Morphological Patterns of Metastases from Combined Merkel cell Carcinomas: study of an Eastern Canadian cohort of cases

Combined Merkel cell carcinomas are hybrid tumors composed of neuroendocrine and other phenotypic (usually squamous) elements. They form a minority of Merkel cell carcinomas (MCCs) as a whole, are usually Merkel cell polyomavirus-negative and have rarely been segregated for specific study. Sporadic reports have indicated that metastases from these tumors can show a combined phenotype. We retrospectively studied 38 cases [24 (63%) male, 14 (37%) female, mean age 78 years (range 46-99)] of combined MCC. Metastases occurred in 20 (53%) patients [at presentation and/or in follow-up (mean 38 months (range 0.6-185)]. Those from 17 (45%) individuals were examined microscopically. These were mainly nodal in distribution. In 12 (71%) patients the secondary deposits were of pure neuroendocrine type while in 5 (29%) combined deposits were identified. Squamous elements were the most common divergent component, in the primary and secondary tumors. The combined metastases varied from obvious squamous nests in a neuroendocrine background to scattered bizarre tumor giant cells expressing CK5/6 on immunohistochemistry. In one case, individual nodes within a single basin displayed purely squamous or purely neuroendocrine deposits. The mean overall survival in the cohort was 48 months (range 30-67) and the mortality was 82%. Our work sheds light on the frequency and patterns of metastases in combined MCCs. In concert with the poor outcome data documented by others, it also raises a question as to the potential prognostic significance of a combined phenotype per se, independent of a virus-negative status and other variables. This issue deserves further study. •Metastases from combined Merkel cell carcinomas have not been well studied.•We show that they vary morphologically.•Most have a pure neuroendocrine phenotype.•Squamous elements are the most common divergent component in combined metastases.•Combined metastases can have admixed or segregated components in different nodes.