is a chronic inflammatory disease that frequently occurs in adolescence. This common condition is often treated with topical or systemic therapies according to severity. Photodynamic therapy (PDT) with topical delta-aminolaevulinic acid is a novel drugsparing, but time-consuming approach. Recently, sunlight exposure has been considered a quicker, safer, cheaper and more agreeable alternative light source for PDT, but efficacy has only been proven in the oncological field. This study aimed to evaluate the efficacy and tolerability of daylight PDT (DL-PDT) for the treatment of inflammatory acne vulgaris of face, chest and trunk lesions. METHODS: Twenty patients with mild-to-moderate acne vulgaris were enrolled and treated with a topical gel based on 5% delta-aminolaevulinic acid, administered 4 times at 14-day intervals. Efficacy was assessed with mean lesion count, Physician Global Assessment (PGA), Investigator's Global Assessment (IGA) and patients' self-assessment (10-point scale). RESULTS: Compared to T0, mean inflammatory lesions count decreased in all patients at FU1, from 16.7±4.4 to 5.2±3.3 (P). No adverse events were reported, and no patients were lost to follow-up. PGA results of "excellent" or "good" improvement were reported in 95% at T3 and 90% at FU1. Patients' self-assessments was 7.6±1.0 (T3). Discomfort was 0.5±0.2 (T3 and FU1). CONCLUSIONS: DL-PDT seems to be an effective and tolerable therapy for the treatment of mild-to-severe inflammatory acne. This novel regimen seems to be a viable option in the panorama of acne therapies.

2021 - Efficacy assessment of a TCA/H2O2 compositum for skin ageing treatment by confocal laser microscopy and optical coherence tomography [Articolo su rivista]
Peccerillo, F.; Odorici, G.; Ciardo, S.; Greco, M.; Guida, S.; Farnetani, F.; Pellacani, G.
abstract

2021 - Facial seborrheic keratosis with unusual dermoscopic patterns can be differentiated from other skin malignancies by in vivo reflectance confocal microscopy [Articolo su rivista]
Farnetani, F.; Pedroni, G.; Lippolis, N.; Giovani, M.; Ciardo, S.; Chester, J.; Kaleci, S.; Pezzini, C.; Cantisani, C.; Dattola, A.; Manfredini, M.; Dika, E.; Patrizi, A.; Pellacani, G.
abstract

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 - Folliculotropism in head and neck lentigo maligna and lentigo maligna melanoma [Articolo su rivista]
Dika, Emi; Lambertini, Martina; Patrizi, Annalisa; Misciali, Cosimo; Scarfì, Federica; Pellacani, Giovanni; Mandel, Victor Desmond; DI TULLIO, Francesca; Stanganelli, Ignazio; Chester, Johanna; Kaleci, Shaniko; Massi, Daniela; DE GIORGI, Vincenzo; Cinotti, Elisa; Rubegni, Pietro; Perrot, Jean-Luc; Farnetani, Francesca
abstract

Background: Lentigo maligna (LM) and lentigo maligna-melanoma (LMM) are histotypes of melanoma arising in skin with cumulative solar radiation damage. The extension of atypical melanocytes to the hair follicle (folliculotropism) is a histopathological feature of LM/LMM. Its role has not been totally clarified, but it may be correlated to treatment response in LM or to progression in LMM. Objective: This retrospective, multicentric study aims to identify dermatoscopic features associated with folliculotropism in LMs/LMMs. Patients and methods: We analyzed cases of head and neck LMs/LMMs diagnosed between 2005-2014 at Melanoma Units, University of Bologna/Modena/Florence/Siena (Italy), Nice (France): 25 LMs and 73 LMMs were included. Results: Grey circles (44 %) indicated an isthmic/bulb level of involvement, which were completely absent in the infundibular LM lesions (P = 0.041). In the group of LMMs, light/dark brown pseudonetwork and light brown structureless areas were an indicator of diffuse distribution of malignant melanocytes in the follicular units (P < 0.001 and P = 0.001, respectively), while grey circles indicated focal or diffuse distribution (P < 0.001). Conclusions: A better understanding of the extension of malignant melanocytes is helpful, aiding clinicians in their decision to perform a radical excision or obtaining a biopsy in the most invasive area of the lesion, which includes potential folliculotropism.

2021 - Hyperdiluted calcium hydroxylapatite for the treatment of skin laxity of the neck [Articolo su rivista]
Guida, S.; Longhitano, S.; Spadafora, M.; Lazzarotto, A.; Farnetani, F.; Zerbinati, N.; Pellacani, G.; Galadari, H.
abstract

Despite being a common concern, there are very few minimally invasive treatments targeting neck skin laxity (NSL) reported in the literature. To assess the efficacy of hyperdiluted calcium hydroxyapatite (hy-CaHA) for the treatment of NSL, according to the NSL scale, and to estimate safety. Twenty patients showing NSL were treated with hy-CaHA 1:2. To evaluate the efficacy of hy-CaHA treatment for NSL, pictures of treated subjects were collected before and 3 months after treatment and graded according to the NSL scale, and T-student's test was applied to estimate differences. Hy-CaHA for the neck was effective according to the previously unreported NSL scale (p < 0.001) and safe. There were no major adverse events reported. This study supports the efficacy (according to the NSL scale) and safety of hy-CaHA (1:2) for NSL. Our results also highlight the utility of the newly developed NSL scale, being a useful tool to evaluate the level of NSL before treatment and to measure the outcome.

2021 - Radiotherapy-induced subclinical skin changes revealed by dynamic optical coherence tomography: a case-controlled pilot study [Articolo su rivista]
Chello, C.; Ciardo, S.; Chester, J.; Guanti, M.; Farnetani, F.; Guida, S.; Sticchi, A.; Giacobazzi, P.; Meduri, B.; Lohr, F.; Pellacani, G.; Manfredini, M.
abstract

2021 - Recurrent aphthous stomatitis: Treatment and management [Articolo su rivista]
Manfredini, M.; Guida, S.; Giovani, M.; Lippolis, N.; Spinas, E.; Farnetani, F.; Dattola, A.; Di Matteo, E.; Pellacani, G.; Giannetti, L.
abstract

Background: Recurrent aphthous stomatitis consists of the presence of abrasions or ulcerations located on mucosae (oral or genital). Objectives: The aim of this article is to review the current literature providing the main causes related to recurrent aphthous stomatitis and insights into treatment and management of this clinical condition Methods: Articles matching terms that correlated with "recurrent aphthous stomatitis"were searched on PubMed, EMBASE, and Cochrane Library and selected according to their pertinence. Results: Several forms of aphthous stomatitis have been described, based on the extent (minor, major), morphology (herpetiform) and associations to other signs (Behçet syndrome or more complex inflammatory syndromes). Topical as well as systemic treatments have been described to obtain a faster remission of the aphthosis or to reduce associated symptoms such as pain. Conclusions: Recurrent aphthous stomatitis can have a mild-to-severe clinical appearance, being mainly localized on the oral mucosa or at the level of the genital area. Different strategies have been described so far for its management and treatment.

2021 - Red dye-related tattoo reactions: Could optical coherence tomography be of help? [Articolo su rivista]
Pezzini, C.; Di Tullio, F.; Pileri, A.; Ciardo, S.; Greco, M.; Dika, E.; Patrizi, A.; Pellacani, G.; Farnetani, F.
abstract

2021 - Reflectance confocal microscopy of neurothekeoma: case report [Articolo su rivista]
Sticchi, A.; Manfredini, M.; Ciardo, S.; Cotena, C.; Longhitano, S.; Chello, C.; Cesinaro, A. M.; Farnetani, F.; Pellacani, G.; Puviani, M.
abstract

2021 - Switching infliximab in psoriatic patients during COVID-19 pandemics: A real-life retrospective study comparing intra-versus interclass switching strategies [Articolo su rivista]
Conti, A.; Damiani, G.; Ruggeri, R.; Odorici, G.; Farnetani, F.; Pigatto, P. D. M.; Pellacani, G.
abstract

During this pandemic, dermatological infusion centers were partially unavailable, suspended or even reconverted to guest COVID-19 patients, consequently infliximab (IFX) infusions became challenging for their both logistic arrangement and also for patients' COVID-19 phobia. This 48 weeks follow-up retrospective observational study included 37 PsO patients that underwent IFX SB2 during pandemic in two primary dermatological referral centers. In 23 (62.1%) we had to switch from IFX to other biologics, not motivated by adverse reactions, contraindication or even loss of response but only to pandemic related conditions. Nine patients underwent interclass switching and 15 underwent intraclass switching; interestingly 2 patients that underwent adalimumab SB-5 switched back to IFX. Interclass switching was privileged in elder patients and smokers. All patients at week 48 achieved PASI 100. Intra- and interclass switchings are both safe and effective strategies in psoriatic patients with COVID-19 phobia and/or difficulties to undergo infliximab infusions.

2021 - The Interplay between HGF/c-met Axis and Nox4 in BRAF Mutated Melanoma [Articolo su rivista]
Beretti, Francesca; Farnetani, Francesca; Reggiani Bonetti, Luca; Fabbiani, Luca; Zavatti, Manuela; Maiorana, Antonino; Pellacani, Giovanni; Maraldi, Tullia
abstract

Melanoma is the leading cause of death due to cutaneous malignancy and its incidence is on the rise. Several signaling pathways, including receptor tyrosine kinases, have a role in the development and progression of melanocytic lesions and malignant melanoma. Among those, the hepatocyte growth factor (HGF)/c-met axis is emerging as a critical player because it can play a role in drug resistance. Indeed, 50% of melanoma patients present BRAF mutations, however, all responders develop resistance to the inhibitors typically within one year of treatment. Interestingly, BRAF inhibitors induce reactive oxygen species (ROS) in melanoma cells, therefore, the aim of this study was to investigate a possible interplay between HGF/c-met and ROS sources, such as NADPH oxidases (Nox).

2020 - A validated photonumeric cellulite severity scale for the area above the knees: the knee cellulite severity score [Articolo su rivista]
Longhitano, S.; Galadari, H.; Cascini, S.; Kaleci, Shaniko; Chester, J.; Farnetani, F.; Pellacani, G.; Urtis, G. G.; Guida, S.
abstract

Background: Treatment for cellulite above the knees is increasingly requested. However, a classification of cellulite of this area has not yet been developed. Objective: To validate the proposed knee cellulite severity score (KCSS) for the assessment of cellulite and skin laxity above the knee. Materials and methods: Based on standardized photographs of cellulite and skin laxity above the knees of 57 females (114 knees), three key morphological aspects of cellulite were identified. A photonumeric KCSS was developed and validated by three independent assessors. Results: The three key cellulite morphological features (number of depressions, depth of depressions and presence of laxity) are each graded from 0 to 3, producing a classification of no lesions (0), mild (1–3), moderate (4–6) and severe (7–9). Evaluators at different time points repeated similar classifications (intraclass correlation coefficient >0.9), which were also similar among the assessors (inter-observer reliability >0.9). All three key morphological aspects were deemed necessary, and positively contributed, to the overall scale (item-total correlation analysis values >0.89, P < 0.05). Conclusions: The KCSS is a consistent, comprehensive, reliable, and reproducible tool for standardized and objective assessment of the severity of cellulite and skin laxity above the knees.

2020 - Atrophic and Hypertrophic Skin Photoaging and MC1R [Articolo su rivista]
Guida, S; Ciardo, S; De Pace, B; De Carvalho, N; Farnetani, F; Pezzini, C; Chester, J; Kaleci, Shaniko; Manganelli, M; Guida, G; Pellacani, G
abstract

2020 - Carbon peel laser technique to improve skin quality: Back to science! [Articolo su rivista]
Guida, S.; Fulgione, E.; D'Ambra, I.; Babino, G.; Pellacani, G.; Farnetani, F.
abstract

2020 - COVID-19 and dermatology: a comprehensive guide for dermatologists [Articolo su rivista]
Fahmy, D. H.; El-Amawy, H. S.; El-Samongy, M. A.; Fouda, A. A.; Soliman, S. H.; El-Kady, A.; Farnetani, F.; Conti, A.; Zoeir, A.; Eissa, A.; Eissa, R.; Puliatti, S.; Sighinolfi, M. C.; Rocco, B.; Pellacani, G.
abstract

2020 - Creatine Phosphokinase Values during Low Starting Dose Isotretinoin Therapy [Articolo su rivista]
Manfredini, M.; Bettoli, V.; Forconi, R.; Pacetti, L.; Farnetani, F.; Corazza, M.; Pellacani, G.
abstract

Background: The value of creatine phosphokinase (CPK) monitoring during isotretinoin therapy is still a matter of debate because of the rarity of muscular and kidney damage in this setting. The aim of the study was to investigate the incidence of CPK elevation during a low starting dose isotretinoin regimen and to discuss the clinical approach to patients with increased CPK. Methods: We reviewed the records of the acne patients from 2015 to 2018 at the University of Ferrara and at the University of Modena and Reggio Emilia. Routine clinical and laboratory follow-up was analyzed. Results: The records of 328 patients were included in the study. Abnormal CPK levels were observed in 5.5% of cases. Revised Leeds acne scores and visual assessment scale (VAS) measurements decreased significantly after isotretinoin therapy. Discussion: The adoption of the low starting dose isotretinoin regimen is associated with low incidence of CPK elevation. The finding of CPK over the conventional value of 5 times above the limit was rarely observed and was never associated with kidney damage. Therefore, it should be interpreted as a relatively benign phenomenon that does not require the interruption of isotretinoin therapy and that should be managed mainly through the reassurance of the patient.

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 - Disguised basal cell carcinomas: how to track them down with reflectance confocal microscopy [Articolo su rivista]
Paganelli, A.; Garbarino, F.; Ciardo, S.; Pellacani, G.; Farnetani, F.
abstract

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 - Hyperdiluted calcium hydroxylapatite for skin laxity and cellulite of the skin above the knee: A pilot study [Articolo su rivista]
Guida, Stefania; Longhitano, Sabrina; Kaleci, Shaniko; Galadari, Hassan; Chester, Johanna; Ciardo, Silvana; Mandel, Victor Desmond; Pellacani, Giovanni; Urtis, Giacomo Giovanni; Farnetani, Francesca
abstract

Despite an increasing request for skin rejuvenation above the knee, very few treatment options have been reported in literature. To evaluate the efficacy and safety of 1:4 hyperdiluted calcium hydroxylapatite (CaHA) in the treatment of skin laxity and dimples of the skin above the knees. A retrospective evaluation of hyperdiluted CaHA treatment for skin laxity and dimples above the knee was performed. Efficacy was classified as blinded evaluation of pre (T0) and 3-month post-treatment (T1) photographs by three investigators according to the validated knee cellulite severity score (KCSS) and patient satisfaction. Safety was evaluated through pain scores and adverse events evaluation. A significant reduction of KCSS at T1, as compared to T0, mainly in subjects with lower KCSS at T0, was observed (P <.05). All blinded assessments resulted in a correct identification of T0 and T1 pictures and evaluations of all investigators were found to be consistent and reliable. All patients were satisfied. Only minor adverse events (swelling, erythema, bruising, and skin irregularities) were reported, lasting 2 to 3 weeks after treatment. Our preliminary results highlight the efficacy and safety of hyperdiluted CaHA in the treatment of skin laxity and cellulite above the knees.

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 - Morphology of congenital nevi in dermoscopy and reflectance confocal microscopy according to age: a pilot study [Articolo su rivista]
Odorici, G.; Longhitano, S.; Kaleci, S.; Chester, J.; Ciardo, S.; Pellacani, G.; Farnetani, F.
abstract

2020 - Nodular skin lesions: correlation of reflectance confocal microscopy and optical coherence tomography features [Articolo su rivista]
Garbarino, F.; Migliorati, S.; Farnetani, F.; De Pace, B.; Ciardo, S.; Manfredini, M.; Reggiani Bonetti, L.; Kaleci, S.; Chester, J.; Pellacani, G.
abstract

Background: Nodular lesions have common clinical appearance but different prognoses. Differential diagnosis between melanoma (MM), basal cell carcinoma (BCC) and dermal naevus (DN) poses a challenge in clinical practice. Reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) are promising non-invasive imaging techniques, potentially able to decrease redundant biopsies. RCM allows in vivo visualization of skin down to the papillary dermis at almost histological resolution, while OCT, particularly dynamic OCT (D-OCT), provides images deeper within the dermis and reveals the vascular pattern. Objectives: To identify correlating features observed with RCM and OCT associated with the different nodular lesion diagnoses. Methods: We retrospectively assessed 68 nodular lesions (30 MM, 20 BCC and 18 DN) with RCM and subsequently OCT. At the end of the study, evaluations were matched with histopathological diagnosis and statistical analysis was performed. Results: In MM, 57% (17/30) evidenced both cerebriform nests at RCM and icicle-shaped structures at OCT, with higher average Breslow index. In 80% of BCCs with basaloid islands at RCM, OCT showed ovoid structures. More than half of DN (56%) showed hyporeflective nests at OCT and either dense nests or dense and sparse nests at RCM. Conclusions: The combined use of RCM and OCT offers a better understanding of the morphological architecture of nodular lesions, correlating RCM parameters with OCT and vice versa, assisting in turn with early differential diagnosis of malignant and benign nodular lesions. The correlation between icicle-shaped structures and cerebriform nests in MM and their association with Breslow index requires future research.

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 - Resurrection of a new old technique: The carbon peel laser [Articolo su rivista]
Guida, S.; Longhitano, S.; Galadari, H.; Spadafora, M.; Urtis, G. G.; Pellacani, G.; Farnetani, F.
abstract

2020 - The association between pesticide use and cutaneous melanoma: a systematic review and meta-analysis [Articolo su rivista]
Stanganelli, Ignazio; DE FELICI, Maria Beatrice; Mandel, Victor Desmond; Caini, Saverio; Raimondi, Sara; Corso, Federica; Bellerba, Federica; Quaglino, Pietro; Sanlorenzo, Martina; Ribero, Simone; Medri, Matelda; Farnetani, Francesca; Feliciani, Claudio; Pellacani, Giovanni; Gandini, Sara; on behalf of IMI, the Italian Melanoma Intergroup
abstract

Background: The incidence of cutaneous melanoma (CM), the deadliest form of skin cancer, has gradually increased in the last decades among populations of European origin. Epidemiological studies suggested that farmers and agricultural workers are at an increased risk of CM because they were exposed to pesticides. However, little is known about the relationship between pesticides and CM. Objectives: To investigate the association between exposure to pesticides and CM by systematically reviewing the literature. Secondary aim was to determine the categories of pesticides mainly involved in CM development. Methods: A systematic review of the literature was performed up to September 2018 using MEDLINE, Embase and Web of Science. Studies assessing CM risk in licensed pesticide applicators were considered. Strict criteria were established to select independent studies and risk estimates; random effect models, taking into account heterogeneity, were applied. A pooled risk estimate for CM was calculated for the use of each type of pesticide and type of exposure. Between-study and estimate heterogeneity was assessed and publication bias investigated. Results: A total of nine studies (two case-controls and seven cohorts) comprising 184 389 unique subjects were included. The summary relative risks for the categories 'herbicides - ever exposure', 'insecticides - ever exposure', 'any pesticide - ever exposure' and 'any pesticide - high exposure' resulted 1.85 [95% confidence interval (CI): 1.01, 3.36], 1.57 (95% CI: 0.58, 4.25), 1.31 (95% CI: 0.85, 2.04) and 2.17 (95% CI: 0.45, 10.36), respectively. Herbicides and insecticides had no between-study heterogeneity (I2 = 0%), while a significant heterogeneity (I2 > 50%) was detected for the high exposure to any pesticide. No indication for publication bias was found. Conclusions: Individuals exposed to herbicides are at an increased risk of CM. Future properly designed observational studies are required to confirm this finding.

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 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 - 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 - Ameloblastom in der Haut: wenn ein sicherer Umgang mit der Nadel nicht ausreicht [Articolo su rivista]
Puviani, M.; Farnetani, F.; Manfredini, M.
abstract

2019 - Ameloblastoma arising in the skin: when safe handling of needles is not enough [Articolo su rivista]
Puviani, M.; Farnetani, F.; Manfredini, M.
abstract

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 - Lesions Mimicking Melanoma at Dermoscopy Confirmed Basal Cell Carcinoma: Evaluation with Reflectance Confocal Microscopy [Articolo su rivista]
Peccerillo, Francesca; Mandel, Victor Desmond; DI TULLIO, Francesca; Ciardo, Silvana; Chester, Johanna; Kaleci, Shaniko; DE CARVALHO, Nathalie; DEL DUCA, Ester; Giannetti, Luca; Mazzoni, Laura; Nisticò, Steven Paul; Stanganelli, Ignazio; Pellacani, Giovanni; Farnetani, Francesca
abstract

Background: Atypical basal cell carcinoma (BCC), characterized by equivocal dermoscopic features typical of malignant melanoma (MM), can be difficult to diagnose. Reflectance confocal microscopy (RCM) enables in vivo imaging at nearly histological resolution. Objectives: To evaluate with RCM atypical melanocytic lesions identified in dermoscopy, according to common RCM criteria for the differential diagnosis of BCC, and to identify representative RCM parameters for superficial (sBCCs) and nonsuperficial (nsBCCs) basal cell carcinomas (BCCs). Methods: A retrospective analysis of consecutive patients evaluated with RCM, selecting excised lesions classified at dermoscopy with ≥1 score from the re visited 7-point checklist, mimicking melanoma, registered between 2010 and 2016. Cluster analysis identified BCC subclassifications. Results: Of 178 atypical lesions, 34 lesions were diagnosed as BCCs with RCM. Lesions were confirmed BCCs with histopathology. Dermoscopic features included atypical network (55.9%) and regression structures (35.5%) associated with sBCCs, and an atypical vascular pattern (58.8%) and irregular blotches (58.8%) with nsBCCs. Hierarchical cluster analysis identified 2 clusters: cluster 1 (100% sBCCs) was characterized by the presence of cords connected to the epidermis (90%, p < 0.001), tumor islands located in the epidermis (100%, p < 0.001), smaller vascular diameter (100%, p < 0.001) and solar elastosis (90%, p = 0.017), and cluster 2 (nsBCCs 85%) was defined by the dermic location of tumor islands (87.5%, p < 0.001) with branch-like structures (70.8%, p = 0.007) and surrounding collagen (83.3%, p = 0.012), peripheral palisading (83.3%, p = 0.012) and coiled vascular morphology (79.2%, p < 0.001) with a larger vascular diameter (50%, p < 0.001). Conclusions: RCM is able to diagnose BCCs mimicking melanoma at dermoscopy and seems able to identify sBCCs and nsBCCs.

2019 - Lesions mimicking melanoma at dermoscopy confirmed basal cell carcinoma: evaluation with reflectance confocal microscopy [Relazione in Atti di Convegno]
Peccerillo, Francesca; Mandel, Victor Desmond; DI TULLIO, Francesca; Ciardo, Silvana; Chester, Johanna; Kaleci, Shaniko; DE CARVALHO, Nathalie; DEL DUCA, Ester; Mazzoni, Laura; Nistico', Steven Paul; Stanganelli, Ignazio; Pellacani, Giovanni; Farnetani, Francesca
abstract

Background Atypical basal cell carcinoma (BCC), characterized by equivocal dermoscopic features typical of malignant melanoma (MM), can be difficult to diagnose. Reflectance confocal microscopy (RCM) enables in vivo imaging at nearly histological resolution. Objectives To evaluate BCCs mimicking melanoma at dermoscopy according to well-known RCM criteria for typical BCCs, and identify discriminate RCM parameters for superficial (sBCCs) and nonsuperficial BCCs (nsBCCs). Material and Methods A retrospective analysis of consecutive patients, evaluated with RCM, selecting excised lesions classified at dermoscopy with ≥1 score from the revisited seven-point checklist, mimicking melanoma, registered between 2010 - 2016. Lesions without RCM melanocytic parameters, were investigated by operators blinded to histopathology diagnoses. Cluster analysis identified BCC sub-classifications. Results Of 178 atypical lesions, 34 lesions were diagnosed BCC with RCM, and diagnoses were confirmed with histopathology. Dermoscopic features observed atypical network (55.9%), and regressions structures (35.5%) associated with sBCCs, and atypical vascular pattern (58.8%) and irregular blotches (58.8%) with nsBCC. Hierarchical cluster analysis identified 2 clusters: cluster 1 (100% sBCCs) was characterized by the presence of cords connected to the epidermis (90%, p<0.001), tumor islands located in the epidermis (100%, p<0.001), smaller vascular diameter (100%, p<0.001) and solar elastosis (90%, p=0.017) and cluster 2 (nsBCCs 85%) by the dermic location of tumor islands (87.5%, p<0.001) with branch-like structures (70.8%, p= 0.007) and surrounding collagen (83.3%, p=0.012), peripheral palisading (83.3%, p=0.012), and coiled vascular morphology (79.2%, p<0.001) with larger vascular diameter (50%, p<0.001). Conclusions RCM is able to diagnose BCCs mimicking melanoma at dermoscopy and seems able to identify sBCCs and nsBCCs. Therefore, the use of RCM may assist in optimizing therapeutic management of these equivocal lesions.

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 - Non-invasive Imaging for Skin Cancers—the European Experience. [Articolo su rivista]
Guida, S; De Pace, B; Ciardo, S; Farnetani, F; Pellacani, G.
abstract

2019 - Reflectance confocal microscopy in the diagnosis of pigmented macules of the face: Differential diagnosis and margin definition [Articolo su rivista]
Farnetani, F.; Manfredini, M.; Chester, J.; Ciardo, S.; Gonzalez, S.; Pellacani, G.
abstract

In vivo reflectance confocal microscopy (RCM) is a noninvasive high-resolution skin imaging tool that has become an important adjunct to clinical exam, dermoscopy and histopathology assessment, in the diagnosis and management of pigmented macules of the face. The diagnosis of early stage lentigo maligna (LM) and lentigo maligna melanoma (LMM) is challenging and RCM improves the diagnostic accuracy in the differential diagnosis of LM with other macules of the face such as solar lentigo (SL), pigmented actinic keratosis (PAK), seborrheic keratosis (SK) and lichen planus-like keratosis (LPLK). Here we review the state-of-the-art of RCM morphologic descriptors, standardized terminology, and diagnostic algorithms for the RCM assessment of pigmented macules of the face including melanocytic, and nonmelanocytic lesions. Clinical applications of RCM are broad and include diagnosis, assessment of large lesions on cosmetically sensitive areas, directing areas to biopsy, delineating margins prior to surgery, detecting response to treatment and assessing recurrence. The present review is intended to summarize the application of RCM for the correct diagnosis of challenging pigmented facial macules and to evaluate its application in LM margin mapping during the pre surgical phase.

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 - The association between pesticide use and cutaneous melanoma: a systematic review and meta-analysis [Poster]
Stanganelli, Ignazio; DE FELICI, Maria Beatrice; Mandel, Victor Desmond; Caini, Saverio; Raimondi, Sara; Corso, Federica; Bellerba, Federica; Quaglino, Pietro; Sanlorenzo, Martina; Ribero, Simone; Medri, Matelda; Farnetani, Francesca; Feliciani, Claudio; Pellacani, Giovanni; Gandini, Sara; on behalf of IMI, the Italian Melanoma Intergroup
abstract

Background: Pesticides directly endanger agricultural workers, neighbouring populations, wildlife, and consumers with a short and long term impact on health biological systems. Ecological wisdom demands to monitor methods of pesticide exposure and to improve the current knowledge based on epidemiological and biological data such as risk assessment indicators. The United States Environmental Protection Agency (USEPA) and the European Environment Agency (EEA) should investigate violations in biocide use, with appropriate public oversight provisions to diminish bias from government and industry. Moreover, USEPA, EEA and all scientific community should improve standards used to determine the safety and relative risk of chemicals allowed on the market. Epidemiological studies suggested that agricultural workers are at an increased risk of CM because they were exposed to pesticides. However, little is known about the relationship between pesticides and cutaneous melanoma. We performed a systematic review and meta-analysis to investigate the possible association between pesticide exposure and CM. Moreover, we tried to determine the categories of pesticides mainly involved in CM development. Methods: Our analysis was performed up to September 2018 using Medline, Embase and Web of Science. Studies assessing CM risk in licensed pesticide applicators were considered. Strict criteria were established to select independent studies and risk estimates; random effect models, taking into account heterogeneity, were applied. A pooled risk estimate for CM was calculated for the use of each type of pesticide and type of exposure. Between-study and estimates heterogeneity was assessed and publication bias investigated. Results: A total of 9 studies comprising 184389 unique subjects were included (1-9). The summary relative risks for the categories “herbicides - ever exposure”, “insecticides - ever exposure”, “any pesticide - ever exposure” and “any pesticide - high exposure” resulted 1.85 (95% CI: 1.01, 3.36), 1.57 (95% CI: 0.58, 4.25), 1.31 (95% CI: 0.85, 2.04) and 2.17 (95% CI: 0.45, 10.36), respectively. Herbicides and insecticides had no between-study heterogeneity (I2=0%), while a significant heterogeneity (I2>50%) was detected for the high exposure to any pesticide. No indication for publication bias was found. Conclusions: Individuals exposed to herbicides are at an increased risk of CM. Future properly designed observational studies are required to confirm this finding.

2019 - The evolution of healthy skin to acne lesions: a longitudinal, in vivo evaluation with reflectance confocal microscopy and optical coherence tomography [Articolo su rivista]
Manfredini, M.; Bettoli, V.; Sacripanti, G.; Farnetani, F.; Bigi, L.; Puviani, M.; Corazza, M.; Pellacani, G.
abstract

Background Comedogenesis is defined as the process of the development of a new comedo, which is of great importance for the understanding of acne. Objective To evaluate the formation and evolution of acne lesions from clinically unaffected skin of patients with mild-moderate acne to characterize the morphological changes and natural resolution by means of in vivo reflectance confocal microscopy (RCM) and dynamic optical coherence tomography (D-OCT). Methods Ten patients with mild-moderate acne, not assuming any topical or systemic therapy, comprised between 12 and 30 years of age, were recruited. A target area of 4 x 4 mm of the face, without acne lesions at baseline, was selected. A set of standardized clinical pictures, RCM and D-OCT images were acquired weekly for 6 weeks and evaluated. Results Seventy full sets of clinical, RCM and D-OCT images were analysed. The appearance of acne lesion is preceded by an increase of large bright follicles in the area corresponding to infundibular keratinization, followed by increment of inflammation parameter, such as increased of small bright cells upon RCM and vascular network upon D-OCT, which return to normal after the resolution of acute inflammation. Conclusion Acne skin dynamics is complex and seems characterized by the early increase in the number of dysmorphic pilosebaceous units and the hyperkeratinization of the acroinfundibulum of the pilosebaceous duct prior to the occurrence of inflammatory events around the follicle. The processes of hyperkeratinization and inflammatory phenomena may generate a pathologic vicious cycle, which characterizes acne through progressive worsening and a self-sustainment mechanism.

2019 - The influence of MC1R on dermal morphological features of photo-exposed skin in women revealed by reflectance confocal microscopy and optical coherence tomography [Articolo su rivista]
Guida, S; Ciardo, S; De Pace, B; De Carvalho, N; Peccerillo, F; Manfredini, M; Farnetani, F; Chester, J; Kaleci, S; Manganelli, M; Guida, G; Pellacani, G.
abstract

2019 - The integration of dermoscopy and reflectance confocal microscopy improves the diagnosis of lentigo maligna [Articolo su rivista]
Cinotti, E.; Fiorani, D.; Labeille, B.; Gonzalez, S.; Debarbieux, S.; Agozzino, M.; Ardigo, M.; Lacarrubba, F.; Farnetani, F.; Carrera, C.; Cevenini, G.; Le Duff, F.; Tognetti, L.; Pellacani, G.; Rubegni, P.; Perrot, J. L.
abstract

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2018 - “Agnelli” vestiti da lupi: quando il carcinoma basocellulare imita il melanoma, ma viene smascherato dalla microscopia laser confocale [Poster]
Peccerillo, Francesca; Mandel, Victor Desmond; DI TULLIO, Francesca; Ciardo, Silvana; Pellacani, Giovanni; Farnetani, Francesca
abstract

Background. Nella pratica clinica, molto spesso, l’esame clinico-dermoscopico del carcinoma basocellulare (BCC) non è sufficiente per una diagnosi corretta e la diagnosi differenziale si pone con il melanoma. La microscopia laser confocale (RCM) è una metodica di diagnosi non invasiva che consente di ottenere immagini in vivo ad alta risoluzione. Obiettivi. Nel nostro studio abbiamo valutato l'affidabilità dei ben noti criteri RCM per i classici BCC in un gruppo di lesioni con presentazione clinica e dermoscopica atipica. Metodi. Abbiamo analizzato retrospettivamente alla RCM tutte le lesioni asportate dal 2010 al 2016 con positività per almeno uno dei criteri dermoscopici della 7-point check list revisitata. Risultati. Tra le lesioni esaminate sono stati identificati 34 casi, confermati istologicamente come BCC (21 nodulari, 13 superficiali) e 143 casi classificati come altre lesioni (DF, Sebk, SCC e altri). Conclusioni. Le caratteristiche in RCM dei BCC che mimano dermoscopicamente il melanoma erano le stesse descritte per i classici BCC. Il nostro studio sottolinea l'importante ausilio della microscopia laser confocale nel corretto inquadramento diagnostico di neoplasie con differente comportamento biologico e nella conseguente gestione terapeutica.

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 - Clinical and Confocal Microscopy Study of Plasma Exeresis for Nonsurgical Blepharoplasty of the Upper Eyelid: A Pilot Study [Articolo su rivista]
Rossi, Elena; Farnetani, Francesca; Trakatelli, Myrto; Ciardo, Silvana; Pellacani, Giovanni
abstract

Plasma exeresis is an evolving technique for nonsurgical treatment of several skin conditions. Reflectance confocal microscopy (RCM) is a noninvasive tool that allows the "in vivo" imaging of the skin.

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 - 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 - Eccrine poroma: dermoscopical and confocal features of five cases [Poster]
DI TULLIO, Francesca; Mandel, Victor Desmond; Peccerillo, Francesca; Ciardo, Silvana; Pellacani, Giovanni; Farnetani, Francesca
abstract

Background: Eccrine poroma (EP) is a rare benign adnexal tumor arising from the intraepidermal ductal portion of the sweat gland. It commonly occurs as a single, slowly growing, erythematous, skin-colored, cyanotic or pigmented papule, plaques or nodule. EP occurs usually at the acral sites, but it can develop in other cutaneous sites. It may occasionally mimic malignant tumors including basal cell carcinoma, squamous cell carcinoma and melanoma. Objective: The aim of this study was to describe dermoscopical and confocal features of EP. Methods: A retrospective analysis of the dermoscopical and confocal characteristics of EP was performed. All diagnosis were confirmed by histological examination. Results: A total of 5 cases of non-pigmented EP was analysed. Dermoscopic evaluation found in all lesions a polymorphous vascular pattern, including at least two type of vessels: hairpin (80%), linear (60%), leaf-like (60%), flower-like (40%) and glomerular (40%) vessels. A white-to-pink halo surrounding the vessels was found in 40% of the lesions. Multiple pink-white structureless areas were found in 4 out of 5 (80%) cases. Only in 2 cases irregular haemorrhagic and blue-white areas were also observed. Reflectance Confocal Microscopy (RCM) revealed the presence of well-demarcated hyporefractile tumor nests, dark holes corresponding to areas of ductal differentiation within the tumor and highly vascularized stroma in all 5 lesions. Conclusions: The great clinical variability of EP gives reason of the appellative of “big simulator”. Dermoscopy does not revealed univocal features except from “leaf-flower-like” vessels that have not been described in other types of skin tumors. This characteristic, when presents, may be considered an useful clue for the diagnosis. RCM examination of EP revealed features (hyporefractile tumor nests and dark holes) that relate with their histopathological findings. Dermoscopy and RCM improve the diagnostic accuracy and help for diagnosis, although they cannot replace histology that is still required.

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 - Image Gallery: Demodex folliculorum longitudinal appearance with reflectance confocal microscopy [Articolo su rivista]
Nazzaro, G.; Farnetani, F.; Moltrasio, C.; Passoni, E.; Pellacani, G.; Berti, E.
abstract

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2018 - Improving mandibular contour: A pilot study for indication of PPLA traction thread use [Articolo su rivista]
Guida, Stefania; Persechino, Flavia; Rubino, Giuseppe; Pellacani, Giovanni; Farnetani, Francesca; Urtis, Giacomo Giovanni
abstract

The request for less-aggressive procedures to improve mandibular contour is increasing. Several kinds of threads have been used for this purpose. Nevertheless, PLLA (poly-L-Lactic acid) traction thread procedure has not been previously described.

2018 - Improving the aging of the neck: combined treatments [Relazione in Atti di Convegno]
Persechino, Flavia; Farnetani, Francesca; Mandel, Victor Desmond; Pellacani, Giovanni; Urtis, Giacomo Giovanni; Guida, Stefania
abstract

INTRODUCTION, OBJECTIVES, PURPOSE OF THE STUDY The request for less aggressive procedures to treat skin laxity of face and neck is increasing. Only a few approaches are available for aesthetic treatments of the neck. Several factors are known to be involved in aging process: skin laxity and photodamage, fat tissue deposition, variation of muscle tone. MATERIALS AND METHODS Clinical evaluation of the patient. Classification and selection of the patient and targeted therapies: from microbotox, bio-stimulation, high intensity focused ultrasound to traction thread. Inclusion criteria: people aged >18 years old; moderate skin laxity and horizontal wrinkles of the neck. Exclusion criteria: severe diseases; skin laxity showing a high grade of severity and severe fat tissue deposition. Different treatments in multiple sessions. Controls at T0 + T30 + T90. Measurement and analysis: standard digital photo. Evaluation of results and satisfaction of patients. RESULTS The targeted approach focused on the correction of specific expressions of the ageing of the neck, showing a variable grading, is effective. The association of target therapy results to satisfy patient expectations. CONCLUSIONS In the field of aesthetic medicine we have available various techniques such as microbotox, bio-stimulation, high intensity focused ultrasound and traction thread. One treatment does not exclude the others. The combination of the two treatment it is possible to optimize the results. The targeted treatment and an appropriate selection of patients are essential to reach satisfactory results in the treatment of imperfections related to the process of ageing of the neck.

2018 - “Lambs” in wolves’ clothing: when basal cell carcinoma mimics melanoma, but it is detected by the use of reflectance confocal microscopy [Relazione in Atti di Convegno]
Peccerillo, Francesca; Mandel, Victor Desmond; DI TULLIO, Francesca; Ciardo, Silvana; Kaleci, Shaniko; Chester, Johanna; Pellacani, Giovanni; Farnetani, Francesca
abstract

Background Basal cell carcinoma (BCC) is the most frequent non-melanoma skin cancer. There are some cases in which clinical and dermoscopic examinations do not allow to formulate a unique diagnosis and in particular can be difficult the differential diagnosis with melanoma. Reflectance confocal microscopy (RCM) is a non-invasive technology, which allows an in vivo imaging of the skin with high resolution. Objectives We addressed our research to evaluate the reliability of the well-known RCM criteria for classic BCCs in a group of lesions with atypical dermoscopy presentation, possibly mimicking melanoma. Methods We retrospectively analyzed at RCM excised lesions presenting in dermoscopy ≥1 score at revisited 7-point checklist. The study population consisted of 177 cases showing no melanocytic RCM findings. Lesions were investigated for distinct non-melanocytic RCM features, while blinded from histopathology. Histopathology matching was performed before statistical analysis. Results Among the lesions classified at RCM with no-melanocytic characteristics, we recognized 34 cases, histopathological confirmed as BCCs (21 nodular BCCs and 13 superficial BCCs) and 143 cases classified as other lesions (DFs, SebKs, SCCs and others). The main features of nBCCs (with histopathological confirm) at RCM are peritumoral clefts (20/21 95,2%; p=0,037), peripheral palisading (19/21 90,5%; p=0,001), increased vascularization (20/21 95,2%; p=0,004). In sBCCs we found mild keratinocytic atypia (13/13 100%; p=<0,001), solar elastosis (12/13 92,3%; p=0,002), cords connected to epidermidis (9/13 69,2%; p=<0,001). Dendritic structures, nests of basaloid cells, inflammatory infiltrate can be seen in all tumors. Conclusions RCM classification proved high agreement with histopathology for BCCs with atypical dermoscopy presentations, allowing an early differential diagnosis and even identification of BCCs subtypes. RCM features in this group of lesions were similar to those described for typical cases of BCCs, and may drive clinicians decisions, helped them in the recognition of melanocytic and non melanocytic lesions, increasing the rate of accurate diagnoses and allowing better therapeutic management.

2018 - Lesions mimicking melanoma at dermoscopy confirmed basal cell carcinomas: evaluation with reflectance confocal microscopy [Relazione in Atti di Convegno]
Peccerillo, Francesca; Mandel, Victor Desmond; DI TULLIO, Francesca; Ciardo, Silvana; Chester, Johanna; Kaleci, Shaniko; DE CARVALHO, Nathalie; DEL DUCA, Ester; Mazzoni, Laura; Nistico', Steven Paul; Stanganelli, Ignazio; Pellacani, Giovanni; Farnetani, Francesca
abstract

Background: Atypical basal cell carcinoma (BCC), characterized by equivocal dermoscopic features typical of malignant melanoma (MM), can be difficult to diagnose. Reflectance confocal microscopy (RCM) enables in vivo imaging at nearly histological resolution. Objectives: To evaluate BCCs mimicking melanoma at dermoscopy according to well-known RCM criteria for typical BCCs, and identify discriminate RCM parameters for superficial (sBCCs) and nonsuperficial BCCs (nsBCCs). Material and Methods: A retrospective analysis of consecutive patients, evaluated with RCM, selecting excised lesions classified at dermoscopy with ≥1 score from the revisited seven-point checklist, mimicking melanoma, registered between 2010 - 2016. Lesions without RCM melanocytic parameters, were investigated by operators blinded to histopathology diagnoses. Cluster analysis identified BCC sub-classifications. Results: Of 178 atypical lesions, 34 lesions were diagnosed BCC with RCM, and diagnoses were confirmed with histopathology. Dermoscopic features observed atypical network (55.9%), and regressions structures (35.5%) associated with sBCCs, and atypical vascular pattern (58.8%) and irregular blotches (58.8%) with nsBCC. Hierarchical cluster analysis identified 2 clusters: cluster 1 (100% sBCCs) was characterized by the presence of cords connected to the epidermis (90%, p<0.001), tumor islands located in the epidermis (100%, p<0.001), smaller vascular diameter (100%, p<0.001) and solar elastosis (90%, p=0.017) and cluster 2 (nsBCCs 85%) by the dermic location of tumor islands (87.5%, p<0.001) with branch-like structures (70.8%, p= 0.007) and surrounding collagen (83.3%, p=0.012), peripheral palisading (83.3%, p=0.012), and coiled vascular morphology (79.2%, p<0.001) with larger vascular diameter (50%, p<0.001). Conclusions: RCM is able to diagnose BCCs mimicking melanoma at dermoscopy and seems able to identify sBCCs and nsBCCs. Therefore, the use of RCM may assist in optimizing therapeutic management of these equivocal lesions.

2018 - New trends in botulinum toxin use in dermatology. [Articolo su rivista]
Guida, S; Farnetani, F; Nisticò, Sp; Mariarosaria, Cg; Babino, G; Pellacani, G; Fulgione, E.
abstract

BACKGROUND: Recent studies have highlighted new botulinum neurotoxin (BoNT) applications in the field of dermatology. OBJECTIVE: To review current knowledge of BoNT use in dermatology. METHODS: The literature of the last 5 five years has been reviewed. RESULTS: We describe interesting protocols of BoNT treatment for hyperhidrosis (HH), hypertrophic scars and keloids, Raynaud phenomenon, facial flushing, oily skin, psoriasis, Hailey-Hailey disease, and cutaneous lesions like painful lesions and periorbital syringomas. CONCLUSIONS: Several skin conditions eligible for BoNT treatment have been described. After the wide application for HH treatment, scars as well as vascular and inflammatory skin disorders, oily skin and cutaneous lesions represent fields of application of BoNT.

2018 - Non ti scordar di me [Poster]
DI TULLIO, Francesca; Mandel, Victor Desmond; Francomano, Mariangela; Farnetani, Francesca; Pellacani, Giovanni
abstract

Un uomo di 78 anni giungeva alla nostra osservazione per una lesione della regione temporale destra che riferiva essere presente da più di 1 anno, ma che negli ultimi mesi era aumentata di dimensioni e facilmente andava incontro a sanguinamento. L’esame obiettivo evidenziava una lesione rotondeggiante delle dimensioni di 3 cm con area ulcerata centrale, pigmentazione grigio-blu e bordi lievemente rilevati, eritematosi, con fine desquamazione biancastra. All’esame dermoscopico si osservava un’area centrale ulcerata ed alla periferia aree prive di struttura bianco-rosa, aree irregolari bianco brillante, alcuni vasi dilatati ed aree eccentriche grigio-blu con velo. Veniva, quindi, posta diagnosi differenziale tra melanoma e carcinoma basocellulare pigmentato. La lesione veniva sottoposta ad escissione chirurgica per esame istologico che rivelava proliferazione di cellule squamose atipiche, melanociti, melanofagi e depositi di melanina. Tale quadro risultava compatibile con un carcinoma squamocellulare pigmentato. Si tratta di una variante che, seppur rara (0,01-7% di tutti i carcinomi squamocellulari), dovrebbe essere presa in considerazione nelle diagnosi differenziale di lesioni pigmentate cutanee benigne, come il melanoacantoma, e maligne, quali il melanoma ed il carcinoma basocellulare pigmentato.

2018 - Osservazioni dermoscopiche ed in microscopia laser confocale sul poroma eccrino: la nostra casistica [Relazione in Atti di Convegno]
DI TULLIO, Francesca; Mandel, Victor Desmond; Peccerillo, Francesca; Farnetani, Francesca; Pellacani, Giovanni
abstract

Il poroma eccrino è una neoplasia benigna che clinicamente può simulare molteplici lesioni cutanee sai benigne che maligne. Le immagini dermoscopiche ed in microscopia laser confocale di cinque poroma eccrini non pigmentati, istologicamente provati, sono stati esaminate da due valutatori indipendenti. Le caratteristiche dermoscopiche più frequentemente osservate sono state il pattern vascolare polimorfo (100% dei casi) e le aree prive di struttura rosa-biancastre (80% dei casi). L’esame alla microscopia laser confocale ha evidenziato nei cinque casi di poroma nidi iporiflettenti ben demarcati circondati da abbondante stroma, assenza di cellule con disposizione a palizzata e “dark holes” corrispondenti ad aree di differenziazione duttale. L’integrazione delle caratteristiche clinico-dermoscopiche con l’osservazione alla microscopia laser confocale risulta utile nella diagnosi differenziale del poroma eccrino con altri tumori cutanei e nella sua corretta gestione terapeutica, sebbene la diagnosi definitiva resta affidata all’esame istologico che rimane imprescindibile nei casi dubbi.

2018 - Plasma exeresis for active acne vulgaris: Clinical and in vivo microscopic documentation of treatment efficacy by means of reflectance confocal microscopy [Articolo su rivista]
Rossi, Elena; Mandel, Victor Desmond; Paganelli, Alessia; Farnetani, Francesca; Pellacani, Giovanni
abstract

[No abstract available]

2018 - Presentazione dermoscopica atipica di lesioni non melanocitarie benigne: quale aiuto dal confocale? [Poster]
Pezzini, Claudia; Mandel, Victor Desmond; Persechino, Flavia; Ciardo, Silvana; Kaleci, Shaniko; Chester, Johanna; DE CARVALHO, Nathalie; Persechino, Severino; Pellacani, Giovanni; Farnetani, Francesca
abstract

Sono sempre più frequenti i report di lesioni cutanee benigne che simulano clinicamente il melanoma; in questi casi spesso mancano i criteri clinico-dermoscopici tipici. Abbiamo analizzato retrospettivamente in microscopia laser confocale (RCM) lesioni che presentassero in dermoscopia punteggio ≥1 alla revisited 7-point checklist, focalizzandoci su quelle prive di criteri melanocitari. Ogni caso è stato indagato quindi per la presenza di caratteristiche RCM non melanocitarie. La selezione ha permesso di raccogliere 117 lesioni a presentazione dermoscopica atipica, classificate al confocale come benigne (71 cheratosi seborroiche e 18 dermatofibromi), maligne (13 basaliomi e 2 spinaliomi), e “non specifiche” (13). Il valore K relativo al matching complessivo con l’istologia è risultato elevato (0.76); per cheratosi seborroiche e dermatofibromi la concordanza è risultata del 97% e 89% rispettivamente. I risultati ottenuti su un gruppo di lesioni di difficile inquadramento clinico, confermano l’utilità del confocale nella diagnosi differenziale non invasiva tra patologie benigne e maligne.

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 - Removal of unwanted hair: efficacy, tolerability, and safety of long-pulsed 755-nm alexandrite laser equipped with a sapphire handpiece. [Articolo su rivista]
Nistico, Sp; Del Duca, E; Farnetani, F; Guida, S; Pellacani, G; Rajabi-Estarabadi, A; Nouri, K.
abstract

Due to the difference in refraction coefficients between air and the corneal epithelium, irradiation of the skin with a light source can lead to reflection of the energy and its leakage to the skin causes epidermal injury. All of which decreases the efficacy of treatment. We evaluated cooling sapphire handpieces' efficacy in decreasing pain and epidermal injuries and enhancing the treatment outcome in laser hair removal. A total of 49 patients with Fitzpatrick skin types of II to IV were treated for laser hair removal on face, limbs, inguinal, and axillary areas with pulsed 755-nm alexandrite laser equipped with a sapphire handpiece and the cooling system. Hair counts were performed by two independent observers at the baseline and 3 months after the final treatment. A marked reduction in hair regrowth was noted 3 months after the final treatment in all body locations studied. Clinical hair reduction was observed and fully assessed. There were no serious side effects with an average pain score of 4.6 out of 40. The cooled sapphire cylinder tip has been shown to minimize epidermal injury and reduce the system energy leaks to the skin.

2018 - Resurfacing with Ablation of Periorbital Skin Technique: Indications, Efficacy, Safety, and 3D Assessment from a Pilot Study. [Articolo su rivista]
Guida, S; Nisticò, Sp; Farnetani, F; Del Duca, E; De Carvalho, N; Persechino, F; Verdina, T; Giannetti, L; D'Alessandro, M; Urtis, Gg; Pellacani, G; D'Alessandro, G.
abstract

OBJECTIVES AND BACKGROUND: Nowadays, several approaches for skin rejuvenation of the lower eyelid are available. We present a new technique of resurfacing with ablation of periorbital skin (RAP) performed in a single session. METHODS: This is a retrospective study involving 20 patients showing skin elastosis with or without evidence of the nasojugal fold and atrophic and dyschromic skin or needing a combined approach of transconjuntival lower blepharoplasty for fat bag removal. RAP technique is assessed in terms of efficacy, safety, and 3D evaluation of results at 6 months' follow-up. RESULTS: Global Assessment Improvement Scale results highlighted an improvement in all cases, for both physicians (blinded to treatment) and individual subjects. Only minor adverse events (edema, erythema, and discoloration) were reported in almost all patients, lasting 2-3 weeks after treatment, and were resolved without intervention. A 3D imaging tool revealed the reduction of medium protrusions and depressions and an improved texture at 2 months. Skin recovery was inversely correlated with hemoglobin reduction. CONCLUSIONS: RAP seems to offer expert dermatologists a safe and clinically effective technique for skin rejuvenation of lower eyelids, without significant adverse events. Further studies will be performed to confirm our results.

2018 - Role of In Vivo Reflectance Confocal Microscopy in the Analysis of Melanocytic Lesions [Articolo su rivista]
Serban, Elena-Daniela; Farnetani, Francesca; Pellacani, Giovanni; Constantin, Maria Magdalena
abstract

Worldwide melanoma incidence and mortality are increasing (1). Despite the ongoing research, advanced melanoma is still incurable; therefore, the most appropriate solution seems to be early detection combined with complete surgical excision (2). Since the diagnostic protocol of suspicious lesions includes a complete excision with safety margins (2), the problem of unnecessary scarring is significant. The real challenge in this case is to have a properly formulated diagnosis before acquiring a biopsy. Currently available non-invasive techniques are coherence tomography, digital dermoscopy, and reflectance confocal microscopy. All these techniques allow for a presumptive diagnosis, but the most promising results are provided by reflectance confocal microscopy. Reflectance confocal microscopy (RCM) is an optical imaging technique that uses a laser diode as a source of coherent monochromatic light which penetrates the tissue and illuminates a single point. Light from the stimulated section is reflected and passes through a filter, thereby forming the image on the detector. This filter enables selective excitation of a particular point on which focus is achieved and rejects reflection from the out-of-focus area, thus obtaining a "confocal" image. Contrast is the result of differences in the refractive index of the cell organelles and microstructures, resulting in white structures on a black background. This technique allows, as opposed to conventional light microscopy, the analysis of sections obtained at a bi- or tri-dimensional level and controlling the depth of the field, permitting out-of-focus artifacts to be eliminated. In dermatology, this technique is useful for both clinical and research purposes. It is the only technique that allows horizontal viewing of the skin up to the superficial dermis (approximately 300 mm, at a cellular level resolution (0.5-1.0 μm in the lateral dimension and 4.0-5.0 μm in the axial dimension) (3). It allows both in vivo and ex vivo diagnosis, while providing the possibility for long-term monitoring. It has proved to be especially valuable for in vivo examinations of melanocytic lesions, whereas melanin and melanosomes are a powerful source of contrast, allowing the individualization of melanocytic cells (4). We report the case of a 65-year-old Caucasian woman who presented to the Dermatology Department of University of Modena and Reggio Emilia, Italy, for the examination of an atypical lesion, of unknown history, localized in the right preauricular area. The patient's personal and family histories were negative for skin malignancies and for other significant medical history. The clinical presentation was highly indicative of malignancy, as it met all the ABCD clinical criteria: an asymmetric papule composed of two areas, one pigmented and another one hypopigmented, with ill-defined borders and a diameter of approximately 2 cm. The dermatoscopic examination revealed an asymmetric multicomponent pattern with atypical network, structureless areas, peripheral irregular globules, and a blue-white veil. Because clinical and dermatoscopic features pointed towards a suspicious lesion which was situated on the face, where unnecessary scarring is unwanted, reflectance confocal microscopy (RCM) examination was proposed and performed (VivaScope 3000; MAVIG GmBH, Munich, Germany) (5). It revealed the following features: the epidermis presented a disarranged pattern; the dermo-epidermal junction and superficial dermis presented a meshwork pattern with edged AND non-edged papillae, non-homogenous junctional clusters, dense nests, dense AND sparse nests, and atypical cells in a sparse distribution (Figure 1). Figure 1. (A) Clinical examination of an atypical melanocytic lesion situated at the right preauricular area. (B) Dermatoscopic examination. (C) Confocal examination of dermo-epidermal junction and superficial dermis which reveals a meshwork pattern (yellow

2018 - Seborrheic keratoses mimicking melanoma unveiled by in vivo reflectance confocal microscopy [Articolo su rivista]
Pezzini, Claudia; Mandel, Victor Desmond; Persechino, Flavia; Ciardo, Silvana; Kaleci, Shaniko; Chester, Johanna; DE CARVALHO, Nathalie; Persechino, Severino; Pellacani, Giovanni; Farnetani, Francesca
abstract

Background: Seborrheic keratoses (SebK) with atypical dermoscopy presentation are increasingly reported. These lesions do not exhibit typical dermoscopy features of SebK and sometimes mimic melanoma, thus complicating the differential diagnosis. Reflectance confocal microscopy (RCM) is a non-invasive tool, which allows an in vivo imaging of the skin. The study objectives were to evaluate the agreement between RCM classification and histological diagnoses, and the reliability of well-known RCM criteria for SebK in the identification of SebK with atypical dermoscopy presentation. Materials and methods: We retrospectively analysed at RCM excised lesions presenting in dermoscopy ≥1 score at revisited 7-point checklist. The study population consisted of cases showing no melanocytic RCM findings. Lesions were investigated for distinct non-melanocytic RCM features, blinded from histopathology diagnoses. Histopathology matching was then performed before statistical analysis. Results: The study consisted of 117 cases, classified at RCM as SebK (71 cases), dermatofibroma (18 cases), basal cell carcinoma (13 cases), squamous cell carcinoma (2 cases), and "non-specific" (13 cases). Overall K strength of agreement at histopathology matching proved 0.76. Of the 71 cases classified at RCM with SebK, agreement was achieved in 97%. Conclusion: Reflectance confocal microscopy classification proved high agreement with histopathology for SebK with atypical dermoscopy presentations, allowing an early differential diagnosis. RCM features in this group of lesions were similar to those described for typical cases of SebK, and may assist clinician therapy decision making, whilst avoiding unnecessary excisions.

2018 - Seborrheic keratoses mimicking melanoma unveiled by in vivo reflectance confocal microscopy [Poster]
Pezzini, Claudia; Mandel, Victor Desmond; Persechino, Flavia; Ciardo, Silvana; Kaleci, Shaniko; Chester, Johanna; DE CARVALHO, Nathalie; Persechino, Severino; Pellacani, Giovanni; Farnetani, Francesca
abstract

Background: Seborrheic keratoses (SebK) with atypical dermoscopy presentation are increasingly reported. These lesions do not exhibit typical dermoscopy features of SebK and sometimes mimic melanoma, thus complicating the differential diagnosis. Reflectance confocal microscopy (RCM) is a non-invasive tool, which allows an in vivo imaging of the skin. Objective: To evaluate the agreement between RCM classification and histological diagnoses, and the reliability of well-known RCM criteria for SebK in the identification of SebK with atypical dermoscopy presentation. Methodology: We retrospectively analysed at RCM excised lesions presenting in dermoscopy ≥1 score at revisited 7-point checklist. The study population consisted of cases showing no melanocytic RCM findings. Lesions were investigated for distinct non-melanocytic RCM features, blinded from histopathology diagnoses. Histopathology matching was then performed before statistical analysis. Results: The study consisted of 117 cases, classified at RCM as SebK (71 cases), dermatofibroma (DF; 18 cases), basal cell carcinoma (BCC; 13 cases), squamous cell carcinoma (SCC; 2 cases), and “non specific” (13 cases). Overall K strength of agreement at histopathology matching proved 0.76. Of the 71 cases classified at RCM with SebK, agreement was achieved in 97%. Conclusions: RCM classification proved high agreement with histopathology for SebK with atypical dermoscopy presentations, allowing an early differential diagnosis. RCM features in this group of lesions were similar to those described for typical cases of SebK, and may assist clinician therapy decision making, whilst avoiding unnecessary excisions.

2018 - Skin above the knees: treatments for a difficult area [Relazione in Atti di Convegno]
Guida, Stefania; Persechino, Flavia; Mandel, Victor Desmond; Pellacani, Giovanni; Urtis, Giacomo Giovanni; Farnetani, Francesca
abstract

INTRODUCTION, OBJECTIVES, PURPOSE OF THE STUDY The interest for non-invasive techniques for skin rejuvenation is increasing. However, lax skin above the knee is often forgotten. As a matter of fact, there were not so many options for its treatment. The aim of our study is to present the application of selected rejuvenation techniques and to define their efficacy and safety. MATERIALS AND METHODS Clinical evaluation of the patient. Classification and selection of the patient and targeted therapies: from calcium hydroxyapatite to microfocused ultrasound. Inclusion criteria: people aged >18 years old; skin laxity. Exclusion criteria: severe diseases and severe skin laxity. Treatment in single or multiple sessions. Controls at T0 + T30 + T90. Measurement and analysis: standard digital photo. Evaluation of results and satisfaction of patients. RESULTS The targeted approach focused on the correction of specific morphologic variations of the skin above the knee, showing a variable grading, is effective and able to satisfy patient expectations. The treatment was well tolerated; we reported only a few adverse events: local reactions (erythema, oedema, swelling). All these effects last few days. CONCLUSIONS The treatment of the skin above the knee is challenging. Our protocols have shown good results in this difficult area and a good tolerability profile. A good selection of patients is mandatory in order to achieve the best result.

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.

2017 - Acne: morphologic and vascular study of lesions and surrounding skin by means of optical coherence tomography [Articolo su rivista]
Manfredini, Marco; Greco, Maurizio; Farnetani, Francesca; Ciardo, Silvana; DE CARVALHO, Nathalie; Mandel, Victor Desmond; Starace, Michela; Pellacani, Giovanni
abstract

Background: Acne vulgaris is a disease of the pilosebaceous unit, characterized by hyper-keratinization process, comedos formation and inflammatory reactions. Objective: The definition of the morphology and the vascularization of acne lesions by means of dynamic optical coherence tomography (D-OCT), to non-invasively define the alterations occurring during the acne development and patient therapeutic management. Methods: A set of standardized clinical pictures and D-OCT images were acquired from 114 acne lesions of 31 volunteers, presenting mild to moderate acne and evaluated by experts. Fifteen patients treated with oral antibiotics were followed during time at 0, 20, 40, and 60 days. Results: Optical coherence tomography enabled to identify vascular and morphological aspects characterizing different types of acne lesions. Oral antibiotic treatment improved the morphologic features and decreased the digitally reconstructed vascular signal during time. Conclusion: The characterization of acne lesions and the identification of vascular pattern in acne lesions through D-OCT, corresponding to blood vessel dilation and inflammatory associated hyper-vascularization, may have important clinical consequences in the assessment of acne severity, therapeutic decisions and treatment efficacy monitoring.

2017 - Congenital melanocytic nevi [Capitolo/Saggio]
Farnetani, F.; Carrera, C.; García, A. P.; Marghoob, A. A.
abstract

Congenital melanocytic nevi (CMN) are classified primarily by their projected adult size (PAS) with small nevi measuring <1.5 cm, medium between 1.5 and 19.9 cm (M1:1.5-10 cm, M2:>10-19.9 cm), large between 20 and 40 cm (L1:>20-30, L2:>3040 cm) and giant measuring >40 cm (G1:>4060 cm, G2:>60 cm). The vast majority of CMN are small.1-3 The PAS of CMN is correlated with the risk for developing melanoma. Small and medium-sized CMN are at low risk with less than 1% of lesions developing melanoma.3 In contrast, for large and giant CMN the risk for developing either cutaneous or extracutaneous melanoma is between 5% and 10%.4-7 It has been shown that small CMN often harbor BRAF mutations and larger CMN are mosaic RASopathies resulting from intrauterine postzygotic mutations in codon 61 of NRAS.8 It is interesting to note that these same somatic mutations are found in 15%-50% (NRAS and BRAF, respectively) of superficial spreading melanoma in adults, and in individuals with CMN these mutations may act as the first step in a multiple hit model toward malignant progression.8,9 Clinical presentation The clinical morphology of CMN is quite variable. Their size can range from tiny subclinical incipient nests of nevo-melanocytes in the dermis to nevi covering over 50% of the body surface area. They can also manifest irregular shapes, rugous to nodular surface, hypertrichosis, and variegation in color. For the smaller CMN, their clinical and dermoscopic morphology can be indistinguishable from acquired nevi. In general, the nevo-melanocytes in smaller CMN tend not to penetrate as deeply into the dermis as compared to the larger CMN-a characteristic that has important implications for selection of CMN amenable to reflectance confocal microscopy (RCM) imaging.

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 - Improving diagnostic sensitivity of combined dermoscopy and reflectance confocal microscopy imaging through double reader concordance evaluation in telemedicine settings: A retrospective study of 1000 equivocal cases [Articolo su rivista]
Witkowski, A. M.; Łudzik, J.; Arginelli, F.; Bassoli, S.; Benati, E.; Casari, A.; De Carvalho, N.; De Pace, B.; Farnetani, F.; Losi, A.; Manfredini, M.; Reggiani, C.; Malvehy, J.; Pellacani, G.
abstract

Background: Reflectance confocal microscopy (RCM) is an imaging device that permits non-invasive visualization of cellular morphology and has been shown to improve diagnostic accuracy of dermoscopically equivocal cutaneous lesions. The application of double reader concordance evaluation of dermoscopy-RCM image sets in retrospective settings and its potential application to telemedicine evaluation has not been tested in a large study population. Objective: To improve diagnostic sensitivity of RCM image diagnosis using a double reader concordance evaluation approach; to reduce mismanagement of equivocal cutaneous lesions in retrospective consultation and telemedicine settings. Methods: 1000 combined dermoscopy-RCM image sets were evaluated in blind by 10 readers with advanced training and internship in dermoscopy and RCM evaluation. We compared sensitivity and specificity of single reader evaluation versus double reader concordance evaluation as well as the effect of diagnostic confidence on lesion management in a retrospective setting. Results: Single reader evaluation resulted in an overall sensitivity of 95.2% and specificity of 76.3%, with misdiagnosis of 8 melanomas, 4 basal cell carcinomas and 2 squamous cell carcinomas. Combined double reader evaluation resulted in an overall sensitivity of 98.3% and specificity of 65.5%, with misdiagnosis of 1 in-situ melanoma and 2 basal cell carcinomas. Conclusion: Evaluation of dermoscopy-RCM image sets of cutaneous lesions by single reader evaluation in retrospective settings is limited by sensitivity levels that may result in potential mismanagement of malignant lesions. Double reader blind concordance evaluation may improve the sensitivity of diagnosis and management safety. The use of a second check can be implemented in telemedicine settings where expert consultation and second opinions may be required.

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 monitoring of topical therapy for acne with reflectance confocal microscopy [Articolo su rivista]
Manfredini, M; Greco, M; Farnetani, F; Mazzaglia, G; Ciardo, S; Bettoli, V; Virgili, A; Pellacani, G
abstract

Acne vulgaris is a common disease of the pilosebaceous unit. The aim of the study was to evaluate compartment-specific treatment action through the microscopic non-invasive imaging of skin changes.

2017 - Non-melanoma skin cancer of the head and neck: the aid of reflectance confocal microscopy for the accurate diagnosis and management [Articolo su rivista]
Ferrari, Barbara; Salgarelli, Attilio Carlo; Mandel, Victor Desmond; Bellini, Pierantonio; Reggiani, Camilla; Farnetani, Francesca; Pellacani, Giovanni; Magnoni, Cristina
abstract

Background: Non-melanoma skin cancer (NMSC) represents the most common cutaneous neoplasms of the head and neck. In recent years, novel non-invasive diagnostic tool have been developed, and among these we have the reflectance confocal microscopy (RCM), that offers the evaluation of the skin at real time with cellular resolution. Numerous studies have identified the main confocal features of skin tumours, demonstrating the good correlation of these features with certain dermatoscopic patterns and histologic findings. Evidence acquisition: The aim of this analysis was to provide new insight into the role of RCM in the diagnosis and management of NMSC of the head and neck. 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 NMSC, without restrictions for age, sex, ethnicity. A search concerning the role of dermoscopy and RCM in the diagnosis of NMSC was performed on Medline. Duplicated studies, single case report and papers with language other than English were excluded from this study. Evidence synthesis: RCM clues were analysed for NMSC in association with clinical, dermoscopic and histopathologic findings. Moreover, some new findings have been described and possible applications for NMSC of the head and neck have been discussed. Conclusions: RCM allows tissue imaging in vivo contributing to a more accurate diagnosis of NMSC of the head and neck, sparing time for the patient and costs for the public health system. RCM can also be used for selection of the biopsy site and it is helpful in defining the surgical safety margins to keep during the excision of skin cancers.

2017 - Permanent implants for lip augmentation: Results from a retrospective study and presentation of tips and tricks [Relazione in Atti di Convegno]
Guida, Stefania; Mandel, Victor Desmond; Victor, Desmond; Pellacani, Giovanni; Urtis, Giacomo Giovanni; Farnetani, Francesca
abstract

Introduction: Lip augmentation request is increasing. Nowadays, several techniques to obtain temporary effects are available. On the other hand, permanent results can be reached through lip prosthesis implantation. This procedure represents an innovation in the field of aesthetic medicine and surgery. Material & Methods: A total of 110 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 analysed. Variations to the original technique were also considered. 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 analysed to prevent complications. Conclusions: The request of permanent results for lip augmentation allowed the development of silicone prosthesis. Advantages of this prosthesis are: safety, definitive result, and reversibility considering the possibility to remove the implanted prosthesis in case of request.

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 - Recurrence of melanocytic lesions after laser treatment: benign vs. malignant upon dermoscopy [Articolo su rivista]
Guida, S.; Bencini, P. L.; Manganoni, A. M.; Gianotti, R.; Lospalluti, L.; Greco, P.; Pellacani, G.; Farnetani, F.
abstract

a

2017 - Reflectance confocal microscopy features of regression in congenital naevus: case report [Articolo su rivista]
Persechino, Flavia; De Pace, Barbara; Cesinaro, A. M.; Pellacani, G.; Farnetani, F.
abstract

a

2017 - Superiority of a vitamin B12-barrier cream compared with standard glycerol-petrolatum-based emollient cream in the treatment of atopic dermatitis: A randomized, left-to-right comparative trial [Articolo su rivista]
Nistico, S. P.; Del Duca, E.; Tamburi, F.; Pignataro, E.; De Carvalho, N.; Farnetani, F.; Pellacani, G.
abstract

Atopic dermatitis (AD) is a result of complex genetic, epigenetic, environmental, and immunological interactions with an overlapping epidermal barrier defect. The study evaluates the efficacy and tolerability of topical Vitamin B12-barrier cream (MB12) compared with standard glycerol-petrolatum-based emollient cream (GPC) used three times a day for mild AD. The study was conducted as a on one hemi-body randomized, controlled, single-blind, intra-patient left-to-right comparative trial by patients with clinical diagnosis of mild AD measured with total SCORAD index over 4 months. MB12 was compared on one hemi-body treated (GPC). The comparisons of score values were performed primarily by using non-parametric procedures: Mann–Whitney-U test (for independent samples) and Wilcoxon test (for dependent samples). All 22 patients were randomized (left or right side treated with MB12 or GPC). At week 12 a reduction from baseline in SCORAD index was assessed in both body sites with 77.6% SCORAD index reduction in the MB12 treated body sites versus 33.5% in the GPC treated body sites. These results suggest that MB12 could represent a new option in the treatment of mild AD.

2017 - Superiority of a vitamin B12-containing emollient compared to a standard emollient in the maintenance treatment of mild-to-moderate plaque psoriasis [Articolo su rivista]
Del Duca, Ester; Farnetani, Francesca; De Carvalho, Nathalie; Bottoni, Ugo; Pellacani, Giovanni; Nisticò, Steven P
abstract

Psoriasis is a chronic inflammatory skin disease affecting 2%–3% of the population. The wide range of drugs currently available for its treatment could be associated, in the long term, with organ toxicity and adverse events, thus, clinical monitoring throughout treatment is required. This investigator-initiated trial (IIT) evaluated the efficacy and the safety of a vitamin B12-containing ointment in comparison with glycerol-petrolatum-based emollient cream used twice a day to treat mild-to-moderate plaque psoriasis for a period over 12 weeks followed by a wash-out observation period of 4 weeks. This study was conducted as a randomized, controlled, single-blind, intra-patient left- to right-side trial comparing the efficacy and safety of vitamin B12-containing ointment (M-treatment) with a glycerol-petrolatum-based emollient cream (C-treatment). The Psoriasis Area Severity Index (PASI) was determined at baseline (T0), at time points T2 (14 days), T4 (4 weeks), T8 (8 weeks), T12 (12 weeks) and 4 weeks after the end of the wash-out period (F1). In total, 24 patients with plaque psoriasis were randomized to receive left- or right-side treatment with B12ointment. From time point T2 to time point F1, there was a statistically significant difference in PASI reduction between M-treatment side and C-treatment side. At time point T 12, the difference between the mean reductions from baseline PASI scores by 5.92 ± 2.49 (87, 6%) in the M-treatment side versus 1.08 ± 1.02 (23, 1%) C-treatment side was statistically highly significant (PWex< 0.001). On the contemporary panorama in the treatment of psoriasis, we conclude that vitamin B12ointment will represent a new concrete therapy option and should be considered in the update of therapeutic algorithm for the treatment of psoriasis.

2017 - Un inusuale pemfigo localizzato [Poster]
Mandel, Victor Desmond; Farnetani, Francesca; Vaschieri, Cristina; Manfredini, Marco; Cesinaro, Anna Maria; Giusti, Francesca; Pellacani, Giovanni
abstract

Si presenta il caso di un uomo di 74 anni giunto alla nostra osservazione per la comparsa da circa 4 mesi di una lesione squamo-crostosa del dorso del naso suggestiva per un epitelioma e con pattern dermoscopico aspecifico. Veniva eseguita la microscopia laser confocale e la tomografia a coerenza ottica che mostravano inaspettate caratteristiche di pemfigo. Per confermare tale ipotesi venivano eseguiti ulteriori accertamenti. L’esame istologico evidenziava acantolisi a livello degli strati spinoso e granuloso, mentre l’immunofluorescenza diretta rivelava depositi di IgG e C3 in tutto lo spessore dell’epidermide. Anticorpi intercellulari soprabasali (1:40) sono stati evidenziati dall’immunofluorescenza indiretta. Infine, l’immunoblot mostrava la presenza nel siero di anticorpi diretti contro gli antigeni 130 kDa e 160 kDa, successivamente identificati come anticorpi diretti contro la desmogleina 1 e 3 mediante sistemi colorimetrici AP. Tali dati deponevano per una forma mista di pemfigo con caratteristiche sia della forma volgare che di quella foliacea.

2016 - Congenital Glioblastoma multiforme and eruptive disseminated Spitz nevi [Articolo su rivista]
Mandel, Victor Desmond; Persechino, Flavia; Berardi, Alberto; Ponti, Giovanni; Ciardo, Silvana; Rossi, Cecilia; Pellacani, Giovanni; Farnetani, Francesca
abstract

Background: Glioblastoma multiforme (GBM) is the deadliest malignant primary brain tumor in adults. GBM develops primarily in the cerebral hemispheres but can develop in other parts of the central nervous system. Its congenital variant is a very rare disease with few cases described in literature. Case presentation: We describe the case of a patient with congenital GBM who developed eruptive disseminated Spitz nevi (EDSN) after chemotherapy. Few cases of EDSN have been described in literature and this rare clinical variant, which occurs predominantly in adults, is characterized by multiple Spitz nevi in the trunk, buttocks, elbows and knees. There is no satisfactory treatment for EDSN and the best therapeutic choice is considered the clinical observation of melanocytic lesions. Conclusion: We recommend a close follow-up of these patients with clinical observation, dermoscopy and reflectance confocal microscopy (RCM). However, we suggest a surgical excision of the lesions suspected of being malignant.

2016 - Congenital melanocytic nevi management: answer [Articolo su rivista]
Guida, Stefania; Urtis, Gg; Rubino, G; Pellacani, Giovanni; Farnetani, Francesca
abstract

NA

2016 - Congenital melanocytic nevi management: Question [Articolo su rivista]
Guida, S.; Urtis, G. G.; Rubino, G.; Pellacani, G.; Farnetani, F.
abstract

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 - 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 - Improving Diagnostic Accuracy of Dermoscopically Equivocal Pink Cutaneous Lesions with Reflectance Confocal Microscopy in Telemedicine Settings: Double Reader Concordance Evaluation of 316 Cases [Articolo su rivista]
Łudzik, J; Witkowski, A. M; Roterman Konieczna, I; Bassoli, Sara; Farnetani, Francesca; Pellacani, Giovanni
abstract

Solitary pink lesions in differential diagnosis with hypopigmented/amelanotic melanoma present a diagnostic challenge in daily practice and are regularly referred for second expert opinion. Reflectance confocal microscopy (RCM) has been shown to improve diagnostic accuracy of dermoscopically equivocal pink lesions. No studies have been performed to evaluate the effect of adding a second expert reader and automatic removal of lesions with discordant management recommendations and its potential effect on diagnostic sensitivity and final management of these lesions in retrospective or telemedicine settings.To improve diagnostic accuracy and reduce potential mismanagement of dermoscopically equivocal pink cutaneous lesions by implementing double reader concordance evaluation of RCM images.316 dermoscopically equivocal pink lesions with dermoscopy-RCM image sets were evaluated retrospectively. Accuracy of three readers was evaluated by single reader evaluation of dermoscopy only and dermoscopy-RCM image sets and finally by double reader evaluation of dermoscopy-RCM image sets. Lesions with discordant diagnosis between two readers were automatically recommended for excision.Dermoscopy only evaluation resulted in an overall sensitivity of 95.9% and specificity of 33.6%, with 1 of 12 amelanotic melanomas mismanaged. Dermoscopy-RCM image set single reader evaluation resulted in an overall sensitivity of 93.9% and overall specificity of 54.2%, with 1 of 12 melanomas mismanaged. Dermoscopy-RCM image set double reader concordance evaluation resulted in an overall sensitivity of 98.3% and specificity of 42.7%, with no amelanotic melanoma mismanagement.Evaluation of dermoscopy-RCM image sets of equivocal pink lesions by a single reader in telemedicine settings is limited by the potential for misdiagnosis of dangerous malignant lesions. Double reader concordance evaluation with automatic referral of lesions for removal in the case of discordant diagnosis improves the diagnostic sensitivity in this subset of lesions and reduce potential misdiagnosis in settings where a second expert opinion may be employed.

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 - Pemphigus with features of both vulgaris and foliaceus variants localized to the nose [Articolo su rivista]
Mandel, Victor Desmond; Farnetani, Francesca; Vaschieri, Cristina; Manfredini, Marco; Cesinaro, Anna Maria; Giusti, Francesca; Pellacani, Giovanni
abstract

We report the case of a 74-year-old man affected by an unusual variant of pemphigus. He presented with a crusty and scaly lesion of the nose. We performed reflectance confocal microscopy and optical coherence tomography on the lesion, which suggested an unexpected diagnosis of pemphigus. Therefore, to confirm our diagnostic suspicions, we executed indirect immunofluorescence and two biopsies, one for histopathological examination and one for direct immunofluorescence. Histopathological evaluation showed acantholysis with formation of clefts in the granular and spinous layers of the epidermis. Direct immunofluorescence revealed immunoglobulin G and C3 deposit to the full thickness of the epidermis. Indirect immunofluorescence showed intercellular antibodies at a titer of 1:40 in the suprabasal epidermis. The immunoblot analysis using epidermal extract revealed the presence of circulating antibodies directed to 130- and 160-kDa antigens in the patient's serum. These two antigens were evidenced from nitrocellulose membrane with colorimetric AP systems, which highlighted the presence of autoantibodies against desmoglein (Dsg)1 and Dsg3 (sodium dodecylsulfate polyacrylamide gel electrophoresis). We also performed an enzyme-linked immunoassay. All these findings suggested that this patient's pemphigus had features of both vulgaris and foliaceus variants.

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 - Pink melanocytic and non-melanocytic lesions: how reflectance confocal microscopy can help in differential diagnosis [Articolo su rivista]
TEIXEIRA DE CARVALHO, Nathalie; Guida, Stefania; Abraham, L. Spagnol; Cesinaro, A. M.; Farnetani, Francesca; Bonamonte, Domenico; Pellacani, Giovanni
abstract

NA

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 - Questionnaire-based evaluation of occupational and non-occupational solar radiation exposure in a sample of Italian patients treated for actinic keratosis and other non-melanoma skin cancers [Articolo su rivista]
Modenese, Alberto; Farnetani, Francesca; Andreoli, Alessandro; Pellacani, Giovanni; Gobba, Fabriziomaria
abstract

Background An adequate evaluation of the ultraviolet (UV) cumulative exposure is a major problem in epidemiological studies on chronic skin damage. Questionnaires may be applied as useful tools. Objective We developed an original questionnaire to evaluate individual cumulative exposure to solar radiation (SR) in patients affected by actinic keratosis (AK), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Method The questionnaire, considering both working and leisure exposure, was applied to evaluate the whole life history of solar UV radiation exposure in a group of patients of the Dermatologic Clinic of UNIMORE. Results In outdoor workers (OW), the co-presence of AK/in situ SCC and invasive non-melanoma skin cancers (NMSCs) was increased compared to indoor workers (IW), as was the frequency of multiple skin lesions. The prevalence of skin lesions of the face was significantly higher in OW. Work 'sometimes' or 'often' in the shades was associated with an absence of skin lesions on the shoulders and neck, while workers adopting 'sometimes' or 'often' a downward bent position were more likely to develop lesions on the top of the head. Considering leisure activities, the use of tanning beds was associated to the presence of skin lesions on the shoulders, neck and chest. Considering vacation periods, subjects spending at least 2 h outdoor in the period 11 am to 1 pm presented earlier diagnoses of skin cancers. Conclusion Results of the original questionnaire developed are coherent with current knowledge and confirm the important role of UV exposure, both occupational and recreational, in the development of AK and NMSCs. Data support the hypothesis that this questionnaire can be applied as useful tool for the evaluation of cumulative UV exposure in future epidemiological studies.

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 - Traduzione in lingua italiana e validazione del Nordic Occupational Skin Questionnaire (NOSQ-2002) [Italian translation and validation of the Nordic Occupational Skin Questionnaire (NOSQ-2002)] [Articolo su rivista]
Chiesi, Andrea; Pellacani, Giovanni; Di Rico, Renato; Farnetani, Francesca; Giusti, Giulia; Pepe, Patrizia; Prampolini, Paola; Gobba, Fabriziomaria
abstract

Because of their frequent occurrence, in various situations it may be appropriate to carry out screening of skin disorders in groups of workers. For this purpose the self-administered standardized questionnaires are of great use. Among the best known is the Nordic Occupational Skin Questionnaire (NOSQ-2002), which had not yet been translated and validated in Italian.

2016 - Un caso di forma eruttiva di nevi di Spitz [Poster]
Mandel, Victor Desmond; Persechino, Flavia; Berardi, Alberto; Ciardo, Silvana; Pellacani, Giovanni; Farnetani, Francesca
abstract

Si presenta il caso di un paziente che aveva avuto un glioblastoma multiforme congenito, per il quale era stato sottoposto ad un intervento chirurgico ed a cicli di chemioterapia. All’età di 16 mesi il paziente giungeva alla nostra attenzione per la comparsa di numerosi nevi. I nevi erano principalmente localizzati al tronco, apparivano di differente colore e morfologia ed avevano una dimensione variabile tra 2 mm e 21 mm. All’esame dermoscopico molti di questi nevi presentavano un pattern starburst, globulare o multicomponente con asimmetriche aree ipopigmentate e bordi irregolari. Tali caratteristiche dermatoscopiche deponevano per nevi di Spitz. Tale diagnosi veniva confermata utilizzando il microscopio confocale. Considerando il numero di nevi di Spitz osservati veniva posta diagnosi di forma eruttiva di nevi di Spitz e veniva deciso di eseguire un rigoroso follow-up di tali lesioni invece di eseguire più escissioni chirurgiche. Ciononostante, durante il follow-up, nel sospetto di essere maligna, veniva asportata una di queste lesioni, che all’esame istologico risultava essere un nevo di Spitz. Attualmente il paziente ha 3 anni di età e durante il follow-up è stata notata la comparsa di altri nevi di Spitz, ma nessun nevo di Spitz è cambiato nel tempo.

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 - 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 - 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 - 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 (< 5 or >5 cells per mm2), overall architecture (ringed, meshwork, clods and non-specific pattern); architectural disorder, presence of cytological atypia (>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 >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 - 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 - Esposizione occupazionale a radiazione solare in un campione di pazienti dermatologici. [Abstract in Atti di Convegno]
Modenese, A; Pellacani, G; Farnetani, F; Andreoli, A; Gobba, F.
abstract

Esposizione occupazionale a radiazione solare in un campione di pazienti dermatologici.

2015 - Giuseppe Mariani: the Biography on the fiftieth anniversary of his death [Articolo su rivista]
Farnetani, Francesca; Manfredini, Marco; Mandel, Victor Desmond; Ponti, Giovanni
abstract

[No abstract available]

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 - La top twelve della ricerca pediatrica italiana (una "spigolatura storica") [The top twelve most important discoveries made by Italian pediatric researchers] [Articolo su rivista]
Farnetani, I.; Farnetani, Francesca
abstract

NA

2015 - Leonardo Martinotti: the biography on the fiftieth anniversary of his death [Articolo su rivista]
Farnetani, Francesca; Manfredini, Marco; Mandel, Victor Desmond; Ponti, Giovanni
abstract

[No abstract available]

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 - 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 & 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 & 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 - Pseudoxanthoma elasticum and Reflectance confocal microscopy: report of two affected young sisters [Relazione in Atti di Convegno]
Mandel, Victor Desmond; Boraldi, Federica; Pellacani, Giovanni; Ciardo, Silvana; Mazzaglia, Giovanna; Farnetani, Francesca
abstract

Introduction & Objectives: Pseudoxanthoma elasticum (PXE) is a rare inherited multisystem disorder that mainly affects skin, eyes and cardiovascular system. The associated clinical signs are due to progressive calcification of elastic fibres and blood vessels, although normal levels of calcium and phosphorus in blood and urine. The first clinical description of the disease was done in 1881 by Rigal, and in 1896 was named PXE by Darier. Transmission of the disease is autosomal recessive. PXE is caused by homozygous or compound heterozygous mutations in the ATP-binding cassette subfamily C member 6 (ABCC6) gene, which encodes a transmembrane transport ADP dependent protein (MRP6). The gene is expressed predominantly in the liver and kidney, and found in low level in the tissue involved by PXE. The clinical expression of PXE is heterogeneous with considerable variation in age of onset, progression and severity of the disease, even in individuals of the same family with identical mutations. We present the case of two young sisters of 13 and 14 years old affected by PXE and the correlation between the histopathology and the reflectance confocal microscopy (RCM). Material & Methods: In our two patients we made diagnosis of PXE using clinical assessment and RCM. RCM (Vivascope 1500®: Caliber I.D., Rochester, USA) is a novel technique, based on a laser light of 830 nm of wavelength (near-infrared), which allows the visualization of skin structures at a nearly histological resolution. A depth of 250  μm can be reached, enabling the examination of the skin up to the upper dermis or to the reticular dermis, in relation of the thickness of the epidermis. The clinical and instrumental diagnosis was also confirmed by histopathological examination. The parents and the brother of 20 years old are also investigated. Moreover, we performed genetic test and counseling to all the family. Results: At dermatological examination of both patients we observed that the skin in the cervical region appeared soft, lax, wrinkled and redundant hanging in folds, while in the axillae and cubital fossae there were coalescent yellowish papules forming plaques with a symmetrically distribution. Ophthalmoscopy identified the presence of angioid streaks in both eyes of the two sisters, confirmed by retinograpy and angiography. Cardiovascular evaluation didn’t show changes in the younger patient while mild mitral valve regurgitation was identified in the older patient. Histopathological examination revealed calcification and fragmentation of elastic fibers in the dermis that appeared distorted. The parents and the brother of 20 years old didn’t show signs and symptoms of the disorder. We found a mutation of the ABCC6 gene in the two sisters while parents and brother carried one copy of the mutated gene. We performed RCM on the skin surface of the neck of our two young patients and we observed curled and fragmented thick fibers of the connective tissue in reticular dermis on both patients, which correspond to the short and curled elastic fibers of the reticular dermis in histopathology. Conclusions: Dermatological, ophthalmological and cardiological evaluation and monitoring is essential for an early diagnosis of PXE, adequate handling and better management of the associated complications when these are present. We suggest that the use of RCM it may be usefool to detect PXE in an early stage.

2015 - Pseudoxanthoma elasticum and reflectance confocal microscopy: report of two affected young sisters [Articolo su rivista]
Mandel, Victor Desmond; Boraldi, Federica; Pellacani, Giovanni; Ciardo, Silvana; Mazzaglia, Giovanna; Farnetani, Francesca
abstract

Pseudoxanthoma elasticum (PXE) is a rare inherited multisystem disorder that mainly affects skin, eyes and cardiovascular system. The associated clinical signs are due to progressive calcification of elastic fibres and blood vessels, despite normal levels of calcium and phosphorus in blood and urine. The first clinical description of the disease was done in 1881 by Rigal, and in 1896 it was named PXE by Darier. Transmission of the disease is autosomal recessive. PXE is caused by homozygous or compound heterozygous mutations in the ATP-binding cassette subfamily C member 6 (ABCC6) gene, which encodes a transmembrane transport ADP-dependent protein (MRP6). The gene is expressed predominantly in the liver and kidney, and found in low level in the tissue involved by PXE. The clinical expression of PXE is heterogeneous with considerable variation in age of onset, progression and severity of the disease, even in individuals of the same family with identical mutations. We present the case of two young sisters affected by PXE and the correlation between the histopathology and the reflectance confocal microscopy (RCM). Parents and brother carry one copy of the mutated gene, without showing signs and symptoms of the disorder. We report the main clinical aspects of PXE and we highlight the importance of early diagnosis of the disease for adequate therapeutical management of associated complications.

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 - 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 - Uno strano caso di pemfigo seborroico [Poster]
Mandel, Victor Desmond; Farnetani, Francesca; Cesinaro, Anna Maria; Manfredini, Marco; Giusti, Francesca; Pellacani, Giovanni
abstract

Riportiamo il caso di un uomo di 74 anni che all’esame obiettivo presentava una lesione eritemato-squamo-crostosa del dorso del naso, di cui riferiva la comparsa e persistenza da 4 mesi. Clinicamente la lesione aveva l’aspetto di un epitelioma. Il paziente nel resto del corpo non presentava altre lesioni, non assumeva farmaci e non riferiva patologie di rilievo. Per un migliore inquadramento diagnostico e per valutare l’estensione della lesione venivano eseguite 5 biopsie (parte superiore, centrale, inferiore, destra e sinistra della lesione). Il referto istologico deponeva per un quadro di cheratosi attinica acantolitica. In considerazione dell’aspetto clinico della lesione si inviava la documentazione fotografica della lesione all’anatomopatologo e si chiedeva una sua rivalutazione. Veniva posta, quindi, diagnosi di pemfigo seborroico con aspetti anche di pemfigo volgare, successivamente confermata con l’immunofluorescenza diretta ed indiretta. Veniva impostata una terapia sistemica steroidea con risoluzione del quadro cutaneo. Il pemfigo seborroico è caratterizzato da piccole bolle a tetto flaccido dalla cui rottura si hanno lesioni squamo-crostose localizzate al centro del viso, cuoio capelluto, regioni medio-toraciche, con decorso lungo e benigno. Il nostro caso è particolare perché il pemfigo seborroico si presentava clinicamente in maniera atipica e per la sovrapposizione di aspetti istologici da pemfigo volgare.

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.

2014 - Brooke-Spiegler syndrome tumor spectrum beyond the skin: a patient carrying germline R936X CYLD mutation and a somatic CYLD mutation in Brenner tumor [Articolo su rivista]
Ponti, Giovanni; Ruini, Cristel; Girolomoni, Giampiero; Pellacani, Giovanni; Farnetani, Francesca; Pastorino, Lorenza; Ghiorzo, Paola; Witkowski Alex, M.; Bianchi Scarrà, Giovanna; Tomasi, Aldo; Loschi, Pietro; Nasti, Sabina
abstract

Brooke–Spiegler syndrome is a hereditary disorder characterized by predisposition to the development of skin appendage tumors and the major and minor salivary glands neoplasms. The role of the CYLD mutation in visceral neoplasms is still unclear, except for parathyroid tumor. We report the case of a 46 year-old patient with multiple cylindromas and trichoepiteliomas, a Brenner tumor of the ovary, and a negative family history for Brooke-Spiegler phenotype. Genetic analysis revealed R936X germline mutation in the proband but not in her relatives. The same somatic mutation was found in the Brenner tumor, together with a novel missense CYLD mutation (D889N), which has never been reported in the literature to our knowledge. A founder effect for R936X has been hypothesized due to its high; surprisingly in our case this mutation seems to be recognized as a de novo mutation. Future studies involving a greater number of cases are necessary to understand possible genotype/phenotype correlations, through the clinical analysis of the familial tumor spectrum.

2014 - [Giuseppe Roberto Burgio (1919-2014)] [Articolo su rivista]
Farnetani, Francesca; Farnetani, I.
abstract

NA

2014 - [History of pediatrics: Jemma, Maggiore and Luna] [Articolo su rivista]
Farnetani, Francesca; Farnetani, I.
abstract

NA

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 - [Obituary: Giorgio Maggioni (1918-2014)] [Articolo su rivista]
Farnetani, I; Farnetani, Francesca
abstract

NA

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 - 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.

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 - 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 - CDKN2A and MC1R variants influence dermoscopic and confocal features of benign melanocytic lesions in Multiple [Articolo su rivista]
Bassoli, Sara; Maurichi, A; Rodolfo, M; Casari, Alice; Frigerio, S; Pupelli, Gaia; Farnetani, Francesca; Pelosi, G; Santinami, M; Pellacani, Giovanni
abstract

Non-invasive diagnostic tools are effective in the histomorphological study of melanocytic lesions. The role of melanoma susceptibility genes on melanocytic nevi histopathological features is not clear. The current study aimed to correlate genetic alterations and histomorphological features of melanocytic nevi. Clinical, dermoscopic and confocal features of 34 multiple melanoma patients and 34 controls were compared. Among patients with melanoma, carriers of CDKN2A mutations and/or MC1R variants, and wild-type genes were also compared. In patients with melanoma, a lighter phototype (P = 0.051), a higher number of nevi (P < 0.01) and clinically atypical nevi (P < 0.01) were observed. At dermoscopy, these nevi showed a complex pattern (P = 0.011), atypical network (P = 0.018) and irregular pigmentation (P = 0.037); at confocal, an irregular meshwork pattern (P = 0.026) with atypical nests (P = 0.016) and an inflammatory infiltrate (P = 0.048) were observed. Among patients with melanoma genetically tested, CDKN2A G101W mutation carriers were more frequently younger (P = 0.023), with clinically atypical nevi (P = 0.050), with cytological atypia (P = 0.033) at confocal. G101W mutation and MC1R variants carriers showed hypopigmented nevi (P = 0.002) and, at confocal, roundish cells infiltrating the junction (P = 0.019). These data suggest an influence of CDKN2A mutation and MC1R variants in the development of dysplastic melanocytic lesions. Non-invasive histomorphological evaluation, together with genetic studies, improves melanoma risk identification and early diagnosis, for a patient-tailored management.

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 - 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 - [Macciotta's disease and the biography of Giuseppe Macciotta] [Articolo su rivista]
Farnetani, Francesca; Farnetani, I.
abstract

Giuseppe Macciotta directed the Pediatric Clinic of Cagliari in Sardinia. He dedicated his work to the study of pathology present in Sardinia and the Mediterranean basin area, He identified a variant of the β thalassemia major (homozygote Cooley's disease). He defined this variant as subchronic erythroblastosis, referred to by many as Macciotta's disease. Subchronic erythroblastosis, whose symptoms include earlier onset and a more difficult course of illness, was characterized by appearance generally at the beginning of the second trimester of the baby's life, and a course of illness between 5 and 10 months and a fatal outcome. The picture of the illness was dominated by hyperemolysis, erythroblastemia, medullar erythroblastosis and hyperbilirubinemia. The rapid course of the illness did not even allow time to damage the skeleton, and thus produced the formation of typical skeletal alterations and cardiomegalia. In the years which followed, transfusional and precocious and rational therapies were carried out which permitted the abeyance of the debilitating course of Macciotta's disease. The symptomatology was interrupted before any picture of greater or lesser seriousness could be drawn.

2013 - Proteomic analysis of PTCH1+/- fibroblast lysate and conditioned culture media isolated from the skin of healthy subjects and Nevoid Basal Cell Carcinoma Syndrome (NBCCS) patients. [Poster]
Pastorino, L.; Bertazzoni, G.; Monari, Emanuela; Cuoghi, A.; Bergamini, Stefania; Bellei, E.; Ruini, C.; Ghiorzo, P.; Bianchi Scarrà, G.; Pellacani, Giovanni; Loschi, P.; Pollio, A.; Tomasi, Aldo; Farnetani, F.; Ponti, Giovanni
abstract

PTCH1 mutations lead to complex syndromes such as the Gorlin Syndrome (GS) also named Nevoid basal Cell Carcinoma Syndrome (NBCCS, OMIM #109400) is a rare autosomal dominant disorder characterized by striking predisposition to the development of multiple basal cell carcinomas (BCCs), keratocystic odontogenic tumors (KOCTs) of the jaws, palmar and/or plantar pits and developmental defects. A variety of other benign or malignant tumors i.e., ovarian fibroma, medulloblastoma, rhabdomyosarcoma, cardiac fibroma and ameloblastoma can be found. The mechanisms underlying the increased predisposition to the development of BCCs in the context of Gorlin-Goltz syndrome is linked to molecular pathways that differ from sporadic cases. Patients with Gorlin syndrome tend to develop multiple BCCs at an early age: moreover, the tumors typically arise on non-sunexposed skin. Fibroblasts of patients with Gorlin Syndrome may display properties determining BCC development. The aim of this study was to compare the proteomic profile of cultured fibroblast and fibroblast conditioned culture media of PTCH1+ and non-mutated fibroblasts. Proteomic analyses was performed using Surface-Enhanced Laser Desorption/Ionization Time-of-Flight mass spectrometry in PTCH1+ fibroblast conditioned media isolated from not affected sun-protected skin areas of Gorlin patients and from healthy subjects. The protein profiles were obtained using Copper pre-activated IMAC30 ProteinChip array. 12 protein cluster peaks, >5 kDa, had statistically significant differences in their peak intensities between PTCH1+ and PTCH1- subject groups (p<0.05). Protein profiles in the fibroblast conditioned media revealed statistically significant differences between two different types (missense vs nonsense) of PTCH1 mutations. These differences could be useful as signatures to identify PTCH1 gene carriers at high risk for the development of NBCCS-associated malignancies, and to develop novel experimental molecular tailored therapies based on these druggable targets. These protein peaks profiles provided better understanding of the complex skin cancer microenvironment and could be useful to select patients at risk to develop multiple and aggressive BCCs and/or other NBCCS-associated malignancies.

2013 - Sphenoid asymmetry associated to other skeletal anomalies in a clear cut case of PTCH1 mutated Gorlin-Goltz syndrome: a novel finding? [Poster]
Ruini, Cristel; Pastorino, Lorenza; Malagoli, Marzio; Bruno, Walter; Ghiorzo, Paola; BIANCHI-SCARRÀ, Giovanna; Loschi, Pietro; Pellacani, Giovanni; Tomasi, Aldo; Farnetani, Francesca; Mandel, Victor Desmond; Ponti, Giovanni
abstract

Gorlin-Goltz syndrome is an autosomal dominantly inherited disorder linked to PTCH1 mutation, recognized by a collection of clinical and radiologic signs (macrocephaly, frontal bossing, multiple intracranial calcifications including falx cerebri and atlanto-occipital ligament). We describe here a the case of a family with clear cut criteria for Gorlin-Goltz syndrome presenting the association of cranio-facial and skeletal anomalies together with a peculiar sphenoid variant. Two patients, father and son, were examined because of multiple basal cell carcinomas and keratocystic odontogenic tumours. Other suggestive findings were multiple positive family history, typical skeletal anomalies and a novel PTCH1 germline mutation (c.1041delAA). Craniofacial and other skeletal anomalies displayed at 3D and helical CT scan were: macrocephaly, skull base asymmetry (positional plagiocephaly), mandibular prognathism, mandibular condylar deformation with hyperplasia of the coronoid process, bifidity of multiple ribs and giant multilocular odontogenic jaw cysts. Extensive multilamellar calcifications were found in falx cerebri, tentorium, falx cerebelli and in the apical segment of the atlanto-occipital ligament. Thoracic anomalies included bifid left 3rd, 4th, 5th and 6th rib, dismorphic body of the 3rd thoracic vertebra, dorsolumbar scoliosis, sacrum acutum. Interestingly, 3D-CT scan showed asymmetry of both sphenoid wings with thickening of the left wing sphenoid wing together with irregularity of the architecture of trabecular bone with alternating osteolytic and sclerotic areas. Abnormalities of the sphenoid bone are not very common, and consist of differently aggressive entities: some of them are typical of the pediatric age in few hereditary and congenital disorders. The application of new criteria (i.e. peculiar calcifications of ligaments and sphenoid asymmetry) to a wider case series can lead to the early diagnosis of Gorlin syndrome, especially in pediatric patients, when the full phenotype is not yet expressed. The inclusion of bifid ribs as a novel major criteria and the recognition of peculiar cranial anomalies such as sphenoid asymmetry, well detected at volume CT reconstruction, might be useful for the recognition and characterization of misdiagnosed cases.

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.

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 - 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 - 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

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2011 - [Biography and bibliography of Francesco Fede, the founder of Italian pediatrics] [Articolo su rivista]
Farnetani, Francesca; Navarra, A; Farnetani, I.
abstract

For the first time, an overall study of the life and works of Francesco Fede, the founder of Italian pediatrics, has been carried out. Unpublished biographical data was collected and the complete bibliographic works of Fede were presented. Fede is the hallmark of both scientific matter, which reached a climax in the definition of the Riga and Fede illness, and for his disinterested dedication as a Member of Parliament to foster development in didactics, research and assistance for pediatrics.

2011 - Libero Martoni: The paediatrician who brought "Nelson" to Italy [Articolo su rivista]
Farnetani, I; Farnetani, Francesca
abstract

Libero Martoni, director of the paediatric clinic in Bologna, brought the study of paediatrics to Italy and through an accurate and precise translation, introduced him to Italian paediatricians. Since 1955, the year of the first Italian translation, it has remained to today the fundamental text of paediatrics. It brought a remarkable contribution to the field of puericulture, hepatology and oncohematolgy, both in research and in manuals.

2011 - [Maria Sandrucci: up-to-date with science, supporter of equal rights] [Articolo su rivista]
Farnetani, I; Farnetani, Francesca; Bona, G; Mussa, G. C.
abstract

This is the first scientific study on Mary Sandrucci, who has been director of the Pediatric Clinic of the University of Turin from 1965-1966 up to 31 December 1989. Prof. Sandrucci led major studies on congenital heart disease, was the first Italian and among the first in Europe to describe phocomelia cases, to report on valuable studies antibiotics, uric acid, pediatric nephrology, nuclear medicine and genetics. She promoted the development of pediatric specialties, but at the same time promoted the study and practice of paediatrics as a whole. This study describes the past half century of medicine, history of Italian pediatrics and progress of the conquest of rights and equal opportunities for women.

2009 - [Pediatric history in Pisa and the birth of world pediatrics] [Articolo su rivista]
Farnetani, I; Farnetani, Francesca
abstract

The University of Pisa was the first in the world to nominate a professor of pediatirics. It was Gaetano Palloni who was nominated professor of ''children diseases'' on April 8(th), 1802 and was assigned to one of the two branch offices of the Pisan University, the one in Florence. He was assigned to ''Ospedale degli Innocenti'' where he taught and also supervised the clinical part. In 1923, he was nominated director of the Gennaro Fiore paediatric clinic and stayed there until 1952 when Augusto Gentili took over. In half a century there were only two professors and this didactic continuity made it possible for Pisa to become one of the greatest Italian pediatric schools.

2008 - History of Italian pediatrics: The origins [Articolo su rivista]
Farnetani, I.; Farnetani, F.
abstract

2008 - Naples: The historic capital of Italian paediatrics [Articolo su rivista]
Farnetani, I; Farnetani, Francesca
abstract

No other Italian city has contributed to the birth and development of paediatrics more than Naples. This is why it can be considered the historic capital of Italian paediatrics. Here are the main reasons: Luigi Somma was the first professor of Italian paediatrics whereas Francesco Fede was the first president of the Italian Paediatrics Association. Neapolitan paediatricians have been the most numerous amongst the founder members. The first three Italian journals of paediatrics were founded in Naples as well as the journal ''La Pediatria'' which was the most distributed and long-lasting journal in this field. Moreover, Neapolitans have been the most numerous presidents of the Italian Paediatrics Association, while Rocco Jemma was the one who remained the longest in charge. ''Rocco Jemma's school'' taught not only to most professors in paediatrics who afterwards taught in most Italian universities, but also four out of five paediatricians who took charge of the position as president. The first regional department of the Italian Paediatrics Association was founded in Naples as well as the Association of Nipiology.

2008 - [Pediatrics in Arezzo: a millennium] [Articolo su rivista]
Farnetani, I; Farnetani, Francesca
abstract

The analysis of the evolution of Pediatrics in Arezzo, from 1100 until today, has been a very positive contribution to the study of pediatric history. It explains health problems and the true suburban environment allowing to verify the effective and operational applications of the laws issued by the central governments. In particular, it describes the care given to foundlings, the development of hospital facilities and the case of the six children who died of sepsis in 1959.

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 - Alessandro Laurinsich, the key player in the progress of paediatrics in the 20th century [Articolo su rivista]
Farnetani, I; Farnetani, Francesca
abstract

Alessandro Laurinsich was one of the greatest Italian paediatricians of the 20(th) century. He was born in Monfalcone (it was the province of Trieste, but now it belongs to Gorizia) on 29(th) May 1899. After having completed secondary school in Trieste, he obtained a medical degree with honours in 1922 at the University of Naples and entered the paediatric clinic run by Rocco Jemma. Laurinsich was in charge of teaching at the clinic of infectious diseases from 1937 to 1940. During this period he focused on the study of tuberculosis in children, the first applications of pnemoencephalography in Italy, but also studied different malignant tumors of the kidney, neurological and psychological disorders in children, as well as educational problems. In 1940 he had a teaching post in the peadiatric clinic at the University of Siena and remained until 1945 when he moved to Parma. He worked with illegitimate children as well as evacuees. During the 1945-46 academic year, Alessandro Laurinsich was called to direct the paediatric clinic of Parma University where he created a series of paediatric centres and took many initiatives in the area. In 1961 he was offered the paediatric teaching post at the University of Milan, but inexplicably refused it. He was Dean of the faculty of Medicine from 1956 to 1968. He passed away on 2(nd) February 1969 in Parma.

2007 - Antonino Longo: The school of Concetti and the birth of paediatrics in Catania [Articolo su rivista]
Farnetani, I; Farnetani, Francesca
abstract

The biography of Antonino Longo gives us the opportunity to gain knowledge in, even in everyday life, Luigi Concetti's school of paediatrics in Rome, the state of the art in some infectious diseases,and the reality of paediatrics in Catania where Longo founded University teachings and organised health care for children.

2007 - Eugenio Schwarz Tiene was the pioneer of the study of congenital metabolic disorders [Articolo su rivista]
Farnetani, I; Farnetani, Francesca
abstract

Eugenio Schwarz Tiene was a key player in the field of Italian Paediatrics for over 30 years, dating back to 1946, when he became director of the Paediatrics Clinic at the University of Sassari and retired in 1976. During this period, he focused on developing the study of congenital metabolic disorders. At that time, very few types were known; subsequently, due to the introduction of new methods of diagnostic research, several thousand types were discovered. Also during this period, Eugenio Schwarz Tiene realised that scientific progress would require specialized training for specialist paediatricians. On this basis, he took charge of the organisation of the clinic in Milan, and, as a result, it was possible, after his retirement, to define a structure of Milanese clinics and hospitals in such a way as to create a series of paediatric centres, each with its own specialized direction. Thus the system currently in use in hospitals and universities can be traced to the one founded in Milan in 1976 by Tiene during his retirement.

2006 - [Ivo Nasso: infection medicine specialist and founder of neonatal intensive care] [Articolo su rivista]
Farnetani, I; Farnetani, Francesca
abstract

Ivo Nasso (1892-1976), graduated in medicine in 1919, dedicated his work to the study of infectious diseases and was responsible for promoting the study of medicine for preterm and small for age patients and neonatal intensive care in Italy. Nasso developed one of the first pilot centres for immature infants. In fact, in the 1950s in Milan the mortality rate for immature infants in their first year of life was approximately 50%, whereas in the United States the figure was around 20-25% and in France around 35%. The installation of an immature infants' unit in Milan signaled a decrease in infant mortality down to 30%. The pilot centre for immature infants of the University of Milan was composed of 2 visiting rooms with wide glass doors, allowing the relatives to see the babies, an area for sterilisation, a milk bar and 4 hospitalisation rooms; one with incubators and one without, the room for babies in pre-discharging stages and one for isolated confinement. Thermostatic and thermo-electric cots were used. During the planning of the pilot centre Nasso arranged the isolated confinement area in such a way as to be able to identify the infections which he held to be of fundamental importance in the care of low weight babies. Particular importance was allotted to the pre-discharging area, which was comprised of a large area in the style of a veranda, enabling easier acclimatization.

2006 - [Who was the very first teacher of paediatrics in Italy?] [Articolo su rivista]
Farnetani, I; Farnetani, Francesca
abstract

It has always been said that the first teachings of paediatrics in Italy were those of Dante Cervesato in Padua. However, documents indicate the historic groundlessness of such information. During the period after the unification of Italy and before Cervesato, teaching was carried out in Venice, Siena, Naples and Genoa. The first teaching post with a teaching hospital was founded in 1882 and appointed to Moisè Raffael Levi as a temporary professor following a national exam in Florence. Cervesato began lessons in May 1882, nevertheless was put in charge without a ward which was only assigned to him in 1889. He became temporary professor in 1885, 13 years after Levi. One cannot conclude without mentioning Aurelio Bianchi, Professor Levi's assistant, who had to abandon his university career in order to become head of the "Meyer" hospital in Florence due to the death of his predecessor.

2006 - [Why was Rocco Jemma the greatest Italian paediatrician?] [Articolo su rivista]
Farnetani, I; Farnetani, Francesca
abstract

Rocco Jemma was the greatest Italian paediatrician, because he left the greatest signs in history. The most important amongst his achievements is certainly the foundation of the Rocco Jemma School which spread all over Italy and provided the greatest number of paediatric teachers who reached excellence levels. He was, among all the presidents of the Italian Society of Paediatrics, the one who was in office for the longest time. The therapy of leishmaniosis, based on antimonial derivatives formulated by Jemma, is still used and respected today.