Journal Article

Morphologic and immunophenotypical features distinguishing Merkel cell polyomavirus-positive and negative Merkel cell carcinoma

Bens, Guido, Samimi, Mahtab, Gambichler, Thilo, Le Corre, Yannick, University Hospital Bochum ; Partenaires INRAE, Herfs, Michaël, Université de Lille, Hôpital René Huguenin [Saint-Cloud] ; Institut Curie - Saint Cloud (ICSC), Guyétant, Serge, Beneton, Nathalie, Tallet, Anne, Service de Dermatologie ; Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre hospitalier universitaire de Poitiers = Poitiers University Hospital (CHU de Poitiers [La Milétrie]), Touzé, Antoine, Houben, Roland, Miquelestorena-Standley, Elodie, Fromont, Gaëlle, Arbion, Flavie, Kervarrec, Thibault, Service de dermatologie, Hainaut-Wierzbicka, Ewa, Leteurtre, Emmanuelle, Centre Hospitalier Régional d'Orléans (CHRO), Infectiologie et Santé Publique (UMR ISP) ; Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Aubin, François, Berthon, Patricia, Université de Liège = University of Liège = Universiteit van Luik = Universität Lüttich (ULiège), Schrama,

2019

Overview

In 2008, Feng et al. identified Merkel cell polyomavirus integration as the primary oncogenic event in ~80% of Merkel cell carcinoma cases. The remaining virus-negative Merkel cell carcinoma cases associated with a high mutational load are most likely caused by UV radiation. The current study aimed to compare the morphological and immunohistochemical features of 80 virus-positive and 21 virus-negative Merkel cell carcinoma cases. Microscopic evaluation revealed that elongated nuclei-similar to the spindle-shape variant of small cell lung cancer-were less frequent in Merkel cell polyomavirus-positive Merkel cell carcinoma compared to the virus-negative subset (p = 0.005). Moreover, virus-negative cases more frequently displayed a \"large-cell neuroendocrine carcinoma\" phenotype with larger cell size (p = 0.0026), abundant cytoplasm (p = 4×10-7) and prominent nucleoli (p = 0.002). Analysis of immunohistochemical data revealed frequent positivity for thyroid transcription factor 1 and cytokeratin 7, either absence or overexpression of p53, as well as frequent lack of neurofilament expression in virus-negative cases. By contrast, cytokeratin 8, 18 and 20 and a CD99 with a dot pattern as well as high EMA expression were identified as characteristic features of virus-positive Merkel cell carcinoma. In particular, the CD99 dot-like expression pattern was strongly associated with presence of the Merkel cell polyomavirus in Merkel cell carcinoma (sensitivity = 81%, specificity = 90%, positive likelihood ratio = 8.08). To conclude, virus-positive and -negative Merkel cell carcinoma are characterized by distinct morphological and immunohistochemical features, which implies a significant difference in tumor biology and behavior. Importantly, we identified the CD99 staining pattern as a marker indicating the virus status of this skin cancer.

• Publisher: Nature Publishing Group: Open Access Hybrid Model Option B,CCSD,Nature Publishing Group US,Elsevier Limited,Nature
• Subject: 12E7 Antigen - biosynthesis / 13/105 / 14/63 / 631/67/1459/1963 / 631/67/1813 / 82/51 / Aged / Aged, 80 and over / Biomarkers, Tumor - analysis / Cancer / Carcinoma, Merkel Cell - pathology / Carcinoma, Merkel Cell - virology / CD99 antigen / Cell size / Cytokeratin / Cytoplasm / Female / Human health and pathology / Human health sciences / Humans / Immunophenotyping / Laboratory Medicine / Life Sciences / Lung cancer / Male / Medicine / Medicine & Public Health / Merkel cell polyomavirus / Morphology / Neuroendocrine tumors / Nucleoli / Oncologie / Oncology / p53 Protein / Pathology / Phenotypes / Polyomavirus Infections - complications / Polyomavirus Infections - pathology / Polyomavirus Infections - virology / Sciences de la santé humaine / Skin cancer / Skin Neoplasms - pathology / Skin Neoplasms - virology / Small cell lung carcinoma / Thyroid transcription factor 1 / Tumor Virus Infections - pathology / Tumor Virus Infections - virology / Ultraviolet radiation
• ISBN: 0004937879000