Sertoli-Leydig Cell Tumors (Androblastomas)

These tumors recapitulate, to a certain extent, the cells of the testis at various stages of development.105 They commonly produce masculinization or at least defeminization, but a few have estrogenic effects. They occur in women of all ages, although the peak incidence is in the second and third decades. The embryogenesis of such male-directed stromal cells remains a puzzle. These tumors are unilateral and may resemble granulosa-theca cell neoplasms.

Morphology. The cut surface is usually solid and varies from gray to golden brown in appearance (Fig. 22-50A). On histologic examination the well-differentiated tumors show tubules composed of Sertoli cells or Leydig cells interspersed with stroma (Fig. 22-50B). The intermediate forms show only outlines of immature tubules and large eosinophilic Leydig cells. The poorly differentiated tumors have a sarcomatous pattern with a disorderly disposition of epithelial cell cords. Leydig cells may be absent. Heterologous elements, such as mucinous glands, bone, and cartilage, may be present in some tumors.

The incidence of recurrence or metastasis by Sertoli-Leydig cell tumors is less than 5%. These neoplasms may block normal female sexual development in children and may cause defeminization of women, manifested by atrophy of the breasts, amenorrhea, sterility, and loss of hair. The syndrome may progress to striking virilization (hirsutism) associated with male distribution of hair, hypertrophy of the clitoris, and voice changes.

Other Sex Cord-Stromal Tumors

The ovarian hilum normally contains clusters of polygonal cells arranged around vessels (hilar cells). Hilus cell tumors (pure Leydig cell tumors) are derived from these cells and are rare, unilateral, and characterized histologically by large lipid-laden cells with distinct borders. A typical cytoplasmic structure characteristic of Leydig cells (Reinke crystalloids) is usually present. Women with hilus cell tumors usually present with evidence of masculinization, hirsutism, voice changes, and clitoral enlargement. The tumors are unilateral. The most consistent laboratory finding is an elevated 17-ketosteroid excretion level unresponsive to cortisone suppression. Treatment is surgical excision. True hilus cell tumors are almost always benign. On occasion, histologically identical tumors occur in the cortical stroma (nonhilar Leydig cell tumors).

In addition to Leydig cell tumors, the stroma may rarely give rise to tumors composed of pure luteinized cells, producing small benign tumors generally less than 3 cm in diameter. The tumor may produce the clinical effects of androgen, estrogen, or progesterone stimulation.

As mentioned before, the ovary in pregnancy may show microscopic nodular proliferation of theca cells in response to gonadotropins. Rarely, a frank tumor may develop (termed pregnancy luteoma) that closely resembles a corpus luteum of pregnancy. These tumors have been associated with virilization in pregnant patients and in their respective female infants.

Gonadoblastoma is an uncommon tumor thought to be composed of germ cells and sex cord-stroma derivatives. It occurs in individuals with abnormal sexual development and in gonads of indeterminate nature. Eighty percent of patients are phenotypic females, and 20% are phenotypic males with undescended testicles and female internal secondary organs. On microscopic examination the tumor consists of a mixture of germ cells and sex cord derivatives resembling immature Sertoli and granulosa cells arranged in nests. A coexistent dysgerminoma occurs in 50% of the cases. The prognosis is excellent if the tumor is completely excised.106