Radiation Oncology/Ovary/Granulosa Cell Tumor

Granulosa Cell Tumor of the Ovary

Epidemiology

 * Uncommon, represents 2-5% of ovarian cancers
 * Incidence 1/100,000
 * Adult GCT
 * 95% of cases
 * Median age at diagnosis: perimenopausal (50-54)
 * Juvenile GCT
 * 5% of cases
 * Usually seen in prepubertal girls and women <30
 * Present with isosexual precocious pseudopuberty, or abdominal/pelvic pain due to large mass
 * Typically favorable prognosis
 * No association with known mutations, including BRCA1/BRCA2
 * Typically present with vaginal bleeding due to increased hormones

Histology

 * Derived from the granulosa cell (estradiol production)
 * Convert androstenedione produced in thecal cells to estradiol via aromatase
 * Categorized as sex cord-stromal tumor
 * Tumor markers
 * Estradiol
 * Even though granulosa cells produce estradiol, it's not a great marker
 * No elevation in ~30% of patients with GCT
 * Inhibin
 * Useful marker of GCT in pre- and post-menopausal women
 * Negative feedback stimulator of FSH
 * Levels should be low in post-menopausal women
 * Mullerian inhibitory substance (MIS)
 * Produced by granulosa cells in developing follicles, and is thus cyclical
 * Undecetable in post-menopausal women

Risk Factors

 * Clinical factors
 * Stage most important
 * Path factors
 * Large tumors (>10-15 cm worse)
 * Tumor rupture
 * High mitotic index

Survival

 * Staging uses FIGO System
 * Majority present with Stage I disease (80-90%)

Treatment Overview

 * Surgery is main initial management
 * Patients are typically in the same way as epithelial ovarian CA
 * Stage IA: Can consider fertility preservation with unilateral SO and careful staging
 * Otherwise: TAH/BSO (2-8% bilateral)
 * Perform endometrial biopsy to rule out concomitant uterine CA
 * Adjuvant therapy
 * Stage I (no RFs): none
 * Stage I (high risk):
 * Chemotherapy (BEP, EP, CAP, or single agent platinum) or
 * RT to whole pelvis or whole abdomen
 * Stage II:
 * Same as high risk Stage I: chemo or RT
 * Stage III/IV:
 * Platinum-based chemo
 * Whole abdomen RT if optimally debulked Stage III
 * Recurrent disease:
 * Secondary surgical debulking if feasible
 * Abdominal RT
 * Platinum-based chemo
 * Hormonal approaches (GNRH, tamoxifen, progestins) in selected patients

Radiation

 * MD Anderson, 1999 (1949-1988) PMID 10094877 -- "Radiation treatment of advanced or recurrent granulosa cell tumor of the ovary." (Wolf JK, Gynecol Oncol. 1999 Apr;73(1):35-41.)
 * Retrospective. 14 patients treated with RT for measurable residual or recurrent disease. Median F/U 13 years
 * RT: 10/14 moving strip whole abdomen to 27-28 Gy, 4/10 pelvic RT to 45-61 Gy
 * Response: 6/14 CR, but 3/6 failed 4-5 years later. 8/14 PD with median survival 12 months
 * Conclusion: RT can induce response, with occasional long-term remission

Review

 * Harvard, 2003 PMID 12637488 -- "Granulosa cell tumor of the ovary." (Schumer ST, J Clin Oncol. 2003 Mar 15;21(6):1180-9.)