Cutaneous Neuroendocrine Mucinous Carcinomas Are Low-grade But May Be Associated With Other Cancers

Primary cutaneous mucinous sweat gland carcinoma is said to be prognostically stratifiable by neuroendocrine differentiation, however, this assertion is based on historical data and older staining techniques. We aimed to evaluate the percentage of mucinous and nonmucinous adnexal tumors expressing the newer, more sensitive neuroendocrine marker insulinoma-associated protein 1 (INSM1), and to assess clinicopathologic features in patients cohorted by this phenotype. Of 12 available adnexal/cutaneous adenocarcinomas, 9 were mucinous, 3/9 of which were INSM1-negative, and 2/3 with nodal metastases. Of 3 nonmucinous cases, all were INSM1-negative, 1/3 with nodal metastasis, and 2/3 with lymphovascular invasion. In contrast, of 6 mucinous INSM1-positive cases, no cases had LVI or metastasis, however, 3 patients died during follow-up, 2 from breast or urothelial cancer. A fourth patient developed breast carcinoma. INSM1-positive tumors, from cheek (3), scalp (2), and chin (1) were estrogen receptor and progesterone receptor positive. No cases of apocrine adenoma or hidrocystoma, basal cell, or sebaceous carcinoma labeled with INSM1. While most primary cutaneous mucinous carcinomas are of the neuroendocrine type, our study confirms the presence of occasional non-neuroendocrine mucinous carcinomas. We validate the association of such tumors and nonmucinous non-neuroendocrine adnexal carcinoma with intermediate-grade behavior, including lymph node metastases, but not death. Conversely, neuroendocrine expressing primary cutaneous mucinous carcinoma may represent the well-differentiated neuroendocrine neoplasm/neuroendocrine tumor primary to skin, with low-grade behavior, but attendant risk of germline susceptibility to other aggressive extracutaneous tumors. Routine assessment of cutaneous adnexal carcinoma with INSM1 and longer term follow-up and cancer screening of patients with positive staining is recommended.