Ovarian and testicular SCST are associated with multiple enchondromatosis (Ollier’s disease) as well as with Peutz-Jeghers syndrome (PJS). Patients with enchondromatosis may develop granulosa cell tumors. Gonadal tumors in PJS include sex cord-stromal tumors with annular tubules (SCST-AT); one third of patients with SCST-AT have PJS. Tumors in patients with PJS tend to present at a younger age and may be bilateral. Patients with PJS may also develop granulosa cell tumors. Peutz-Jegher syndrome is associated with germ line mutations in STK11/LKB1 tumor suppressor gene located on chromosome 19p13.3. Most gonadal stromal tumors, however, are not associated with any of these established familial tumor syndromes.
Testicular juvenile granulosa cell tumors have sometimes been associated with Y chromosome structural abnormalities and with ambiguous genitalia. In contrast to the epithelial ovarian cancers, there is no known association between BRCA1 or BRCA2 germline mutations and gonadal SCST.
The International OTST Registry committee recently described ovarian sex cord stromal tumors, particularly Sertoli-Leydig cell tumors (SLCT), but also juvenile granulosa cell tumors and gynandroblastomas, in association with Pleuropulmonary Blastoma (PPB), a rare lung tumor of early childhood. DICER1 mutations are common in children and families with a history of PPB and have been observed in children and adolescents with ovarian sex cord stromal tumors (SLCT, juvenile granulosa cell tumors and/or gynandroblastoma) and a personal or family history of PPB or other conditions seen in this familial syndrome such as renal tumors, lung cysts, additional gonadal tumors or childhood sarcomas. Sertoli-Leydig tumors are also sometimes associated with nodular thyroid disease and this association has been reported in constellation with DICER1 mutations.
When a person is diagnosed with an ovarian or testicular stromal tumor, they should be carefully evaluated for a personal or family history of dysplastic or neoplastic conditions.
Most children with ovarian or testicular stromal tumors are currently thought to have sporadic tumors and the prevalence of germline DICER1 gene mutations in these children is unknown. It is also not yet clear how DICER1 germline mutations lead to the development of gonadal stromal tumors and if there are any implications for treatment and prognosis. We hope that additional research will lead to answers to some of these difficult questions.