Primary Cutaneous Apocrine Carcinoma: Clinicopathologic, Immunohistochemical, and Molecular Characterization of Twenty-Seven Cases.
case_series · Level IV
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- Also identified by DOI 10.1016/j.modpat.2026.101082.
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Abstract
We present the clinicopathologic, immunohistochemical, and molecular findings of 27 primary cutaneous apocrine carcinoma (PCACs). Most patients were male (67%) and the axilla was the most common site (52%). Regional lymph node metastasis was seen in 14 patients (56%) and both lymph node and distant metastasis in one patient (4%). Eight patients (32%) were deceased at last follow-up. PCACs exhibit various morphologies including papillary, tubular, cribriform, solid, and signet ring cell/histiocytoid. The signet ring cell/histiocytoid morphology was seen adjacent to a tubular component in six cases (22%). An in-situ component was seen in 14 cases (52%). Perineural invasion and lymphovascular invasion were seen in 9 (33%) and 6 (22%) cases, respectively. All PCACs showed diffuse and strong androgen receptor (AR) expression (23/23; 100%); estrogen receptor (ER) (6/25; 24%) and progesterone receptor (PR) expression (4/23; 17%) was seen in subset of cases. Six cases showed 3+ HER2 expression; three showed HER2 amplification. Gross cystic disease fluid protein-15 (GCDFP-15) expression was seen in 20/20 (100%). Adipophilin was seen in 1/15 (7%), keratin 5/6 in 13/17 (76.5%), and mammaglobin in 5/16 (31%). Targeted DNA sequencing and fusion assays were performed on 12 and 9 cases, respectively. Recurrently mutated genes include ERBB2 (5/11, 45%), KMT2C (5/11, 45%), PIK3CA (3/12, 25%), TP53 (2/12, 17%), and SETD2 (2/11, 17%). One case harbored both an ERBB2::PPP1R1B fusion and an AR-V7 splice variant. Another case harbored only an AR-V7 splice variant; a RARA intronic deletion was seen in one case. In summary, PCACs frequently occur in the axilla of males, demonstrate a variety of histomorphologies, and may have an in-situ component; they are AR+, ER +/-, PR +/- and can have HER2 amplification. ERBB2, KMT2C, and PIK3CA recurrent alterations were observed. These findings may allow for both distinction from histopathologic mimics and for the use of targeted therapy.