Abstract

Somatic BRAF V600E mutations in primary cutaneous adnexal neoplasms are uncommon and have been observed in digital papillary adenocarcinoma, syringocystadenoma papilliferum, tubular apocrine adenoma, and papillary eccrine adenoma. Herein, we report the first instance of primary cutaneous adnexal carcinoma with neuroendocrine differentiation (PCACND) bearing BRAF V600E mutation in a 50-year-old woman who presented with a 2.7 cm scalp nodule. Biopsy revealed a poorly differentiated carcinoma predominantly involving the dermis and subcutis, with focal epidermal involvement, and tumoral necrosis. The tumor displayed a mainly solid growth pattern, with an occasional tubular or cord-like growth pattern. Immunohistochemical analysis showed positive expression of CK7, CK19, synaptophysin, chromogranin, INSM1, TRPS1, ER, and GATA3 (patchy), calretinin (patchy), and SOX11 (rare cells), and BRAF V600E. However, CK5/6, CK20, p63, TTF1, S100, D2-40, MCPyV, and adipophilin were not expressed. Next-generation sequencing identified somatic mutations in BRAF (c.1799T>A) and TP53 along with MYC amplification. Despite favoring primary cutaneous adnexal carcinoma, the comprehensive histopathologic and molecular features did not align with any previously known PCACNDs, including sweat gland carcinoma with neuroendocrine differentiation/low-grade neuroendocrine carcinoma of the skin (a recently described entity predominantly seen in men along the trunk’s milk lines). Imaging studies revealed no internal malignancies, particularly of breast origin, yet multiple lymphadenopathies and liver/bone lesions were detected, raising concerns for possible metastases. Subsequent biopsies from neck lymph nodes confirmed metastases. This unprecedented case might represent an undefined aggressive PCACND with BRAF V600E mutation, potentially susceptible to anti-BRAF therapy.