Sinonasal Lymphoepithelial Carcinoma With Insulinoma-Associated Protein 1 (INSM1) Expression: A Potential Pitfall

Sinonasal lymphoepithelial carcinoma (SNLEC) is a rare malignancy composed of poorly differentiated epithelial cells with syncytial morphology and a variably dense lymphoplasmacytic infiltrate. Nearly all reported tumors are associated with Epstein-Barr virus (EBV), which can be demonstrated by in situ hybridization for EBV-encoded RNA. We present a diagnostically challenging lesion of SNLEC in a 60-year-old woman with a right nasal cavity mass and cervical lymphadenopathy. Histological sections showed sheets of malignant cells with vesicular nuclei, prominent nucleoli, and indistinct borders. Immunohistochemistry revealed diffuse nuclear expression of insulinoma-associated protein 1 (INSM1), raising initial concern for poorly differentiated neuroendocrine carcinoma. However, the tumor lacked classic light microscopic features of neuroendocrine differentiation, was negative for synaptophysin and chromogranin, and, most importantly, was strongly positive for EBV, findings that argue against neuroendocrine carcinoma and support the diagnosis of SNLEC. This case report highlights a potential diagnostic pitfall, as INSM1 expression may be misleading in EBV-associated carcinomas lacking true neuroendocrine differentiation. Integration of morphology, immunoprofile, and EBV status is essential to avoid misclassification.