Vulvar small cell neuroendocrine carcinoma arising from differentiated vulvar intraepithelial neoplasia: evidence of a clonal relationship by mutation analysis.

Primary neuroendocrine carcinomas of the vulva are rare and poorly characterised. We report a case of small cell neuroendocrine carcinoma in a 90-year-old woman, associated with differentiated vulvar intraepithelial neoplasia and superficially invasive squamous cell carcinoma. Immunohistochemistry confirmed neuroendocrine differentiation and excluded Merkel cell carcinoma. Next-generation sequencing performed on both the intraepithelial and neuroendocrine components identified identical pathogenic mutations in TP53 and CDKN2A, supporting a clonal relationship. Loss of RB1 expression was observed across all tumor components. HPV testing was negative. These findings support the hypothesis of stepwise tumor progression from a squamous precursor with RB1 and TP53 alterations, suggesting a mechanism for neuroendocrine transdifferentiation.