Clinical Pearls & Morning Reports
Published August 23, 2023
The designation of juvenile granulosa-cell tumors was developed approximately 50 years ago to differentiate these tumors, which are encountered in young patients, from the more familiar neoplasms that typically occur in the late reproductive and early postmenopausal years and are now referred to as adult granulosa-cell tumors. Read the NEJM Case Records of the Massachusetts General Hospital here.
Q: What are some of the features of juvenile granulosa-cell tumors?
A: Juvenile granulosa-cell tumors account for only 2 to 5% of all ovarian tumors, but they are the most common malignant sex cord–stromal tumors of the ovary in adolescents, occurring at a mean age of 13 years. Granulosa-cell tumors are typically unilateral and appear as septated, cystic or solid masses on imaging. They are frequently associated with ascites and intratumor hemorrhage. Patients typically present with abdominal pain.
Q: How do juvenile and adult granulosa-cell tumors differ?
A: Juvenile granulosa-cell tumors are characterized by more primitive nuclei with brisker mitotic activity, a more haphazard pattern of follicles, and more abundant, typically eosinophilic cytoplasm of the neoplastic cells. The designation “juvenile” encapsulates the histologic features that typically occur in young patients, and the designation “adult” encapsulates those that typically occur in older patients, but as with so many aspects of neoplasms, there are exceptions to these general rules. For example, adult granulosa-cell tumors can occur in children, and in a large study of juvenile granulosa-cell tumors, approximately 3% of the tumors occurred in patients older than 30 years of age.
A: Inhibin A and B are glycoproteins secreted by granulosa cells to regulate follicle-stimulating hormone, which induces both the synthesis and the secretion of inhibin. Inhibin B is secreted by the granulosa cells of developing follicles, with the level peaking in the early-to-mid-follicular phase, whereas inhibin A is secreted by the corpus luteum, with the level peaking in the mid-luteal phase. In patients with granulosa-cell tumors that secrete inhibin B, high levels of inhibin B can suppress the normal follicle-stimulating hormone response, which in turn can lead to irregular menses or even amenorrhea. In addition, most patients with granulosa-cell tumors have an elevated estradiol level due to both secretion by granulosa cells and peripheral conversion of androstenedione secreted by granulosa cells. Elevated estradiol levels can lead to precocious (early) puberty in children and can cause endometrial hypertrophy in postpubertal or peripubertal patients.
A: There is consensus that localized juvenile granulosa-cell tumors can be managed with surgery alone, with an excellent prognosis. It is equally clear that treatment with chemotherapy is indicated when these tumors have spread beyond the primary lesion to mesenteric lymph nodes, the peritoneal surface, or liver or lung. Despite the use of chemotherapy, disseminated disease is associated with a much poorer long-term outcome. In cases in which the tumor capsule has been disrupted but there is no clear evidence of tumor spread, the use of chemotherapy as adjuvant treatment remains controversial.