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)