Ovarian sex cord-stromal tumors originate from the sex cords and mesenchymal tissues of the primitive gonads, accounting for 5–8% of ovarian tumors. These tumors are more commonly observed in females during puberty, reproductive age, and perimenopause. During normal embryonic development, the sex cord tissues of the primitive gonads evolve into Sertoli cells of the seminiferous tubules in males or granulosa cells of the ovaries in females, while the specialized mesenchymal tissue develops into Leydig cells in male testes or theca cells in female ovarian follicles. Ovarian sex cord-stromal tumors arise from abnormal differentiation or proliferation of these sex cord or specialized mesenchymal tissues, retaining their endocrine activity, which is why they are also known as functional ovarian tumors. These tumors may be composed of a single type of cell or a mixture of different cell types.
Pathology
Granulosa-Stromal Cell Tumors
These tumors are composed of granulosa cells derived from the sex cords and stromal components such as fibroblasts and theca cells.
Granulosa Cell Tumors
Granulosa cell tumors are classified into adult and juvenile types, with 95% being of the adult type. These are low-grade malignancies that can occur at any age but are most common between the ages of 45 and 55. These tumors often secrete estrogen, leading to symptoms such as precocious puberty in prepubertal patients, menstrual irregularities in reproductive-age women, and irregular vaginal bleeding in postmenopausal women. They are frequently associated with endometrial hyperplasia and, in some cases, endometrial cancer. Most tumors are unilateral, round or oval, with a lobulated appearance and a smooth surface. They are typically solid-cystic, though some may be entirely solid or cystic. The cut surface is soft, yellow to brown, and may show areas of hemorrhage and necrosis. Microscopically, granulosa cells exhibit various growth patterns, with the diffuse pattern being the most common, where tumor cells grow in sheets. Other patterns include trabecular, cord-like, and ribbon-like arrangements. A characteristic feature is the Call-Exner body, where granulosa cells form rosette-like structures around small spaces containing eosinophilic material and nuclear debris. Tumor cells have scant, pale cytoplasm, indistinct cell borders, and round to oval nuclei with nuclear grooves. Prognoses are generally favorable, with a 5-year survival rate exceeding 80%, though there is a risk of late recurrence.
Juvenile granulosa cell tumors account for only 5% of granulosa cell tumors. These tumors primarily affect adolescents and young women, with an average age of 13 years. Microscopically, the tumor often shows nodular or diffuse growth, with irregular follicle-like structures of varying size and shape. The cells have abundant cytoplasm, lack nuclear grooves, and exhibit higher mitotic activity. Prognoses are good since most patients present with early-stage disease localized to one ovary. However, ruptured tumors, positive cytology in ascitic fluid, or extra-ovarian growth increase the risk of postoperative recurrence.
Theca Cell Tumors
Theca cell tumors are stromal cell tumors that are typically benign. These tumors are most common in women over the age of 40 and are usually unilateral, round, oval, or lobulated in shape, with a thin, shiny fibrous capsule covering the surface. The cut surface is solid and gray-yellowish. Microscopically, tumor cells resemble theca cells, appearing as short spindle-shaped cells with lipid-rich cytoplasm, arranged in interwoven bundles or diffusely. Elevated estrogen levels in these patients can lead to endometrial hyperplasia and, in some cases, endometrial cancer. Malignant cases are rare, and their prognosis is more favorable compared to epithelial ovarian cancer.
Fibroma
Fibromas account for 2–5% of ovarian tumors and are most common in middle-aged women, with unilateral cases being predominant. These tumors have a smooth or nodular surface and are solid, hard, and gray-white on cross-section. Microscopically, the tumor is composed of spindle-shaped cells arranged in a woven pattern. When associated with ascites and pleural effusion, these cases are termed Meigs syndrome, with the effusions resolving spontaneously after tumor excision.
Sertoli-Leydig Cell Tumors
Sertoli-Leydig cell tumors are rare and mostly occur in women under the age of 40. Between 40% and 60% of patients exhibit masculinization. Most cases are unilateral, and the tumors are usually small, with a smooth or sometimes lobulated surface. They are solid or solid-cystic, with a gray-yellow cut surface. The tumors are classified into well-differentiated, moderately differentiated, and poorly differentiated types based on the differentiation of the Sertoli cell tubular structures and the amount of primitive gonadal stroma. Well-differentiated tumors are benign, while moderately and poorly differentiated tumors are malignant. Five-year survival rates range from 70% to 90%.
Diagnosis
The clinical manifestations of ovarian sex cord-stromal tumors are often nonspecific. Granulosa cell tumors and theca cell tumors with endocrine function may result in symptoms related to high estrogen levels, such as abnormal vaginal bleeding, endometrial thickening, or postmenopausal bleeding. Sertoli-Leydig cell tumors secreting androgens may lead to symptoms of masculinization. Granulosa cells can secrete estrogen and inhibin, which serve as markers for serum testing. The definitive diagnosis of ovarian sex cord-stromal tumors relies on histopathological examination.
Treatment
Benign Sex Cord-Stromal Tumors
The treatment strategy is similar to that for benign epithelial ovarian tumors.
Malignant Sex Cord-Stromal Tumors
Surgical Treatment
Surgical management follows the principles used for epithelial ovarian cancer. For patients without fertility-preservation requirements, comprehensive staging surgery is indicated. For young patients with stage IA or IC disease desiring fertility preservation, unilateral salpingo-oophorectomy may be performed while sparing fertility, and lymph node dissection can be avoided if lymph nodes are not enlarged. Active surgical intervention is recommended for recurrent sex cord-stromal tumors.
Postoperative Adjuvant Therapy
Low-risk stage I patients are advised to undergo regular follow-ups after surgery. High-risk stage I patients (stage IC, grade 3, or tumors exceeding 10 cm in diameter) may consider chemotherapy or continued observation. Chemotherapy based on platinum-containing regimens is recommended postoperatively for patients with stage II–IV disease. Preferred regimens include paclitaxel combined with carboplatin (TC), or alternatively bleomycin, etoposide, and cisplatin (BEP). Radiation may be considered for localized lesions.