Ovarian Sex Cord Stromal Tumors (OSCSTs)

Patients with OSCSTs characteristically present with abdominal distension and may often suffer from abdominal discomfort and pain1. Hormone secreting tumors may present with signs of precocious puberty such as breast swelling, pubic hair, vaginal bleeding – characteristic of estrogen-secreting GrCTs – or virilisation and hirsutism – characteristic of androgen-secreting SLCTs.8 Some patients may present with symptoms of acute abdomen, caused by adnexal/ovarian torsion. Malignant GCTs and small cell carcinomas of the ovary, hypercalcemic type (SMARCA4 deficient) present the two most relevant differential diagnoses of OSCSTs. OSCSTs are different from GCTs in terms of their clinical presentation and their biology including associated genetic tumor predisposition syndromes.10
OSCSTs are histologically heterogeneous and include GrCTs, SLCTs, pure Sertoli cell and Leydig cell tumors, as well as theca and granulosa-theca tumors, sclerosing stromal tumors, sex cord-stromal tumors with annular tubules, and gynandroblastomas with simultaneous Sertoli and granulosa cell differentiation. They may arise in the context of several defined hereditary disorders. Juvenile GrCTs may be associated with multiple enchondromatosis, syn. Ollier’s disease.11, 12 Otherwise, no pathognomonic genetic aberration has been defined for juvenile GrCTs, but approximately one third may show point mutations of stimulatory G proteins.13
SLCTs are consistently associated with mutations of the DICER1gene.3, 14, 15 A report from the International Ovarian and Testicular (OTST) Registry found germline DICER1 mutations in approximately half of patients with SLCTs 4. In this group, a spectrum of other cancers has been reported, of which thyroid cancer was seen in 4/25 patients. These findings have significant impact on long-term follow-up of these patients and the surveillance of potentially affected family members. 16
Last, there is a pronounced association of Peutz-Jeghers syndrome with sex cord stromal tumors with annular tubules (SCTAT) of both the testis and ovary.12, 17 Approximately one third of SCTAT appear to develop in the context of Peutz-Jeghers syndrome. These tumors usually develop at a younger age than in otherwise healthy patients and may develop bilaterally.

Diagnostic work-up (Table III)