Nonsmall cell neuroendocrine
carcinoma (NSCNEC) of the ovary is a rare and aggressive
tumor commonly associated with other surface epithelial and
germ cell neoplasms. In this study, we present the clinicopathologic and immunohistochemical features of 11 such cases seen at The University of Texas M.D. Anderson
Cancer Center in a 16-year period (1990 to 2005). Patients ranged in age from 22 to 63 years (mean 46.7). The most common presentation was abdominal/
pelvic pain (6 cases), followed by
ascites (2 cases), pelvic mass,
vaginal bleeding, and abdominal bloating (1 case each).
Tumors were mostly unilateral, cystic, or solid/cystic and ranged in size from 5 to 26 cm (mean 16.2). In 8 cases, NSCNEC was associated with other
epithelial neoplasms, including
mucinous neoplasms of low malignant potential,
mucinous carcinoma,
endometrioid carcinoma, mixed endometrioid and
mucinous carcinoma, and a high-grade
carcinoma, not otherwise specified. In 2 cases, the
tumor was associated with a mature cystic
teratoma; one of them also containing an invasive moderately differentiated
adenocarcinoma. A single case was associated with a benign
ovarian cyst. The latter case had a
dermoid cyst in the contralateral ovary. NSCNEC represented anywhere from 10% to 90% of the ovarian
tumor. Microscopically, the neuroendocrine component was usually composed of large and/or intermediate oval to round cells. In 2 cases, the intermediate cells were intermixed with small cells. Three cases had also spindle cells. The neoplastic cells were mostly arranged in a solid pattern, nests, or trabeculae. All
tumors had a brisk mitotic activity. Immunoperoxidase studies for
keratin cocktail,
cytokeratin (CK) 7, CK20, CAM 5.2,
chromogranin A,
synaptophysin, NSE, CD56, and c-kit were performed and the cases stained as follows:
keratin cocktail 6/6, CK7 4/5, CK20 3/5, CAM 5.2 3/3,
chromogranin A 8/11,
synaptophysin 9/9, NSE 1/1, CD56 4/8, and c-kit 5/7. According to the International Federation of Gynecology and Obstetrics staging system, 4 cases were stage I
tumors, 3 cases were stage III
tumors, and 4 cases were stage IV
tumors. Seven patients were treated with total abdominal
hysterectomy and bilateral
salpingo-oophorectomy followed by
chemotherapy. One patient had a bilateral
salpingo-oophorectomy with omentectomy and
appendectomy followed by
chemotherapy; 1 patient had a total abdominal
hysterectomy with right
salpingo-oophorectomy followed by
chemotherapy; one had a bilateral
salpingo-oophorectomy followed by
chemotherapy, and one had a right
salpingo-oophorectomy with
appendectomy followed by
chemotherapy. Five patients died of disease at 2, 3, 9, 20, and 36 months. One patient is alive with disease at 8 months and 5 are alive without evidence of disease at 11, 28, 37, 66, and 68 months. Four of 5 patients who died of disease had either stage III or IV
tumors and 3 of 5 patients who are alive without evidence of disease have stage I
tumors. In summary, ovarian NSCNEC is an aggressive
tumor with a tendency to present at advanced stage and cause death within a mean of 17 months after diagnosis; however, some patients, particularly those with stage I disease and/or those who have received
platinum-based
therapy, may have a more favorable prognosis.