Management of Granulosa Theca Cell Tumors
The management of granulosa theca cell tumors should prioritize fertility-sparing surgery for early-stage disease in young patients, with unilateral salpingo-oophorectomy being the standard surgical approach, while reserving adjuvant chemotherapy for advanced stages or high-risk features. 1
Diagnostic Workup
- Initial evaluation should include pelvic ultrasound, abdomino-pelvic CT scan, chest X-ray, and in selected cases, PET scan 1
- Laboratory tests should include tumor markers such as inhibin B, estradiol, LDH, and in young patients, complete blood count and liver and renal function tests 1
- Histological confirmation by an expert pathologist is essential, with immunohistochemistry panel including inhibin alpha, calretinin, and FOXL2 in morphologically ambiguous cases 1
Surgical Management
Early-Stage Disease (Stage I)
For young patients desiring fertility preservation:
- Unilateral salpingo-oophorectomy with preservation of the contralateral ovary and uterus is the standard surgical treatment 1
- No systematic biopsy of the contralateral ovary is necessary when it appears macroscopically normal 1
- Endometrial curettage must be performed to rule out concomitant uterine cancers 1
- Retroperitoneal lymph node dissection is not mandatory due to the very low incidence of retroperitoneal metastases in early-stage disease 1
For postmenopausal women or those with completed childbearing:
- Abdominal hysterectomy and bilateral salpingo-oophorectomy with careful surgical staging 1
Advanced-Stage Disease (Stage II-IV)
- Debulking surgery remains the most effective treatment of advanced or recurrent granulosa cell tumors 1
- Fertility-sparing surgery should be considered even in advanced disease due to the high chemosensitivity of these tumors 1
- Nodal debulking surgery is only required in cases of residual disease after chemotherapy 1
Adjuvant Therapy
Early-Stage Disease (Stage I)
- Stage IA adult granulosa cell tumor has excellent prognosis after surgery alone and does not require adjuvant therapy 1
- Adjuvant therapy should be considered for:
Advanced-Stage Disease (Stage II-IV)
- Platinum-based chemotherapy is the treatment of choice 1
- BEP (bleomycin, etoposide, cisplatin) regimen is most commonly used:
- Alternative chemotherapy options include:
Recurrent Disease Management
- Debulking surgery is the most effective treatment when feasible 1
- For platinum-sensitive relapse (progression >4-6 weeks after completion of chemotherapy), platinum-based combinations should be considered 1
- For platinum-resistant disease, options include:
- Hormonal therapies including GnRH agonists, tamoxifen, progestins, and aromatase inhibitors have shown responses in adult granulosa cell tumors 1
Follow-up
- Follow-up visits should include history, physical examination with pelvic examination, and tumor markers every 3 months for the first 2 years, then every 6 months during years 3-5 1
- Long-term follow-up is essential as recurrences can occur up to 20 years after primary diagnosis 1
- Pelvic ultrasound and CT scan of abdomen, pelvis, and chest (if lung metastases are suspected) are the most common imaging techniques for surveillance 1
- Serum tumor markers including inhibin B, estradiol, and AMH (anti-Müllerian hormone) can be useful for monitoring 1
Special Considerations and Pitfalls
- Tumor rupture during surgery should be avoided as it may upstage the disease and require adjuvant chemotherapy 3, 4
- Fertility outcomes are generally favorable after fertility-sparing surgery, with multiple reports of successful pregnancies 5, 4, 6
- After completion of family planning, completion surgery with hysterectomy and removal of remaining adnexa should be considered due to the risk of late recurrence 6
- The indolent nature of these tumors requires long-term surveillance, as recurrences can occur decades after initial diagnosis 1