Ovarian neuroendocrine carcinomas of non-small-cell type associated with surface epithelial adenocarcinomas. A study of five cases and review of the literature.

Five primary ovarian carcinomas composed of a high-grade neuroendocrine tumor of non-small-cell type and a surface-epithelial-stromal tumor are reported. The five tumors presented in women aged 36 to 77 (mean, 57) years with abdominal distension or a palpable mass in three cases, right lower quadrant pain with tenderness and fever in one case, and a cervicovaginal smear showing a high estrogen effect in one postmenopausal patient. The tumors were unilateral, 9 to 30 (mean, 16) cm in greatest dimension, and had solid and cystic components. Three tumors were stage I; one, stage II; and one, stage III. Two patients who received chemotherapy died of tumor 8 and 36 months postoperatively, another who refused chemotherapy but later received radiation died of tumor after 19 months, a fourth was lost to follow-up, and a fifth was treated recently. Microscopically, the neuroendocrine components of all the tumors were composed predominantly of sheets, closely packed islands, cords, and trabeculae of epithelial cells with little intervening stroma. The tumor cells in the neuroendocrine areas were medium-sized to large compared with the cells of small cell carcinoma, and they contained scanty to moderate amounts of cytoplasm and hyperchromatic nuclei with coarse chromatin clumping in three cases and abundant cytoplasm and vesicular nuclei with single, large eosinophilic nucleoli in the other two. In all the cases, areas of necrosis and single-cell necrosis were extensive, and mitotic figures were abundant. Positive argyrophil and argentaffin reactions were observed in occasional to many cells in all cases. The glandular components of the tumors were grade 1/3 endometrioid adenocarcinoma (one case), grade 2/3 mucinous adenocarcinoma (2 cases), and mucinous borderline tumor with small foci of mucinous adenocarcinoma (two cases). Numerous enterochromaffin cells were identified in hematoxylin and eosin sections of the borderline mucinous components of two tumors; occasional nonargentaffin argyrophilic cells were present in the endometrioid and mucinous carcinoma components. Luteinized stromal cells were present focally in two cases, including the case in which there was evidence of a high estrogen level. Immunohistochemical studies in five cases showed staining of most cells in the solid components for cytokeratin and chromogranin A and some to most cells for serotonin and neuron-specific enolase. Neuropeptides that were detected in the solid component of one or more of the cases included vasoactive intestinal peptide, somatostatin, gastrin, and glucagon; negative results were obtained for pancreatic polypeptide and insulin. Flow cytometry in four tumors revealed that the neuroendocrine component was aneuploid in two, suspicious for aneuploidy in one, and diploid in one. Tumors of the type described are distinct pathologically from primary ovarian carcinoid tumors and small cell carcinoma of pulmonary type. Although experience with this type of tumor is limited, the prognosis appears to be poor.