Cutaneous and Breast Apocrine Carcinoma: A Diagnostic Dilemma Between Two Mimicking Malignancies Particularly in Axillary Tumors

Abstract

Cutaneous apocrine carcinoma is an extremely rare adnexal malignancy arising from cutaneous apocrine sweat glands, with an incidence of approximately 0.14–0.18 cases per million person-years. In contrast, breast apocrine carcinoma is an uncommon subtype accounting for approximately 0.4–4% of all breast cancers and represents a carcinoma of mammary epithelial origin showing apocrine metaplasia rather than a tumor arising from apocrine sweat glands. Despite their distinct tissue origins, these tumors share strikingly similar histopathological and immunohistochemical features because of their common apocrine differentiation. Accurate distinction is clinically important because cutaneous apocrine carcinoma generally carries a poorer prognosis, whereas breast apocrine carcinoma has been reported to have a more favorable outcome than non-apocrine triple-negative breast cancer and is managed according to breast cancer treatment strategies. The diagnostic challenge becomes particularly evident when apocrine carcinoma arises in the axilla, where both tumors may occur. The axilla is not only one of the most common sites of cutaneous apocrine carcinoma because of its abundance of apocrine sweat glands, but also the most common site of ectopic breast tissue, from which breast apocrine carcinoma may arise. However, because of the rarity of both tumors, systematic comparative studies remain limited, and no reliable diagnostic strategy has yet been established. We reviewed the available clinicopathological, immunohistochemical, and molecular evidence comparing cutaneous and breast apocrine carcinoma, with particular emphasis on diagnostic challenges in the axillary region. Overall, conventional apocrine markers, including androgen receptor (AR) and gross cystic disease fluid protein 15 (GCDFP-15), consistently supported apocrine differentiation but showed substantial overlap between the two entities. Although several markers, including estrogen receptor (ER), trichorhinophalangeal syndrome type 1 (TRPS1), tumor protein p63 (p63), cytokeratin 5/6 (CK5/6), cytokeratin 14 (CK14), and podoplanin (PDPN), demonstrated differential expression tendencies, none showed sufficient consistency to serve as a stand-alone diagnostic marker because of limited cohort sizes and methodological heterogeneity across studies. These findings highlight the current limitations of immunohistochemistry alone for determining tumor origin. Emerging transcriptome-based molecular approaches may provide complementary diagnostic information and represent a promising future direction for improving the differential diagnosis of these rare tumors.