Immunohistochemical Analysis of INSM1, MCPyV, and PHOX2B Expression in Merkel Cell Carcinoma

Background: Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine malignancy with distinct etiological pathways, including Merkel cell polyomavirus (MCPyV) infection and ultraviolet (UV)-induced carcinogenesis. Owing to the lack of large case series, the etiology of MCC in Turkey remains unclear. INSM1 is a highly specific neuroendocrine marker that supports the diagnosis of MCC. PHOX2B, although known to be expressed in neuroblastoma, has been only rarely investigated in MCC. Methods: We retrospectively evaluated 14 MCC cases diagnosed between 2008 and 2023 at Istanbul Training and Research Hospital. Immunohistochemical analysis was performed using antibodies against INSM1 (A-8), MCPyV (Ab3), and PHOX2B (EP312). The extent and pattern of staining were assessed and correlated with clinicopathological findings and existing literature. Results: All cases demonstrated INSM1 expression, with predominantly diffuse nuclear staining. MCPyV positivity was observed in 78.6% of cases. PHOX2B expression was detected in only one case, showing focal and weak nuclear positivity, while all other cases were negative. Conclusion: Our findings support the high diagnostic utility of INSM1 and confirm that MCPyV is present in most MCC cases in our cohort. The use of the Ab3 antibody may enhance detection of MCPyV due to its higher sensitivity. Since neuroblastoma and Merkel cell carcinoma are morphologically similar on first glance with sheets of small blue cells, PHOX2B serves as an effective discriminatory marker. It tests positive in neuroblastoma and negative in Merkel cell carcinoma, as demonstrated in our cohort of patients. These findings highlight the importance of appropriate marker selection in the diagnostic evaluation of MCC. Merkel cell carcinomas secondary to viral etiology appear to be the predominant form in Turkey.