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American Journal of Surgical Pathology:
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Small Cell Carcinoma of the Ovary, Hypercalcemic Type: A Clinicopathological Analysis of 150 Cases.

Young, Robert H. M.D.; Oliva, Esther M.D.; Scully, Robert E. M.D.

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Abstract

The clinical and pathological features of 150 cases of ovarian small cell carcinoma of the hypercalcemic type are described. The patients ranged from 9 to 43 (average 23.9) years of age. The serum calcium level was known to be elevated in 49 of the 79 patients (62%) whose preoperative calcium levels were measured. Four of these patients had symptoms of hypercalcemia, and one of them had undergone neck exploration with negative results before the ovarian tumor was discovered. At laparotomy the tumor was unilateral in 148 cases (99%). Extraovarian spread was present in approximately half the cases. The tumors ranged from 6 to 26 (average 15.3) cm in greatest dimension. Microscopic examination disclosed various patterns, the most common of which was diffuse sheets of cells punctured by variable numbers of follicle-like spaces; the tumor cells also grew in nests, cords, clusters, and singly. The follicle-like spaces, which were present in 80% of the cases, contained fluid that was almost always eosinophilic and rarely basophilic. Glands or cysts lined by mucinous epithelial cells were present in 12% of the neoplasms. The neoplastic cells were typically small and round with hyperchromatic nuclei and brisk mitotic activity. Fifty percent of the tumors, however, also had a variable component of cells with moderate to abundant amounts of eosinophilic cytoplasm, which sometimes contained large hyaline globules and large nuclei that were typically paler and had more prominent nucleoli than the small cells. Immunohistochemical staining confirmed the epithelial nature of the tumors, as did electron microscopy, which characteristically showed abundant dilated rough endoplasmic reticulum. Five of seven tumors investigated by immunohistochemical staining for parathyroid hormone-related protein showed positive results. All 23 tumors examined by flow cytometry with interpretable results were diploid. Fourteen of 42 patients (33%) with stage IA disease for whom follow-up information is available remained well and free of disease 1-13 (average 5.7) years postsurgery; 23 died of their disease, usually within 2 years; and five had recurrences but were alive at last follow-up. Almost all the patients with tumors of a stage higher than IA died of disease, but one patient with stage IIB disease who received intensive chemotherapy and radiation therapy is alive and apparently free of disease at 7 years. Features in stage IA tumors that appeared to be associated with a more favorable outcome included an age > 30 years, a normal preoperative calcium determination, a tumor size < 10 cm, and an absence of large cells. The tumors in this series were frequently misinterpreted initially as a variety of other ovarian neoplasms, most commonly adult or juvenile granulosa cell tumors or a primitive germ cell tumor, but the characteristic microscopic features of the small cell carcinoma facilitate its distinction from those tumors and others with which it may be confused. Analysis of the various types of therapy in the present series suggests that a procedure that includes bilateral salpingo-oophorectomy may be optimal for patients with stage IA tumors. The role of adjuvant therapy is unclear. Combination chemotherapy and radiation therapy for high-stage and recurrent tumors has been generally disappointing, but it has occasionally resulted in long-term survival and possible cure.

(C) Lippincott-Raven Publishers.

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