Paraganglioma of the ovary: report of three cases of a rare ovarian neoplasm, including two exhibiting inhibin positivity.

Paraganglioma is one of the rarest neoplasms to involve the ovary, whether primary or metastatic, with only two previous reports. We describe three examples that occurred in patients 22, 58, and 68 years of age. Two patients had hypertension. Two tumors involved the left ovary and one the right ovary; they ranged from 8 to 22 cm, were solid, and were tan, brown, or yellow. One tumor was confined to the ovary; in the second case, there were tumor deposits on the posterior surface of the uterus and the contralateral ovary; in the other case, there was peri-aortic lymph node involvement and peritoneal deposits. In all cases, however, radiologic investigations did not reveal an alternative primary site. On microscopic examination, all three tumors showed a predominantly nested "zellballen" pattern with groups of cells surrounded by a vascular stroma. Tumor cells largely had abundant granular eosinophilic cytoplasm with, in 2 cases, focal clear cell areas. In 1 case, bizarre tumor giant cells were present. Immunohistochemically, all neoplasms were cytokeratin negative and diffusely positive with neuroendocrine markers. In 1 case, there was an S-100-positive population of sustentacular cells. Two cases were positive for inhibin, one focal and one diffuse, and the other was focally positive for calretinin. Electron microscopy performed in 2 cases revealed dense core neuroendocrine granules. One patient has been followed up for 15 years and is alive and well. Although metastatic spread from an undetected primary outside the ovary cannot be totally excluded for the 2 cases with extraovarian disease, we think that the neoplasms most likely represent primary ovarian paragangliomas. Because various neoplasms in the sex cord-stromal and steroid categories are likely to enter into the differential diagnosis, inhibin and calretinin positivity represents a significant potential diagnostic pitfall. The differential is broad and may include many other ovarian tumors, particularly those with an oxyphilic cell type. Possible theories of histogenesis of primary ovarian paraganglioma include an origin from extra-adrenal paraganglia in the region of the ovary or unidirectional differentiation within a teratoma.