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Merkel cell carcinoma

Abstract

Merkel cell carcinoma (MCC) is a rare but highly aggressive skin cancer with neuroendocrine features. MCC pathogenesis is associated with either the presence of Merkel cell polyomavirus or chronic exposure to ultraviolet light (UV), which can cause a characteristic pattern of multiple DNA mutations. Notably, in the Northern hemisphere, the majority of MCC cases are of viral aetiology; by contrast, in areas with high UV exposure, UV-mediated carcinogenesis is predominant. The two aetiologies share similar clinical, histopathological and prognostic characteristics. MCC presents with a solitary cutaneous or subcutaneous nodule, most frequently in sun-exposed areas. In fact, UV exposure is probably involved in both viral-mediated and non-viral-mediated carcinogenesis, by contributing to immunosuppression or DNA damage, respectively. Confirmation of diagnosis relies on analyses of histological features and immunological marker expression profiles of the lesion. At primary diagnosis, loco-regional metastases are already present in 30% of patients. Excision of the tumour is the first-line therapy; if not feasible, radiotherapy can often effectively control the disease. Chemotherapy was the only alternative in advanced-stage or refractory MCC until several clinical trials demonstrated the efficacy of immune-checkpoint inhibitors.

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Figure 1: Hypothetical cells of origin, causal events and tissue markers for MCC.
Figure 2: Circular map of MCPyV and linear maps of the MCPyV early genes.
Figure 3: Genetic aberrations in MCC.
Figure 4: Clinical presentations of MCC.
Figure 5: Histopathological and immunohistochemical features of MCC.
Figure 6: Simplified evaluation and treatment of primary MCC.

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Acknowledgements

J.C.B. is funded by the European Commission Grant Agreement #277775/IMMOMEC, the BMBF 03VP01062/CTCelect and the Hiege Stiftung. A.S. receives a grant from the German Federal Ministry of Education and Science (BMBF), grant number 01ER1305. J.A.D. was supported in part by US Public Health Service grants R01CA63113, R01CA173023, P01CA050661 and P01CA203655, the DFCI Helen Pappas Merkel Cell Research Fund and the Claudia Adams Barr Program in Cancer Research. P.N. was supported in part by US Public Health Service grants K24-CA139052 and RO1-CA176841 and the University of Washington MCC Gift Fund.

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Introduction (J.C.B.); Epidemiology (A.S.); Mechanisms/pathophysiology (J.A.D. and J.C.B.); Diagnosis, screening and prevention (L.C.); Management (C.L., P.N., M.V. and J.C.B.); Quality of life (M.V.); Outlook (J.C.B.); Overview of Primer (J.C.B.).

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Correspondence to Jürgen C. Becker.

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Competing interests

J.C.B. has received speaker honoraria from Amgen, Merck Serono and Pfizer; he has received advisory board honoraria from Amgen, CureVac, eTheRNA, Lytix, Merck Serono, Novartis, Rigontec, and Takeda; and he has received research funding from Boehringer Ingelheim, Bristol-Myers Squibb (BMS) and Merck Serono. J.C.B.'s activities with BMS, Merck Serono and Pfizer are related to the submitted report (therapy for advanced-stage MCC). A research project in J.A.D.'s laboratory is supported by Constellation Pharmaceuticals. C.L. has received honoraria from Amgen, BMS, MSD, Novartis and Roche, and research funding from BMS and Roche; she has a consulting or advisory role for Amgen, BMS, MSD, Novartis and Roche; she is part of speakers’ bureaus for Amgen, BMS, Novartis and Roche; and she has received compensation for travel, accommodation and expenses from Amgen, BMS, Novartis and Roche. P.N. has served as a consultant for EMD Serono, Merck and Pfizer and has received research support to his institution from BMS. A.S., L.C. and M.V. declare no competing interests.

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Becker, J., Stang, A., DeCaprio, J. et al. Merkel cell carcinoma. Nat Rev Dis Primers 3, 17077 (2017). https://doi.org/10.1038/nrdp.2017.77

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