Secretory carcinoma of the skin harboring ETV6 gene fusions

Mammary analogue secretory carcinoma is a low-grade salivary gland carcinoma that exhibits analogous features to secretory carcinoma of the breast including the presence of a t(12;15) translocation resulting in the ETV6-NTRK3 gene fusion. Rare cases of purported secretory carcinoma of the skin adnexa have been reported, but their relationship to true secretory carcinoma of the breast and salivary glands is unclear, as they generally do not harbor ETV6 rearrangements. Cases of cutaneous neoplasms with histologic features identical to secretory carcinoma of the breast and salivary glands were identified from the consultation files of 3 academic medical institutions. Immunohistochemistry was performed for S100 protein, mammaglobin and STAT5a. Break-apart fluorescence in situ hybridization was used evaluate for disruption of the ETV6 gene. Six cases of cutaneous secretory carcinoma were identified. The tumors arose in 4 women and 2 men, ranging from 24 to 71 years in age (mean, 47 y). The carcinomas presented in the skin of the axilla (n=4), ventral neck (n=1), and cheek (n=1). The tumors arose in the superficial dermis in association with adnexal structures. None of the patients had a prior or concurrent breast or salivary gland tumor. They were histologically characterized by well-circumscribed but unencapsulated proliferations of bland, eosinophilic cells arranged in microcysts and follicles with intraluminal secretions. Ectopic breast or salivary gland tissue was not identified. The cases were diffusely positive for S100 protein (6 of 6), mammaglobin (6 of 6), and STAT5a (5 of 5). All 6 cases harbored rearrangements of ETV6. All tumors were treated by simple excision alone. No recurrences or metastases developed in the 2 cases with follow-up. Secretory carcinoma of the skin represents a phenotypic, immunohistochemical, and genetic counterpart to secretory carcinoma of the breast and salivary glands. This tumor entity is less anatomically restricted than previously supposed.