Metastatic Merkel Cell Carcinoma with Undifferentiated Sarcomatous Transformation: Evolution Following Immunotherapy

Summary: Objective: Merkel cell carcinoma (MCC) with sarcomatous differentiation is extremely rare, with only two previously reported cases with immunohistochemically undifferentiated sarcomatous components. Methods: We reported the clinicopathological features of a metastatic MCC of unknown primary with undifferentiated sarcomatous transformation in an 82-year-old woman. We documented its morphologic appearance before and after pembrolizumab therapy. Results: Initial core biopsy of an axillary mass revealed a biphasic tumor. The epithelioid component showed characteristic dot-like keratin 20 positivity and expressed neuroendocrine markers (CD56, chromogranin, synaptophysin). The spindle cell component lacked specific differentiation markers. Both components were negative for Merkel cell polyomavirus (MCPyV), TTF1, SS18-SSX, S100, and Sox10. Following pembrolizumab therapy, the excised lymph node demonstrated predominantly fibrosis and a focus of undifferentiated spindle cells negative for keratin 20, neuroendocrine markers, and myogenic markers. The epithelioid or neuroendocrine component is not seen in the excision specimen. The patient remained disease-free at follow-up. Conclusion: This case highlights some unique features in MCC with sarcomatous differentiation: (1) the presence of an immunohistochemically undifferentiated rather than lineage-specific sarcomatous component, (2) MCPyV-negative, (3) and only the sarcomatous component seen post immunotherapy. These findings expand our understanding of the morphologic spectrum of MCCs and suggest potential implications for therapeutic response.