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Albino ECCHER
Professore Ordinario
Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto
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Pubblicazioni
2023
- A fatal case of spleen rupture secondary to thrombosed aneurysm of the splenic vein
[Articolo su rivista]
Raniero, Dario; Gibelli, Filippo; Eccher, Albino; Brunelli, Matteo; Turrina, Stefania; De Leo, Domenico
abstract
Vascular abnormalities of the spleen are infrequently encountered in medical practice and, among these, an aneurysm of the splenic vein is a rare event, being only a few dozen cases reported to date in the literature. The rarity of this clinical condition hinders the understanding of its clinical history, related medical management and potential complications, which are currently unclear. In this article, we report an autopsy case observed in the practice of forensic medicine concerning a 45-year-old woman, anaemic, who died at home a few hours after a previous hospital evaluation for abdominal pain and vaginal spotting. The autopsy revealed a massive secondary hemoperitoneum caused by a laceration of the spleen. On examination of the organ, an aneurysm of the proximal branch of the splenic vein was detected, affected by complete thrombotic occlusion. This case offers a new perspective regarding the clinical evolution of splenic vein aneurysm to death, unprecedented in the current literature.
2023
- Application of Digital Imaging and Artificial Intelligence to Pathology of the Placenta
[Articolo su rivista]
Marletta, Stefano; Pantanowitz, Liron; Santonicco, Nicola; Caputo, Alessandro; Bragantini, Emma; Brunelli, Matteo; Girolami, Ilaria; Eccher, Albino
abstract
Digital imaging, including the use of artificial intelligence, has been increasingly applied to investigate the placenta and its related pathology. However, there has been no comprehensive review of this body of work to date. The aim of this study was to therefore review the literature regarding digital pathology of the placenta. A systematic literature search was conducted in several electronic databases. Studies involving the application of digital imaging and artificial intelligence techniques to human placental samples were retrieved and analyzed. Relevant articles were categorized by digital image technique and their relevance to studying normal and diseased placenta. Of 2008 retrieved articles, 279 were included. Digital imaging research related to the placenta was often coupled with immunohistochemistry, confocal microscopy, 3D reconstruction, and/or deep learning algorithms. By significantly increasing pathologists' ability to recognize potentially prognostic relevant features and by lessening inter-observer variability, published data overall indicate that the application of digital pathology to placental and perinatal diseases, along with clinical and radiology correlation, has great potential to improve fetal and maternal health care including the selection of targeted therapy in high-risk pregnancy.
2023
- Artificial intelligence-based tools applied to pathological diagnosis of microbiological diseases
[Articolo su rivista]
Marletta, Stefano; L'Imperio, Vincenzo; Eccher, Albino; Antonini, Pietro; Santonicco, Nicola; Girolami, Ilaria; Tos, Angelo Paolo Dei; Sbaraglia, Marta; Pagni, Fabio; Brunelli, Matteo; Marino, Andrea; Scarpa, Aldo; Munari, Enrico; Fusco, Nicola; Pantanowitz, Liron
abstract
: Infectious diseases still threaten the global community, especially in resource-limited countries. An accurate diagnosis is paramount to proper patient and public health management. Identification of many microbes still relies on manual microscopic examination, a time-consuming process requiring skilled staff. Thus, artificial intelligence (AI) has been exploited for identification of microorganisms. A systematic search was carried out using electronic databases looking for studies dealing with the application of AI to pathology microbiology specimens. Of 4596 retrieved articles, 110 were included. The main applications of AI regarded malaria (54 studies), bacteria (28), nematodes (14), and other protozoa (11). Most publications examined cytological material (95, 86%), mainly analyzing images acquired through microscope cameras (65, 59%) or coupled with smartphones (16, 15%). Various deep-learning strategies were used for the analysis of digital images, achieving highly satisfactory results. The published evidence suggests that AI can be reliably utilized for assisting pathologists in the detection of microorganisms. Further technologic improvement and availability of datasets for training AI-based algorithms would help expand this field and widen its adoption, especially for developing countries.
2023
- Characteristics and clinical behavior of acute myeloid leukemia harboring rare non-A/B/D nucleophosmin (NPM1) gene mutation subtypes: a single-center experience and review of the literature
[Articolo su rivista]
Mutti, M.; Cordella, S.; Parisotto, A.; Bettelli, F.; Morselli, M.; Cuoghi, A.; Bresciani, P.; Messerotti, A.; Gilioli, A.; Pioli, V.; Giusti, D.; Colaci, E.; Cassanelli, L.; Paolini, A.; Martinelli, S.; Maffei, R.; Riva, G.; Nasillo, V.; Sarti, M.; Trenti, T.; Comoli, P.; Tagliafico, E.; Manfredini, R.; Eccher, A.; Lagreca, I.; Barozzi, P.; Potenza, L.; Marasca, R.; Candoni, A.; Luppi, M.; Forghieri, F.
abstract
2023
- Digital Examination of LYmph node CYtopathology Using the Sydney system (DELYCYUS). An international, multi-institutional study
[Articolo su rivista]
Caputo, Alessandro; Fraggetta, Filippo; Cretella, Pasquale; Cozzolino, Immacolata; Eccher, Albino; Girolami, Ilaria; Marletta, Stefano; Troncone, Giancarlo; Vigliar, Elena; Acanfora, Gennaro; Zarra, Karen Villar; Torres Rivas, Héctor Enrique; Fadda, Guido; Field, Andrew; Katz, Ruth; Vielh, Philippe; Eloy, Catarina; Rajwanshi, Arvind; Gupta, Nalini; Al-Abbadi, Mousa; Bustami, Nadwa; Arar, Tala; Calaminici, Maria; Raine, Juliet I; Barroca, Helena; Canão, Pedro Amoroso; Ehinger, Mats; Rajabian, Nilofar; Dey, Pranab; Medeiros, L Jeffrey; El Hussein, Siba; Lin, Oscar; D'Antonio, Antonio; Bode-Lesniewska, Beata; Rossi, Esther Diana; Zeppa, Pio
abstract
Background: After a series of standardized reporting systems in cytopathology, the Sydney system was recently introduced to address the need for reproducibility and standardization in lymph node cytopathology. Since then, the risk of malignancy for the categories of the Sydney system has been explored by several studies, but no studies have yet examined the interobserver reproducibility of the Sydney system. Methods: The authors assessed interobserver reproducibility of the Sydney system on 85 lymph node fine-needle aspiration cytology cases reviewed by 15 cytopathologists from 12 institutions in eight different countries, resulting in 1275 diagnoses. In total, 186 slides stained with Diff-Quik, Papanicolaou, and immunocytochemistry were scanned. A subset of the cases included clinical data and results from ultrasound examinations, flow cytometry immunophenotyping, and fluorescence in situ hybridization analysis. The study participants assessed the cases digitally using whole-slide images. Results: Overall, the authors observed an almost perfect agreement of cytopathologists with the ground truth (median weighted Cohen κ = 0.887; interquartile range, κ = 0.210) and moderate overall interobserver concordance (Fleiss κ = 0.476). There was substantial agreement for the inadequate and malignant categories (κ = 0.794 and κ = 0.729, respectively), moderate agreement for the benign category (κ = 0.490), and very slight agreement for the suspicious (κ = 0.104) and atypical (κ = 0.075) categories. Conclusions: The Sydney system for reporting lymph node cytopathology shows adequate interobserver concordance. Digital microscopy is an adequate means to assess lymph node cytopathology specimens.
2023
- Digital diagnostic cytopathology: has the pandemic brought us closer?
[Articolo su rivista]
Girolami, Ilaria; Eccher, Albino
abstract
: The Covid-19 pandemic has acted as a powerful change driver in the field of pathology and has had relevant consequences on the practice of cytopathology, in terms of changes in workload, rates of malignancy, and performance of cytology. At the same time, regulatory authorities have relaxed their requirements for the deployment of digital pathology for remote diagnostic reporting. However, most of these improvements concerned digital histopathology. Data from literature search show that experiences in digital cytopathology during the pandemic concerned mainly educational and academic activities. From a broader point of view, when searching for all published literature on digital pathology, only a minority of papers deal with cytopathology, but a noticeable increase in publications has been seen in the last ten years, with a continuous trend toward this increase with a maximum of papers in 2021. Indeed, the pandemic has led to greater awareness of the opportunity of digital for cytopathology as well.
2023
- Effect of Radio-Chemotherapy on PD-L1 Immunohistochemical Expression in Head and Neck Squamous Cell Carcinoma
[Articolo su rivista]
Girolami, Ilaria; Marletta, Stefano; Fiorentino, Vincenzo; Battocchio, Simonetta; Cerbelli, Bruna; Fiamengo, Barbara; Gerosa, Clara; Gianatti, Andrea; Morelli, Luca; Riva, Giulio; Zagami, Maria Giovanna; Fusco, Nicola; Munari, Enrico; L'Imperio, Vincenzo; Pagni, Fabio; Morbini, Patrizia; Martini, Maurizio; Eccher, Albino
abstract
Background: Programmed death-ligand 1 (PD-L1) checkpoint inhibitors represent a mainstay of therapy in head and neck squamous cell cancer (HNSCC). However, little is known about the influence of combined therapy on PD-L1 expression. The study aims to gather evidence on this topic. Methods: A systematic search was carried out in electronic databases Pubmed-MEDLINE and Embase to retrieve studies on the comparison of PD-L1 expression before and after conventional therapy. Data were extracted and a quantitative analysis with pooled odds ratios (ORs) was performed when applicable. Results: Of 5688 items, 15 were finally included. Only a minority of studies assessed PD-L1 with the recommended combined positive score (CPS). The results are highly heterogeneous, with some studies reporting an increase in PD-L1 expression and others reporting a decrease. Three studies allowed for quantitative analysis and showed a pooled OR of 0.49 (CI 0.27-0.90). Conclusions: From the present evidence, a clear conclusion towards an increase or decrease in PD-L1 expression after combined therapy cannot be drawn, but even with few studies available, a trend towards an increase in expression in tumor cells at a cutoff of 1% can be noted in patients undergoing platinum-based therapy. Future studies will provide more robust data on the effect of combined therapy on PD-L1 expression.
2023
- Fluorescence confocal microscopy on liver specimens: could it be a game changer in transplantation pathology?
[Articolo su rivista]
Eccher, Albino; Segev, Dorry; Boggi, Ugo
abstract
No abstract available
2023
- Histology for nephrology, from pre-implantation to post-transplant kidney biopsy. Lesson learned from ReBIrth (Renal BIopsy for Kidney Transplantation Therapy)
[Articolo su rivista]
Caliò, Anna; Barreca, Antonella; Marletta, Stefano; Achenza, Maria Italia Sara; Alessi, Marianna; Angelico, Roberta; Apicella, Luca; Argiolas, Davide; Bossini, Nicola; Carrano, Rosa; Carriero, Concetta; Castellano, Giuseppe; Comai, Giorgia; Di Bella, Caterina; D'Ignoto, Francesco; Gallico, Agnese; Gastaldon, Fiorella; Merlotti, Guido; Paloschi, Vera; Panarese, Alessandra; Parodi, Angelica; Perna, Francesco; Picciotto, Daniela; Regalia, Anna; Rossini, Michele; Russo, Enrico; Salerno, Maria Paola; Toti, Luca; Tulissi, Patrizia; Vischini, Gisella; Zaza, Gianluigi; Eccher, Albino
abstract
: A meeting entitled Renal BIopsy for Kidney Transplantation Therapy (ReBIrth) took place on May 31st, 2022 in Bologna, Italy. The meeting drew together nephrologists, surgeons, and pathologists and recognized as experts in the field of kidney transplantation in Italy. In this paper, we present our experience working with kidney transplants in the current era of immunosuppression therapy. The primary aim is to report the histopathological characteristics of failed kidney allografts after a consensus of experts reviewed the cases on a wholeslide imaging digital platform. Regardless of the cases discussed, digital pathology was reliable in identifying all the morphological and immunohistochemical features required to improve the correct use of immunosuppressive therapy to prevent graft failure and optimize patient management.
2023
- Horizon of the pre-implantation kidney biopsy for allocation: multidisciplinarity, methodology and innovation
[Articolo su rivista]
Eccher, Albino; Girolami, Ilaria; Becker, Jan Ulrich
abstract
No abstract available
2023
- Impact of a centralized archive for pathology laboratories on the health system
[Articolo su rivista]
Eccher, Albino; Scarpa, Aldo; Dei Tos, Angelo Paolo
abstract
: The pathology archive of any hospital is likely to contain tens of thousands of slides and formalin-fixed and paraffin-embedded (FFPE) blocks, with their number constantly increasing. As a result, serious space and management issues are created. There has always been a favorable location for the pathology laboratory to rapidly and efficiently collect specimens and to meet the different service requirements of clinicians and patients. However, archiving may be one of the most neglected issues in the planning of spaces and activities, so much so that many laboratories are currently in trouble and looking for space inside and outside their hospitals. Another crucial issue is related to the environmental conditions of the identified preservation place, which, based on their characteristics, probably provide suboptimal habitats in most cases. For FFPE blocks, controlled temperature (<27 °C) and humidity (>30% and <70%) are recommended, with control systems for parasite infestation. For glass slides, systems suitable for guaranteeing their safety, traceability and conservation suitable for possible revision are recommended. The aim of this position paper is to outline the issues that currently exist in archives and to suggest a rational health policy solution to overcome the problems raised.
2023
- Relevance of the College of American Pathologists' Guideline for Validating Whole Slide Imaging for Diagnostic Purposes to Cytopathology
[Articolo su rivista]
Antonini, Pietro; Santonicco, Nicola; Pantanowitz, Liron; Girolami, Ilaria; Rizzo, Paola Chiara; Brunelli, Matteo; Bellevicine, Claudio; Vigliar, Elena; Negri, Giovanni; Troncone, Giancarlo; Fadda, Guido; Parwani, Anil; Marletta, Stefano; Eccher, Albino
abstract
Whole slide imaging (WSI) allows pathologists to view virtual versions of slides on computer monitors. With increasing adoption of digital pathology, laboratories have begun to validate their WSI systems for diagnostic purposes according to reference guidelines. Among these the College of American Pathologists (CAP) guidelines include three strong recommendations (SRs) and nine good practice statements (GPSs). To date, the application of WSI to cytopathology has been out of scope of the CAP guideline due to limited evidence. Herein we systematically reviewed the published literature on WSI validation studies in cytology.
2023
- Revolutionizing Cancer Research: The Impact of Artificial Intelligence in Digital Biobanking
[Articolo su rivista]
Frascarelli, C.; Bonizzi, G.; Musico, C. R.; Mane, E.; Cassi, C.; Guerini Rocco, E.; Farina, A.; Scarpa, A.; Lawlor, R.; Reggiani Bonetti, L.; Caramaschi, S.; Eccher, A.; Marletta, S.; Fusco, N.
abstract
Background: Biobanks are vital research infrastructures aiming to collect, process, store, and distribute biological specimens along with associated data in an organized and governed manner. Exploiting diverse datasets produced by the biobanks and the downstream research from various sources and integrating bioinformatics and "omics" data has proven instrumental in advancing research such as cancer research. Biobanks offer different types of biological samples matched with rich datasets comprising clinicopathologic information. As digital pathology and artificial intelligence (AI) have entered the precision medicine arena, biobanks are progressively transitioning from mere biorepositories to integrated computational databanks. Consequently, the application of AI and machine learning on these biobank datasets holds huge potential to profoundly impact cancer research. Methods: In this paper, we explore how AI and machine learning can respond to the digital evolution of biobanks with flexibility, solutions, and effective services. We look at the different data that ranges from specimen-related data, including digital images, patient health records and downstream genetic/genomic data and resulting "Big Data" and the analytic approaches used for analysis. Results: These cutting-edge technologies can address the challenges faced by translational and clinical research, enhancing their capabilities in data management, analysis, and interpretation. By leveraging AI, biobanks can unlock valuable insights from their vast repositories, enabling the identification of novel biomarkers, prediction of treatment responses, and ultimately facilitating the development of personalized cancer therapies. Conclusions: The integration of biobanking with AI has the potential not only to expand the current understanding of cancer biology but also to pave the way for more precise, patient-centric healthcare strategies.
2023
- Second Opinion in the Italian Organ Procurement Transplantation: The Pathologist Is In
[Articolo su rivista]
Eccher, Albino; Malvi, Deborah; Novelli, Luca; Mescoli, Claudia; D'Errico, Antonietta
abstract
: Second opinion consultation is a well-established practice in different clinical settings of diagnostic medicine. However, little is known about second opinion consultation activity in transplantation, and even less is known about it concerning donor assessment. The consultations provided by the second opinion service led to the safer and homogeneous management of donors with a history of malignancy or ongoing neoplasm by transplant centers. Indeed, two of the most important aspects are the reduction of semantic differences in cancer reporting and the standardization of procedures, which are mainly due to the different settings and logistics of different pathology services. This article aims to discuss the role and the future of the second opinion in Italy during organ procurement, highlighting the critical issues and areas for improvement.
2023
- Spatial resolution of renal amyloid deposits through MALDI-MSI: a combined digital and molecular approach to monoclonal gammopathies
[Articolo su rivista]
Bindi, Greta; Smith, Andrew; Oliveira, Glenda; Eccher, Albino; Vatrano, Simona; Alberici, Federico; Cazzaniga, Giorgio; Galimberti, Stefania; Capitoli, Giulia; Magni, Fulvio; Pagni, Fabio; L'Imperio, Vincenzo
abstract
Aims: Identification and characterisation of monoclonal gammopathies of renal significance (MGRS) is critical for therapeutic purposes. Amyloidosis represents one of the most common forms of MGRS, and renal biopsy remains the gold standard for their classification, although mass spectrometry has shown greater sensitivity in this area. Methods: In the present study, a new in situ proteomic technique, matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI), is investigated as an alternative to conventional laser capture microdissection MS for the characterisation of amyloids. MALDI-MSI was performed on 16 cases (3 lambda light chain amyloidosis (AL), 3 AL kappa, 3 serum amyloid A amyloidosis (SAA), 2 lambda light chain deposition disease (LCDD), 2 challenging amyloid cases and 3 controls). Analysis began with regions of interest labelled by the pathologist, and then automatic segmentation was performed. Results: MALDI-MSI correctly identified and typed cases with known amyloid type (AL kappa, AL lambda and SAA). A 'restricted fingerprint' for amyloid detection composed of apolipoprotein E, serum amyloid protein and apolipoprotein A1 showed the best automatic segmentation performance (area under the curve >0.7). Conclusions: MALDI-MSI correctly assigned minimal/challenging cases of amyloidosis to the correct type (AL lambda) and identified lambda light chains in LCDD cases, highlighting the promising role of MALDI-MSI for amyloid typing.
2023
- Value of Artificial Intelligence in Evaluating Lymph Node Metastases
[Articolo su rivista]
Caldonazzi, Nicolò; Rizzo, Paola Chiara; Eccher, Albino; Girolami, Ilaria; Fanelli, Giuseppe Nicolò; Naccarato, Antonio Giuseppe; Bonizzi, Giuseppina; Fusco, Nicola; D'Amati, Giulia; Scarpa, Aldo; Pantanowitz, Liron; Marletta, Stefano
abstract
: One of the most relevant prognostic factors in cancer staging is the presence of lymph node (LN) metastasis. Evaluating lymph nodes for the presence of metastatic cancerous cells can be a lengthy, monotonous, and error-prone process. Owing to digital pathology, artificial intelligence (AI) applied to whole slide images (WSIs) of lymph nodes can be exploited for the automatic detection of metastatic tissue. The aim of this study was to review the literature regarding the implementation of AI as a tool for the detection of metastases in LNs in WSIs. A systematic literature search was conducted in PubMed and Embase databases. Studies involving the application of AI techniques to automatically analyze LN status were included. Of 4584 retrieved articles, 23 were included. Relevant articles were labeled into three categories based upon the accuracy of AI in evaluating LNs. Published data overall indicate that the application of AI in detecting LN metastases is promising and can be proficiently employed in daily pathology practice.
2022
- Artificial Intelligence for Predicting Microsatellite Instability Based on Tumor Histomorphology: A Systematic Review
[Articolo su rivista]
Park, Ji Hyun; Kim, Eun Young; Luchini, Claudio; Eccher, Albino; Tizaoui, Kalthoum; Shin, Jae Il; Lim, Beom Jin
abstract
: Microsatellite instability (MSI)/defective DNA mismatch repair (dMMR) is receiving more attention as a biomarker for eligibility for immune checkpoint inhibitors in advanced diseases. However, due to high costs and resource limitations, MSI/dMMR testing is not widely performed. Some attempts are in progress to predict MSI/dMMR status through histomorphological features on H&E slides using artificial intelligence (AI) technology. In this study, the potential predictive role of this new methodology was reviewed through a systematic review. Studies up to September 2021 were searched through PubMed and Embase database searches. The design and results of each study were summarized, and the risk of bias for each study was evaluated. For colorectal cancer, AI-based systems showed excellent performance with the highest standard of 0.972; for gastric and endometrial cancers they showed a relatively low but satisfactory performance, with the highest standard of 0.81 and 0.82, respectively. However, analyzing the risk of bias, most studies were evaluated at high-risk. AI-based systems showed a high potential in predicting the MSI/dMMR status of different cancer types, and particularly of colorectal cancers. Therefore, a confirmation test should be required only for the results that are positive in the AI test.
2022
- Artificial intelligence applications for pre-implantation kidney biopsy pathology practice: a systematic review
[Articolo su rivista]
Girolami, Ilaria; Pantanowitz, Liron; Marletta, Stefano; Hermsen, Meyke; van der Laak, Jeroen; Munari, Enrico; Furian, Lucrezia; Vistoli, Fabio; Zaza, Gianluigi; Cardillo, Massimo; Gesualdo, Loreto; Gambaro, Giovanni; Eccher, Albino
abstract
Background: Transplant nephropathology is a highly specialized field of pathology comprising both the evaluation of organ donor biopsy for organ allocation and post-transplant graft biopsy for assessment of rejection or graft damage. The introduction of digital pathology with whole-slide imaging (WSI) in clinical research, trials and practice has catalyzed the application of artificial intelligence (AI) for histopathology, with development of novel machine-learning models for tissue interrogation and discovery. We aimed to review the literature for studies specifically applying AI algorithms to WSI-digitized pre-implantation kidney biopsy. Methods: A systematic search was carried out in the electronic databases PubMed-MEDLINE and Embase until 25th September, 2021 with a combination of the key terms "kidney", "biopsy", "transplantation" and "artificial intelligence" and their aliases. Studies dealing with the application of AI algorithms coupled with WSI in pre-implantation kidney biopsies were included. The main theme addressed was detection and quantification of tissue components. Extracted data were: author, year and country of the study, type of biopsy features investigated, number of cases, type of algorithm deployed, main results of the study in terms of diagnostic outcome, and the main limitations of the study. Results: Of 5761 retrieved articles, 7 met our inclusion criteria. All studies focused largely on AI-based detection and classification of glomerular structures and to a lesser extent on tubular and vascular structures. Performance of AI algorithms was excellent and promising. Conclusion: All studies highlighted the importance of expert pathologist annotation to reliably train models and the need to acknowledge clinical nuances of the pre-implantation setting. Close cooperation between computer scientists and practicing as well as expert renal pathologists is needed, helping to refine the performance of AI-based models for routine pre-implantation kidney biopsy clinical practice.
2022
- Artificial intelligence in head and neck cancer diagnosis
[Articolo su rivista]
Bassani, Sara; Santonicco, Nicola; Eccher, Albino; Scarpa, Aldo; Vianini, Matteo; Brunelli, Matteo; Bisi, Nicola; Nocini, Riccardo; Sacchetto, Luca; Munari, Enrico; Pantanowitz, Liron; Girolami, Ilaria; Molteni, Gabriele
abstract
Introduction: Artificial intelligence (AI) is currently being used to augment histopathological diagnostics in pathology. This systematic review aims to evaluate the evolution of these AI-based diagnostic techniques for diagnosing head and neck neoplasms. Materials and methods: Articles regarding the use of AI for head and neck pathology published from 1982 until March 2022 were evaluated based on a search strategy determined by a multidisciplinary team of pathologists and otolaryngologists. Data from eligible articles were summarized according to author, year of publication, country, study population, tumor details, study results, and limitations. Results: Thirteen articles were included according to inclusion criteria. The selected studies were published between 2012 and March 1, 2022. Most of these studies concern the diagnosis of oral cancer; in particular, 6 are related to the oral cavity, 2 to the larynx, 1 to the salivary glands, and 4 to head and neck squamous cell carcinoma not otherwise specified (NOS). As for the type of diagnostics considered, 12 concerned histopathology and 1 cytology. Discussion: Starting from the pathological examination, artificial intelligence tools are an excellent solution for implementing diagnosis capability. Nevertheless, today the unavailability of large training datasets is a main issue that needs to be overcome to realize the true potential.
2022
- Atlas of PD-L1 for Pathologists: Indications, Scores, Diagnostic Platforms and Reporting Systems
[Articolo su rivista]
Marletta, Stefano; Fusco, Nicola; Munari, Enrico; Luchini, Claudio; Cimadamore, Alessia; Brunelli, Matteo; Querzoli, Giulia; Martini, Maurizio; Vigliar, Elena; Colombari, Romano; Girolami, Ilaria; Pagni, Fabio; Eccher, Albino
abstract
Innovative drugs targeting the PD1/PD-L1 axis have opened promising scenarios in modern cancer therapy. Plenty of assays and scoring systems have been developed for the evaluation of PD-L1 immunohistochemical expression, so far considered the most reliable therapeutic predictive marker.
2022
- CD13 is a useful tool in the differential diagnosis of meningiomas with potential biological and prognostic implications
[Articolo su rivista]
Marletta, Stefano; Luchini, Claudio; Sperandio, Nicola; Torresani, Evelin; Sorio, Alessandro; Girolami, Ilaria; Scarpa, Aldo; Eccher, Albino; Ghimenton, Claudio
abstract
: Meningiomas are common tumors of the central nervous system. Although their histological diagnosis is usually straightforward, their differential diagnosis versus other tumors may be challenging at times. The objective of this study is to assess the diagnostic value of CD13 immunoexpression in the differential diagnosis between meningiomas and their morphological mimics. Immunohistochemical analysis for CD13, epithelial membrane antigen, SOX10, and STAT6 was carried out in a large cohort of primary meningeal tumors comprising 225 meningiomas, 15 schwannomas, and 20 solitary fibrous tumor/hemangiopericytomas. Within the meningioma group, the expression of CD13 and epithelial membrane antigen was distinguished in three categories using a semiquantitative score. Most of meningiomas expressed CD13 (94%) and epithelial membrane antigen (96%) while none of the schwannomas nor of the solitary fibrous tumor/hemangiopericytomas was positive for either the two markers. Diffuse positivity for CD13 and epithelial membrane antigen was more common in low-grade meningiomas than in anaplastic ones, which were also more often negative for such markers, especially for CD13 (32%). CD13 is a helpful immunohistochemical marker for the differential diagnosis of meningiomas and their mimics, achieving in combination with epithelial membrane antigen maximal sensitivity (100%) and showing statistically relevant difference of expression in comparison with both schwannomas (p < 0.0001) and solitary fibrous tumor/hemangiopericytomas (p < 0.0001). Furthermore, loss of CD13 expression could be related to outcome as it is associated with worrisome histological findings, mainly in the setting of anaplastic meningiomas.
2022
- Comparison of three validated PD-L1 immunohistochemical assays in urothelial carcinoma of the bladder: interchangeability and issues related to patient selection
[Articolo su rivista]
Munari, Enrico; Querzoli, Giulia; Brunelli, Matteo; Marconi, Marcella; Sommaggio, Marco; Cocchi, Marco A; Martignoni, Guido; Netto, George J; Calio, Anna; Quatrini, Linda; Mariotti, Francesca R; Luchini, Claudio; Girolami, Ilaria; Eccher, Albino; Segala, Diego; Ciompi, Francesco; Zamboni, Giuseppe; Moretta, Lorenzo; Bogina, Giuseppe
abstract
Different programmed cell death-ligand 1 (PD-L1) assays and scoring algorithms are being used in the evaluation of PD-L1 expression for the selection of patients for immunotherapy in specific settings of advanced urothelial carcinoma (UC). In this paper, we sought to investigate three approved assays (Ventana SP142 and SP263, and Dako 22C3) in UC with emphasis on implications for patient selection for atezolizumab/pembrolizumab as the first line of treatment. Tumors from 124 patients with invasive UC of the bladder were analyzed using tissue microarrays (TMA). Serial sections were stained with SP263 and SP142 on Ventana Benchmark Ultra and with 22C3 on Dako Autostainer Link 48. Stains were evaluated independently by two observers and scored using the combined positive score (CPS) and tumor infiltrating immune cells (IC) algorithms. Differences in proportions (DP), overall percent agreement (OPA), positive percent agreement (PPA), negative percent agreement (NPA), and Cohen kappa were calculated for all comparable cases. Good overall concordance in analytic performance was observed for 22C3 and SP263 with both scoring algorithms; specifically, the highest OPA was observed between 22C3 and SP263 (89.6%) when using CPS. On the other hand, SP142 consistently showed lower positivity rates with high differences in proportions (DP) compared with 22C3 and SP263 with both CPS and IC, and with a low PPA, especially when using the CPS algorithm. In conclusion, 22C3 and SP263 assays show comparable analytical performance while SP142 shows divergent staining results, with important implications for the selection of patients for both pembrolizumab and atezolizumab.
2022
- Digital pathology all stars
[Articolo su rivista]
Eccher, Albino; Girolami, Ilaria; Scarpa, Aldo
abstract
Digital pathology plays an important role in accelerating the progression of healthcare and the potential benefits of adopting digital technologies have been solidly established. Despite this, real-world data suggest that a fully digital approach to the histological workflow has been implemented in a minority only of pathology laboratories. The e-learning event "Digital Pathology All Stars" was conceived by the University and Hospital Trust of Verona and comprised traditional lectures made by well-recognized experts in Digital Pathology from all over the world. The meeting aimed to promote the exchange of knowledge to support and strengthen digital pathology adoption and implementation.
2022
- Estimating survival after salvage surgery for recurrent salivary gland cancers: Systematic review
[Articolo su rivista]
Mannelli, G.; Comini, L. V.; Sacchetto, A.; Santoro, R.; Spinelli, G.; Bonomo, P.; Desideri, I.; Bossi, P.; Orlandi, E.; Alderotti, G.; Franchi, A.; Palomba, A.; Eccher, A.; Marchioni, D.; Nocini, R.; Piazza, C.; Molteni, G.
abstract
Recurrent salivary gland carcinomas (RSCs) are poorly characterized and their clinical features and treatment options have not yet been fully described. The goal of this study was to analyze the therapeutic strategies and oncological outcomes of RSC patients through a literature review analysis. This systematic review was performed according to the PRISMA statements. Inclusion criteria for the systematic review were based on the population, intervention, comparison, and outcomes according to (PICO) framework. Two thousand seven hundred and four records were selected and 1817 recurrences were studied. Three hundred and sixty-five patients underwent salvage surgery (20.1%) and their 5-year mortality rate, overall survival and disease-free survival were 35%, 70%, and 42%, respectively. RSCs are aggressive neoplasms with a high rate of distant metastases (28.9%). Salvage surgery can be considered in patients with limited local and/or regional recurrences, even in case of single distant relapse, appearing within the first 3 years of follow-up.
2022
- Evidence-based diagnostic performance of novel biomarkers for the diagnosis of malignant mesothelioma in effusion cytology
[Articolo su rivista]
Girolami, Ilaria; Lucenteforte, Ersilia; Eccher, Albino; Marletta, Stefano; Brunelli, Matteo; Graziano, Paolo; Pisapia, Pasquale; Malapelle, Umberto; Troncone, Giancarlo; Scarpa, Aldo; Huang, Tao; Pantanowitz, Liron
abstract
Cytology effusions are often the only material available for diagnosing malignant pleural mesothelioma (MPM). However, the cytomorphological features alone are not always diagnostic, and cytology samples preclude an assessment for pleural tissue invasion. Accordingly, immunohistochemical, soluble, and molecular biomarkers have been developed. The aim of this study is to provide quantitative evidence regarding the diagnostic performance of novel biomarkers. To that end, a systematic literature review was performed of articles dealing with a loss of BRCA1-associated protein 1 (BAP1), methylthioadenosine (MTAP), 5-hydroxymethylcitosine (5-hmC), glucose transporter 1 (GLUT1), insulin like-growth factor II messenger RNA-binding protein 3 (IMP3), enhanced zeste homologue 2 (EZH2) staining, cyclin-dependent kinase inhibitor 2A (CDKN2A) homozygous deletion (HD) testing, soluble mesothelin, and microRNA quantification in cytological samples for the diagnosis of MPM versus reactive atypical mesothelial cells. Sensitivity and specificity were extracted, and a meta-analysis was performed. The quality of the studies was assessed with Quality Assessment of Diagnostic Accuracy Studies 2, and the quality of the evidence was evaluated with the Grading of Recommendations Assessment, Development, and Evaluation approach. Seventy-one studies were included. BAP1 loss showed a sensitivity of 0.65 (confidence interval [CI], 0.59-0.71) and a specificity of 0.99 (CI, 0.93-1.00). MTAP loss and p16 HD showed 100% specificity with sensitivities of 0.47 (CI, 0.38-0.57) and 0.62 (CI, 0.53-0.71), respectively. BAP1 loss and CDKN2A HD combined showed maximal specificity and a sensitivity of 0.83 (CI, 0.78-0.89). GLUT1 and IMP3 showed sensitivities of 0.82 (CI, 0.70-0.90) and 0.65 (CI, 0.41-0.90), respectively, with comparable specificity. Mesothelin showed a sensitivity of 0.73 (CI, 0.68-0.77) and a specificity of 0.90 (CI, 0.84-0.93). In conclusion, some of the recently emerging biomarkers are close to 1.00 specificity. Their moderate sensitivity on their own, however, can be significantly improved by the use of 2 biomarkers, such as a combination of BAP1 and CDKN2A with fluorescence in situ hybridization or a combination of BAP1 and MTAP immunohistochemistry.
2022
- Impact of mobile devices on cancer diagnosis in cytology
[Articolo su rivista]
Santonicco, Nicola; Marletta, Stefano; Pantanowitz, Liron; Fadda, Guido; Troncone, Giancarlo; Brunelli, Matteo; Ghimenton, Claudio; Antonini, Pietro; Paolino, Gaetano; Girolami, Ilaria; Eccher, Albino
abstract
Digital pathology has widened pathologists' opportunities to examine both surgical and cytological samples. Recently, portable mobile devices like tablets and smartphones have been tested for application with digital technologies including static, dynamic, and more recently whole slide imaging. This study aimed to review the published literature on the impact of mobile devices on cancer diagnoses in cytology. This analysis focused on their diagnostic potential, technical details, critical issues and pitfalls, and economical aspects.
2022
- Ki-67 assessment of pancreatic neuroendocrine neoplasms: Systematic review and meta-analysis of manual vs. digital pathology scoring
[Articolo su rivista]
Luchini, Claudio; Pantanowitz, Liron; Adsay, Volkan; Asa, Sylvia L; Antonini, Pietro; Girolami, Ilaria; Veronese, Nicola; Nottegar, Alessia; Cingarlini, Sara; Landoni, Luca; Brosens, Lodewijk A; Verschuur, Anna V; Mattiolo, Paola; Pea, Antonio; Mafficini, Andrea; Milella, Michele; Niazi, Muhammad K; Gurcan, Metin N; Eccher, Albino; Cree, Ian A; Scarpa, Aldo
abstract
: Ki-67 assessment is a key step in the diagnosis of neuroendocrine neoplasms (NENs) from all anatomic locations. Several challenges exist related to quantifying the Ki-67 proliferation index due to lack of method standardization and inter-reader variability. The application of digital pathology coupled with machine learning has been shown to be highly accurate and reproducible for the evaluation of Ki-67 in NENs. We systematically reviewed all published studies on the subject of Ki-67 assessment in pancreatic NENs (PanNENs) employing digital image analysis (DIA). The most common advantages of DIA were improvement in the standardization and reliability of Ki-67 evaluation, as well as its speed and practicality, compared to the current gold standard approach of manual counts from captured images, which is cumbersome and time consuming. The main limitations were attributed to higher costs, lack of widespread availability (as of yet), operator qualification and training issues (if it is not done by pathologists), and most importantly, the drawback of image algorithms counting contaminating non-neoplastic cells and other signals like hemosiderin. However, solutions are rapidly developing for all of these challenging issues. A comparative meta-analysis for DIA versus manual counting shows very high concordance (global coefficient of concordance: 0.94, 95% CI: 0.83-0.98) between these two modalities. These findings support the widespread adoption of validated DIA methods for Ki-67 assessment in PanNENs, provided that measures are in place to ensure counting of only tumor cells either by software modifications or education of non-pathologist operators, as well as selection of standard regions of interest for analysis. NENs, being cellular and monotonous neoplasms, are naturally more amenable to Ki-67 assessment. However, lessons of this review may be applicable to other neoplasms where proliferation activity has become an integral part of theranostic evaluation including breast, brain, and hematolymphoid neoplasms.
2022
- Livedoid skin reaction to 2nd dose of mRNA Covid-19 vaccine
[Articolo su rivista]
Girolami, Ilaria; Eisendle, Klaus; Kluge, Reinhard Walther; Hanspeter, Esther; Eccher, Albino; Vizziello, Leonardo; Zampieri, Pierfrancesco; Mazzoleni, Guido
abstract
Skin often represents a target organ for adverse drug reactions and this also applies to the mRNA vaccines against Sars-CoV-2. Here we present a case of extensive livedoid reaction after 2nd dose of BNT162b-2 vaccine with massive blood skin extravasation and no systemic symptoms apart from anemization. The 30-year-old woman developed progressively enlarging livedoid lesions on limbs and abdomen. Histology showed a near-normal epidermis and a very mild interstitial mixed inflammatory infiltrate with extensive blood extravasation in mid- and deep dermis. Diagnosis was adverse reaction to vaccine with skin capillary hyperpermeability and anaemization with lower than diagnostic features of cutaneous small vessel vasculitis. To date, no cases of a livedoid skin reaction associated to Covid-19 vaccine have been reported, and this case illustrates that massive livedoid reaction can be another kind of skin reaction to mRNA Covid-19 vaccine.
2022
- MDM2 gene amplification as selection tool for innovative targeted approaches in PD-L1 positive or negative muscle-invasive urothelial bladder carcinoma
[Articolo su rivista]
Brunelli, Matteo; Tafuri, Alessandro; Cima, Luca; Cerruto, Maria Angela; Milella, Michele; Zivi, Andrea; Buti, Sebastiano; Bersanelli, Melissa; Fornarini, Giuseppe; Vellone, Valerio Gaetano; Rebuzzi, Sara Elena; Procopio, Giuseppe; Verzoni, Elena; Bracarda, Sergio; Sabbatini, Roberto; Baldessari, Cinzia; Eccher, Albino; Passalacqua, Rodolfo; Perrucci, Bruno; Giganti, Maria Olga; Donini, Maddalena; Panni, Stefano; Tucci, Marcello; Prati, Veronica; Ortega, Cinzia; Caliò, Anna; Alongi, Filippo; Munari, Enrico; Pappagallo, Giovanni; Iacovelli, Roberto; Mosca, Alessandra; Porta, Camillo; Martignoni, Guido; Antonelli, Alessandro
abstract
AIMS: According to The Cancer Genome Atlas (TCGA), around 9% of bladder carcinomas usually show abnormalities of the murine double minute 2 (MDM2) gene, but a few studies have been investigated them. We profiled MDM2 gene amplification in a series of urothelial carcinomas (UC) considering the molecular subtypes and expression of programmed death ligand 1 (PD-L1).METHODS: 117 patients with muscle-invasive UC (pT2-3) without (N0) or with (N+) lymph-node metastases were revised. Only cases with availability of in toto specimens and follow-up were studied. Tissue microarray was built. p53, ER, RB1, GATA-3, CK20, CK5/6, CD44 and PD-L1 (clone sp263) immunoexpression was evaluated. Fluorescent in situ hybridisation was assessed by using the HER-2/neu, FGFR-3, CDKN2A and MDM2 probes. True (ratio 12q/CEP12 >2) MDM2 gene amplification was distinguished from polyploidy/gains (ratio <2, absolute copy number of MDM-2 >2). MDM2 and PD-L1 values were correlated to the TCGA molecular phenotypes. Statistical analysis was performed.RESULTS: 6/50 (12%) cases (5 N0 and 1 N+) were amplified for MDM2 without matching to molecular phenotypes. Of 50, 14 (37%) cases expressed PD-L1 at 1% cut-off; 3/50 (9%) at >50% cut-off; of these, 2 cases on side of neoplasia among inflammatory cells. Only one out of six (17%) cases amplified for MDM2 showed expression (>50% cut-off) of PD-L1. MDM2 amplification was independent to all documented profiles (k test=0.3) and was prevalent in recurrent UC.CONCLUSION: MDM2 amplification has been seen in both PD-L1 positive and negative muscle-invasive bladder UC independently from the TCGA molecular phenotypes. MDM2 and PD-L1 might be assessed in order to predict a better response to combo/single targeted therapies.
2022
- PD-L1 in oral squamous cell carcinoma: A key biomarker from the laboratory to the bedside
[Articolo su rivista]
Nocini, Riccardo; Vianini, Matteo; Girolami, Ilaria; Calabrese, Luca; Scarpa, Aldo; Martini, Maurizio; Morbini, Patrizia; Marletta, Stefano; Brunelli, Matteo; Molteni, Gabriele; Parwani, Anil; Pantanowitz, Liron; Eccher, Albino
abstract
Objectives and background: Oral squamous cell carcinoma (OSCC) is a highly malignant disease with an increasing incidence. The need to improve therapeutic strategies for patients affected by OSCC is an urgent challenge. Currently, the advent of immunotherapy represents an important step toward this aim. Programmed cell death-ligand 1 (PD-L1), a membrane protein that can be expressed on tumor and inflammatory cells is a key biomarker whose expression is determined by means of immunohistochemistry and is necessary for selecting patients for immunotherapy. Methods: In this study, we review the methods of PD-L1 assessment and outcomes achieved with immunotherapy in the treatment of OSCC patients. Results: Based on a meta-analysis we demonstrate a lack of prognostic significance of PD-L1 in OSCC. Conclusions: We also highlight unresolved issues including difficulties in standardizing PD-L1 evaluation and discuss future opportunities such as leveraging digital pathology.
2022
- Program death ligand-1 immunocytochemistry in lung cancer cytological samples: A systematic review
[Articolo su rivista]
Satturwar, Swati; Girolami, Ilaria; Munari, Enrico; Ciompi, Francesco; Eccher, Albino; Pantanowitz, Liron
abstract
: In this era of personalized medicine, targeted immunotherapies like immune checkpoint inhibitors (ICI) blocking the programmed death-1 (PD-1)/program death ligand-1 (PD-L1) axis have become an integral part of treating advanced stage non-small cell lung carcinoma (NSCLC) and many other cancer types. Multiple monoclonal antibodies are available commercially to detect PD-L1 expression in tumor cells by immunohistochemistry (IHC). As most clinical trials initially required tumor biopsy for PD-L1 detection by IHC, many of the currently available PD-1/PD-L1 assays have been developed and validated on formalin fixed tissue specimens. The majority (>50%) of lung cancer cases do not have a surgical biopsy or resection specimen available for ancillary testing and instead must rely primarily on fine needle aspiration biopsy specimens for diagnosis, staging and ancillary tests. Review of the literature shows multiple studies exploring the feasibility of PD-L1 IHC on cytological samples. In addition, there are studies addressing various aspects of IHC validation on cytology preparations including pre-analytical (e.g., different fixatives), analytical (e.g., antibody clone, staining platforms, inter and intra-observer agreement, cytology-histology concordance) and post-analytical (e.g., clinical outcome) issues. Although promising results in this field have emerged utilizing cytology samples, many important questions still need to be addressed. This review summarizes the literature of PD-L1 IHC in lung cytology specimens and provides practical tips for optimizing analysis.
2022
- Risk factors of extraneural spreading in astrocytomas and oligodendrogliomas in donors with gliomas: A systematic review
[Articolo su rivista]
Ammendola, Serena; Barresi, Valeria; Bariani, Elena; Girolami, Ilaria; D'Errico, Antonia; Brunelli, Matteo; Cardillo, Massimo; Lombardini, Letizia; Carraro, Amedeo; Boggi, Ugo; Cain, Owen; Neil, Desley; Eccher, Albino
abstract
Patients with a history of primary brain tumors can be eligible for organ donation under extended criteria. The risk assessment of tumor transmission via organ transplant in primary brain tumors is primarily based on the assessment of tumor histotype and grade. Previous surgeries, chemo-/radiotherapy, and ventriculo-peritoneal shunt placement can lead to a disruption of the blood-brain barrier, concurring to an increase in the transmission risk.
2022
- Technical and Diagnostic Issues in Whole Slide Imaging Published Validation Studies
[Articolo su rivista]
Rizzo, Paola Chiara; Girolami, Ilaria; Marletta, Stefano; Pantanowitz, Liron; Antonini, Pietro; Brunelli, Matteo; Santonicco, Nicola; Vacca, Paola; Tumino, Nicola; Moretta, Lorenzo; Parwani, Anil; Satturwar, Swati; Eccher, Albino; Munari, Enrico
abstract
Digital pathology with whole-slide imaging (WSI) has many potential clinical and non-clinical applications. In the past two decades, despite significant advances in WSI technology adoption remains slow for primary diagnosis. The aim of this study was to identify common pitfalls of WSI reported in validation studies and offer measures to overcome these challenges.
2022
- Validation of a Novel Three-Dimensional (3D Fusion) Gross Sampling Protocol for Clear Cell Renal Cell Carcinoma to Overcome Intratumoral Heterogeneity: The Meet-Uro 18 Study
[Articolo su rivista]
Brunelli, M.; Martignoni, G.; Malpeli, G.; Volpe, A.; Cima, L.; Raspollini, M. R.; Barbareschi, M.; Tafuri, A.; Masi, G.; Barzon, L.; Ammendola, S.; Villanova, M.; Cerruto, M. A.; Milella, M.; Buti, S.; Bersanelli, M.; Fornarini, G.; Rebuzzi, S. E.; Vellone, V. G.; Gaggero, G.; Procopio, G.; Verzoni, E.; Bracarda, S.; Fanelli, M.; Sabbatini, R.; Passalacqua, R.; Perrucci, B.; Giganti, M. O.; Donini, M.; Panni, S.; Tucci, M.; Prati, V.; Ortega, C.; Calio, A.; Eccher, A.; Alongi, F.; Pappagallo, G.; Iacovelli, R.; Mosca, A.; Umari, P.; Montagnani, I.; Gobbo, S.; Atzori, F.; Munari, E.; Maruzzo, M.; Basso, U.; Pierconti, F.; Patriarca, C.; Colombo, P.; Lapini, A.; Conti, G.; Salvioni, R.; Bollito, E.; Cossarizza, A.; Massari, F.; Rizzo, M.; Franco, R.; Zito-Marino, F.; Plata, Y. A.; Galuppini, F.; Sbaraglia, M.; Fassan, M.; Dei Tos, A. P.; Colecchia, M.; Moch, H.; Scaltriti, M.; Porta, C.; Delahunt, B.; Giannarini, G.; Bortolus, R.; Rescigno, P.; Banna, G. L.; Signori, A.; Obispo, M. A. L.; Perris, R.; Antonelli, A.
abstract
We aimed to overcome intratumoral heterogeneity in clear cell renal cell carcinoma (clear-RCC). One hundred cases of clearRCC were sampled. First, usual standard sampling was applied (1 block/cm of tumor); second, the whole tumor was sampled, and 0.6 mm cores were taken from each block to construct a tissue microarray; third, the residual tissue, mapped by taking pieces 0.5 × 0.5 cm, reconstructed the entire tumor mass. Precisely, six randomly derived pieces of tissues were placed in each cassette, with the number of cassettes being based on the diameter of the tumor (called multisite 3D fusion). Angiogenic and immune markers were tested. Routine 5231 tissue blocks were obtained. Multisite 3D fusion sections showed pattern A, homogeneous high vascular density (10%), pattern B, homogeneous low vascular density (8%) and pattern C, heterogeneous angiogenic signatures (82%). PD-L1 expression was seen as diffuse (7%), low (33%) and absent (60%). Tumor-infiltrating CD8 scored high in 25% (pattern hot), low in 65% (pattern weak) and zero in 10% of cases (pattern desert). Grading was upgraded in 26% of cases (G3–G4), necrosis and sarcomatoid/rhabdoid characters were observed in, respectively, 11 and 7% of cases after 3D fusion (p = 0.03). CD8 and PD-L1 immune expressions were higher in the undifferentiated G4/rhabdoid/sarcomatoid clearRCC subtypes (p = 0.03). Again, 22% of cases were set to intermediate to high risk of clinical recurrence due to new morphological findings of all aggressive G4, sarcomatoid/rhabdoid features by using 3D fusion compared to standard methods (p = 0.04). In conclusion, we propose an easy-to-apply multisite 3D fusion sampling that negates bias due to tumor heterogeneity.
2022
- Validation of portable tablets for transplant pathology diagnosis according to the College of American Pathologists Guidelines
[Articolo su rivista]
Marletta, Stefano; Pantanowitz, Liron; Malvi, Deborah; Novelli, Luca; Mescoli, Claudia; Cardillo, Massimo; D'Errico, Antonietta; Girolami, Ilaria; Eccher, Albino
abstract
Despite increased use of digital pathology, its application in the transplantation setting remains limited. One of the restraints is related to concerns that this technology is inadequate for supporting diagnostic work. In this study, we sought to establish non inferiority of whole slide imaging (WSI) to light microscopy (LM) for intraoperative transplantation diagnosis using inexpensive portable devices. A validation study was conducted according to updated guidelines from the College of American Pathologists (CAP) utilizing 80 intraoperative transplantation cases. Two pathologists reviewed glass slides with LM and digital slides on two different tablets after a washout period of 4 weeks. Diagnostic concordance and intra-observer agreement were recorded. A total of 45 (56%) cases were suitable for rendering transplant diagnoses and 35 (44%) for assessing cancer risk. Intra-observer agreement was 95.1% for organ suitability and 100% for cancer risk. There were no major discordances that could affect patient transplant management. Digital evaluation of intraoperative transplant specimens using tablets to view whole slide images was non-inferior to LM for primary diagnosis. This suggests that after validating WSI these digital tools can be safely used for remote intraoperative transplantation diagnostic work.
2022
- Value of a Multidisciplinary Approach in Sinonasal Inverted Papilloma with Extensive Ossification
[Articolo su rivista]
Barioglio, B.; Paolino, G.; Girolami, I.; Bariani, E.; Santonicco, N.; Marletta, S.; Ammendola, S.; Brunelli, M.; Marchioni, D.; Pisapia, P.; Eccher, A.; Molteni, G.
abstract
Objective: Background: Casa Report: Conclusions: Rare disease Inverted papilloma is a benign epithelial lesion of the nasal cavities. Although commonly encountered in clinical practice, it rarely presents with extensive ossification and few cases have been described in the literature. Herein, we describe the case of a 51-year-old man who presented to clinical attention for persistent right nasal obstruction. Magnetic resonance imaging (MRI) and computed tomography (CT) scans of the facial bones showed a lobated lesion with ossification occupying most of the right nasal cavity. The lesion was removed by endoscopic sinus surgery, leaving the surrounding bone structures intact. On pathological examination, mature bone tissue was found within an inverted papilloma. The pathologist contacted the surgeon, who confirmed that no healthy bone tissue was removed during the procedure. Therefore, a diagnosis of inverted papilloma with ossification could be made without the use of ancillary techniques. Inverted papilloma with ossification is a common lesion with a rare feature. Our report investigates the diagnostic difficulties of a paradigmatic case, highlighting the importance of multidisciplinary teamwork in reach-ing the final diagnosis.
2022
- WSI validation studies in breast and gynecological pathology
[Articolo su rivista]
Mastrosimini, Maria Gaia; Eccher, Albino; Nottegar, Alessia; Montin, Umberto; Scarpa, Aldo; Pantanowitz, Liron; Girolami, Ilaria
abstract
In the last two decades, there has been marked development in virtual slide technology as well as its application in various subspecialties of pathology. In particular, there have been several studies examining the utility of whole slide imaging (WSI) in breast and gynecological pathology. The aim of this systematic review is to analyse published evidence regarding validation studies of WSI applied specifically to the female genital tract and breast pathology.
2021
- Challenges Facing Pathologists Evaluating PD-L1 in Head & Neck Squamous Cell Carcinoma
[Articolo su rivista]
Girolami, Ilaria; Pantanowitz, Liron; Barberis, Massimo; Paolino, Gaetano; Brunelli, Matteo; Vigliar, Elena; Munari, Enrico; Satturwar, Swati; Troncone, Giancarlo; Eccher, Albino
abstract
Programmed death-ligand 1 (PD-L1) expression with combined positive score (CPS) ≥1 is required for administration of checkpoint inhibitor therapy in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). The 22C3 pharmDx Dako immunohistochemical assay is the one approved as companion diagnostic for pembrolizumab, but many laboratories work on other platforms and/or with other clones, and studies exploring the potential interchangeability of assays have appeared. After review of the literature, it emerges that the concordance among assays ranges from fair to moderate, with a tendence of assay SP263 to yield a higher quota of positivity and of assay SP142 to stain better immune cells. Moreover, pathologists achieve very good concordance in assessing PD-L1 CPS, particularly with SP263. Differences in terms of platforms, procedures and study design still preclude a quantitative synthesis of evidence and clearly further work is needed to draw stronger conclusions on the interchangeability of PD-L1 assays in HNSCC.
2021
- Clinical-Pathological, Immunohistochemical, and Genetic Characterization of a Series of Posterior Pituitary Tumors
[Articolo su rivista]
Barresi, Valeria; Simbolo, Michele; Gessi, Marco; Rossi, Sabrina; Caffo, Maria; Eccher, Albino; Angileri, Filippo Flavio; Cannavò, Salvatore; Brunelli, Matteo; Scarpa, Aldo
abstract
Posterior pituitary tumors are supposed to represent the morphological spectrum of a single entity. Herein, we report the clinical-pathological, immunohistochemical, and genetic features of 5 spindle cell oncocytomas (SCOs), 3 pituicytomas, and 1 granular cell tumor (GCT). SCOs had the highest local invasiveness and affected older subjects. The 3 histotypes differed in the content of spindle cells (predominant in pituicytoma and absent in GCT), presence of lymphocytic infiltrate (in SCO and GCT, but not in the pituicytoma) and EMA/GFAP staining (negative in GCT; EMA-positive/GFAP-negative in 4/5 SCO and GFAP-positive in 3/3 pituicytomas). Three SCOs and 1 pituicytoma analyzed with next-generation sequencing had no mutations in 409 genes. However, 1 SCO had previously unreported homozygous deletion of CDKN2A/B and another of SMARCA4, SMARCB1, and NF2. All 3 SCOs had loss of heterozygosity of chromosome 1p, while the pituicytoma had chromosome 19 homozygous loss and chromosomes 10, 13q, and 18q loss of heterozygosity. Since 1p and 13q losses were previously reported in 1 pituicytoma and 1 SCO, respectively, our data demonstrate that posterior pituitary tumors share common genetic alterations. The possibility that posterior pituitary tumors are SMARCA4/SMARCB1-deficient should be kept in mind in the differential diagnosis toward other entities.
2021
- Commentary: The Digital Fate of Glomeruli in Renal Biopsy
[Articolo su rivista]
Girolami, Ilaria; Marletta, Stefano; Eccher, Albino
abstract
No abstract available; Comment on J Pathol Inform. 12(1):13.
2021
- Congenital granular cell epulis of newborn: importance of prenatal diagnosis
[Articolo su rivista]
Torresani, Evelin; Girolami, Ilaria; Marletta, Stefano; Eccher, Albino; Ghimenton, Claudio
abstract
Congenital granular cell epulis is a rare benign lesion usually arising as single mass from the alveolar ridge of maxillary bone of female newborns, composed of polygonal granular cells that typically stain negative for S-100, in contrast to the adult counterpart. Larger lesions can disturb breathing and breast-feeding, requiring surgery. Prenatal diagnosis is achieved in few cases, even if this would be important for best management of delivery and therapy. Here we present a case of multiple CGCE in a female newborn discovered at birth, together with a brief review of pathogenesis, differential diagnoses and treatment implications of early diagnosis.
2021
- Consultation between forensic and clinical pathologists for histopathology examination after forensic autopsy
[Articolo su rivista]
Cirielli, Vito; Bortolotti, Federica; Cima, Luca; De Battisti, Zeno; Del Balzo, Giovanna; De Salvia, Alessandra; Laposata, Chiara; Raniero, Dario; Vermiglio, Elisa; Portas, Margherita; Rodegher, Pamela; Ghimenton, Claudio; Martignoni, Guido; Eccher, Albino; Narayanasamy, Murali; Vergine, Marco; Turrina, Stefania; Tagliaro, Franco; De Leo, Domenico; Brunelli, Matteo
abstract
The magnitude of the diagnostic benefit conferred by performing histopathological examinations after medico-legal/forensic autopsies remains debatable. We have tried to address this issue by reviewing a series of histopathology referrals concerning medico-legal autopsies in real-world routine practice. We present an audit of the consultations provided to forensics by clinical pathologists at our institute between 2015 and 2018. Over this period, 493 post-mortem examinations were performed by forensic pathologists. Of these cases, 52 (11%) were referred for histopathology. Gross assessment was requested in 22/52 (42%) cases. Histopathology examination was performed on single organs in 15/52 (29%) cases, primarily on the lung and heart, whereas parenchymatous multi-organ analysis was carried out in 14/52 (27%) cases. Bone-marrow sampling was studied in 4/52 (8%) cases. Immunohistochemistry was needed in 16/52 (31%) cases, special stains in 9/52 (21%) cases and molecular analysis in 4/52 (8%) cases. Focusing on technical processes, standard methodology on pre-analytical procedures was changed in 10/52 (19%) cases in order to answer specific diagnostic questions. We showed that although most of the time the diagnosis is clear by the end of dissection on the basis of the macroscopic findings, histopathology can provide, modify or confirm the cause of death in many medico-legal/forensic cases. Therefore, it is desirable that forensic pathologists and clinical pathologists establish robust working relationships in a cooperative environment. We conclude that it is important to implement guidelines based on real-world routine practice in order to identify cases where histopathology can provide useful contributions, which in our experience applied to 11% of forensic cases.
2021
- Diagnostic mesothelioma biomarkers in effusion cytology
[Articolo su rivista]
Eccher, Albino; Girolami, Ilaria; Lucenteforte, Ersilia; Troncone, Giancarlo; Scarpa, Aldo; Pantanowitz, Liron
abstract
Malignant mesothelioma is a rare malignancy with a poor prognosis whose development is related to asbestos fiber exposure. An increasing role of genetic predisposition has been recognized recently. Pleural biopsy is the gold standard for diagnosis, in which the identification of pleural invasion by atypical mesothelial cell is a major criterion. Pleural effusion is usually the first sign of disease; therefore, a cytological specimen is often the initial or the only specimen available for diagnosis. Given that reactive mesothelial cells may show marked atypia, the diagnosis of mesothelioma on cytomorphology alone is challenging. Accordingly, cell block preparation is encouraged, as it permits immunohistochemical staining. Traditional markers of mesothelioma such as glucose transporter 1 (GLUT1) and insulin-like growth factor 2 mRNA-binding protein 3 (IMP3) are informative, but difficult to interpret when reactive proliferations aberrantly stain positive. BRCA1-associated protein 1 (BAP1) nuclear staining loss is highly specific for mesothelioma, but sensitivity is low in sarcomatoid tumors. Cyclin-dependent kinase inhibitor 2A (CDKN2A)/p16 homozygous deletion, assessed by fluorescence in situ hybridization, is more specific for mesothelioma with better sensitivity, even in the sarcomatoid variant. The surrogate marker methylthioadenosine phosphorylase (MTAP) has been found to demonstrate excellent diagnostic correlation with p16. The purpose of this review is to provide an essential appraisal of the literature regarding the diagnostic value of many of these emerging biomarkers for malignant mesothelioma in effusion cytology.
2021
- Digital Slide Assessment for Programmed Death-Ligand 1 Combined Positive Score in Head and Neck Squamous Carcinoma: Focus on Validation and Vision
[Articolo su rivista]
Eccher, Albino; Girolami, Ilaria; Troncone, Giancarlo; Pantanowitz, Liron
abstract
No abstract available
2021
- Digital Slides as an Effective Tool for Programmed Death Ligand 1 Combined Positive Score Assessment and Training: Lessons Learned from the "Programmed Death Ligand 1 Key Learning Program in Head-and-Neck Squamous Cell Carcinoma"
[Articolo su rivista]
Eccher, Albino; Fontanini, Gabriella; Fusco, Nicola; Girolami, Ilaria; Graziano, Paolo; Rocco, Elena Guerini; Martini, Maurizio; Morbini, Patrizia; Pantanowitz, Liron; Parwani, Anil; Pisano, Anna Maria; Troncone, Giancarlo; Vigliar, Elena
abstract
No abstract available
2021
- Discovered cancers at postmortem donor examination: A starting point for quality improvement of donor assessment
[Articolo su rivista]
Girolami, I; Neil, D; Segev, Dl; Furian, L; Zaza, G; Boggi, U; Gambaro, G; De Feo, T; Casartelli-Liviero, M; Cardillo, M; Lombardini, L; Zampicinini, L; D'Errico, A; Eccher, A.
abstract
Background: clinical and imaging investigations allow a detailed assessment of an organ donor, but a quota of cancer still elude detection. Complete autopsy of donors is even less frequently performed, due to economic issues and increasing availability of high-quality imaging. The aim of this study is to gather evidence from the literature on donor malignancy discovered at autopsy following organ donation and to discuss the utility and limitations of autopsy practice in the field of transplantation. Methods: A systematic search according to PRISMA guidelines was carried out in Pubmed and Embase databases until September 2020 to select articles with reporting of cancer discovered in a donor at postmortem examination. Cancer discover in not-transplant setting were excluded. A descriptive synthesis was provided. Results: Of 7388 articles after duplicates removal, 56 were included. Fifty-one studies reported on complete autopsy, while 5 dealt only with limited autopsy (prostate and central nervous system). The number of autopsies ranged between 1 and 246 with a total of 823 autopsies performed. The most frequent cancer discovered at autopsy was lymphoma (n = 13, 15%), followed by renal cell carcinoma (RCC) (n = 11, 13%), non-small cell lung cancer (NSCLC) (n = 10, 11%), melanoma (n = 10, 11%), choriocarcinoma (n = 6, 7%) and glioblastoma (GBM) (n = 6, 7%). Conclusions: Lymphoma and melanoma are still difficult-to-detect cancers both during donor investigation and at procurement, whilst prostate cancer and choriocarcinoma are almost always easily detected nowadays thank to blood markers and clinical examination. There have been improvements with time in pre-donation detection procedures which are now working well, particularly when complete imaging investigations are performed, given that detection rate of CT/MRI is high and accurate. Autopsy can play a role to help to establish the correct donor management pathways in case of cancer discover. Furthermore, it helps to better understand which cancers are still eluding detection and consequently to refine guidelines' assessment procedures.
2021
- Donor-Transmitted Cancers in Transplanted Livers: Analysis of Clinical Outcomes
[Articolo su rivista]
Eccher, Albino; Girolami, Ilaria; Marletta, Stefano; Brunelli, Matteo; Carraro, Amedeo; Montin, Umberto; Boggi, Ugo; Mescoli, Claudia; Novelli, Luca; Malvi, Deborah; Lombardini, Letizia; Cardillo, Massimo; Neil, Desley; D'Errico, Antonietta
abstract
The risk of transmission of malignancy from donor to recipient is low; however, this occurrence has dramatic consequences. Many reports of donor derived cancers in liver transplant recipients have been published, but they have not been a systematically summarized into a lucid and unified analysis. The present study is an attempt to provide clarity to this unusual, but clinically important problem. We systematically reviewed all case reports, case series, and registries published on cancer transmission events through the end of December 2019. We identified a total of 67 publications with 92 transmission events. The most frequently transmitted cancers were lymphomas (30 [32.6%]), melanomas (8 [8.7%]), and neuroendocrine tumors (8 [8.7%]). Most of the melanomas were metastasizing, while most of the lymphomas were localized to the graft. The median time to cancer diagnosis after transplantation was 7 months, with 78% of diagnoses established in the first year. Melanoma carried the worst prognosis, with no recipients alive at 1 year after cancer diagnosis. Lymphoma recipients had a better outcome, with more than 75% surviving at 2 years. Conclusion: A metastatic cancer carries a worse prognosis for recipients, also because recipients with localized cancer can benefit from the chance to undergo transplantation again. The findings confirm the need to pay attention to donors with a history of melanoma but also suggest the need for a more careful evaluation of groups of donors, such as those dying from cerebral hemorrhage. Finally, recipients of organs from donors with cancer should be carefully followed to detect potential transmission.
2021
- HLA-G expression in melanomas
[Articolo su rivista]
Marletta, Stefano; Girolami, Ilaria; Munari, Enrico; Pantanowitz, Liron; Bernasconi, Riccardo; Torresani, Evelin; Brunelli, Matteo; Eccher, Albino
abstract
Human leukocyte antigen G (HLA-G) is a non-classical HLA class I molecule involved in inducing tolerance at the feto-maternal interface and in escape of immune response by tumor cells. The aim of the study is to review the published literature on the expression of HLA-G in malignant melanomas and its clinicopathological and prognostic correlates.
2021
- Impact of PD-L1 and PD-1 Expression on the Prognostic Significance of CD8+ Tumor-Infiltrating Lymphocytes in Non-Small Cell Lung Cancer
[Articolo su rivista]
Munari, Enrico; Marconi, Marcella; Querzoli, Giulia; Lunardi, Gianluigi; Bertoglio, Pietro; Ciompi, Francesco; Tosadori, Alice; Eccher, Albino; Tumino, Nicola; Quatrini, Linda; Vacca, Paola; Rossi, Giulio; Cavazza, Alberto; Martignoni, Guido; Brunelli, Matteo; Netto, George J; Moretta, Lorenzo; Zamboni, Giuseppe; Bogina, Giuseppe
abstract
The immune infiltrate within tumors has proved to be very powerful in the prognostic stratification of patients and much attention is also being paid towards its predictive value. In this work we therefore aimed at clarifying the significance and impact of PD-L1 and PD-1 expression on the prognostic value of CD8(+) tumor infiltrating lymphocytes (TILs) in a cohort of consecutive patients with primary resected non-small cell lung cancer (NSCLC). Tissue microarrays (TMA) were built using one representative formalin fixed paraffin embedded block for every case, with 5 cores for each block. TMA sections were stained with PD-L1 (clone SP263), PD-1 (clone NAT105) and CD8 (clone SP57). Number of CD8(+) cells per mm(2) were automatically counted; median, 25(th) and 75(th) percentiles of CD8(+) cells were used as threshold for statistical clinical outcome analysis and evaluated in patients subgroups defined by expression of PD-L1 and PD-1 within tumors. We found an overall strong prognostic value of CD8(+) cells in our cohort of 314 resected NSCLC, especially in PD-L1 negative tumors lacking PD-1(+) TILs, and demonstrated that in PD-L1 positive tumors a higher density of CD8(+) lymphocytes is necessary to improve the prognosis. Our data strengthen the concept of the importance of the assessment and quantification of the immune contexture in cancer and, similarly to what has been carried on in colorectal cancer, promote the efforts for the establishment of an Immunoscore for NSCLC for prognostic and possibly predictive purposes.
2021
- Impact of the COVID-19 pandemic on melanoma diagnosis
[Articolo su rivista]
Gisondi, Paolo; Cazzaniga, Simone; Di Leo, Sara; Piaserico, Stefano; Bellinato, Francesco; Pizzolato, Miriam; Gatti, Alessandro; Eccher, Albino; Brunelli, Matteo; Saraggi, Deborah; Girolomoni, Giampiero; Naldi, Luigi
abstract
Many health-care systems have responded the COVID-19 pandemic by delaying and/or cancelling elective surgical procedures, particularly during the lockdown.1-3 There is a concern that this could have affected the early diagnosis of malignant melanoma (MM) that is critical to improve its prognosis.4,5 The objective of this observational study was to investigate whether a reduction in the incidence of new diagnoses of MM has occurred following the COVID-19 outbreak. All the consecutive histological diagnoses of MM were retrospectively collected in the pathological laboratories of 4 provinces of the Veneto region in northern Italy, namely Verona, Vicenza, Rovigo and Treviso, between 1st March and 31st October 2020 and the same period of 2019. All cases were stratified in three categories according to Breslow thickness: in situ, <1 mm and ≥1 mm. The date of MM excision was considered for all the time-related analyses. The period March-October 2020 was compared with the same period of 2019.
2021
- Ki67/MART1 and p63/SOX10 Dual Immunohistochemistry Allows a Correct Interpretation of the Melanocytic Component in the Diagnosis of Pigmented Pilomatricoma
[Articolo su rivista]
Ammendola, Serena; Bariani, Elena; Tsvetkova, Vassilena; Gisondi, Paolo; Rosina, Paolo; Girolami, Ilaria; Coato, Michele; Brunelli, Matteo; Eccher, Albino; Colato, Chiara
abstract
: Pilomatricoma is a relatively common benign cutaneous adnexal tumor and a well-recognized entity, while its pigmented variant is far less common and less reported. Its estimated frequency ranges from 11 to 24%, according to a limited number of published case series. This article describes the case of a 42-year-old man presenting a firm subcutaneous nodule of the periareolar region. Histopathologic examination revealed a cystic lesion composed of matrical and supramatrical cells accompanied by a foreign body granulomatous cell reaction. Interestingly, a hyperpigmented area with numerous hyperplastic melanocytes and few mitoses was detectable. In order to assess the cell lineage of the mitotically active component in the hyperpigmented area, double immunohistochemistry with Ki67/Mart1 and p63/SOX10 was performed. Pigmented pilomatricoma is an underrecognized, underreported variant, and double immunohistochemistry stain is an effective tool in providing the correct interpretation of the proliferative activity in the different cellular populations.
2021
- Methods for actionable gene fusion detection in lung cancer: now and in the future
[Articolo su rivista]
Pisapia, Pasquale; Pepe, Francesco; Sgariglia, Roberta; Nacchio, Mariantonia; Russo, Gianluca; Gragnano, Gianluca; Conticelli, Floriana; Salatiello, Maria; De Luca, Caterina; Girolami, Ilaria; Eccher, Albino; Iaccarino, Antonino; Bellevicine, Claudio; Vigliar, Elena; Malapelle, Umberto; Troncone, Giancarlo
abstract
Although gene fusions occur rarely in non-small-cell lung cancer (NSCLC) patients, they represent a relevant target in treatment decision algorithms. To date, immunohistochemistry and fluorescence in situ hybridization are the two principal methods used in clinical trials. However, using these methods in routine clinical practice is often impractical and time consuming because they can only analyze single genes and the quantity of tissue material is often insufficient. Thus, novel technologies, able to test multiple genes in a single run with minimal sample input, are being under investigation. Here, we discuss the utility of next-generation sequencing and nCounter technologies in detecting simultaneous gene fusions in NSCLC patients.
2021
- PD-1/PD-L1 in Cancer: Pathophysiological, Diagnostic and Therapeutic Aspects
[Articolo su rivista]
Munari, Enrico; Mariotti, Francesca R; Quatrini, Linda; Bertoglio, Pietro; Tumino, Nicola; Vacca, Paola; Eccher, Albino; Ciompi, Francesco; Brunelli, Matteo; Martignoni, Guido; Bogina, Giuseppe; Moretta, Lorenzo
abstract
Immune evasion is a key strategy adopted by tumor cells to escape the immune system while promoting their survival and metastatic spreading. Indeed, several mechanisms have been developed by tumors to inhibit immune responses. PD-1 is a cell surface inhibitory receptor, which plays a major physiological role in the maintenance of peripheral tolerance. In pathological conditions, activation of the PD-1/PD-Ls signaling pathway may block immune cell activation, a mechanism exploited by tumor cells to evade the antitumor immune control. Targeting the PD-1/PD-L1 axis has represented a major breakthrough in cancer treatment. Indeed, the success of PD-1 blockade immunotherapies represents an unprecedented success in the treatment of different cancer types. To improve the therapeutic efficacy, a deeper understanding of the mechanisms regulating PD-1 expression and signaling in the tumor context is required. We provide an overview of the current knowledge of PD-1 expression on both tumor-infiltrating T and NK cells, summarizing the recent evidence on the stimuli regulating its expression. We also highlight perspectives and limitations of the role of PD-L1 expression as a predictive marker, discuss well-established and novel potential approaches to improve patient selection and clinical outcome and summarize current indications for anti-PD1/PD-L1 immunotherapy.
2021
- PD-L1 evaluation in head and neck squamous cell carcinoma: Insights regarding specimens, heterogeneity and therapy
[Articolo su rivista]
Paolino, Gaetano; Pantanowitz, Liron; Barresi, Valeria; Pagni, Fabio; Munari, Enrico; Moretta, Lorenzo; Brunelli, Matteo; Bariani, Elena; Vigliar, Elena; Pisapia, Pasquale; Malapelle, Umberto; Troncone, Giancarlo; Girolami, Ilaria; Eccher, Albino
abstract
Immunohistochemical assessment with combined positive score (CPS) of programmed death-ligand 1 (PD-L1) is the prerequisite for administration of checkpoint inhibitor therapy in head and neck squamous cell carcinoma (HNSCC). Practicing pathologists are required to assess PD-L1 in routinary work and can be faced up with practical issues not always addressed in clinical trials or guidelines, such as choice of specimen to test, the intrinsic heterogeneity in PD-L1 expression in tumors and the potential impact of already administered therapy, given that patients' material can be procured at several times of cancer natural history. In the present work, we review and discuss the recent literature regarding the assessment of PD-L1 in HNSCC from the perspective of the practicing pathologist, providing some evidence on the single issues. It emerges a general trend to an underestimation of PD-L1 expression in biopsies compared to resection specimens and to a higher degree of positivity in metastatic lymph nodes in respect to primary tumors. Moreover, therapy shows to have contrasting effect on PD-L1 expression. Although further studies are needed, taking into account the intrinsic heterogeneity in PD-L1 expression and the conflicting evidences, it may be speculated that the most recent material of patients in respect to the natural history of tumor can be the most reliable to evaluate PD-L1 expression.
2021
- Postmortem Findings Associated With SARS-CoV-2: Systematic Review and Meta-analysis
[Articolo su rivista]
Satturwar, Swati; Fowkes, Mary; Farver, Carol; Wilson, Allecia M; Eccher, Albino; Girolami, Ilaria; Pujadas, Elisabet; Bryce, Clare; Salem, Fadi; El Jamal, Siraj M; Paniz-Mondolfi, Alberto; Petersen, Bruce; Gordon, Ronald E; Reidy, Jason; Fraggetta, Filippo; Marshall, Desiree A; Pantanowitz, Liron
abstract
Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome-associated Coronavirus 2 (SARS-CoV-2), has become a global threat to public health. COVID-19 is more pathogenic and infectious than the prior 2002 pandemic caused by SARS-CoV-1. The pathogenesis of certain disease manifestations in COVID-19 such as diffuse alveolar damage (DAD) are thought to be similar to SARS-CoV-1. However, the exact pathogenesis of COVID-19 related deaths remains poorly understood. The aim of this article was to systematically summarize the rapidly emerging literature regarding COVID-19 autopsies. A meta-analysis was also conducted based on data accrued from preprint and published articles on COVID-19 (n=241 patients) and the results compared with postmortem findings associated with SARS-CoV-1 deaths (n=91 patients). Both autopsy groups included mostly adults of median age 70 years with COVID-19 and 50 years with SARS-CoV-1. Overall, prevalence of DAD was more common in SARS-CoV-1 (100.0%) than COVID-19 (80.9%) autopsies (P=0.001). Extrapulmonary findings among both groups were not statistically significant except for hepatic necrosis (P <0.001), splenic necrosis (P<0.006) and while pulp depletion (P <0.001) that were more common with SARS-CoV-1. Remarkable postmortem findings in association with COVID-19 apart from DAD include pulmonary hemorrhage, viral cytopathic effect within pneumocytes, thromboembolism, brain infarction, endotheliitis, acute renal tubular damage, white pulp depletion of the spleen, cardiac myocyte necrosis, megakaryocyte recruitment, and hemophagocytosis.
2021
- The histopathological diagnosis of atypical meningioma: glass slide versus whole slide imaging for grading assessment
[Articolo su rivista]
Ammendola, Serena; Bariani, Elena; Eccher, Albino; Capitanio, Arrigo; Ghimenton, Claudio; Pantanowitz, Liron; Parwani, Anil; Girolami, Ilaria; Scarpa, Aldo; Barresi, Valeria
abstract
Limited studies on whole slide imaging (WSI) in surgical neuropathology reported a perceived limitation in the recognition of mitoses. This study analyzed and compared the inter- and intra-observer concordance for atypical meningioma, using glass slides and WSI. Two neuropathologists and two residents assessed the histopathological features of 35 meningiomas-originally diagnosed as atypical-in a representative glass slide and corresponding WSI. For each histological parameter and final diagnosis, we calculated the inter- and intra-observer concordance in the two viewing modes and the predictive accuracy on recurrence. The concordance rates for atypical meningioma on glass slides and on WSI were 54% and 60% among four observers and 63% and 74% between two neuropathologists. The inter-observer agreement was higher using WSI than with glass slides for all parameters, with the exception of high mitotic index. For all histological features, we found median intra-observer concordance of ≥ 79% and similar predictive accuracy for recurrence between the two viewing modes. The higher concordance for atypical meningioma using WSI than with glass slides and the similar predictive accuracy for recurrence in the two modalities suggest that atypical meningioma may be safely diagnosed using WSI.
2020
- A sticky, palpable area of the perinephric adipose tissue at organ donor procurement: highlights on the diagnostic challenge and transplant management
[Articolo su rivista]
Novelli, Luca; Mescoli, Claudia; Malvi, Deborah; Girolami, Ilaria; Eccher, Albino
abstract
No abstract available; case report
2020
- Diagnostic concordance between whole slide imaging and conventional light microscopy in cytopathology: A systematic review
[Articolo su rivista]
Girolami, Ilaria; Pantanowitz, Liron; Marletta, Stefano; Brunelli, Matteo; Mescoli, Claudia; Parisi, Alice; Barresi, Valeria; Parwani, Anil; Neil, Desley; Scarpa, Aldo; Rossi, Esther Diana; Eccher, Albino
abstract
Many studies have examined the diagnostic concordance of whole slide imaging (WSI) and light microscopy (LM) for surgical pathology. In cytopathology, WSI use has been more limited, mainly because of technical issues. The aim of this study was to review the literature and determine the overall diagnostic concordance of WSI and LM in cytopathology. A systematic search of PubMed, Scopus, and the Cochrane Library was performed, with data extracted from the included articles. A quality assessment of studies was performed with a modified Quality Assessment of Diagnostic Accuracy Studies 2 tool. The primary outcome was concordance for the diagnoses rendered by WSI and LM as shown by the concordance rate with the original diagnosis, intra-observer and interobserver concordance with the κ coefficient, or a percentage. Secondary outcomes included the time taken to reach a diagnosis and the quality and perception of WSI. A descriptive survey was provided. Among 1867 publications, a total of 19 studies (1%) were included. Overall, the concordance between WSI and the original diagnosis was 84.1%, the intra-observer concordance between WSI and LM was 92.5% with a κ coefficient of 0.66, and the interobserver κ coefficient was 0.69. The time to reach a diagnosis was longer with WSI in all studies. The quality of WSI was good, but diagnostic confidence and cytologist preference were higher for LM. In conclusion, the concordance of WSI with LM is acceptable and in line with systematic reviews in surgical pathology. However, the time required for scanning and technical issues represent barriers to complete adoption. It is foreseeable that technical advances and rigorous validation study design will help to improve the diagnostic concordance of WSI with LM in cytopathology.
2020
- Diffuse gliomas in patients aged 55 years or over: A suggestion for IDH mutation testing
[Articolo su rivista]
Barresi, V; Eccher, A; Simbolo, M; Cappellini, R; Ricciardi, Gk; Calabria, F; Cancedda, M; Mazzarotto, R; Bonetti, B; Pinna, G; Sala, F; Ghimenton, C; Scarpa, A
abstract
Diffuse gliomas are defined on the isocitrate dehydrogenase (IDH) gene (IDH) mutational mutational status. The most frequent IDH mutation is IDH1 R132H, which is detectable by immunohistochemistry; other IDH mutations are rare (10%). IDH mutant gliomas have better prognosis. Further, IDH wild-type low-grade (II/III) gliomas have clinical behaviors similar to those of glioblastoma (GBM) and it was suggested that they are submitted to similar post-surgical treatment. The incidence of IDH mutant gliomas (2%) and that of GBMs with non-canonical IDH mutations (< 1%) are very low in patients ≥ 55 years. For this reason, it was suggested that immunohistochemistry against IDH1 R132H is sufficient to classify GBM as IDH wild-type in this age group. However, no indication was provided for IDH mutational testing in low-grade diffuse gliomas. To address this issue, 273 diffuse gliomas were tested for IDH1 R132H immunohistochemistry. 2/4 diffuse astrocytomas (DAs), 4/9 anaplastic astrocytomas (AAs), 2/256 GBMs, and 4/4 oligodendrogliomas had positive staining. No other IDH mutations were found in immuno-negative low-grade cases by DNA sequencing. To validate our findings, we considered 311 diffuse gliomas in patients ≥ 55 years in The Cancer Genome Atlas database. Fifty-five out of 311 gliomas had IDH R132H mutations (9/16 DAs; 8/48 AAs; 3/211 GBMs; 35/36 oligodendrogliomas), one DA, and one oligodendroglioma had other IDH mutations. IDH mutant gliomas had significantly higher frequency of O-6-methylguanine-DNA methyltransferase promoter methylation (P = 0.0008) and longer overall survival (P < 0.0001). In conclusion, low-grade gliomas are a minor part of gliomas (117/584) in patients ≥ 55 years, albeit they represent most IDH mutant gliomas in this age group (64/69 cases). IDH non-canonical mutations can be found in immunonegative low-grade gliomas (2/54). In view of its significance for prognosis and therapeutic management, our results suggest that IDH mutational status is assessed in all diffuse gliomas in patients ≥ 55 years by immunohistochemistry, followed by IDH sequencing in low-grade immunonegative cases.
2020
- Digital pathology for second opinion consultation and donor assessment during organ procurement: Review of the literature and guidance for deployment in transplant practice
[Articolo su rivista]
Eccher, Albino; Girolami, Ilaria; Brunelli, Matteo; Novelli, Luca; Mescoli, Claudia; Malvi, Deborah; D'Errico, Antonia; Luchini, Claudio; Furian, Lucrezia; Zaza, Gianluigi; Cardillo, Massimo; Boggi, Ugo; Pantanowitz, Liron
abstract
Telepathology has been an important application for second opinion consultation ever since the introduction of digital pathology. However, little is known regarding teleconsultation for second opinion in transplantation. There is also limited literature on telepathology during organ donor procurement, typically utilized when general pathologists on-call request back-up to help assess donor biopsies for organ suitability or to diagnose newly discovered tumors with urgent time constraints. In this review, we searched Pubmed/Embase and websites of transplant organizations to collect and analyze published evidence on teleconsultation for donor evaluation and organ procurement. Of 2725 records retrieved using the key terms 'telepathology', 'second opinion' and 'transplantation', 26 suitable studies were included. Most records were from North America and included validation studies of telepathology being used for remote frozen section interpretation of donor biopsies with whole slide imaging. The data from these published studies supports the transition towards digital teleconsultation in transplant settings where consultations among pathologists are still handled by pathologists being called on site, via telephone and/or email.
2020
- Donor-transmitted cancer in kidney transplant recipients: a systematic review
[Articolo su rivista]
Eccher, Albino; Girolami, Ilaria; Motter, Jennifer Danielle; Marletta, Stefano; Gambaro, Giovanni; Momo, Rostand Emmanuel Nguefuet; Nacchia, Francesco; Donato, Paola; Boschiero, Luigino; Boggi, Ugo; Lombardini, Letizia; Cardillo, Massimo; D'Errico, Antonietta; Neil, Desley; Segev, Dorry Lidor; Zaza, Gianluigi
abstract
The transmission of cancer from a donor organ is a rare event but has important consequences. Aim of this systematic review was to summarize all the published evidence on cancer transmission in kidney recipients. We reviewed published case reports and series describing the outcome of recipients with donor-transmitted cancer until August 2019. A total of 128 papers were included, representing 234 recipients. The most common transmitted cancers were lymphoma (n = 48, 20.5%), renal cancer (42, 17.9%), melanoma (40, 17.1%), non-small cell lung cancer (n = 13, 5.6%), neuroendocrine cancers comprising small cell lung cancer (n = 11, 4.7%) and choriocarcinoma (n = 10, 4.3%). There was a relative lack of glioblastoma and gastrointestinal cancers with only 6 and 5 cases, respectively. Melanoma and lung cancer had the worst prognosis, with 5-years overall survival of 43% and 19%, respectively; while renal cell cancer and lymphomas had a favorable prognosis with 5-years overall survival of 93 and 63%, respectively. Metastasis of cancer outside the graft was the most important adverse prognostic factor. Overall reporting was good, but information on donors' cause of death and investigations at procurement was often lacking. Epidemiology of transmitted cancer has evolved, thanks to screening with imaging and blood tests, as choriocarcinoma transmission have almost abolished, while melanoma and lymphoma are still difficult to detect and prevent.
2020
- Impact of Image Analysis and Artificial Intelligence in Thyroid Pathology, with particular reference to cytological aspects
[Articolo su rivista]
Girolami, Ilaria; Marletta, Stefano; Pantanowitz, Liron; Torresani, Evelin; Ghimenton, Claudio; Barbareschis, Mattia; Scarpa, Aldo; Brunelli, Matteo; Barresi, Valeria; Trimboli, Pierpaolo; Eccher, Albino
abstract
Thyroid pathology has great potential for automated/artificial intelligence (AI) algorithm application as the incidence of thyroid nodules is increasing and the indeterminate interpretation rate of fine-needle aspiration remains relatively high. The aim of the study is to review the published literature on automated image analysis and AI applications to thyroid pathology with whole-slide imaging (WSI).
2020
- Impact of bariatric surgery-induced weight loss on circulating PCSK9 levels in obese patients
[Articolo su rivista]
Zenti, Maria G; Lupo, Maria G; De Martin, Sara; Altomari, Anna; Galvan, Serena; Aventaggiato, Marta; Maneschi, Chiara; Sandri, Damiano; Paiola, Elena; Battistoni, Marco; Eccher, Albino; Targher, Giovanni; Bonora, Enzo; Ruscica, Massimiliano; Ferri, Nicola
abstract
BACKGROUND AND AIMS: To investigate the effect of obesity and bariatric-induced weight loss on circulating levels of proprotein convertase subtilisin/kexin 9 (PCSK9) in severely obese patients.METHODS AND RESULTS: In this non-randomized interventional study, we enrolled 36 severely obese patients (BMI 43.7±5.6kg/m2), of which 20 underwent bariatric surgery, and 12 nonobese healthy controls. An oral glucose tolerance test (75-g OGTT) was performed in 31 of these obese patients at baseline (T0) and in 14 patients at 6 months after bariatric surgery (T6) to assess plasma glucose, insulin and PCSK9 levels. Plasma PCSK9 levels were also measured in 18 of these obese patients at T0 during a 2-hhyperinsulinemic-euglycemic clamp (HEC). At T0, PCSK9 levels were higher in obese patients than in controls (274.6±76.7ng/mL vs. 201.4±53.3ng/mL) and dropped after bariatric surgery (T6; 205.5±51.7ng/mL) along with BMI (from 44.1±5.9kg/m2 to 33.1±5.6kg/m2). At T6, there was also a decrease in plasma glucose (T0 vs. T6: 6.0±1.8 vs. 5.0±0.5mmol/L) and insulin (15.7±8.3 vs. 5.4±2.1mU/L) levels. At T0, plasma PCSK9 levels decreased during OGTT in obese patients, reaching a nadir of 262.0±61.4ng/mL at 120min with a hyperinsulinemic peak of 75.1±40.0mU/L, at 60min. Similarly, at T0 insulin infusion during 2-hHEC acutely reduced plasma PCSK9 levels in obese patients. The aforementioned OGTT-induced changes in plasma PCSK9 levels were not observed neither in nonobese healthy controls nor in obese patients after bariatric-surgery weight loss.CONCLUSIONS: These results suggest a pivotal role of adipose tissue and insulin resistance on PCSK9 homeostasis in severely obese patients.
2020
- Mesothelial/monocytic incidental cardiac excrescence in autoimmune disease
[Articolo su rivista]
Cetera, Vera; de Manna, Nunzio Davide; Girolami, Ilaria; Cavallo, Enrico; Eccher, Albino; Rungatscher, Alessio; Luciani, Giovanni Battista; Milano, Aldo D; Faggian, Giuseppe
abstract
Mesothelial/monocytic incidental cardiac excrescence (MICE) is a rare benign finding made of mesothelial cells, histiocytes, and fibrin, usually found during heart valve surgery. The clinical relevance resides in the potential misdiagnosis as metastatic carcinoma or arterial embolism. The pathogenesis remains uncertain, with artifactual and reactive hypotheses. Here we present a case of MICE with paradigmatic clinical, imaging, and histological features in a 28-year-old woman with undifferentiated connective tissue disease without previous cardiac catheterization with possible pathogenesis, highlighting the importance of awareness of the existence of this lesion in patients with autoimmune disease.
2020
- Pre-implantation kidney biopsy: value of the expertise in determining histological score and comparison with the whole organ on a series of discarded kidneys
[Articolo su rivista]
Girolami, Ilaria; Gambaro, Giovanni; Ghimenton, Claudio; Beccari, Serena; Caliò, Anna; Brunelli, Matteo; Novelli, Luca; Boggi, Ugo; Campani, Daniela; Zaza, Gianluigi; Boschiero, Luigino; López, José Ignacio; Martignoni, Guido; D'Errico, Antonia; Segev, Dorry; Neil, Desley; Eccher, Albino
abstract
Evidence about the reliability of pre-implantation biopsy is still conflicting, depending on both biopsy type and pathologist's expertise. Aim of the study is to evaluate the agreement of general v specialist pathologists and to compare scores on biopsy and whole organs in a set of discarded kidneys.
2020
- Prevalence of PD-L1 expression in head and neck squamous precancerous lesions: a systematic review and meta-analysis
[Articolo su rivista]
Girolami, I.; Pantanowitz, L.; Munari, E.; Martini, M.; Nocini, R.; Bisi, N.; Molteni, G.; Marchioni, D.; Ghimenton, C.; Brunelli, M.; Eccher, A.
abstract
Background: Studies concerning programmed death-ligand 1 (PD-L1) expression in precancerous lesions of head and neck (HN) region have shown variable results. Methods: We systematically reviewed the published evidence on PD-L1 expression in HN precancerous lesions. Results: Of 1058 original articles, 14 were included in systematic review and 9 in meta-analysis. The pooled estimate of PD-L1 expression was 48.25% (confidence interval [CI] 21.07-75.98, I2 98%, tau2 0.18). PD-L1 expression appeared to be more frequent in precancerous lesions than in normal mucosa (risk ratio [RR] 1.65, CI 0.65-4.03, I2 91%, tau2 0.82) and less frequent than in invasive squamous cell carcinoma (RR 0.68, CI 0.43-1.08, I2 91%, tau2 0.22). Conclusions: PD-L1 expression could reflect a point of balance between host immune response and cancer escape ability. High heterogeneity and moderate quality suggest that further studies with larger sample size and more rigorous case selection will allow more precise assessment of PD-L1 expression in HN precancerous lesions.
2020
- Programmed Death-Ligand 1 (PD-L1) Is a Potential Biomarker of Disease-Free Survival in Papillary Thyroid Carcinoma: a Systematic Review and Meta-Analysis of PD-L1 Immunoexpression in Follicular Epithelial Derived Thyroid Carcinoma
[Articolo su rivista]
Girolami, Ilaria; Pantanowitz, Liron; Mete, Ozgur; Brunelli, Matteo; Marletta, Stefano; Colato, Chiara; Trimboli, Pierpaolo; Crescenzi, Anna; Bongiovanni, Massimo; Barbareschi, Mattia; Eccher, Albino
abstract
The expression of programmed death-ligand 1 (PD-L1) is an established prerequisite for the administration of checkpoint inhibitor therapy and is of prognostic value in several cancer types. Data concerning the potential effect of PD-L1 on the prognosis of thyroid carcinoma are limited. Therefore, this study aimed to provide a systematic review of the published data on this topic. The literature was reviewed to gather and quantify evidence on the prognostic role of PD-L1 in follicular epithelial derived thyroid carcinomas and determine its association with clinicopathological parameters. A meta-analysis was performed using the DerSimonian-Laird random-effects model. The quality of studies was evaluated with the Newcastle-Ottawa Scale and a modified GRADE approach used to rate the quality of evidence. Out of 445 papers, 18 were included and 15 provided adequate data for meta-analysis. The quality of evidence ranged from low to high. PD-L1 expression was significantly associated with a reduced disease-free survival (DFS) (RR 1.63, CI 1.04-2.56, p = 0.03, I2 68%, τ2 0.19 and HR 1.90, CI 1.33-2.70, p< 0.001, I2 0%, τ2 0.00); however, no association was found with the overall survival (OS). Furthermore, a significant association was found with respect to underlying chronic lymphocytic thyroiditis and BRAFV600E mutation status in papillary thyroid carcinomas. In the subgroup analysis, the association of PD-L1 and DFS remained strong in papillary thyroid carcinoma when compared with dedifferentiated thyroid carcinomas (anaplastic and poorly differentiated thyroid carcinomas) that failed to demonstrate a significant association with respect to PD-L1. These findings underscore the role of PD-L1 immunohistochemistry as a potential prognostic biomarker of disease recurrence in patients with papillary thyroid carcinoma.
2020
- Thyroid Fine-Needle Aspiration Cytology: Focusing on Adherence to Guidelines and Hospital Organization
[Articolo su rivista]
Ammendola, Serena; Girolami, Ilaria; Bovo, Chiara; Paini, Marina; Castelli, Claudia; Bruno, Costanza; Schenal, Giacomo; Brazzarola, Paolo; Mezzetto, Luca; Veraldi, Gian Franco; Novelli, Luca; Brunelli, Matteo; Montemezzi, Stefania; Eccher, Albino
abstract
BACKGROUND The complications of fine-needle aspiration cytology (FNAC) are rare but can be challenging for performing physicians to diagnose and manage. This type of procedure is perceived as routine and devoid of substantial risks, but uncommon complications can occur and need to be addressed with careful workup. CASE REPORT A FNAC procedure for a young female patient with multiple thyroid nodules was requested by her general practitioner. After the FNAC thyroid procedure, a carotid wall hematoma was suspected and could not be excluded with ultrasound (US) alone. Thus, the patient underwent a computed tomography angiogram (CTA) that excluded blood extravasation from the carotid, confirming the suspicion of perivascular blood accumulation. As a precaution, the patient was hospitalized, with US follow-up; she was dismissed the day after her hospital admission with a diagnosis of a benign thyroid nodule in multinodular goiter according to SIAPEC-IAP classification. CONCLUSIONS This case highlights how a routine-perceived procedure such as FNAC could present a challenge to the performing physicians, pathologist, and radiologist, raising the suspicion of a severe complication that needs to be addressed with a readily available emergency service that may be accessible only within a central hospital-level organization. This case reinforces the point that more careful adherence to clinic-radiological guidelines is needed to avoid potentially inappropriate and harmful procedures. A review of the literature concerning guidelines for FNAC procedure, diagnostic classifications, and reported complications is provided as part of this case report.
2019
- A Meta-Analysis Evaluating Clinical Outcomes of Patients with Renal Cell Carcinoma Harboring Chromosome 9P Loss
[Articolo su rivista]
Di Nunno, Vincenzo; Mollica, Veronica; Brunelli, Matteo; Gatto, Lidia; Schiavina, Riccardo; Fiorentino, Michelangelo; Santoni, Matteo; Montironi, Rodolfo; Caliò, Anna; Eccher, Albino; Milella, Michele; Martignoni, Guido; Brunocilla, Eugenio; Massari, Francesco
abstract
9p loss appears a reliable and promising marker able to differentiate specific categories of patients with renal cell carcinoma associated with a worse prognosis.
2019
- Autophagy pathways in drug abusers after forensic autopsy: LC3B, ph-mTOR and p70S6K analysis
[Articolo su rivista]
Chindemi, Chiara; Cirielli, Vito; Cima, Luca; Danzi, Olivia; Raniero, Dario; Tagliaro, Franco; Turrina, Stefania; Eccher, Albino; Ghimenton, Claudio; Bortolotti, Federica; Brunelli, Matteo; De Leo, Domenico
abstract
INTRODUCTION: Autophagy plays a role in various central nervous system diseases. Little is known about its molecular activation in drug addiction. Our aim was to investigate the signalling pathways of autophagy in brain tissues from drug abusers. METHODS: Twenty-five drug abusers with acute lethal intoxication and 10 controls were medico-legally autopsied. Brain-tissue samples from the parietal cortex and cerebellum were obtained. Expression of LC3B, phospho-mTOR (ph-mTOR) and phospho70S6 Kinase (p70S6K) was identified in tissue microarrays, with three tissue spots per case. Blood, urine or vitreous humour were tested in all cases to identify the acute intoxication. Hair analysis was performed in 14 cases to confirm chronic intoxication; the remaining cases had a documented medical history of chronic abuse. RESULTS: The autophagy marker LC3B was always positive on both the cortex and the cerebellum, stratified as strongly in 18 (72%) cases and weakly positive in seven (28%) cases. ph-mTOR was negative in all cases. The p70S6K molecule showed positivity in 14 (56%) cases on cortex tissue. The cerebellum was always negative, except for Purkinje cells. Drug abusers had statistically more double positive cases (LC3B-p70S6K) than controls ( p=0.0094). CONCLUSION: Autophagy pathways were activated in our series, and 56% of drug abusers showed simultaneous LC3B-p70S6K immunoexpression on tissue from the parietal cortex and cerebellum. This may be of value in autopsy practice as an indicator of brain damage due to drug abuse and could serve as alternative or additional double sensitive diagnostic method to detect drug-related deaths using a tissue-based rationale.
2019
- Demographic, Clinical and Hematological Predictors of Carotid Atherosclerotic Plaque Histology
[Abstract in Rivista]
Luca Salvagno, Gian; Mezzetto, Luca; Eccher, Albino; Scorsone, Lorenzo; Macrì, Marco; Fabio, Simoncini; Criscenti, Paolo; Lippi, Giuseppe; Franco Veraldi, Gian
abstract
Aims: This retrospective observational study was aimed to identify hematological predictors of histological heterogeneity of carotid atherosclerotic plaques (CAPs). Results: The mean values of all demographic, clinical and haematological parameters did not differ between patients with or without symptomatic CAD. In univariate analysis, intraplaque hemorrhage was associated with male sex (r=0.18; p=0.032), superficial thrombosis with low hemoglobin (r=- 0.18; p=0.033), fibrosis with enhanced RDW (r=0.24; p=0.005), presence of foam cells with high WBC count (r=0.22; p=0.001), neovascularisation with high WBC count (r=0.17; p=0.048), whilst the presence of inflammatory infiltrate was also associated with high WBC count (r=0.17; p=0.043). Conlusions: The results of this retrospective observational study confirm that some traditional and inexpensive hematological parameters such as WBC count, hemoglobin and RDW may help identifying patients with more severe forms of CAD.
2019
- Extra-axial anaplastic astroblastoma in a 67-year-old woman
[Articolo su rivista]
Bernasconi, Riccardo; Eccher, Albino; Girolami, Ilaria; Boldrini, Marcello; Masotto, Barbara; Barresi, Valeria
abstract
Astroblastoma is a rare glial neoplasia of the central nervous system. It is histologically defined by the presence of neoplastic cells with non- or slightly tapering processes arranged around blood vessels (astroblastic rosettes) and conventionally subdivided into well-differentiated and anaplastic. It commonly affects children and young adults, although cases and due to its superficial location in the brain cortex, it can mimic an extra-axial mass on magnetic resonance imagining. Herein, we describe a unique case of pure extra-axial anaplastic astroblastoma in an elderly woman. Awareness that astroblastoma may be also extra-axial and affect older subjects, may be helpful for its identification and differential diagnosis toward more common entities at this site and age of onset, and for appropriate therapeutic management as well.
2019
- From fine-needle aspiration cytology to fluorescent in-situ hybridization in an unusual case of pharyngeal synovial sarcoma
[Articolo su rivista]
Paolino, G.; Girolami, I.; Bernasconi, R.; Beccari, S.; Marchioni, D.; Molteni, G.; De Robertis, R.; Ghimenton, C.; Calio, A.; Brunelli, M.; Eccher, A.
abstract
Synovial sarcoma arising in the pharynx is a rare entity, with very few cases described in literature, mainly as surgical-oriented case reports. We report the case of a healthy 20-year old man who presented with a painless right neck mass, clinically suspicious for a thyroid nodule. Ultrasound scan and fine-needle aspiration cytology failed to provide a definitive result, although suggesting a mesenchymal proliferation, in accordance with magnetic resonance imaging findings. Therefore, the lesion was removed with a minimally invasive surgical intervention. Definitive histologic and immunohistochemical examination of the surgical specimen revealed a biphasic synovial sarcoma, further validated by the detection of SS18 gene rearrangement on fluorescent in-situ hybridization examination. Although rarely, synovial sarcoma may arise in the pharynx. Radiological, cytological, histological and molecular findings are needed along each step of the diagnostic process.
2019
- Histopathology and Long-Term Outcome of Kidneys Transplanted From Donors With Severe Acute Kidney Injury
[Articolo su rivista]
Cima, L; Nacchia, F; Ghimenton, C; Valotto, G; Boschiero, L; Gobbo, S; Zaza, G; Neil, D; Mescoli, C; Vanzo, Francesca; D'Errico, A; Ghimenton, C; Rugge, M; Casartelli-Liviero, M; Brunelli, M; Novelli, L; Eccher, A.
abstract
Background: Acute kidney injury is a treatable entity although difficult to recognize without diagnostic biopsy. We investigated the potential association between clinically defined deceased donors and acute kidney injury with preimplantation histological findings and recipient outcomes. Methods: Kidney biopsies from donors were classified using the Acute Kidney Injury Network criteria and assessed for percentage glomerulosclerosis, tubular atrophy, interstitial fibrosis, and vascular narrowing with the Remuzzi score and for acute tubular necrosis. Differences in incidence rates of delayed graft function (DGF) and cumulative rejection episodes were compared between recipients transplanted with normal and 3 levels of acute kidney injury using the analysis of variance with Bonferroni correction (P ¼ .0012). Results: Sixteen out of 335 donors showed a severe acute kidney injury level 3 with a median serum creatinine of 458 mmol/L. Fourteen (88%) had 0-3 Remuzzi score and were used for single kidney transplantation and 2 (12%) were used for dual kidney transplantation (score: 4-6). Recipients who received a kidney from a donor with level 3 acute kidney injury had a higher percentage of DGF (47%) without statistical significance (P ¼ .008). The rate of cumulative rejection (45%) at 2 years was not significantly increased (P ¼ .09). Conclusions: Recipients receiving level 3 acute kidney injury kidneys, selected with Remuzzi histopathological score and acute tubular necrosis assessment, had a greater incidence of DGF but a similar long-term cumulative rejection compared to no injury and level 1 and level 2 acute kidney injury donors. The application of the histopathological examination allowed expansion of the kidney donor pool.
2019
- How safe are organs from deceased donors with neoplasia? The results of the Italian Transplantation Network
[Articolo su rivista]
Eccher, Albino; Lombardini, Letizia; Girolami, Ilaria; Puoti, Francesca; Zaza, Gianluigi; Gambaro, Giovanni; Carraro, Amedeo; Valotto, Giovanni; Cima, Luca; Novelli, Luca; Neil, Desley; Montin, Umberto; Scarpa, Aldo; Brunelli, Matteo; Nanni Costa, Alessandro; D'Errico, Antonia
abstract
Guidelines for donor selection have changed to expand the donor pool, considering potential donors affected by a neoplasm. Aim of this retrospective study is to look at the use of organs from donors with a current or history of neoplasm within the Italian Transplant Network. Data, collected and validated by Italian National Health Institute for the time interval 2006-2015, have been reviewed retrospectively by mean of multivariable pivot tables. Donors with neoplasia represented about 5% of all donors, resulting in about 4% of all transplants. Donors presented a benign neoplasm in 29.08% of cases, a malignancy with variable risk of transmission in 69.75% while in 1.34% the nature of neoplasm could not be assessed. Considering all procedures, rate of transmission of a malignancy was 0.03% (10 cases) of all 29858 transplants of the time interval. Notably, cases of transmission were not from donors of this pool, but from donors that, according to our protocols, had no elements of suspect at time of donation. As recipient safety is always the priority and as guidelines have set exclusion criteria for donors with some specific types of malignancy, these results show that use of this type of donors is safe and improve organ pool. Furthermore represent basis for improvement and standardization of donor assessment protocols suggesting that efforts in data collection systems, to produce complete and homogeneous data, are mandatory.
2019
- Keratocystoma of the parotid gland is rare and requires an integrated multidisciplinary approach: Report of a case and a literature review
[Articolo su rivista]
Aresta, A.; Girolami, I.; Paolino, G.; Molteni, G.; Sacchetto, L.; Marchioni, D.; El-Dalati, G.; Sina, S.; Brunelli, M.; Manfrin, E.; Eccher, A.
abstract
2019
- Liver Metastases From Renal Oncocytoma With Vascular Extension
[Articolo su rivista]
Cacciamani, Giovanni; Cima, Luca; Ficial, Miriam; Novella, Giovanni; Siracusano, Salvatore; Tedeschi, Umberto; Balzarro, Matteo; Montin, Umberto; Cerruto, Maria A; De Marco, Vincenzo; Porcaro, Antonio B; Hes, Ondrej; Dʼerrico, Antonia; Martignoni, Guido; Ghimenton, Claudio; Zaza, Gianluigi; Artibani, Walter; Brunelli, Matteo; Eccher, Albino
abstract
The 2016 World Health Organization Renal Tumor Classification defines renal oncocytoma (RO) as a benign epithelial tumor; however, malignant histopathologic features have been documented. Rare cases with metastases have been reported. We describe the case of a 62-year-old woman who was referred to the Urology Clinic for a routine work-up. Magnetic resonance imaging and computerized tomography showed a 7-cm mass in the middle and lower portions of the left kidney and 2 suspected liver metastases. The patient underwent surgery. Microscopically both renal and liver lesions presented solid, solid-nested, and microcystic architecture, composed predominantly of large eosinophilic cells without any worrisome pattern except the vascular extension. The cells were positive for S100A1, CD117, and PAX-8 and negative for CAIX, CK7, and AMACR. Fluorescence in situ hybridization showed a disomic profile for the chromosomes 1, 2, 6, 7, 10, 17. No mutation of coding sequence of the SDHB, SDHC, SDHD, VHL, and BHD genes and no loss of heterozygosity at 3p were found. The final diagnosis was “RO” according to the 2016 World Health Organization Renal Tumor Classification with “liver metastases.” This report provides a wide clinical-pathologic, immunophenotypical and molecular documentation of a RO with liver metastases
2019
- Management of Thyroid Nodules in Deceased Donors With Comparison Between Fine Needle Aspiration and Intraoperative Frozen Section in the Setting of Transplantation
[Articolo su rivista]
Eccher, Albino; Girolami, Ilaria; D'Errico, Antonia; Zaza, Gianluigi; Carraro, Amedeo; Montin, Umberto; Boggi, Ugo; Scarpa, Aldo; Brunelli, Matteo; Martignoni, Guido; Segev, Dorry; Rossi, Esther Diana; Pantanowitz, Liron
abstract
Newly discovered thyroid nodules in deceased donors are investigated to rule out cancer that can be transmitted, but there are no established protocols. The aim of the study was to compare fine needle aspiration versus intraoperative frozen section in the donor management with limited time.
2019
- The Landscape of Digital Pathology in Transplantation: From the Beginning to the Virtual E-Slide
[Articolo su rivista]
Girolami, Ilaria; Parwani, Anil; Barresi, Valeria; Marletta, Stefano; Ammendola, Serena; Stefanizzi, Lavinia; Novelli, Luca; Capitanio, Arrigo; Brunelli, Matteo; Pantanowitz, Liron; Eccher, Albino
abstract
Digital pathology has progressed over the last two decades, with many clinical and nonclinical applications. Transplantation pathology is a highly specialized field in which the majority of practicing pathologists do not have sufficient expertise to handle critical needs. In this context, digital pathology has proven to be useful as it allows for timely access to expert second-opinion teleconsultation. The aim of this study was to review the experience of the application of digital pathology to the field of transplantation.
2019
- Tracheobronchopathia Osteochondroplastica: A Case Report Illustrating the Importance of Multilevel Workup Clinical, Endoscopic and Histological Assessment in Diagnosis of an Uncommon Disease
[Articolo su rivista]
Riva, Giulio; Girolami, Ilaria; Luchini, Claudio; Villanova, Manuela; Valotto, Giovanni; Cima, Luca; Carella, Rodolfo; Riva, Maurizio; Fraggetta, Filippo; Novelli, Luca; Eccher, Albino
abstract
BACKGROUND Tracheobronchopathia osteochondroplastica (TO) is a rare idiopathic disease with a stable course, which involves the lumen of the tracheobronchial tree. Clinical manifestations at time of presentation may differ, typically including hoarseness, persistent and/or productive cough, hemoptyses, and dyspnea. There are no well-established guidelines for diagnostic workup and treatment. Our aim here is to present a paradigmatic case of TO together with a concise survey of the most important clinical, radiological, and histological criteria. CASE REPORT We report a case of a 62-year-old non-smoker male with persisting cough and no prior history of respiratory disease. Chest radiography (RX) and computed tomography (CT) were unremarkable. Given the persistence of symptoms, the patient underwent bronchoscopic examination, which revealed protruding sessile nodules into the tracheal lumen, with cobblestone appearance. Histopathological examination of biopsies taken during bronchoscopy showed cartilaginous and osseous submucosal nodules consistent with the diagnosis of TO. CONCLUSIONS TO is not always an easily recognized disease, and a multidisciplinary team work is often required for diagnosis, with particular importance of endoscopic-pathological correlation.
2019
- Urachal carcinoma: from gross specimen to morphologic, immunohistochemical, and molecular analysis
[Articolo su rivista]
Riva, G; Mian, C; Luchini, C; Girolami, I; Ghimenton, C; Cima, L; Novelli, L; Hanspeter, E; Mazzoleni, Giada; Schwienbacher, C; Pycha, S; D'Elia, C; Trenti, E; Pycha, A; Martignoni, G; Hes, O; Eccher, A; Nesi, G; Brunelli, M
abstract
Urachal carcinoma (UrC) is an exceedingly rare neoplasm that develops from the urachus, an embryologic remnant of the urogenital sinus and allantois. The most commonly encountered histologic subtype is adenocarcinoma. The aim of this study is to characterize a series of UrC by morphology, immunohistochemistry, and molecular analysis. We retrospectively investigated seven cases of UrCs and assessed patient symptoms, imaging, histologic features, immunohistochemical profile, molecular characteristics, pathologic stages, and type of treatment. Immunostaining for CK7, CK20, Muc-2, CDX2, GATA3, β-catenin, and CK34βE12 was carried out on each neoplasm and on seven non-neoplastic urachal remnants as the control group. Additionally, a mutational analysis was performed using the QIAact Actionable Insights Tumor Panel Kit, which analyzes KRAS, NRAS, KIT, BRAF, PDGFRA, ALK, EGFR, ERBB2, PIK3CA, ERBB3, ESR1, and RAF1. Our cohort comprised five females and two males with a mean age of 64 years. UrCs consisted of two mucinous cystadenocarcinomas and five invasive, non-cystic adenocarcinomas. Carcinoma antigen expression profile was positive for CK20 and negative for CK34βE12 and GATA3 in all cases. Five of seven cases stained positively for Muc-2 and CDX2. On the contrary, non-neoplastic urachal remnants were immunoreactive for CK34βE12, CK7, and GATA3. Mutational analysis gave a positive result in four out of seven (57.1%) cases. All four positive tumors showed RAS mutation and one an additional mutation in PIK3CA. Urachal tumors exhibit peculiar morphologic, immunohistochemical, and molecular features. Due to the advanced stage at presentation, individualized treatment should be undertaken.
2018
- A microRNA signature from serum exosomes of patients with glioma as complementary diagnostic biomarker
[Articolo su rivista]
Santangelo, Alessandra; Imbruce', Pietro; Gardenghi, Beatrice; Belli, Laura; Agushi, Rina; Tamanini, Anna; Munari, Silvia; Bossi, Alessandra Maria; Scambi, Ilaria; Benati, Donatella; Mariotti, Raffaella; DI GENNARO, Gianfranco; Sbarbati, Andrea; Eccher, Albino; Ricciardi, GIUSEPPE KENNETH; Ciceri, Elisa Maria; Sala, Francesco; Pinna, Giampietro; Lippi, Giuseppe; Cabrini, Giulio; Dechecchi, Maria Cristina
abstract
Malignant gliomas, the most frequent primary brain tumors, are characterized by a dismal prognosis. Reliable biomarkers complementary to neuroradiology in the differential diagnosis of gliomas and monitoring for post-surgical progression are unmet needs. Altered expression of several microRNAs in tumour tissues from patients with gliomas compared to normal brain tissue have been described, thus supporting the rationale of using microRNA-based biomarkers. Although different circulating microRNAs were proposed in association with gliomas, they have not been introduced into clinical practice so far. Blood samples were collected from patients with high and low grade gliomas, both before and after surgical resection, and the expression of miR-21, miR-222 and miR-124-3p was measured in exosomes isolated from serum. The expression levels of miR-21, miR-222 and miR-124-3p in serum exosomes of patients with high grade gliomas were significantly higher than those of low grade gliomas and healthy controls and were sharply decreased in samples obtained after surgery. The analysis of miR-21, miR-222 and miR-124-3p in serum exosomes of patients affected by gliomas can provide a minimally invasive and innovative tool to help the differential diagnosis of gliomas at their onset in the brain and predict glioma grading and non glial metastases before surgery.
2018
- Consultation interface between Pathologist and Forensic Science Experts for histopathology examination
[Abstract in Atti di Convegno]
Cirielli, V.; Brunelli, M.; Bortolotti, F.; De Battisti, Z.; Del Balzo, G.; De Salvia, A.; Eccher, A.; Laposata, C.; Ghimenton, C.; Raniero, D.; Vermiglio, E.; Portas, M.; Scarpa, A.; Tagliaro, F.; Turrina, S.; De Leo, D.
abstract
Debate remains to how much the magnitude of histopathologic examination may be of benefit to medicolegal purposes. We sought to address the question after reviewing consultation cases requested to pathologists from forensics.
2018
- Cortical Expression of the Polysialylated Isoform of the Neural Cell Adhesion Molecule on Brain Tissue to Recognize Drug-Related Death: An Exploratory Analysis
[Articolo su rivista]
Cirielli, V; Cima, L; Chindemi, C; Danzi, O; Ghimenton, C; Eccher, A; Mauriello, S; Bortolotti, F; De Leo, D; Brunelli, M; Tagliaro, F.
abstract
The polysialylated isoform of the neural cell adhesion molecule (PSA-NCAM) has been shown to be a key player in neuroplastic changes and is expressed in various disorders. We investigated the PSANCAM expression on brain cortical tissue in a cohort of drug-related deaths. Brains from 25 drug abusers and 10 control subjects were removed at autopsy, and 2 samples of the right parietal lobe of each case were obtained. The polysialylated isoform of NCAM was evaluated on formalinfixed and paraffin-embedded tissues. Eleven patients were polydrug abusers; 14 used a single substance. The mechanisms of death were acute respiratory failure (n = 19), cardiorespiratory failure (n = 4), acute heart failure (n = 1), and brain injury (n = 1). Toxicological analyses of blood were available for all cases, and urine and bile analyses for 19 of 25 cases. The polysialylated isoform of NCAM immunoexpression in the neuronal soma and dendritic spines was observed in 18 (72%) of 25 drug abusers and in 2 (20%) of 10 control subjects. Drug abusers were statistically more positive for PSA-NCAM than control subjects (P = 0.0082). The expression of PSA-NCAM in the parietal cortex could be an indicator of brain damage due to drug abuse, and its availability could allow the forensic pathologists to develop rapid and low-cost additional or alternative method to improve detection of drug-related deaths
2018
- Innovation in Transplantation: The Digital Era
[Articolo su rivista]
Eccher, A; Brunelli, M; Pantanowitz, L; Parwani, A; Girolami, I; Scarpa, A
abstract
The international symposium entitled "Innovation in Transplantation: The Digital Era" took place on June 7 and 8, 2018 in Verona, Italy. This meeting was borne out of the productive collaboration between the Universities and Hospital Trusts of Verona and Padua in Italy, in the context of a vast regional project called Research and innovation project within the Health Technology Assessment. The project aimed to create an innovative digital platform for teleconsultation and delivering diagnostic second opinions in the field of organ transplantation within the Veneto region. This conference brought together pathologists, health informatics leaders, clinicians, researchers, vendors, and health-care planners from all around the globe. The symposium was conceived to promote the exchange of knowledge and kindle fertile discussion among the 130 attendees from 15 different countries. This article conveys the highlights of this symposium.
2018
- Lymphnode metastasis of thyroid cancer misinterpreted as lateral aberrant thyroid 40 years before identification of primary tumor. Case report and review of the literature
[Articolo su rivista]
Riva, G; Villanova, M; Francia, G; Valotto, G; Mezzetto, L; Toaiari, Marco; Eccher, A; Novelli, L
abstract
The differential diagnosis between lateral ectopic thyroid tissue with orthotopic normal gland and metastatic thyroid carcinoma is challenging. Lateral cervical site is a very rare location for ectopic tissue since only a few cases have been reported. The peculiarity of this clinical case is the finding of a thyroid carcinoma forty years after surgical resection of the ectopic thyroid lesion. This asynchronous association, never reported in literature, raises the question of the differential diagnosis between a true ectopic aberrant thyroid and an early lymph node metastasis from an occult thyroid carcinoma, evident in the primitive site many years later. Several elements, which will be matter of discussion, seem to favour the latter hypothesis.
2018
- Mesothelial/monocytic incidental cardiac excrescences (MICE): report of a case and review of literature with focus on pathogenesis
[Articolo su rivista]
Girolami, Ilaria; Eccher, Albino; Gilioli, Eliana; Novelli, Luca; Di Stefano, Gioia; Brunelli, Matteo; Cima, Luca
abstract
Mesothelial/monocytic incidental cardiac excrescence (MICE) is a benign lesion composed of histiocytes and mesothelial cells, usually found during cardiac surgery. To date, no more than 50 cases are reported in literature, and pathogenesis is still unclear even if different theories have been proposed. Here we report a case of MICE encountered during aortic valve replacement with typical histological features and extensive immunohistochemical investigation. To date, little information is available about the pathogenesis of MICE. We review the current literature focusing on the role of adhesion molecules such as CD31.
2018
- Metastatic malignant melanoma to the gallbladder. Case report and review of the literature
[Articolo su rivista]
Riva, Giulio; Villanova, Manuela; Eccher, A; Luchini, C; Motta, F; Bernasconi, Riccardo; Barbareschi, M
abstract
Solitary metastasis of malignant melanoma (MM) to the gallbladder (GB) is rare and generally originates from skin melanoma. MM is a neoplasm with an often unpredictable course and metastases can potentially affecting all organs. The occurrence of metastasis in the GB is unusual and has only been exceptionally reported in the literature. We describe a case of an 86-year-old man with an isolated MM metastasis located within the GB presenting with symptoms mimicking acute cholecystitis. Anamnestically, he presented a history of malignant melanoma (Clark level III) resected from his left leg 17 years ago. Furthermore we provide a review of the literature with a focus on diagnostic clues to distinguish between primary versus secondary GB MMs and on the best surgical management that should be used.
2018
- NRASQ61K mutated diffuse leptomeningeal melanomatosis in an adult patient with a brief review of the so-called "forme fruste" of neurocutaneous melanosis
[Articolo su rivista]
Girolami, Ilaria; Cima, Luca; Ghimenton, Claudio; Zannoni, Marina; Mombello, Aldo; Riva, Giulio; Cirielli, Vito; Corradi, Gabriele; Vogrig, Alberto; Di Stefano, Gioia; Novelli, Luca; Gessi, Marco; Eccher, Albino
abstract
Primary melanocytic tumors of central nervous system represent rare tumors arising from melanocytes of the leptomeninges. These neoplasms include focal forms like melanocytoma and primary malignant melanoma and diffuse forms like leptomeningeal melanocytosis and primary leptomeningeal melanomatosis. The clinical diagnosis remains challenging, with clinical and radiologic features overlapping with other more common diseases. Here we present a case of a 38 years old male with primary diffuse leptomeningeal melanomatosis with presence of a NRASQ61K mutation without features of neurocutaneous melanosis.
2018
- Oil Red O Is a Useful Tool to Assess Donor Liver Steatosis on Frozen Sections During Transplantation
[Articolo su rivista]
Riva, G; Villanova, M; Cima, L; Ghimenton, C; Bronzoni, C; Colombari, R; Crestani, M; Sina, S; Brunelli, M; D'Errico, Alessandro; Montin, U; Novelli, L; Eccher, A
abstract
Oil Red O is a useful tool to assess donor liver steatosis on frozen sections during transplantation. Steatosis is a frequent finding in liver evaluation during transplantation, accounting for 9% to 26% of biopsied donor liver. The degree of macrovesicular steatosis is classified as mild, moderate, and severe; the latter is considered an absolute contraindication to liver transplantation because it is associated with poor allograft outcome. Because of the scarcity of organs, there is a debate whether livers with less severe macrovesicular steatosis are still suitable for transplant. Consequently, tools or methods that allow a more accurate intraoperative assessment of steatosis on frozen sections are mandatory. The aim of this study is to improve intraoperative evaluation of steatosis during transplantation using Oil Red O stain on liver biopsies.
2018
- Proximal CD13 Versus Distal GATA-3 Expression in Renal Neoplasia According to WHO 2016 Classification
[Articolo su rivista]
Brunelli, Matteo; Erdini, Francesco; Cima, Luca; Eccher, Albino; Fioravanzo, Adele; Gobbo, Stefano; Segala, Diego; Ghimenton, Claudio; Mazzoleni, Guido; Munari, Enrico; Carella, Rodolfo; Martignoni, Guido
abstract
Little is known about the aminopeptidase CD13 in renal neoplasia according to the new 2016 World Health Organization renal tumor classification. We selected 175 cases, including 79 clear cell, 31 papillary, 24 chromophobe, 8 clear cell papillary renal cell carcinomas (RCCs), 21 oncoytomas, and 12 microphthalmia transcription factor family translocation RCCs: 4 t(6;11)/transcription factor EB (TFEB), 7 t(Xp11) with 2 cystic variants and 1 t(X;17). GATA binding protein 3 (GATA-3) was inserted as control. Expression of proximal antigen CD13 was observed in 63/79 (80%) clear cell, 25/31 (81%) papillary, 3/8 (37%) clear cell papillary, 1/4 (25%) t(6;11)/TFEB, 2/7 (28%) cystic t(Xp11), and in 1/1 t(X;17) RCCs. All chromophobe RCC (0/24) and all oncocytomas (0/21) resulted negative. CD10 was seen in 76/79 (96%) clear cell, 15/31 (48%) papillary, 10/24 (42%) chromophobe, 1/8 (12%) clear cell papillary RCCs, 4/21 (19%) oncocytomas, 1/4 (25%) t(6;11)/TFEB, 2/7 (29%) cystic t(Xp11), and in 1/1 t(X;17) RCCs. GATA-3 was positive in 3/7 (42%) clear cell papillary RCCs and negative in all remaining RCCs, except a single chromophobe RCC and a single oncocytoma. We concluded that: (1) CD13 and GATA-3 immunostains may serve as a diagnostic aid in differentiating subtypes of RCC; (2) CD13 is always absent in chromophobe RCC and oncocytomas, whereas CD10 can be immunoexpressed in both; (3) CD13 should be included in a panel of antibodies to distinguish "proximal renal tumors" from "distal renal tumors" and between clear cell RCC versus microphthalmia transcription factor family translocations RCCs; and (4) when present, GATA-3 is specific for clear cell papillary RCC.
2018
- Pulmonary Adenocarcinoma With Enteric Differentiation: Immunohistochemistry and Molecular Morphology
[Articolo su rivista]
Nottegar, Alessia; Tabbò, Fabrizio; Luchini, Claudio; Brunelli, Matteo; Bria, Emilio; Veronese, Nicola; Santo, Antonio; Cingarlini, Sara; Gilioli, Eliana; Ogliosi, Chiara; Eccher, Albino; Montagna, Licia; Pedron, Serena; Doglioni, Claudio; Cangi, Maria G; Inghirami, Giorgio; Chilosi, Marco
abstract
Pulmonary adenocarcinoma with enteric differentiation (PAED) is a rare subtype of lung adenocarcinoma recently recognized in the WHO classification. It is defined as an adenocarcinoma in which the enteric component exceeds 50% and have to show the expression of at least 1 immunohistochemical marker of enteric differentiation. Although the definition of this tumor type is very important, above all in the differential diagnosis between a primary lung tumor and a metastasis of colorectal adenocarcinoma, this cancer still lacks a distinctive immunohistochemical and molecular signature. We recruited the largest series in the literature of PAEDs according to the morphology and the positivity for intestinal markers. Then, we evaluated the immunohistochemical and molecular profile of these adenocarcinomas. In our series, CDX-2 and CK7 were the immunohistochemical markers mostly expressed by PAEDs. There was an inverse relationship between the expression of pnuemocytes markers, such as TTF-1, and intestinal markers. Molecular analysis revealed KRAS as the most frequently mutated gene (>60% of cases), with very few cases harboring abnormalities affecting EGFR, BRAF, and ALK genes. PAEDs are morphologically very heterogenous. The immunohistochemical profile based on CDX-2 and CK7 positivity of PAEDs appears very robust to support this diagnosis, and it is applicable also on small biopsies. KRAS appears as the most important mutated gene in such tumors.
2018
- Pulmonary Fat Embolism and Coronary Amyloidosis
[Articolo su rivista]
Lever, Veronica; Erdini, Francesco; Ghimenton, Claudio; Novelli, Luca; Brunelli, Matteo; Barbareschi, Mattia; Mazzoleni, Guido; Vermiglio, Elisa; Mantovani, Alessandro; Cima, Luca; Valotto, Giovanni; Eccher, Albino
abstract
BACKGROUND Fat embolism syndrome is a well-known complication in orthopedic and trauma surgery, caused by a massive release of fat into the circulation that can lead to cardiopulmonary insufficiency and multiorgan failure. CASE REPORT We present the case of a 72-year-old man with osteoarthritis who underwent an elective right cementless total hip arthroplasty. Two hours after surgery, the patient lost consciousness and was found hypotensive and with reduced oxygen saturation, with a severe right heart dilatation at echocardiographic evaluation. Death occurred after cardiopulmonary resuscitation attempts. Post-mortem microscopic examination revealed that the final cause of death was pulmonary fat embolism associated with coronary amyloidosis and atherosclerosis. CONCLUSIONS This case called our attention on the sudden onset of fat embolism syndrome after arthroplasty and the insidious nature of amyloidosis infiltrative disease. The autopsy findings substantially aided understanding the immediate cause of death.
2018
- Surgical Treatment of Symptomatic Aortic Aneurysm in a Patient with Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis: Case Report and Review of the Literature
[Articolo su rivista]
Veraldi Gian, Franco; Mezzetto, Luca; Scorsone, Lorenzo; Sacco, Michele; Eccher, Albino; Idolazzi, Luca
abstract
Vasculitis is an heterogeneous group of syndromes, which shares inflammation of blood vessel wall as the main feature. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a necrotizing vasculitis, with few or no immune deposits, predominantly affecting small vessels (i.e., capillaries, venules, arterioles, and small arteries), associated with ANCAs specific for myeloperoxidase or proteinase 3. Clinical manifestations may be heterogeneous but an involvement of lungs and kidneys frequently occurs. AAV of large vessels is a very rare condition whose standard therapy is medical approach. Surgical revascularization has been described in selected patients after medical failure or in emergent settings. We report the case of a patient affected by symptomatic infrarenal aortic aneurysm related to AAV, who underwent in-situ reconstruction by means of cryopreserved homograft.
2018
- Validation of Remote Digital Frozen Sections for Cancer and Transplant Intraoperative Services
[Articolo su rivista]
Cima, Luca; Brunelli, Matteo; Parwani, Anil; Girolami, Ilaria; Ciangherotti, Andrea; Riva, Giulio; Novelli, Luca; Vanzo, Francesca; Sorio, Alessandro; Cirielli, Vito; Barbareschi, Mattia; D'Errico, Antonietta; Scarpa, Aldo; Bovo, Chiara; Fraggetta, Filippo; Pantanowitz, Liron; Eccher, Albino
abstract
Whole-slide imaging (WSI) technology can be used for primary diagnosis and consultation, including intraoperative (IO) frozen section (FS). We aimed to implement and validate a digital system for the FS evaluation of cancer and transplant specimens following recommendations of the College of American Pathologists.
2018
- Virtual Autopsy as a Screening Test Before Traditional Autopsy: The Verona Experience on 25 Cases
[Articolo su rivista]
Cirielli, Vito; Cima, Luca; Bortolotti, Federica; Narayanasamy, Murali; Scarpelli, Maria Pia; Danzi, Olivia; Brunelli, Matteo; Eccher, Albino; Vanzo, Francesca; Ambrosetti, Maria Chiara; El-Dalati, Ghassan; Vanezis, Peter; De Leo, Domenico; Tagliaro, Franco
abstract
Interest has grown into the use of multidetector computed tomography (CT) and magnetic resonance imaging as an adjunct or alternative to the invasive autopsy. We sought to investigate these possibilities in postmortem CT scan using an innovative virtual autopsy approach.
2017
- ALK gene copy number in lung cancer: Unspecific polyploidy versus specific amplification visible as double minutes
[Articolo su rivista]
Calio', Anna; Bria, Emilio; Pilotto, Sara; Gilioli, Eliana; Nottegar, Alessia; Eccher, Albino; Cima, Luca; Santo, Antonio; Pedron, Serena; Turri, Giona; Knuutila, Sakari; Chilosi, Marco; Vanzo, Francesca; Bogina, Giuseppe; Terzi, Alberto; Tortora, Giampaolo; Scarpa, Aldo; Loda, Massimo; Martignoni, Guido; Brunelli, Matteo
abstract
Gains of a gene due to DNA polyploidy versus amplification of the specific locus are distinct molecular alterations in tumors.
2017
- Cathepsin K expression in castration-resistant prostate carcinoma: a therapeutical target for patients at risk for bone metastases
[Articolo su rivista]
Munari, Enrico; Cima, Luca; Massari, Francesco; Bertoldo, Francesco; Porcaro, Antonio Benito; Caliò, Anna; Riva, Giulio; Ciocchetta, Elisa; Ciccarese, Chiara; Modena, Alessandra; Iacovelli, Roberto; Sava, Teodoro; Eccher, Albino; Ghimenton, Claudio; Tortora, Giampaolo; Artibani, Walter; Novella, Giovanni; Bogina, Giuseppe; Zamboni, Giuseppe; Sanguedolce, Francesca; D'Amuri, Alessandro; Martignoni, Guido; Brunelli, Matteo
abstract
Background: The lysosomal cysteine protease cathepsin K is involved in bone remodeling and is also expressed in the peritumoral stroma of carcinomas arising from different organs. A new generation of cathepsin K inhibitors blocking the RANKL/RANK pathway are being developed. We sought to investigate cathepsin K expression in a cohort of castration-resistant prostate carcinomas. Methods: Sixteen cases of castration-resistant disease with at least 5 years of follow-up were selected from a cohort of 280 patients who underwent surgery. Cathepsin K was evaluated on formalin-fixed and paraffin-embedded tissue microarrays with 5 tissue spots per case. These were scored as high 2+ (>= 30% of cells), low 1+ (<30% of cells) or zero (absence), distinguishing tumor cells and peritumoral stroma cells. Low (1+) and absence (0) of scoring were interpreted as negative, and high (2+) as positive. Results: The castration-resistant group was composed of 15 acinar adenocarcinomas and 1 neuroendocrine carcinoma, and all showed at least Gleason score 8 at prostatectomy. Two out of 16 cases (12%) scored positive for cathepsin K in tumor cells; and 5 of 16 cases (31%) scored positive in peritumoral stroma cells. The neuroendocrine and acinar subtypes of carcinoma with positive immunoexpression in neoplastic cells developed bone metastases after 4 and 5 years, respectively, and subsequently died. Conclusions: Patients affected by castration-resistant prostate carcinoma may be tested for cathepsin K, and a positive strong expression (2+) could be a useful predictive biomarker of response to targeted agents, aiding in the selection of patients eligible for these treatments.
2017
- Fast Chromotrope Aniline Blue Special Stain Is a Useful Tool to Assess Fibrosis on Liver Biopsy During Transplantation
[Articolo su rivista]
Cima, L; Riva, G; D'Errico, A; CASARTELLI LIVIERO, Marilena; Capelli, Paola; Tomezzoli, Anna; Montin, U; Carraro, A; Scarpa, Aldo; Ghimenton, Claudio; Colombari, Romano; Brunelli, Matteo; Eccher, Albino
abstract
Assessment of potential liver allograft donors with frozen sections has clinical relevant consequences for the transplant recipient. Several clinical risk factors have been identified that increase the risk of transplantation failure and it is critical for the pathologist to become familiar with the histologic criteria for donor liver suitability. In this setting an accurate and reliable assessment of fibrosis is crucial. We sought to report the value of the rapid chromotrope aniline blue stain (CAB) in a transplantation clinical work-flow for scoring liver fibrosis.
2017
- Next-generation repeat-free FISH probes for DNA amplification in glioblastoma in vivo: Improving patient selection to MDM2-targeted inhibitors
[Articolo su rivista]
Brunelli, Matteo; Eccher, Albino; Cima, Luca; Trippini, Tobia; Pedron, Serena; Chilosi, Marco; Barbareschi, Mattia; Scarpa, Aldo; Pinna, Giampietro; Cabrini, Giulio; Pilotto, Sara; Carbognin, Luisa; Bria, Emilio; Tortora, Giampaolo; Fioravanzo, Adele; Schiavo, Nicola; Meglio, Mario; Sava, Teodoro; Belli, Laura; Martignoni, Guido; Ghimenton, Claudio
abstract
A next-generation FISH probe mapping to the MDM2 locus-specific region has recently been designed. The level of MDM2 gene amplification (high versus low) may allow selection of patients for cancer treatment with MDM2 inhibitors and may predict their responsiveness. We investigated the spectrum of MDM2 gene alterations using the new probes in vivo after visualizing single neoplastic cells in situ from a series of glioblastomas. Signals from next-generation repeat-free FISH interphase probes were identified in tissue microarrays that included 3 spots for each of the 48 cases. The murine double minutes (MDM2)-specific DNA probe and the satellite enumeration probe for chromosome 12 were used. Three cases (6%) showed more than 25 signals (high gene amplification), and 7 (15%) showed 3-10 signals (gains); among these, 4 cases (8%) had an equal number of MDM2 and centromeric signals on chromosome 12 (polyploidy). Genomic heterogeneity was observed only in 3 cases with low gene amplification. In our series, 6% of glioblastomas exhibited high MDM2 amplification (in vivo) with a pattern related to the known double minutes/chromothripsis phenomenon (in situ), and only cases with low amplification showed genomic heterogeneity. We concluded that the rate of MDM2 gene amplification can be a useful predictive biomarker to improve patient selection.
2017
- Primary cutaneous B-cell lymphoma and chronic leg ulcers in a patient with type 2 diabetes
[Articolo su rivista]
Mantovani, Alessandro; Perrone, Fabrizia; Stoico, Vincenzo; Pichiri, Isabella; Salvotelli, Laura; Teobaldi, Ilaria; Bruti, Massimiliano; Conti, Michela; Cima, Luca; Eccher, Albino; Bonora, Enzo
abstract
The incidences of type 2 diabetes mellitus and many cancers are rapidly increasing worldwide. Diabetes is a strong risk factor for some cancers (including lymphomas) and is also associated with adverse cancer outcomes. After gastrointestinal tract, the skin is the second most frequent extranodal site involved by non-Hodgkin lymphomas and the cutaneous B-cell lymphomas (CBCLs) range from 25% to 30% of all primary cutaneous lymphomas. The primary cutaneous diffuse large B-cell lymphoma (PCDLBCL) is an aggressive lymphoma with a poor prognosis, representing roughly 20% of all primary CBCLs. Classically, the cutaneous manifestation of this lymphoma is a red or violaceous tumors arising on a leg. To date, despite the large body of evidence suggesting that diabetes is strongly associated with an increased risk of some cancers, very little information is available regarding a possible association between type 2 diabetes and primary cutaneous diffuse large B-cell lymphoma. In this report, we will present the case of a white adult patient with type 2 diabetes with chronic leg ulcers complicated by a primary cutaneous diffuse large B-cell lymphoma.
2017
- Rapid screening for malignancy in organ donors. 15 years experience with the Verona "Alert" protocol and review of the literature
[Articolo su rivista]
Eccher, Albino; Cima, Luca; Ciangherotti, Andrea; Montin, Umberto; Violi, Paola; Carraro, Amedeo; Tedeschi, Umberto; Nacchia, Francesco; Fior, Francesca; Rostand, Momo; Boschiero, Luigino; D'Errico, Antonietta; Scarpa, Aldo; CASARTELLI LIVIERO, Marilena; Ferrari, Giuseppe; Rodini, Viviana; Tomaselli, Elisabetta; Zampicinini, Laura; Vanzo, Francesca; Bovo, Chiara; Feltrin, Giuseppe; Neil, Desley; Brunelli, Matteo
abstract
Prevention of transmission of malignancy from donors to recipients is an aim of donor assessment. We report the most stringent interpretation of the Italian National Guidelines.
2017
- Reprofiling Metastatic Samples for Chromosome 9p and 14q Aberrations as a Strategy to Overcome Tumor Heterogeneity in Clear-cell Renal Cell Carcinoma
[Articolo su rivista]
Massari, Francesco; Ciccarese, Chiara; Bria, Emilio; Porta, Camillo; LA RUSSA, Francesca; Knuutila, Sakari; Artibani, Walter; Porcaro, Antonio Benito; Bimbatti, Davide; Modena, Alessandra; Sava, Teodoro; Tortora, Giampaolo; Cheng, Liang; Eccher, Albino; Cima, Luca; Pedron, Serena; Ghimenton, Claudio; Martignoni, Guido; Brunelli, Matteo
abstract
Losses of chromosomes 9p and 14q are associated with worse outcomes in patients affected by clear-cell renal cell carcinoma (RCC) and are helpful for prognostic risk stratification. Both chromosomal loci harbor several hot-spot molecular pathways suitable for targeted therapeutic interventions. Intratumor heterogeneity may foster tumor adaptation and therapeutic failure. We sought to investigate the presence of losses of the hot spots of chromosomal loci 9p and 14q in primary clear-cell RCC and matched metastatic tissues. CD10 and CD13 were performed on 7 cases of clear-cell RCC with hematogenous tissue metastases. Cytogenetic fluorescence in situ hybridization analysis was performed on primary and matched metastatic tissues using specific probes mapping the 9p and the 14q loci. The loss of chromosome 9p was observed in 85% of both primary clear-cell RCCs and in matched metastases; 14% showed discordance between primary and matched metastases showing gains. The loss of chromosome 14q was observed in 58% of both primary and matched metastases. Only 3/7 (42%) did show an equal status of loss of chromosome 14q. Heterogeneity of the cytogenetic status between metastatic and primary clear-cell RCCs is observed for the loss of chromosome 14q rather than chromosome 9p. The impact of chromosome 14q cytogenetic status, harboring the HIF1 gene, a major driver for the angiogenenic switch, may drive the efficacy of targeted inhibitors, whereas the loss of chromosome 9p, harboring other hot-spot genes, seems to be related to the metastatic behavior per se, without cytogenetic modulation. Reprofiling the metastatic tissue, as compared with the primary tumor, in patients affected by metastatic RCC could be a novel approach to overcome resistance to VEGF(Rs)-targeting agents.
2016
- De Novo Renal Neoplasia After Kidney Transplantation According to New 2016 WHO Classification of Renal Tumors
[Articolo su rivista]
Eccher, Albino; Boschiero, Luigino; Delahunt, Brett; Cima, Luca; Fior, Francesca; Nacchia, Francesco; Rostand, Momo; Carraro, Amedeo; Tedeschi, Umberto; Zaza, Gianluigi; CASARTELLI LIVIERO, Marilena; Zampicinini, Laura; Chilosi, Marco; Feltrin, Giuseppe; Rago, Claudio; D'Errico, Antonietta; Ghimenton, Claudio; Martignoni, Guido; Brunelli, Matteo
abstract
BACKGROUND De novo renal neoplasia developing after kidney transplantation at Verona Kidney Transplant Center were reviewed according to new 2016 WHO Renal Tumor Classification. MATERIAL AND METHODS Primary renal tumors developed in native or transplanted kidneys de novo following renal transplantation were retrieved and histologically reviewed by three expert uropathologists. Immunoexpression of the diagnostic antigens CD13, CD10, CK7, CK34bE12, AMACR, CAIX, AE1/AE3, CK14, GATA-3, HMB-45, cathepsin-k, S100A1, and parvalbumin was assessed. Predictive antigens ph-mTOR and ph-p70S6k were also tested. RESULTS Two thousands and sixteen kidney transplantations have been carried out from 1968-2015. Follow-up was available per 1,646 patients (mean 8.4 years). We observed 16 cases of de novo renal neoplasia arising in patients 16 to 286 months post-transplantation. Nine clear cell, two papillary RCCs and a single case of the new WHO entity denominated "acquired cystic disease-associated RCC" were identified in native kidneys. Another new WHO tumor entity called "clear cell papillary RCC" was diagnosed and a new variant of papillary RCC with diffuse clear cytoplasm was also identified. The majority of tumors were low stage and low grade according to the new ISUP grading system. Seven patients were additionally treated with mTOR inhibitors. Post-cancer follow-up ranged from 62 to 281 months. One patient showed a recurrence (a lung metastases) and died. Of the remaining patients, three died of non-cancer-related causes. CONCLUSIONS The application of the new WHO 2016 classification has importance as it identifies new (18% of tumors) morphotypes that are likely to behave in a less aggressive fashion.
2016
- Digital reporting of whole-slide images is safe and suitable for assessing organ quality in preimplantation renal biopsies
[Articolo su rivista]
Eccher, Albino; Neil, Desley; Ciangherotti, Andrea; Cima, Luca; Boschiero, Luigino; Martignoni, Guido; Ghimenton, Claudio; Chilosi, Marco; Giobelli, Luca; Zampicinini, Laura; Casartelli, Marilena; Brunelli, Matteo
abstract
Digital pathology allows networks of "remote" specialist pathologists to report the findings of preimplantation kidney biopsies. We sought to validate the assessment of preimplantation kidney transplant biopsies for diagnostic purposes using whole-slide images according to the recommendations of the College of American Pathologists. Sixty-two consecutive, previously reported, preimplantation kidney biopsies were scanned using the ScanScope Digital Slide Scanner at 0.5 μm/pixel (20× objective). The slides were assessed for percent glomerulosclerosis, tubular atrophy, interstitial fibrosis and vascular narrowing using the Remuzzi criteria by two pathologists, one using glass slides and the other using the whole-slide images viewed on a widescreen computer monitor. After a 2-week washout period, all of the slides were re-assessed by the same pathologists using the opposite mode of reporting to that used in the first evaluation. Very high glass-digital intraobserver concordance was achieved for the overall score and for individual grades by both pathologists (κ range, 0.841-0.973). The overall scores obtained by both pathologists and using both methods were identical. The times needed to assess the biopsies were 14 minutes when using a light microscope and 18 minutes, including scanning time, which averaged 2 minutes 20 seconds per slide, when using digital microscopy. Digital microscopy is a reliable, fast, and safe method for the assessment of preimplantation kidney biopsies.
2016
- LC3B and ph-S6K are both expressed in epithelioid and classic renal angiomyolipoma: a rationale tissue-based evidence for combining use of autophagic and mTOR targeted drugs
[Articolo su rivista]
Fiorini, Claudia; Brunelli, Matteo; Cima, Luca; Eccher, Albino; Boschiero, Luigino; Carraro, Amedeo; Zaza, Gianluigi; Artibani, Walter; Porcaro, Antonio Benito; Cacciamani, Giovanni; Tedeschi, U; Montin, U; Violi, P; Ghimenton, Claudio; Burato, Giulia; Iacovelli, Roberto; Pedron, Serena; Chilosi, Marco; Martignoni, Guido
abstract
Background: Targeted drugs to the autophagy processes are emerging in clinical trials. The aim of this work is to assess the magnitude of autophagic expression in renal angiomyolipoma. Methods: Fourteen cases of renal angiomyolipoma were recruited. Anti-LC3B-II and anti-phospho-S6K were detected by Western blot analysis. For immunohistochemical staining, sections were stained with the antibodies LC3B-II and cathepsin-K. LC3B-II was also analyzed by immunofluorescence. We have also carried out electron microscopy analysis on tumor cells. Results: 13 classic and 1 epithelioid renal angiomyolipoma were recruited. The Western-blot LC3B-II analysis shows increasing in protein expression in all cases, however quantitative protein expression ranged from 1 to 15 (mean 5). The autophagosome protein LC3B-I also significantly increased in all tumor extraction. The expression of LC3B-II protein was confirmed in tumoral samples by immunofluorescence. The lysosomal marker cathepsin-K was observed by immunohistochemistry on all tumours. The Western-blot ph-S6K analysis showed significant protein overexpression along all cases after evaluation of the quantitative S6K/Ponceaus ratio. In 6/14 (52%) the expression was high, with a quantitative increase of ≥3 fold induction in 4 angiomyolipoma compared to normal tissue. At electron microscopy, cancer cells evidenced round or oval electron-dense granules associated with membranes and granules with double membrane. Conclusion: Both autophagic LC3B-II and ph-S6K molecules are over-represented in both epithelioid and classic renal angiomyolipoma and a combined use of inhibitors to the autophagic and mTOR processes may be designed in clinical trials, when enrolling patients affected by tumours in tuberous sclerosis or angiomyolipoma at risk of bledding.
2016
- Magnitude of PD-1, PD-L1 and T Lymphocyte Expression on Tissue from Castration-Resistant Prostate Adenocarcinoma: An Exploratory Analysis
[Articolo su rivista]
Massari, Francesco; Ciccarese, Chiara; Calio', Anna; Munari, Enrico; Cima, Luca; Porcaro, Antonio Benito; Novella, Giovanni; Artibani, Walter; Sava, Teodoro; Eccher, Albino; Ghimenton, Claudio; Bertoldo, Francesco; Scarpa, Aldo; Sperandio, Nicola; Porta, Camillo; Bronte, Vincenzo; Chilosi, Marco; Bogina, Giuseppe; Zamboni, Giuseppe; Tortora, Giampaolo; Samaratunga, Hemamali; Martignoni, Guido; Brunelli, Matteo
abstract
Background and Aim Recent therapeutic strategies for castration-resistant prostate cancer have focused on immunomodulation, especially the PD-1/PD-L1 pathway related to tumor-infiltrating lymphocytes. Few cases of castration-resistant prostate adenocarcinoma have been tested simultaneously for PD-1, PD-L1 and T lymphocytes in cancerous tissue. We quantified the PD-1/PDL1 immune pathway and T lymphocyte infiltrates in a series of patients with castrate-resistant prostate adenocarcinoma. Patients and Methods Expression of PD-1, PD-L1, CD3 and FOXP3 was identified in tissue microarrays, with five tissue spots per patient from 16 patients over at least 5 years of follow-up. Two scores were defined. The first described the percentage of PD-1-positive T lymphocytes (CD3+): negative (0), < 5 %; low (1+), 5-30 %; high (2+), > 30 %. The second described PD-L1 staining intensity: 0 (no signal), 1+ (light signal), 2+ (high signal) in > 50 % of neoplastic cells. Results Tumor-infiltrating T lymphocytes (CD3+) were seen in 11/16 cases (69 %). Nine of 16 cases expressed PD-1 (56 %), among which 19 % were scored 2+. Eight of 16 cases expressed PD-L1 (50 %), with 19 % scored as strong 2+. The subgroup with high PD1/PD-L1 also exhibited FOXP3 expression. Conclusions Approximately 19 % of patients in our series showed simultaneous high PD-1/PD-L1 immunoscores, and were the best candidates for receiving targeted anti-PD-1/PDL1 immunotherapy, as determined using a tissue based rationale.
2016
- miRNA array screening reveals cooperative MGMT-regulation between miR-181d-5p and miR-409-3p in glioblastoma
[Articolo su rivista]
Khalil, Susanna; Fabbri, Enrica; Santangelo, Alessandra; Bezzerri, Valentino; Cantù, Cinzia; DI GENNARO, Gianfranco; Finotti, Alessia; Ghimenton, Claudio; Eccher, Albino; Dechecchi, Maria; Scarpa, Aldo; Hirshman, Brian; Chen, Clark; Ferracin, Manuela; Negrini, Massimo; Gambari, Roberto; Cabrini, Giulio
abstract
The levels of expression of O6-methylguanine-DNA methyltransferase (MGMT) are relevant in predicting the response to the alkylating chemotherapy in patients affected by glioblastoma. MGMT promoter methylation and the published MGMT regulating microRNAs (miRNAs) do not completely explain the expression pattern of MGMT in clinical glioblastoma specimens. Here we used a genome-wide microarray-based approach to identify MGMT regulating miRNAs. Our screen unveiled three novel MGMT regulating miRNAs, miR-127-3p, miR-409-3p, and miR-124-3p, in addition to the previously identified miR-181d-5p. Transfection of these three novel miRNAs into the T98G glioblastoma cell line suppressed MGMT mRNA and protein expression. However, their MGMT- suppressive effects are 30-50% relative that seen with miR-181d-5p transfection. In silico analyses of The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) revealed that miR-181d-5p is the only miRNA that consistently exhibited inverse correlation with MGMT mRNA expression. However, statistical models incorporating both miR-181d-5p and miR-409-3p expression better predict MGMT expression relative to models involving either miRNA alone. Our results confirmed miR-181d-5p as the key MGMT-regulating miRNA. Other MGMT regulating miRNAs, including the miR-409-3p identified in this report, modify the effect of miR-181d-5p on MGMT expression. MGMT expression is, thus, regulated by cooperative interaction between key MGMT-regulating miRNAs.
2015
- Monosomy of chromosome 17 in breast cancer during interpretation of HER2 gene amplification
[Articolo su rivista]
Brunelli, Matteo; Nottegar, Alessia; Bogina, Giuseppe; Calio', Anna; Cima, Luca; Eccher, Albino; Vicentini, Caterina; Marcolini, Lisa; Scarpa, Aldo; Pedron, Serena; Brunello, Eleonora; Knuutila, Sakari; Sapino, Anna; Marchiò, Caterina; Bria, Emilio; Molino, Annamaria; Carbognin, Luisa; Tortora, Giampaolo; Jasani, Bharat; Miller, Keith; Merdol, Ibrahim; Zanatta, Lucia; Laurino, Licia; Wirtanen, Tiina; Zamboni, Giuseppe; Marconi, Marcella; Chilosi, Marco; Manfrin, Erminia; Martignoni, Guido; Bonetti, Franco
abstract
Monosomy of chromosome 17 may affect the assessment of HER2 amplification. Notably, the prevalence ranges from 1% up to 49% due to lack of consensus in recognition. We sought to investigate the impact of monosomy of chromosome 17 to interpretation of HER2 gene status. 201 breast carcinoma were reviewed for HER2 gene amplification and chromosome 17 status. FISH analysis was performed by using double probes (LSI/CEP). Absolute gene copy number was also scored per each probe. HER2 FISH test was repeated on serial tissue sections, ranging in thickness from 3 to 20 µm. Ratio was scored and subsequently corrected by monosomy after gold control test using the aCGH method to overcome false interpretation due to artefactual nuclear truncation. HER2 immunotests was performed on all cases. 26/201 cases were amplified (13%). Single signals per CEP17 were revealed in 7/201 (3.5%) cases. Five out of 7 cases appeared monosomic with aCGH (overall, 5/201, 2.5%) and evidenced single signals in >60% of nuclei after second-look on FISH when matching both techniques. Among 5, one case showed amplification with a pattern 7/1 (HER2/CEP17>2) of copies (3+ at immunotest); three cases revealed single signals per both probes (LSI/CEP=1) and one case revealed a 3:1 ratio; all last 4 cases showed 0/1+ immunoscore. We concluded that: 1) monosomy of chromosome 17 may be observed in 2.5% of breast carcinoma; 2) monosomy of chromosome 17 due to biological reasons rather than nuclear truncation was observed when using the cut-off of 60% of nuclei harboring single signals; 3) the skewing of the ratio due to single centromeric 17 probe may lead to false positive evaluation; 4) breast carcinomas showing a 3:1 ratio (HER2/CEP17) usually show negative 0/1+ immunoscore and <6 gene copy number at FISH.
2015
- Regulation of IL-8 gene expression in gliomas by microRNA miR-93
[Articolo su rivista]
Fabbri, Enrica; Brognara, Eleonora; Montagner, Giulia; Ghimenton, Claudio; Eccher, Albino; Cantù, Cinzia; Khalil, Susanna; Bezzerri, Valentino; Provezza, Lisa; Bianchi, Nicoletta; Finotti, Alessia; Borgatti, Monica; Moretto, Giuseppe; Chilosi, Marco; Cabrini, Giulio; Gambari, Roberto
abstract
Different strategies have been proposed to target neoangiogenesis in gliomas, besides those targeting Vascular Endothelial Growth Factor (VEGF). The chemokine Interleukin-8 (IL-8) has been shown to possess both tumorigenic and proangiogenic properties. Although different pathways of induction of IL-8 gene expression have been already elucidated, few data are available on its post-transcriptional regulation in gliomas.
2014
- ALK/EML4 Fusion Gene May Be Found in Pure Squamous Carcinoma of the Lung
[Articolo su rivista]
Caliò, A; Nottegar, Alessia; Gilioli, Eliana; Bria, Emilio; Pilotto, Sara; Peretti, U; Kinspergher, S; Simionato, F; Pedron, Serena; Knuutila, S; Tortora, Giampaolo; Eccher, Albino; Santo, A; Tondulli, L; Inghirami, G; Tabbò, F; Martignoni, Guido; Chilosi, Marco; Scarpa, Aldo; Brunelli, Matteo
abstract
INTRODUCTION:The report of cases of lung squamous cell cancers harboring anaplastic lymphoma kinase (ALK) gene rearrangements raises the question whether this histologic subtype should be also evaluated for such molecular predictive test.METHODS:A consecutive series of 40 lung pure squamous cell carcinomas were analyzed for ALK gene status by fluorescence in situ hybridization. Squamous differentiation was validated using an immunohistochemical panel including n-p63 (p40), cytokeratin (CK) 5/6, sex-determining region Y (SRY)-Box2 (SOX2), thyroid transcription factor 1, CK7, and Napsin-A.RESULTS:Squamous differentiation was confirmed in all tumors as they stained positive for n-p63 and CK5/6 and negative for thyroid transcription factor 1 and Napsin-A. One of 40 cases (2.5%) showed an ALK rearrangement on fluorescence in situ hybridization analysis.CONCLUSIONS:ALK translocation may be found in lung pure squamous cell carcinomas. Our data suggest the opportunity to test ALK rearrangements on biopsy samples harboring squamous cell cancer differentiation.
2014
- Donor kidneys with miliary papillary renal cell neoplasia: the role of the pathologist in determining suitability for transplantation
[Articolo su rivista]
Eccher, Albino; Boschiero, L; Fior, F; Casartelli Liviero, M; Zampicini, L; Ghimenton, Claudio; D'Errico Grigioni, A; Caliò, A; Martignoni, Guido; Delahunt, B; Brunelli, Matteo
abstract
BACKGROUND:
Kidneys with single or multiple tumors, provided that they have histological features recognized as being associated with low risk of recurrence, are considered suitable for transplantation. It is known that kidneys with multiple primary renal tumors show poor renal function and that function dramatically declines when tumors have a miliary configuration. Despite this, no guidelines are in place to differentiate between multifocal tumors and those that are miliary in nature.
CASE REPORT:
We report a case in which initial examination revealed papillary renal cell neoplasia in deceased donor kidneys, which were later confirmed on histological and genetic testing to be multiple and miliary in distribution. Gross examination showed closely opposed neoplasms, and on histological examination these were found to be papillary renal cell carcinomas and renal papillary adenomas. This ultimately led to the decision that both kidneys were unsuitable for transplantation.
CONCLUSIONS:
At present there are no recommendations as to how tumor-bearing donor kidneys should be handled in order to determine if miliary neoplasia is present. From our case it is apparent that, in addition to obvious tumor nodules, at least 3 samples of cortex should be examined. This case highlights the important role of the pathologist in assessing donor kidneys with evidence of neoplasia.
2014
- Pediatric optic nerve sheath meningioma
[Articolo su rivista]
Beccari, Serena; Cima, Luca; Posenato, Ilaria; Sala, Francesco; Ghimenton, Claudio; Brunelli, Matteo; Eccher, Albino
abstract
No abstract available
2014
- Uptake by human glioma cell lines and biological effects of a peptide-nucleic acids targeting miR-221
[Articolo su rivista]
Brognara, E; Fabbri, E; Bazzoli, Elena; Montagner, G; Ghimenton, Claudio; Eccher, Albino; Cantù, C; Manicardi, A; Bianchi, N; Finotti, A; Breveglieri, G; Borgatti, M; Corradini, R; Bezzerri, Valentino; Cabrini, Giulio; Gambari, R.
abstract
MicroRNAs are a family of small noncoding RNAs regulating gene expression by sequence-selective mRNA targeting, leading to a translational repression or mRNA degradation. The oncomiR miR-221 is highly expressed in human gliomas, as confirmed in this study in samples of low and high grade gliomas, as well in the cell lines U251, U373 and T98G. In order to alter the biological functions of miR-221, a peptide nucleic acid targeting miR-221 (R8-PNA-a221) was produced, bearing a oligoarginine peptide (R8) to facilitate uptake by glioma cells. The effects of R8-PNA-a221 were analyzed in U251, U373 and T98G glioma cells and found to strongly inhibit miR-221. In addition, the effects of R8-PNA-a221 on p27(Kip1) (a target of miR-221) were analyzed in U251 and T98G cells by RT-qPCR and by Western blotting. No change of p27(Kip1) mRNA content occurs in U251 cells in the presence of PNA-a221 (lacking the R8 peptide), whereas significant increase of p27(Kip1) mRNA was observed with the R8-PNA-a221. These data were confirmed by Western blot assay. A clear increment of p27(Kip1) protein expression in the samples treated with R8-PNA-a221 was detected. In addition, R8-PNA-a221 was found able to increase TIMP3 expression (another target of miR-221) in T98G cells. These results suggest that PNAs against oncomiRNA miR-221 might be proposed for experimental treatment of human gliomas.
2014
- iPathology cockpit diagnostic station: validation according to College of American Pathologists Pathology and Laboratory Quality Center recommendation at the Hospital Trust and University of Verona
[Articolo su rivista]
Brunelli, Matteo; Beccari, Serena; Colombari, R; Gobbo, S; Giobelli, L; Pellegrini, A; Chilosi, Marco; Lunardi, M; Martignoni, Guido; Scarpa, Aldo; Eccher, Albino
abstract
BACKGROUND:
Validation of digital whole slide images is crucial to ensure that diagnostic performance is at least equivalent to that of glass slides and light microscopy. The College of American Pathologists Pathology and Laboratory Quality Center recently developed recommendations for internal digital pathology system validation. Following these guidelines we sought to validate the performance of a digital approach for routine diagnosis by using an iPad and digital control widescreen-assisted workstation through a pilot study.
METHODS:
From January 2014, 61 histopathological slides were scanned by ScanScope Digital Slides Scanner (Aperio, Vista, CA). Two independent pathologists performed diagnosis on virtual slides in front of a widescreen by using two computer devices (ImageScope viewing software) located to different Health Institutions (AOUI Verona) connected by local network and a remote image server using an iPad tablet (Aperio, Vista, CA), after uploading the Citrix receiver for iPad. Quality indicators related to image characters and work-flow of the e-health cockpit enterprise system were scored based on subjective (high vs poor) perception. The images were re-evaluated two weeks apart.
RESULTS:
The whole glass slides encountered 10 liver: hepatocarcinoma, 10 renal carcinoma, 10 gastric carcinoma and 10 prostate biopsies: adenocarcinoma, 5 excisional skin biopsies: melanoma, 5 lymph-nodes: lymphoma. 6 immuno- and 5 special stains were available for intra- and internet remote viewing. Scan times averaged two minutes and 54 seconds per slide (standard deviation 2 minutes 34 seconds). Megabytes ranged from 256 to 680 (mean 390) per slide storage. Reliance on glass slide, image quality (resolution and color fidelity), slide navigation time, simultaneous viewers in geographically remote locations were considered of high performance score. Side by side comparisons between diagnosis performed on tissue glass slides versus widescreen were excellent showing an almost perfect concordance (0.81, kappa index).
CONCLUSIONS:
We validated our institutional digital pathology system for routine diagnostic facing with whole slide images in a cockpit enterprise digital system or iPad tablet. Computer widescreens are better for diagnosing scanned glass slide that iPad. For urgent requests, iPad may be used. Legal aspects have to be soon faced with to permit the clinical use of this technology in a manner that does not compromise patient care.
2013
- Application of 2D-DIGE to formalin-fixed diseased tissue samples from hospital repositories: results from four case studies
[Articolo su rivista]
Tanca, A; Pisanu, S; Biosa, G; Pagnozzi, D; Antuofermo, E; Burrai, Gp; Canzonieri, V; Cossu Rocca, P; De Re, V; Eccher, Albino; Fanciulli, G; Rocca, S; Uzzau, S; Addis, Mf
abstract
PURPOSE:
In the recent past, the potential suitability of fixed samples to 2-D DIGE studies has been demonstrated on model tissues, but not on "real-world" archival tissues. Therefore, this study was aimed to assess the quality of the results delivered by 2-D DIGE on samples retrieved from hospital tissue repositories.
EXPERIMENTAL DESIGN:
Diseased and normal tissue samples (namely, human gastric adenocarcinoma and normal gastric tissue, human lung neuroendocrine tumors, canine mammary tubulo-papillary carcinoma and normal mammary tissue, sheep liver with cloudy swelling degeneration and normal liver tissue) were retrieved from human and veterinary biorepositories and subjected to full-length protein extraction, cyanine labeling, 2-D DIGE separation, image analysis, MS analysis, and protein identification.
RESULTS:
Archival samples could be successfully subjected to 2-D DIGE, providing maps of satisfactory resolution, although with varying pattern complexity (possibly influenced by pre-analytical variables). Moreover, differentially expressed protein identities were consistent with the disease biology.
CONCLUSIONS AND CLINICAL RELEVANCE:
2-D DIGE can support biomarker discovery and validation studies on large sample cohorts. In fact, although some information complexity is lost when compared to fresh-frozen tissues, their vast availability and the associated patient information can considerably boost studies suffering limited sample availability or involving long-distance exchange of samples.
2012
- Oncocytic papillary renal cell carcinoma: potential pitfall in small enucleation
[Articolo su rivista]
Munari, E; Eccher, Albino; Segala, D; Iannucci, Antonio; Gobbo, S; Chilosi, Marco; Brunelli, Matteo; Martignoni, Guido
abstract
OBJECTIVE:
We describe an emerging entity, recently recognized as a pitfall in the diagnostic practice among eosinophilic renal cell tumours.
METHODS:
A 60-year-old male underwent enucleation of a 1.2 cm nodule. Immunohistochemistry and FISH analysis were performed.
RESULTS:
Histology revealed a neoplasm composed of large cells with eosinophilic cytoplasm, Fuhrman grade 3, arranged in papillae. At the immunohistochemical level, cells showed positivity for AMACR and CD10. Fluorescence in situ hybridization (FISH) demonstrated gains of chromosomes 7 and 17 and loss of Y. A diagnosis of oncocytic papillary renal cell carcinoma was made.
CONCLUSIONS:
The distinction between renal oncocytoma and oncocytic papillary renal cell carcinoma is of substantial importance because of their different behaviour and prognosis, since the latter has malignant potential. Although the available evidence supporting tumour enucleation as the surgical treatment for renal cortical tumours < or = 4 cm, due to aforementioned clinicopathological features such tumours need to be evaluated using appropriate immunophenotypical and cytogenetic analyses.
2012
- True 3q Chromosomal Amplification in Squamous Cell Lung Carcinoma by FISH and aCGH Molecular Analysis: Impact on Targeted Drugs
[Articolo su rivista]
Brunelli, Matteo; Bria, Emilio; Nottegar, Alessia; Cingarlini, S; Simionato, F; Caliò, A; Eccher, Albino; Parolini, C; Iannucci, Antonio; Gilioli, Eliana; Pedron, Serena; Massari, F; Tortora, Giampaolo; Borze, I; Knuutila, S; Gobbo, S; Santo, A; Tondulli, L; Calabrò, F; Martignoni, Guido; Chilosi, Marco
abstract
Squamous lung carcinoma lacks specific "ad hoc" therapies. Amplification of chromosome 3q is the most common genomic aberration and this region harbours genes having role as novel targets for therapeutics. There is no standard definition on how to score and report 3q amplification. False versus true 3q chromosomal amplification in squamous cell lung carcinoma may have tremendous impact on trials involving drugs which target DNA zones mapping on 3q. Forty squamous lung carcinomas were analyzed by FISH to assess chromosome 3q amplification. aCGH was performed as gold-standard to avoid false positive amplifications. Three clustered patterns of fluorescent signals were observed. Eight cases out of 40 (20%) showed ≥8 3q signals. Twenty out of 40 (50%) showed from 3 to 7 signals. The remaining showed two fluorescent signals (30%). When corrected by whole chromosome 3 signals, only cases with ≥8 signals maintained a LSI 3q/CEP3 ratio >2. Only the cases showing 3q amplification by aCGH (+3q25.3-3q27.3) showed ≥8 fluorescent signals at FISH evidencing a 3q/3 ratio >2. The remaining cases showed flat genomic portrait at aCGH on chromosome 3. We concluded that: 1) absolute copy number of 3q chromosomal region may harbour false positive interpretation of 3q amplification in squamous cell carcinoma; 2) a case results truly "amplified for chromosome 3q" when showing ≥8 fluorescent 3q signals; 3) trials involving drugs targeting loci on chromosome 3q in squamous lung carcinoma therapy have to consider false versus true 3q chromosomal amplification.
2011
- IMMUNOPHENOTYPICAL CHARACTERIZATION OF LUNG ADENOCARCINOMAS: MOLECULAR AND CLINICAL CORRELATIONS
[Altro]
Eccher, Albino
abstract
Lung cancer is the most common cancer worldwide and the leading cause of cancer-related mortality. The lung cancer classification of the World Health Organization (WHO, 2004) can efficiently distinguish small-cell (SCLC) and non-small-cell lung carcinomas (NSCLC) but it results inadequate when facing prognosis and therapeutic decisions, especially for the entity of adenocarcinoma. Knowledge concerning the molecular pathogenesis of this tumor type is far from complete and diagnostic problems are mainly related to the poor reproducibility of morphological and histological criteria. Lung adenocarcinoma represents indeed a heterogeneous group of tumours characterized by different morphological and immunophenotypical features and molecular pathogenesis. Since updated therapeutic approaches are available (e.g. molecular-targeted therapies using tyrosine kinase inhibitors), exact histological classification is required for proper therapy and prognostic estimates. Aim of this study is to distinguish different lung tumour entities outlining a classification on the basis of the neoplastic immunophenotype. One hundred and fifty-nine cases of lung neoplasm were retrieved from the archives of five institutions (Anatomia Patologica of Verona, Negrar, Mestre, Trento, Forlì). All the cases were diagnosed as NSCLC carcinomas according to the WHO classification of 2004 and reviewed by two pathologists (MC and AE) to confirm the diagnosis and to select a significative paraffin block containing both tumor and adjacent non-neoplastic lung tissue. For each case multiple (30) paraffine sections were obtained in order to perform immunohistochemistry. The immunohistochemical panel included the following antibodies: CD56 (123C3.D5, Neomarkers), CK20 (IT-KS20.8, Biogenex), CK7 (OV-TL12/30, Biogenex), TTF-1 (8G7G3/1, Dako), NAPSIN A (TMU-A d02, Arp), SP A-1 (PE-10, Dako), CD208 (I10-1112, Beckton Dickinson), CC10 (rabbit, Dako), MUC5 (CLH2, Novocastra), CK5 (XM26, Novocastra), P63 (4A4, Santacruz), VILLINA (CWWB1, Novocastra), CDX2 (CDX2-88, Biogenex), P53 (DO-7, Novocastra), P21 (SX-118, Dako), P16 (JC8, Neomarkers) and DELTA-N-P63 (rabbit, Oncogene). Of 159 patients, 69 underwent surgery in Verona in 2007-2008; of these, clinical data were available for 34 cases and included smoke, type of surgery, adjuvant therapy, relapse, disease free survival (DFS), type of chemotherapy and overall survival (OS). We classified the tumors on the basis of the immunophenotype. In summary, 43% of the cases were “alveolar” carcinomas, 24% were “bronchiolar” carcinomas, 16% were carcinomas with “Clara cells features”, 9% were “metaplastic-enteric type”, 4% were sarcomatoid carcinomas, 3% were neuroendocrine carcinomas and 1% were “metaplastic-squamous type”. The mean age was 64, 113 were males (70%) and 46 were females (30%). The mean tumor size was 3,3 cm. The cases with available clinical data were 34, of which 17 were “alveolar” carcinomas, 8 were “bronchiolar” carcinomas, 4 were carcinomas with “Clara cells features”, 3 were “metaplastic-enteric type” and 2 were sarcomatoid carcinomas. Six patients (18%) never smoked, 9 patients (26%) quit smoking and 19 patients (56%) are currently smokers. Pathological stage according to Cancer staging (6th edition) was IA in 12 cases (35%), IIA in 6 cases (18%), IIB in 6 cases (18%), IIIA in 6 cases (18%) and IV in 4 cases (11%). Seven patients (20%) underwent neoadjuvant radiotherapy. The disease recurred in 12 patients (35%) with a mean DFS of 9 months and a predilection (66%) of recurrency in mediastinal lymphnodes. In seven patients (20%) we did not observe any recurrency while in 15 patients (45%) the data were not available. Surgery type, regarding the resection margins was R0 in 26 cases (76%) and R1 in 8 cases (24%). In 18 cases OS was available with a mean period of 19,8 months. The goal of our classification is not only to provide the most accurate diagnosis but also to m
2011
- Proteomic analysis of formalin-fixed, paraffin-embedded lung neuroendocrine tumor samples from hospital archives
[Articolo su rivista]
Tanca, A; Addis, Mf; Pagnozzi, D; Cossu Rocca, P; Tonelli, R; Falchi, G; Eccher, Albino; Roggio, T; Fanciulli, G; Uzzau, S.
abstract
Hospital tissue repositories host an invaluable supply of diseased samples with matched retrospective clinical information. In this work, a recently optimized method for extracting full-length proteins from formalin-fixed, paraffin-embedded (FFPE) tissues was evaluated on lung neuroendocrine tumor (LNET) samples collected from hospital repositories. LNETs comprise a heterogeneous spectrum of diseases, for which subtype-specific diagnostic markers are lacking. Six archival samples diagnosed as typical carcinoid (TC) or small cell lung carcinoma (SCLC) were subjected to a full-length protein extraction followed by a GeLC-MS/MS analysis, enabling the identification of over 300 distinct proteins per tumor subtype. All identified proteins were categorized through DAVID software, revealing a differential distribution of functional classes, such as those involved in RNA processing, response to oxidative stress and ion homeostasis. Moreover, using spectral counting for protein abundance estimation and beta-binomial test as statistical filter, a list of 28 differentially expressed proteins was generated and submitted to pathway analysis by means of Ingenuity Pathway Analysis software. Differential expression of chromogranin-A (more expressed in TCs) and stathmin (more expressed in SCLCs) was consistently confirmed by immunohistochemistry. Therefore, FFPE hospital archival samples can be successfully subjected to proteomic investigations aimed to biomarker discovery following a GeLC-MS/MS label-free approach.
2010
- Diagnostic usefulness of fluorescent cytogenetics in differentiating chromophobe renal cell carcinoma from renal oncocytoma: a validation study combining metaphase and interphase analyses
[Articolo su rivista]
Brunelli, Matteo; Delahunt, B.; Gobbo, Stefano; Tardanico, R.; Eccher, Albino; Bersani, Samantha; COSSU ROCCA, P.; Parolini, Claudia; Balzarini, P.; Menestrina, Fabio; Cheng, L.; Eble, J. N.; Martignoni, Guido
abstract
We investigated the usefulness of interphase
fluorescence in situ hybridization (FISH) analysis
to differentiate between 11 chromophobe renal
carcinomas and 12 renal oncocytomas, showing
different clinical outcomes, when compared with
conventional metaphase cytogenetics by karyotyping.
Karyotypically, 3 chromophobe renal cell
carcinomas showed losses of chromosomes, 3 were
polyploid, 1 was normal, and 4 failed to grow. Of 12
oncocytomas, 5 showed a normal numeric karyotype
and 6 additional structural rearrangements. FISH
on chromophobe renal cell carcinomas showed a
high percentage of cases (10/11 [91%]) with multiple
numeric losses among chromosomes 1, 2, 6, 10, and 17;
this interphase pattern was observed irrespective of the
3 different metaphase karyotypes. Of 12 oncocytomas,
11 (92%) revealed a normal numeric chromosomal
status showing at least 2 chromosomes without
aneusomy by interphase FISH.
The study demonstrates that indeed FISH
performed on formalin-fixed, paraffin-embedded tissue
can provide clinically useful information more reliably
than karyotyping of most of these tumors.
2009
- Expression of GATA-3 among renal cell and urothelial neoplasms
[Relazione in Atti di Convegno]
Segala, Diego; Gobbo, Stefano; Brunelli, Matteo; Eccher, Albino; Gobbato, Marta; Vergine, Marco; Chilosi, Marco; Bonetti, Franco; Menestrina, Fabio; Martignoni, Guido
abstract
2009
- Flat epithelial atypia on core needle biopsy: which is the right management?
[Articolo su rivista]
Piubello, Q; Parisi, Alice; Eccher, Albino; Barbazeni, G; Franchini, Z; Iannucci, Antonio
abstract
The clinical significance and management (surgical excision vs. follow-up) of the patients with the diagnosis of flat epithelial atypia (FEA) on core needle biopsy (CNB) are actually under discussion. Using standardized criteria and precise terminology, we analyzed retrospectively our CNB diagnosis of FEA, dividing patients with pure FEA as the most advanced pathologic lesion from patients with FEA associated to atypical ductal hyperplasia (FEA+ADH). Both the categories were correlated with radiologic data and findings on subsequent surgery. We evaluated 875 core needle biopsies (11-gauge stereotactic vacuum-assisted procedure), performed over a 5-year period. A CNB diagnosis of pure FEA was made in 33/875 (3.7%) cases; in other 11 (1.2%) cases we observed the coexistence of FEA and ADH. Subsequent surgical excisions were available in 20/33 pure FEA and in 10/11 FEA+ADH: of the 20 patients with pure FEA on CNB, none had either ductal carcinoma in situ or invasive carcinoma in their excisional biopsy, whereas 3/10 (30%) FEA+ADH on CNB showed, at subsequent surgery, more advanced lesions (2 ductal carcinoma in situ, 1 invasive carcinoma). Our results suggest that patients with an 11-gauge vacuum-assisted CNB diagnosis of pure FEA (especially if related to a small radiologic target, completely or almost completely removed by the needle biopsy procedure) could be spared surgical excision and managed with close radiologic follow-up
2009
- Genotypic Intratumoral Heterogeneity in Breast Carcinoma with HER2/neu Amplification Evaluation According to ASCO/CAP Criteria
[Articolo su rivista]
Brunelli, Matteo; Manfrin, Erminia; Martignoni, Guido; Miller, K; Remo, Andrea; Reghellin, Daniela; Bersani, Samantha; Gobbo, Stefano; Eccher, Albino; Chilosi, Marco; Bonetti, Franco
abstract
Abstract: We evaluated intratumoral heterogeneity of 30 ductal breast carcinomas with HER2/neu amplification, scored by the American Society of Clinical Oncology/ College of American Pathologists (ASCO/CAP) criteria, and 3+ immunoexpression. High-grade (ratio > or =4.0) vs low-grade amplification (ratio >2.2 to <4.0) and chromosome 17 polysomy were also evaluated. On whole tissue sections, 20 tumors (67%) showed high-grade and 10 (33%) showed low-grade HER2/ neu amplification. Of 20 tumors with high-grade amplification, 14 (70%) showed no intratumoral genotypic heterogeneity; 6 (30%) showed at least 1 core with low-grade amplification. Of 10 cases with low-grade amplification, 6 (60%) showed no intratumoral heterogeneity; 4 (40%) showed chromosome 17 polysomy without gene amplification in 2 of 3 cores per case. Of 30 cases with gene amplification, 4 (13%) showed a "not-amplified pattern" in other parts of the tumor. The routine assessment of HER2/neu amplification using the ASCO/CAP criteria on whole tissue sections is not significantly confounded by intratumoral heterogeneity in breast cancer with high-grade amplification; however, genetic heterogeneity exists in a subset of breast carcinomas with low-grade amplification. The clinical relevance and impact on treatment outcome of intratumoral heterogeneity in breast cancer with low-grade HER2/neu amplification or chromosome 17 polysomy need further investigation.
2009
- Her-2/neu evaluation in Sister Mary Joseph's nodule from breast carcinoma: a case report and review of the literature
[Articolo su rivista]
Brunelli, Matteo; Manfrin, Erminia; Miller, K; Eccher, Albino; Gobbo, Stefano; Reghellin, Daniela; Chilosi, Marco; Remo, Andrea; Martignoni, Guido; Menestrina, Fabio; Bonetti, Franco
abstract
Abstract: Sister Mary Joseph's nodule (SMJN) involving the umbilicus can often be a clinical sign of metastatic cancer, but rarely cancer originating from the breast. We report a rare case of umbilical metastases from breast cancer and reviewed the literature. A 54-year-old woman was referred to a pre-surgery clinic for an examination of an umbilical nodule. The patient had a history of ductal breast carcinoma. Cytological smear from fine needle aspiration showed epithelial neoplastic cells resembling those of breast carcinoma. Neoplastic cells from tissue were positive for cytokeratin 8-18, estrogen and progesterone receptor and negative for E-cadherin and had a low proliferative index. Her-2/neu immunodetection showed a 2+ equivocal positive rate, but Her-2/neu gene amplification was found on the cytological smear by fluorescence in situ hybridization analysis. Similar results were obtained within a tissue section. Concordant findings have been obtained when comparing the recent American Society of Clinical Oncology/College of American Pathologists scoring system. Fine needle aspiration from the SMJN is a useful tool for the diagnosis of metastatic breast cancer. Furthermore, the predictive biomarkers for tumors of the breast, hormonal receptors and Her-2/neu not only assist with the identification of the source of the metastatic disease but also provide clinical information for patient management.
2009
- Human aspartic protein napsin-A: immunoistochemical detection among renal cell neoplasms
[Relazione in Atti di Convegno]
Segala, Diego; Gobbo, Stefano; Brunelli, Matteo; Eccher, Albino; Chilosi, Marco; Bonetti, Franco; Menestrina, Fabio; Martignoni, Guido
abstract
2009
- Patterns of 1p/19q chromosomal abnormalities among glial neoplasms
[Relazione in Atti di Convegno]
Schiavo, Nicola; Brunelli, Matteo; Martignoni, Guido; Menestrina, Fabio; Gobbo, Stefano; Eccher, Albino; Ghimenton, C.
abstract
2009
- S-100A1 is a reliable marker in distinguishing nephrogenic adenoma from prostatic adenocarcinoma
[Articolo su rivista]
Cossu Rocca, P; Contini, Marcella; Brunelli, Matteo; Festa, Antonella; Pili, Francesca; Gobbo, Stefano; Eccher, Albino; Mura, A; Massarelli, G; Martignoni, Guido
abstract
Nephrogenic adenoma is a benign lesion that may occur at any site of the genitourinary tract, usually in association with previous urothelial injuries. Although its pathogenesis is still debated, recent studies seem to confirm its derivation from renal tubular epithelium, rather than from a metaplastic process of urothelium. In addition to its uncertain origin, there can be diagnostic difficulty in distinguishing nephrogenic adenoma from prostatic adenocarcinoma, particularly with lesions arising in the prostatic urethra. So far, immunohistochemical stains are often needed to make such a distinction, and several markers have been proposed, often with controversial results. S100A1 is a calcium binding protein that has been recently reported to be expressed in renal tubular cells and in a subset of renal cell neoplasms. Alpha-methylacyl-CoA racemase (AMACR), a recently identified prostate cancer marker, has also been found to be expressed in renal tubules and in some renal epithelial neoplasms. In this study, we investigated the expression of S100A1 and AMACR in 18 nephrogenic adenomas and in 100 prostatic adenocarcinomas. A strong and distinct cytoplasmic or nucleocytoplasmic staining of S100A1 was found in 17 out of 18 cases of nephrogenic adenoma (94%), but never in prostatic adenocarcinoma. In contrast, AMACR expression was detected in 14 of 18 nephrogenic adenomas (78%) and in 96 of 100 prostatic adenocarcinomas (96%). We conclude that (1) S100A1 is a specific and sensitive immunohistochemical marker to differentiate nephrogenic adenoma from prostatic adenocarcinoma; (2) AMACR immunostaining does not seem to be a useful marker in distinguishing between these 2 lesions; (3) given that both S100A1 and AMACR have been reported to be expressed in renal tubular cells and in a subset of renal cell neoplasms, our findings confirm the histogenetic relationship between nephrogenic adenoma and renal tubular epithelium.
2009
- Subepithelial Pelvic Hematoma (Antopol-Goldman Lesion) Simulating Renal Neoplasm: Report of a Case and Review of the Literature
[Articolo su rivista]
Eccher, Albino; Brunelli, Matteo; Gobbo, Stefano; Ghimenton, C; Grosso, G; Iannucci, Antonio; Palma, Pd; Menestrina, Fabio; Martignoni, Guido
abstract
The Antopol-Goldman lesion is a subepithelial pelvic hematoma simulating a renal neoplasm. We report the clinico-pathological features of a single case and a review of the literature. A 76-year-old man presented with flank pain and hematuria. Computed tomography showed a hypodense lesion of 6 cm at the left kidney with filling defect at pyelogram. The patient underwent nephroureterectomy for suspected neoplasm. Macroscopically, a mass of 6 cm was present impinging on the pelvi-caliceal system. Microscopically, the lesion was composed by hemorragic material with feature of an hematoma. A diffuse eosinophilic amorphous material suspicious for amyloid was observed among intra- and extraparenchymal vessels. The Congo-Red staining verified the presence of amyloid. The diagnosis was subepithelial pelvic hematoma with severe amyloidosis. Antopol-Goldman lesion should be kept in mind as a possible differential diagnosis of upper urinary tract lesion to avoid unnecessary nephrectomies. The anamnestic knowledge of amiloydosis may increase this diagnostic hypothesis.
2009
- Utility of tissue microarrays for assessment of diagnostic chromosomal abnormalities in chromophobe renal cell carcinoma
[Articolo su rivista]
Brunelli, Matteo; Delahunt, B; Ficarra, Vincenzo; Gobbo, Stefano; Eccher, Albino; Cossu Rocca, P; Zattoni, Filiberto; Cheng, L; Eble, Jn; Martignoni, Guido
abstract
OBJECTIVE:
To compare the results of numerical chromosomal changes in chromophobe renal cell carcinoma obtained from whole tissue sections with those of tissue microarrays.
STUDY DESIGN:
Standard sections and tissue microarrays constructed from formalin-fixed and paraffin-embedded chromophobe renal cell carcinomas from 6 patients were subjected to interphase fluorescence in situ hybridization (FISH) using centromeric probes for chromosome 1, 2, 6, 10 and 17. Tissue microarrays were constructed with 3 cores per tumor and 2 cores of normal renal tissue controls.
RESULTS:
Whole sections of chromophobe renal cell carcinoma showed multiple chromosomal abnormalities in 3 out of 6 cases (case 1, 2, 5). In 2 cases all 5 chromosomes were lost in both whole and tissue microarray cores (cases 2 and 5), and for 1 case (case 1) losses of chromosomes 2, 10 and 17 were detected on both whole and tissue microarray cores. In another 2 cases there were 2 fluorescence signals for chromosomes 1 in the majority of malignant cells (cases 3 and 6), loss of chromosome 6 (case 3), loss of chromosome 2 (case 6) and a mosaic pattern with nuclei showing a mixture of signal losses and gains for the other chromosomes. The remaining tumor did not show abnormalities (case 4). When 2 core biopsies per tumor were examined, the level of substantial concordance of results ranged from 92% to 98%.
CONCLUSION:
In this study we have demonstrated that tissue microarrays are a valid substitute for whole tissue sections in large cohort studies of chromophobe renal cell carcinoma when FISH analysis is undertaken. Concordance of results was improved when the number of analyzed cores was increased from 2 to 3, at which point a concordance index ranging from substantial to almost perfect was observed.
2008
- Analisi citogenetica in metafase ed interfase nel carcinoma renale cromofobo e nell'onocitoma del rene
[Relazione in Atti di Convegno]
Brunelli, Matteo; Gobbo, Stefano; Eccher, Albino; Segale, D; Cossu Rocca, P; Tardanico, R; Balzarini, P; Bonetti, Franco; Chilosi, Marco; Menestrina, Fabio; Martignoni, Guido
abstract
2008
- Carcinoma a cellule renali associato ad evidente proliferazione stromale leiomiomatosa
[Relazione in Atti di Convegno]
Segala, Diego; Vergine, Marco; Gobbo, Stefano; Brunelli, Matteo; Eccher, Albino; Tardanico, R; Barzon, L; Chilosi, Marco; Bonetti, Franco; Scarpa, Aldo; Menestrina, Fabio; Martignoni, Guido
abstract
2008
- Carcinoma renale a cellule chiare papillare: una distinta entità istopatologica e genetica
[Relazione in Atti di Convegno]
Gobbo, Stefano; Brunelli, Matteo; Segala, Diego; Eccher, Albino; Chilosi, Marco; Bonetti, Franco; Menestrina, Fabio; Cheng, L; Martignoni, Guido
abstract
2008
- Carcinomi renali papillari con aree di cellule chiare
[Relazione in Atti di Convegno]
Gobbo, Stefano; Brunelli, Matteo; Segala, Diego; Eccher, Albino; Chilosi, Marco; Bonetti, Franco; Menestrina, Fabio; Cheng, L; Martignoni, Guido
abstract
2008
- Clear-cell papillary renal cell carcinoma: a distinct histopathological and molecular genetic entity
[Relazione in Atti di Convegno]
Gobbo, S; Eccher, A; Eble, J; Grignon, D; Martignoni, G; Maclennan, G; Shah, R; Zhang, Sb; Brunelli, M; Cheng, L
abstract
No abstract available
2008
- Due casi di neoplasia primitiva maligna con aspetti gliali e neuronali
[Relazione in Atti di Convegno]
Ghimenton, C; Eccher, Albino; Pizzini, Francesca; Parisi, Alice; Piubello, Q; Schiavo, Nicola; Tomezzoli, A; Iannucci, Antonio; Martignoni, Guido; Menestrina, Fabio
abstract
2008
- Epithelioid hemangioma of the thoracic wall mimicking breast tumor: a case report
[Articolo su rivista]
Dalfior, Daniela; Eccher, Albino; Menestrina, Fabio; Mariella, Bonzanini; Gordan, Dvornik
abstract
2008
- Espressione di CD23 nelle neoplasie cutanee annessiali
[Relazione in Atti di Convegno]
Eccher, Albino; Zannoni, M; Parisi, Alice; Brunelli, Matteo; Gobbo, Stefano; Piubello, Q; Iannucci, Antonio; Martignoni, Guido; Menestrina, Fabio; Ghimenton, C.
abstract
2008
- I tumori ibridi nell'oncocitosi renale sono l'anello di congiunzione tra oncocitoma renale e il carcinoma renale di tipo cromofobo?
[Relazione in Atti di Convegno]
Gobbo, Stefano; Brunelli, Matteo; Cossu Rocca, P; Segala, Diego; Eccher, Albino; Chilosi, Marco; Bonetti, Franco; Menestrina, Fabio; Cheng, L; Martignoni, Guido
abstract
2008
- Loss of chromosome 9p is an independent prognostic factor in patients with clear cell renal cell carcinoma
[Articolo su rivista]
Brunelli, Matteo; Eccher, Albino; Gobbo, Stefano; Ficarra, Vincenzo; Novara, Giacomo; Paolo Cossu, Rocca; Bonetti, Franco; Menestrina, Fabio; Liang, Cheng; John N., Eble; Martignoni, Guido
abstract
Loss of chromosome 9p has been implicated in the progression of renal cell carcinoma. We evaluated the clinical utility of fluorescence in situ hybridization analysis of loss of chromosome 9p in 73 patients with clear cell renal cell carcinomas with varied stage, size, grade, necrosis (SSIGN) scores. Loss of chromosome 9p was observed in 13 tumors (18%). The 5-year cancer-specific survival of patients without loss of chromosome 9p was 88% and was 43% in those with loss of chromosome 9p (P<0.001). Local extension of the primary tumor according to the 2002 TNM staging system, lymph node involvement, the presence of distant metastases, and the SSIGN score were the other variables that predicted cancer-specific survival in univariate analysis. Loss of chromosome 9p was an independent prognostic factor in multivariate analysis. Our data indicate that the detection of chromosome 9p loss by fluorescence in situ hybridization analysis of clear cell renal cell carcinoma adds prognostic information beyond the pathological factors included in the current predictive models for renal cell carcinoma, such as SSIGN score.
2008
- Periorbital subcutaneous tumor-like lesion due to Dirofilaria repens
[Articolo su rivista]
Eccher, A; Dalfior, D; Gobbo, S; Martignoni, G; Brunelli, M; Decaminada, W; Bonetti, F; Rivasi, Francesco; Barbareschi, M; Menestrina, F.
abstract
Dirofilariasis is a zoonotic infection, which is occasionally seen in humans and rarely found as a subcutaneous orbital swelling. The authors report a case of a 62-year-old woman presented with a 3-month history of a right periorbital subcutaneous nodule. Treatment with antibiotics and corticosteroids was not satisfactory. Magnetic resonance imaging analysis showed a nodule with a central colliquative area. The lesion displaced the eyeball superiorly but did not affect the intraorbital muscles. The patient was subjected to excisional biopsy and the nodule measured 15 mm. Histological findings showed microabscess reaction with heterogeneous lymphoid infiltration. Additional consecutive sections finally showed Dirofilaria repens, curled up in spirals with external cuticular ridges in an environment characterized by epithelioid cells. The lesion did not recur for 5 months. Periorbital swelling can be rarely caused by Dirofilaria repens; therefore, this diagnosis should be considered in all cases of subcutaneous inflammatory or tumor-like lesion of unknown etiology.
2008
- Primary pleomorphic rhabdomyosarcoma of the kidney in an adult
[Articolo su rivista]
Dalfior, D; Eccher, Albino; Gobbo, Stefano; Brunelli, Matteo; Martignoni, Guido; Menestrina, Fabio; Dalla, Pp; Dvornik, G.
abstract
Sarcoma of the kidney is uncommon and represents between 1% and 3% of all malignant renal tumors. Primary rhabdomyosarcoma of the kidney in adult age is unusual, and only sporadic cases have been reported. This is a very aggressive tumor with dismal prognosis. We report a new case of pleomorphic rhabdomyosarcoma of the kidney in an adult patient.
2008
- Schwannoma del rene
[Relazione in Atti di Convegno]
Vergine, Marco; Gobbo, Stefano; Brunelli, Matteo; Eccher, Albino; Segala, Diego; Chilosi, Marco; Bonetti, Franco; Menestrina, Fabio; Cheng, L; Martignoni, Guido
abstract
2008
- Significato prognostico della perdita del cromosoma 9P nei carcinomi renali a cellule chiare stratificati per UISS e SSIGN score
[Relazione in Atti di Convegno]
Brunelli, Matteo; Gobbo, Stefano; Eccher, Albino; Segala, D; Ficarra, Vincenzo; Novara, G; Galfano, A; Cossu Rocca, P; Bonetti, Franco; Menestrina, Fabio; Martignoni, Guido
abstract
2008
- Utilità del tissue microarray nella valutazione delle anomalie cromosomiche del carcinoma renale di tipo cromofobo
[Relazione in Atti di Convegno]
Brunelli, Matteo; Eccher, Albino; Gobbo, Stefano; Ficarra, Vincenzo; Cossu Rocca, P; Bonetti, Franco; Menestrina, Fabio; Martignoni, Guido
abstract
2007
- Chondroid syringoma with extensive ossification
[Articolo su rivista]
Eccher, Albino; Brunelli, Matteo; Gobbo, Stefano; Dalfior, Daniela; Dvornik, G; Barbareschi, M; Parolini, Claudia; Menestrina, Fabio; Martignoni, Guido
abstract
2007
- Diagnostic utility of S100A1 expression in renal cell neoplasms: an immunohistochemical and quantitative RT-PCR study
[Articolo su rivista]
Rocca, Pc; Brunelli, Matteo; Gobbo, Stefano; Eccher, Albino; Bragantini, E; Mina, Maria Mihaela; Ficarra, Vincenzo; Zattoni, F; Zamo', Alberto; Pea, M; Scarpa, Aldo; Chilosi, Marco; Menestrina, Fabio; Bonetti, Franco; Eble, Jn; Martignoni, G.
abstract
S100A1 is a calcium-binding protein, which has been recently found in renal cell neoplasms. We evaluated the diagnostic utility of immunohistochemical detection of S100A1 in 164 renal cell neoplasms. Forty-one clear cell, 32 papillary, and 51 chromophobe renal cell carcinomas, and 40 oncocytomas, 164 samples of normal renal parenchyma adjacent to the tumors and 13 fetal kidneys were analyzed. The levels of S100A1 mRNA detected by quantitative RT-PCR analysis of frozen tissues from seven clear cell, five papillary, and six chromophobe renal cell carcinomas, four oncocytomas, and nine samples of normal renal tissues adjacent to neoplasms were compared with the immunohistochemical detection of protein expression. Clear cell and papillary renal cell carcinomas showed positive reactions for S100A1 in 30 out of 41 tumors (73%) and in 30 out of 32 (94%) tumors, respectively. Thirty-seven renal oncocytomas out of 40 (93%) were positive for S100A1, whereas 48 of 51 (94%) chromophobe renal cell carcinomas were negative. S100A1 protein was detected in all samples of unaffected and fetal kidneys. S100A1 mRNA was detected by RT-PCR in all normal kidneys and renal cell neoplasms, although at very different levels. Statistical analyses comparing the different expression of S100A1 in clear cell and chromophobe renal cell carcinomas observed by immunohistochemical and RT-PCR methods showed significant values (P<0.001), such as when comparing by both techniques the different levels of S100A1 expression in chromophobe renal cell carcinomas and oncocytomas (P<0.001). Our study shows that S100A1 protein is expressed in oncocytomas, clear cell and papillary renal cell carcinomas but not in chromophobe renal cell carcinomas. Its immunodetection is potentially useful for the differential diagnosis between chromophobe renal cell carcinoma and oncocytoma. Further, S100A1 protein expression is constantly detected in the normal parenchyma of the adult and fetal kidney.
2007
- Giant Brunner's gland adenoma
[Relazione in Atti di Convegno]
Eccher, Albino; Brunelli, Matteo; Gobbo, Stefano; Pecori, S; Capelli, Paola; Cannizzaro, C; Falconi, M; Pederzoli, P; Angelini, G; Martignoni, Guido; Menestrina, Fabio
abstract
2007
- La perdita del 9p è un fattore prognostico nei pazienti affetti da carcinoma a cellule chiare del rene
[Relazione in Atti di Convegno]
Eccher, Albino; Brunelli, Matteo; Gobbo, Stefano; Cossu Rocca, P; Ficarra, Vincenzo; Zattoni, F; Bonetti, Franco; Menestrina, Fabio; Martignoni, Guido
abstract
2007
- Subepithelial haematoma of the renal pelvis (Antopol-Goldman lesion)
[Relazione in Atti di Convegno]
Eccher, Albino; Brunelli, Matteo; Polara, A; Amenta, M; Gobbo, Stefano; Pea, Maurizio; Bonetti, Franco; Grosso, G; Menestrina, Fabio; Martignoni, Guido
abstract
2007
- Utilità diagnostica della valutazione della ploidia con citometria a flusso nella diagnosi differenziale delle neoplasie a cellule renali
[Relazione in Atti di Convegno]
Parolini, Claudia; Eccher, Albino; Brunelli, Matteo; Gobbo, Stefano; Chilosi, Marco; Menestrina, Fabio; Martignoni, Guido
abstract
2007
- Utilità diagnostica di CD13 e CD10 nelle neoplasie a cellule renali
[Relazione in Atti di Convegno]
Brunelli, Matteo; Gobbo, Stefano; Eccher, Albino; Parisi, Alice; Gobbato, Marta; Dalfior, D; Chilosi, Marco; Menestrina, Fabio; Martignoni, Guido
abstract
2006
- L'ESPRESSIONE DI CITOCHERATINE E' IN ACCORDO CON LA DIFFERENZIAZIONE EPITELIALE DELLE NEOPLASIE RENALI HMB45 POSITIVE CON TRASLOCAZIONE T(6;11)
[Relazione in Atti di Convegno]
Gobbo, Stefano; Martignoni, Guido; Brunelli, Matteo; Pea, M; Eccher, Albino; Menestrina, Fabio
abstract