INSM1: A Novel Nuclear Marker in Merkel Cell Carcinoma (Cutaneous Neuroendocrine Carcinoma)

Merkel cell carcinoma (MCC) is a rare, clinically aggressive, cutaneous neuroendocrine (NE) neoplasm. As a tumor with small, round, blue cells, the histologic differential diagnosis for MCC can include melanoma, metastatic small cell carcinoma (SCC), nodular hematopoietic tumors, basal cell carcinoma (BCC), atypical variants of squamous carcinoma, and the uncommon occurrence of primary cutaneous Ewing sarcoma. In cases with atypical histology or without the classic immunophenotype the diagnosis can be challenging. Ultimately, immunohistochemistry (IHC) is essential to the definitive diagnosis of MCC, and in difficult cases the diagnosis may hinge entirely on the immunophenotype of the tumor cells. INSM1 is a transcription factor expressed in tissues undergoing terminal NE differentiation. As a nuclear protein tied both to differentiation and the cell-cycle, INSM1 may offer additional utility in comparison to traditional, cytoplasmic markers of NE differentiation.