[Apocrine lesions of the breast]

Apocrine breast lesions encompass a spectrum of histopathological abnormalities, ranging from benign apocrine metaplasia to invasive apocrine carcinomas. Their defining feature lies in cells with abundant eosinophilic cytoplasm and round nuclei with prominent nucleoli. These cells strongly express the androgen receptor while lacking estrogen receptor-alpha and progesterone receptor expression. Benign lesions, frequently associated with mammary cysts or papillomas, lack nuclear and architectural atypia. In contrast, atypical apocrine lesions exhibit significant nuclear and structural abnormalities, posing diagnostic challenges when distinguishing them from apocrine ductal or lobular carcinoma in situ. Diagnosis relies on the extent of atypia and the presence of tumor necrosis. Invasive apocrine carcinomas are rare, accounting for less than 1% of all breast cancers, and predominantly occur in postmenopausal women. Histologically, they are often grade 1 or 2 tumors. Approximately 50% exhibit HER2 amplification and overexpression. Immunohistochemically, they are characterized by positivity for FOXA1 and GATA3, and negativity for FOXC1 and SOX10, and variable expression of TRPS1. These carcinomas belong to the molecular apocrine carcinoma family, which includes HER2-enriched tumors driven by HER2 addiction and androgen receptor-positive luminal tumors, a subtype of triple-negative breast cancers. The latter are defined by androgen receptor pathway activation and are frequently associated with PI3K pathway alterations and cell cycle dysregulation, suggesting potential therapeutic targets.