Merkel Cell Polyomavirus-Negative Merkel Cell Carcinoma Presenting in the Parotid Gland: Precise Diagnosis and Complete Pathological Response to Nivolumab.

Background/Aim: Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine carcinoma that may present diagnostic challenges, particularly in Merkel cell polyomavirus (MCPyV)-negative cases. Distinguishing MCC from other high-grade neuroendocrine carcinomas is critical because treatment strategies differ. Case report: We report a case of a 77-year-old Caucasian male with a history of multiple non-melanoma skin cancers who presented with rapidly enlarging left parotid and cervical lymph node masses with suspected osseous metastasis to the fourth cervical vertebra (C4). Fine needle aspiration of the parotid mass demonstrated high-grade neuroendocrine carcinoma, positive for synaptophysin, focally and weakly positive for cytokeratin 20 (CK20), and negative for thyroid transcription factor 1 (TTF-1) and Merkel cell polyomavirus (MCPyV) immunoreactivity. Initial molecular classification favored small cell carcinoma. However, additional mutational signature analysis demonstrated an ultraviolet (UV) mutational profile consistent with cutaneous origin, supporting MCPyV-negative Merkel cell carcinoma. The diagnosis was revised following multidisciplinary review, and planned treatment was changed from carboplatin-etoposide chemotherapy to three months of nivolumab, a programmed death-1 (PD-1) inhibitor. Surgical resection of the parotid gland demonstrated complete pathologic response with no residual viable carcinoma identified. At the two-year follow-up, the patient was doing well with no MCC recurrence or metastasis identified. Conclusion: This case highlights the diagnostic difficulty of MCPyV-negative MCC presenting in an extracutaneous location and mimicking small cell carcinoma. In diagnostically challenging MCCs, molecular profiling and UV mutational signature analysis may play a key role in establishing correct diagnosis and treatment.