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.)