Primary cutaneous apocrine carcinoma with RARA::NPEPPS fusion

Abstract

AbstractGene fusions have emerged as crucial molecular drivers of oncogenesis in a subset of cutaneous adnexal neoplasms, including poroid neoplasms and hidradenomas. We present a unique case of primary cutaneous apocrine carcinoma harboring RARA::NPEPPS fusion, broadening the spectrum of fusion‐associated cutaneous adnexal neoplasms. A 77‐year‐old African American male presented with an ulcerated thigh nodule. Histopathologically, the predominantly dermal‐based adenocarcinoma exhibited papillary, micropapillary, cribriform, and solid growth patterns with central comedonecrosis, set in a fibrotic/desmoplastic stroma. Immunophenotypically, the neoplastic cells were positive for CK7, CK19, GATA3, TRPS1, HER2, CK5/6, calretinin, p63, and DPC4 (no loss), while lacking immunoreactivity for CK20, CDX2, TTF1, napsin‐A, PAX8, arginase‐1, adipophilin, NKX3.1, uroplakin II, and D2‐40. The immunoprofile and clinical and radiographic absence of any internal malignancy, including breast carcinoma, except for multiple lymphadenopathy, supported the diagnosis of primary cutaneous apocrine carcinoma. Next‐generation sequencing unveiled the novel RARA::NPEPPS fusion, concurrent ERBB2 amplification, and multiple somatic mutations involving TP53, CDKN2A, BRCA2, PIK3CA, PIK3R1, and others. The patient developed widespread metastases within a year after the initial diagnosis, indicating the tumor's aggressive behavior. This novel fusion, unprecedented in any human malignancies including primary cutaneous adnexal carcinomas, may suggest a potential new subtype within primary cutaneous adnexal carcinoma.