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Radiation Oncology/Ovary/Granulosa Cell Tumor

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< Radiation Oncology | Ovary
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Granulosa Cell Tumor of the Ovary


Epidemiology

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  • 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

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  • 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

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


Survival

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


Stage 5-year OS 10-year OS
I 95% 90%
II 65% 55%
III/IV 35% 25%


Treatment Overview

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  • 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

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  • 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

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