Abstract

Cutaneous metastases from non-cutaneous neuroendocrine neoplasms are exceedingly rare, with literature limited to case reports and few case studies. We performed a retrospective review from September 1st, 2010 to September 30th, 2020 of the histopathologic, immunohistochemical and clinical characteristics of metastatic neuroendocrine neoplasms to the skin from non-cutaneous primaries. 14 patients were identified for the study (9 males and 5 females; mean age of 59.5 years). 15 skin specimens from 14 patients were available for review. At the time of skin biopsy, a known non-cutaneous neuroendocrine neoplasm was present in 7/14 of patients. Primary sites of neuroendocrine carcinoma included lung (n=5), terminal ileum (n=2), and 1 each from prostate, breast, rectum, uterus, esophagus, and sinus, with one unknown (suspected bladder malignancy). 11/14 patients are dead of disease; 1/14 was lost to follow up. All 15 specimens showed subcutaneous/deep dermal involvement with 6/15 involving the papillary dermis and 1 involving the epidermis. The tumors ranged from well- to poorly-differentiated. 2/15 specimens showed focal CK20 positivity (one metastatic uterine small cell carcinoma and one metastatic ileal carcinoid). TTF-1 was performed in 13 specimens and was positive in 6, of which 2/6 were of non-pulmonary origin. Cutaneous metastases from non-cutaneous neuroendocrine neoplasms are rare, however, distinction from primary neuroendocrine carcinomas of the skin (Merkel cell carcinoma) guides clinical management. While immunohistochemical stains, in particular CK20, CK7 and TTF-1, are integral in the work up of confirming the origin of neuroendocrine tumors found in the skin, results vary and are often non-specific for a single primary site. Therefore, clinical imaging should be recommended to further aid in the identification of a non-cutaneous primary neoplasm.

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