Primary Neuroendocrine Carcinoma of the Vagina With Merkel Cell Carcinoma Phenotype

Abstract

We describe a case of primary neuroendocrine carcinoma arising from the anterior vaginal wall of a 67-year-old woman. Primary neuroendocrine carcinoma of the vagina is a rare entity with only 25 previously reported cases in the literature. In previous reports, these tumors have not been distinguished from primary neuroendocrine carcinoma of the skin (Merkel cell carcinoma). The tumor was composed of cells that showed neuroendocrine-type nuclear features with hyperchromasia, nuclear molding, occasional small nucleoli, and a chromatin pattern that was finely granular. The tumor cells were positive for cytokeratin 20 (CK20), neuron specific enolase, pancytokeratin, epithelial membrane antigen, and chromogranin A expression. Ki-67, a marker of proliferation, was also positive in>90% of cells. The tumor cells showed intense expression of Bcl-2 oncoprotein and mild to moderate expression of c-KIT. Synaptophysin, neurofilament, CD45, CD56, CD10, S-100, HMB-45, cytokeratin 7, and thyroid transcription factor 1 were negative. This pattern of staining is consistent with a Merkel cell carcinoma. This is the first report of a primary neuroendocrine carcinoma of the vagina with a Merkel cell phenotype. Previous studies have not distinguished primary neuroendocrine carcinoma of the vagina from Merkel cell carcinoma of the skin. Positive expression of CK20 in primary small cell carcinoma of the vagina might represent a Merkel cell carcinoma subtype of this tumor.

Merkel cell carcinoma: what we know now

“…In 1996, its expression was seen in 15 out of 20 MCC tumors in two studies [63,64]. Over the years, the finding has been verified by other groups as well [65][66][67]. Specifically,…”

Extracutaneous Merkel cell carcinomas harbor polyomavirus DNA

“…Tumors sharing the same features have been reported in other sites such as lymph nodes [20,21], parotid gland [16,17], oral cavity [18], breast [14,15], and vagina [19]. Trisomy of chromosome 6, the most frequent cytogenetic alteration reported in 47% of cutaneous MCCs, has been also detected in 50% of nodal MCCs [21].…”

“…Tumors identical to MCC of the skin in terms of histology, immunohistochemistry, and cytogenetics have been reported in several organs including breast [14,15], salivary glands [16,17], oral mucosa [18] and vaginal wall [19] as well as lymph nodes [20,21].…”

A Case of Small Cell Carcinoma of the Vagina

“…4 Immunohistochemical staining was positive for CK20, cytokeratin (AE1/AE3, CAM5.2), NSE, chromogranin A, and synaptophysin. 4,5 Also in our case, small cell carcinoma was diagnosed on the basis of the following findings: alveolar growth of atypical cells with a high N/C ratio in the biopsy tissue of the vaginal tumor and immunostaining positive for chromogranin A and synaptophysin.…”