Histopathologic and Immunophenotypic Properties of Primary Cutaneous Large Cell Neuroendocrine Carcinomas

Cutaneous large cell neuroendocrine carcinoma (LCNEC) is a rare and poorly understood malignancy. Here we describe the clinicopathological characteristics of six cutaneous LCNEC case. A retrospective chart and slide review of PCLCNEC cases at a large commercial dermatopathology practice from January 2017 to May 2025 was performed. Patient characteristics, histopathologic features, and immunohistochemical profiles, including Merkel cell polyoma virus large T antigen/MCPyV antigenicity, were summarized. Demographically, PCLCNEC occurred in elderly white patients, presenting as a rapidly progressing nodule in sun-exposed skin. Histologically, the tumors were characterized by predominantly infiltrative growth patterns with varying levels of neuroendocrine architectural and cytologic features, including rosette and trabeculae formation, organoid nesting, and peripheral palisading. All were positive for CK7 and neuroendocrine markers and negative for MCPyV, CK20, and TTF1 expression by immunohistochemistry. Metastasis was identified in one patient, while the remaining five patients had no evidence of disease following wide local excision with a median follow-up period of 25 months. This series contributes valuable insights into the characterization and diagnosis of primary cutaneous LCNEC. In conjunction with previously reported data, we suggest that the morphology and immunophenotype support further inquiry into its potential distinction as a unique cutaneous entity.