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Am J Surg Pathol. 2007 May;31(5):774-82.

Ovarian nonsmall cell neuroendocrine carcinoma: a clinicopathologic and immunohistochemical study of 11 cases.

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  • 1Department of Pathology, The University of Texas Medical School at Houston, Houston, TX 77030, USA.


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.

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