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01-05-2018 | Original Article

Detection of the Merkel cell polyomavirus in the neuroendocrine component of combined Merkel cell carcinoma

Authors: Thibault Kervarrec, Mahtab Samimi, Pauline Gaboriaud, Tarik Gheit, Agnès Beby-Defaux, Roland Houben, David Schrama, Gaëlle Fromont, Massimo Tommasino, Yannick Le Corre, Eva Hainaut-Wierzbicka, Francois Aubin, Guido Bens, Hervé Maillard, Adeline Furudoï, Patrick Michenet, Antoine Touzé, Serge Guyétant

Published in: Virchows Archiv | Issue 5/2018

Abstract

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin. The main etiological agent is Merkel cell polyomavirus (MCPyV), detected in 80% of cases. About 5% of cases, called combined MCC, feature an admixture of neuroendocrine and non-neuroendocrine tumor cells. Reports of the presence or absence of MCPyV in combined MCC are conflicting, most favoring the absence, which suggests that combined MCC might have independent etiological factors and pathogenesis. These discrepancies might occur with the use of different virus identification assays, with different sensitivities. In this study, we aimed to determine the viral status of combined MCC by a multimodal approach. We histologically reviewed 128 cases of MCC and sub-classified them as “combined” or “conventional.” Both groups were compared by clinical data (age, sex, site, American Joint Committee on Cancer [AJCC] stage, immunosuppression, risk of recurrence, and death during follow-up) and immunochemical features (cytokeratin 20 and 7, thyroid transcription factor 1 [TTF1], p53, large T antigen [CM2B4], CD8 infiltrates). After a first calibration step with 12 conventional MCCs and 12 cutaneous squamous cell carcinomas as controls, all eight cases of combined MCC were investigated for MCPyV viral status by combining two independent molecular procedures. Furthermore, on multiplex genotyping assay, the samples were examined for the presence of other polyoma- and papillomaviruses. Combined MCC differed from conventional MCC in earlier AJCC stage, increased risk of recurrence and death, decreased CD8 infiltrates, more frequent TTF1 positivity (5/8), abnormal p53 expression (8/8), and frequent lack of large T antigen expression (7/8). With the molecular procedure, half of the combined MCC cases were positive for MCPyV in the neuroendocrine component. Beta papillomaviruses were detected in 5/8 combined MCC cases and 9/12 conventional MCC cases. In conclusion, the detection of MCPyV DNA in half of the combined MCC cases suggests similar routes of carcinogenesis for combined and conventional MCC.

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Title: Detection of the Merkel cell polyomavirus in the neuroendocrine component of combined Merkel cell carcinoma
Authors: Thibault Kervarrec
Mahtab Samimi
Pauline Gaboriaud
Tarik Gheit
Agnès Beby-Defaux
Roland Houben
David Schrama
Gaëlle Fromont
Massimo Tommasino
Yannick Le Corre
Eva Hainaut-Wierzbicka
Francois Aubin
Guido Bens
Hervé Maillard
Adeline Furudoï
Patrick Michenet
Antoine Touzé
Serge Guyétant
Publication date: 01-05-2018
Publisher: Springer Berlin Heidelberg
Published in: Virchows Archiv / Issue 5/2018
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-018-2342-0

At a glance: The STEP trials

Springer Medicine

Detection of the Merkel cell polyomavirus in the neuroendocrine component of combined Merkel cell carcinoma

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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