Pathogenesis

About 15% to 20% of cases with endometrioid carcinoma coexist with endometriosis, although an origin directly from ovarian surface epithelium is also possible. The women with associated endometriosis are usually about a decade younger than women with endometrioid carcinoma that is not associated with endometriosis. Molecular studies have found relatively frequent mutations in the PTEN tumor suppressor gene and in the KRAS and β-catenin oncogenes, as well as microsatellite instability.90 Similar to endometrioid carcinomas of the endometrium, p53 mutations are common in the poorly differentiated tumors. Interestingly, in endometrioid carcinomas associated with endometriosis, identical PTEN mutations have been detected in both the carcinoma and the endometriosis, suggesting that PTEN mutations may precede the development of malignancy.91

Morphology. In gross appearance, endometrioid carcinomas present as a combination of solid and cystic areas, similar to other cystadenocarcinomas. Forty percent involve both ovaries, and such bilaterality usually, though not always, implies extension of the neoplasm beyond the genital tract. These are low-grade tumors that reveal glandular patterns bearing a strong resemblance to those of endometrial origin. The 5-year survival rate for patients with stage I tumors is approximately 75%.

Clear Cell Adenocarcinoma

Benign and borderline clear cell tumors are exceedingly rare, and clear cell carcinomas are uncommon. They are characterized by large epithelial cells with abundant clear cytoplasm similar to hypersecretory gestational endometrium. Because these tumors sometimes occur in association with endometriosis or endometrioid carcinoma of the ovary and resemble clear cell carcinoma of the endometrium, they are now thought to be of müllerian origin and variants of endometrioid adenocarcinoma.75 Little is currently known about the molecular alterations that underlie the pathogenesis of these tumors. The clear cell tumors of the ovary can be predominantly solid or cystic. In the solid neoplasm, the clear cells are arranged in sheets or tubules. In the cystic variety, the neoplastic cells line the spaces. The 5-year survival rate is approximately 65% when the tumors are confined to the ovaries; however, these tumors tend to be aggressive, and with spread beyond the ovary, a survival of 5 years is exceptional.

Cystadenofibroma

Cystadenofibromas are variants in which there is more pronounced proliferation of the fibrous stroma that underlies the columnar lining epithelium. These benign tumors are usually small and multilocular and have simple papillary processes that do not become as complicated and branching as those found in the ordinary cystadenoma. They may be composed of mucinous, serous, endometrioid, and transitional (Brenner tumors) epithelium. Borderline lesions with cellular atypia and, rarely, tumors with focal carcinoma occur, but metastatic spread of either is extremely uncommon.

Brenner Tumor

Brenner tumors are classified as adenofibromas in which the epithelial component consists of nests of transitional-type epithelial cells resembling those lining the urinary bladder. Less frequently, the nests contain microcysts or glandular spaces lined by columnar, mucin-secreting cells.

Morphology. These neoplasms may be solid or cystic, are usually unilateral (approximately 90%), and vary in size from small lesions less than 1 cm in diameter to massive tumors up to 20 and 30 cm (Fig. 22-41A). The fibrous stroma, resembling that of the normal ovary, is marked by sharply demarcated nests of epithelial cells resembling the epithelium of the urinary tract, often with mucinous glands in their center (Fig. 22-41B). Infrequently, the stroma is composed of somewhat plump fibroblasts resembling theca cells; such neoplasms may have hormonal activity. Most Brenner tumors are benign, but borderline (proliferative Brenner tumor) and malignant counterparts have been reported.

Several reports have emphasized the occurrence of ovarian tumors that are composed in part or entirely of neoplastic epithelium similar to transitional carcinoma of the bladder but without a coexisting Brenner component. Though often referred to as transitional cell carcinoma, these tumors are frequently seen in association with conventional serous or endometrioid carcinomas and probably represent altered differentiation patterns of the tumor cells.

GERM CELL TUMORS

Germ cell tumors constitute 15% to 20% of all ovarian tumors.75 Most are benign cystic teratomas, but the remainder, which are found principally in children and young adults, have a higher incidence of malignant behavior and pose problems in histologic diagnosis and in therapy. They bear a remarkable similarity to germ cell tumors in the male testis (Chapter 21) and arise in a similar manner (Fig. 22-42).