Granulosa cell tumors, which secrete estrogen, are seen in women of all ages. They are found in prepubertal girls in 5% of cases; the remainder are found in women throughout their reproductive and postmenopausal years (422). Granulosa cell tumors are bilateral in only 2% of patients.
Granulosa cell tumors range from a few millimeters to 20 cm or more in diameter. The tumors are rarely bilateral and have a smooth, lobulated surface. The solid portions of the tumor are granular, frequently trabeculated, and yellow or gray-yellow in color. After clear cell carcinoma, the granulosa-theca cell tumor is probably the most inaccurately diagnosed tumor of the female gonad. Of 477 ovarian tumors from the Emil Novak Ovarian Tumor Registry diagnosed initially as granulosa-theca cell tumors, almost 15% were reclassified after histologic review. Lesions misdiagnosed as granulosa cell tumors included primary or metastatic carcinomas, teratoid tumors, and poorly differentiated mesothelial tumors (419).
The classic adult granulosa cell is round or ovoid with scant cytoplasm. The nucleus contains compact, finely granular chromatin and is either euchromatic or hypochromatic (3). “Coffee bean” grooved nuclei are characteristic; mitotic figures may be present, but numerous mitotic figures should prompt consideration for poorly differentiated or undifferentiated carcinoma. In the most common variety, the adult granulosa cells show a tendency to arrange themselves in small clusters or rosettes around a central cavity, so there is a resemblance to primordial follicles (i.e., Call-Exner bodies) (Fig. 37.23). The stroma is similar to the theca and may be luteinized. In children and adolescents, the granular cell tumors are often cystic, contain luteinized cells, and can be associated with precocious puberty. Juvenile granulosa cell tumors, so named because of their tendency to occur in younger patients, feature rounder, more hyperchromatic nuclei and may contain numerous mitotic figures. The presence of large, irregular follicle spaces is an additional distinguishing feature of the juvenile granulosa cell tumor. The adult granulosa cell tumor tends to occur in older women and the juvenile tumor in children and young women, but the diagnosis is not based on age of presentation, but on histology. Adult granulosa cell tumors, but not juvenile granulose cell tumors, harbor a somatic mutation in the FOXL2 gene (426).
Figure 37.23 Granulosa cell tumor of the ovary. Note the classic Call-Exner bodies with a minimal stromal component in this tumor of folliculoid pattern. (Arrow points to an example.)
Granulosa cell tumors, which secrete estrogen, are seen in women of all ages. They are found in prepubertal girls in 5% of cases (typically the juvenile form); the remainder are distributed throughout the reproductive and postmenopausal years (422– 425). They are bilateral in only 2% of patients.
Of the rare prepubertal lesions, 75% are associated with sexual pseudoprecocity because of the estrogen secretion (422). Most reproductive-age patients have menstrual irregularities or secondary amenorrhea, and, frequently, cystic hyperplasia of the endometrium. Abnormal uterine bleeding is often the initial symptom for postmenopausal women. The estrogen secretion in these patients can be sufficient to stimulate the development of endometrial cancer. Low-grade endometrial cancer occurs in association with granulosa cell tumors in at least 5% of cases, and 25% to 50% are associated with endometrial hyperplasia (2,413,419–422,426).