Malignant sex cord stromal tumor of ovary (ORPHA:35808)
Malignant sex cord stromal tumor (SCST) of ovary is a rare ovarian cancer (see this term) arising from granulosa, theca, sertoli and leydig cells or stromal fibroblasts, occurring at any age and presenting with abdominal or pelvic mass, and characterized (with the exception of fibroma) by the production of sex steroids resulting in manifestations of hormone excess, with a relatively favorable prognosis.
Epidemiology
Age related incidence rate was found to be 1 per 500,000 women. Sex cord stromal tumors constitute about 5% of ovarian malignancies.
Clinical description
Malignant SCST of ovary may occur at any age but usually occurs in child bearing or post menopausal age groups, presenting with manifestations of mass effect (abdominal pain or distention, gastrointestinal symptoms, or abdominal mass) and/or signs of sex hormone production (isosexual precocity including breast swelling and vaginal bleeding, primary or secondary amenorrhea, and/or virilization). Malignant SCST of ovary comprises the following 4 histological forms: gynandroblastoma; malignant granulosa cell tumor of ovary; malignant Sertoli-Leydig cell tumor of ovary; and malignant steroid cell tumor of ovary, not otherwise specified (see these terms).
Etiology
Mutations in the DICER1 (14q32.13) gene have been found to be a susceptibility factor for SCST, particularly in malignant Sertoli-Leydig cell tumor of ovary.
Diagnostic methods
Diagnosis is based on clinical features, particularly hormonal manifestations, and is supported by imaging (ultrasonogram, computed tomography) and tumor markers. Malignant granulosa cell tumor of ovary produces inhibin A and B which is helpful in diagnosis and follow-up. A FOXL2 mutation (3q23) has been found in most malignant granulosa cell tumors of the ovary, in adults. Chromosomal abnormalities have been recently detected among granulosa cell tumors and they include trisomy 12, monosomy 22 and chromosome 6 deletion. Diagnosis is confirmed by histological examination.
Differential diagnosis
Differential diagnoses include the more common malignant ovarian germ cell tumor of ovary, small cell carcinoma of the ovary (see this term) and ovarian metastasis of non-gonadal tumors. Malignant SCST of ovary is also found in association with enchondromatosis, Peutz Jeghers syndrome (see these terms) and Maffuci syndrome.
Management and treatment
Surgery is performed for staging, histological confirmation and debulking. Total abdominal hysterectomy and bilateral salphingo-oopherectomy is often the initial management. Fertility sparing surgery is offered to patients with localized disease. In the absence of significant infiltration, preservation of the uterus along with the contralateral tube and ovary is attempted in children. Adjuvant chemotherapy is given to patients with advanced tumors.
Prognosis
Hormonal symptoms lead to earlier diagnosis and hence a better prognosis in many malignant SCST tumors of ovary. Initial stage at diagnosis is the main prognostic factor. Histological type, presence of atypia and mitotic rate are other important prognostic factors. Stage, tumor size and presence of residual tumor after surgery influence the risk of recurrence

                            Last update: 
                            October 2014


                            - Expert reviewer(s): 
                            Pr Mojgan DEVOUASSOUX  - Pr Isabelle RAY-COQUARD