Sex Cord-Stromal Tumors of the Ovary: Diagnostic and Treatment Approach
Initial Diagnostic Workup
For any patient with suspected sex cord-stromal tumor, obtain pelvic ultrasound, abdomino-pelvic CT scan, and chest X-ray immediately 1. This imaging triad forms the foundation of diagnostic evaluation and staging.
Essential Laboratory Testing
- In premenopausal and young adult patients: Measure serum inhibin B, hCG, α-fetoprotein (AFP), LDH, complete blood count, and liver/renal function tests 1
- Inhibin B is the most sensitive tumor marker for granulosa cell tumors and should be obtained in all suspected cases 1, 2
- For premenarche girls with suspected gonadoblastoma: Obtain preoperative karyotype due to association with dysgenetic gonads 1
Pathological Confirmation
- Always obtain histological second opinion by an expert gynecologic pathologist trained in ovarian malignancies 1
- For morphologically ambiguous cases: Use immunopanel including inhibin alpha, calretinin, and FOXL2, plus FOXL2 mutational analysis (402C-G) to confirm adult granulosa cell tumors 1
- Standard immunohistochemical markers (α-inhibin, calretinin, SF-1, FOXL2) confirm sex cord-stromal differentiation but have limited utility distinguishing between subtypes 3
Surgical Management
Fertility-Sparing Approach (Preferred for Reproductive-Age Women)
Unilateral salpingo-oophorectomy with preservation of the contralateral ovary and uterus is the standard surgical treatment for stage I disease in women desiring fertility 1, 4. This approach is justified even in advanced disease due to high chemosensitivity 1.
Complete surgical staging includes:
- Infracolic omentectomy 1
- Peritoneal biopsies (diaphragmatic peritoneum, paracolic gutters, pelvic peritoneum) 1
- Peritoneal washings 1, 4
- No systematic lymphadenectomy is required - retroperitoneal evaluation is not mandatory for SCSTs 1, 4
- Lymph node dissection only if grossly abnormal nodes identified 1
Critical caveat: Perform endometrial curettage in all patients with granulosa cell tumors to rule out concomitant endometrial hyperplasia or adenocarcinoma, which occurs in 26.5% and 8.8% of cases respectively 1, 5.
Radical Surgery (Postmenopausal or Advanced Disease)
For postmenopausal women or advanced-stage disease with bilateral involvement: Perform total abdominal hysterectomy with bilateral salpingo-oophorectomy and complete surgical staging 1, 4.
Adjuvant Chemotherapy Indications
High-Risk Features Requiring Chemotherapy
Adjuvant platinum-based chemotherapy is indicated for:
- Stage IC disease (tumor rupture, surface involvement, positive washings) 4
- Poor differentiation (Grade 3) 1, 4
- Presence of heterologous elements 1, 4
- Retiform pattern in Sertoli-Leydig cell tumors 4
For stage IA well-differentiated SCSTs: Surgery alone is adequate with excellent prognosis (90% long-term disease-free survival) 1, 2.
Chemotherapy Regimens
BEP (bleomycin, etoposide, cisplatin) for 3-4 cycles is the standard first-line regimen 1, 4. Administer 3 cycles for completely resected disease and 4 cycles for macroscopic residual disease 1.
Important toxicity consideration: Do not give bleomycin to patients >40 years old or with pre-existing pulmonary disease due to excessive toxicity 1.
Alternative platinum-based regimens when BEP contraindicated:
- Carboplatin/paclitaxel 1, 4
- Etoposide/cisplatin (EP) 1
- Cyclophosphamide/doxorubicin/cisplatin (CAP) 1, 4
Non-randomized series suggest carboplatin/paclitaxel may be as effective as BEP with better tolerability in older patients 1.
Advanced and Recurrent Disease Management
Debulking surgery remains the most effective treatment for metastatic or recurrent granulosa cell tumors whenever feasible 1, 2. Platinum-based chemotherapy achieves 63-80% overall response rates in advanced/recurrent SCSTs 1.
Hormonal Therapy for Recurrent Disease
Consider hormonal therapy specifically for recurrent adult granulosa cell tumors that have failed or are not candidates for surgery and chemotherapy 2. Do not use as primary treatment for early-stage disease 2.
Evidence-based hormonal options:
- Aromatase inhibitors (letrozole) - documented responses 1, 2
- Tamoxifen - documented activity 1, 2
- Progestins - shown activity 1, 2
Critical pitfall: Do not substitute hormone therapy for platinum-based chemotherapy in treatment-naive advanced disease - chemotherapy remains first-line systemic therapy 2.
Surveillance Strategy
For Granulosa Cell Tumors (Indolent Course)
SCSTs require lifelong surveillance due to late recurrence risk - median time to relapse is 4-6 years, with documented recurrences up to 37 years after diagnosis 1, 2.
Follow-up schedule:
- Years 1-2: Every 3 months with clinical examination, pelvic exam, and inhibin B (if initially elevated) 1, 4, 2
- Year 3: Every 6 months 1, 4
- Years 4+: Every 6 months indefinitely 1, 2
Imaging surveillance:
- Pelvic ultrasound every 6 months for fertility-sparing surgery patients 1, 4, 2
- CT abdomen/pelvis when clinically indicated based on symptoms or tumor marker elevation 1, 2
Most common recurrence sites: Upper abdomen (55-70%) and pelvis (30-45%) 1.
Critical Clinical Pitfalls to Avoid
Do not perform radical surgery in reproductive-age patients with stage I disease - this compromises fertility without improving outcomes 4
Do not omit adjuvant chemotherapy in poorly differentiated stage IC tumors - poor differentiation is a clear high-risk feature requiring systemic therapy 1, 4
Do not discontinue follow-up prematurely - relapses occur decades later, necessitating lifelong surveillance 4, 2
Do not perform systematic lymphadenectomy - given very low incidence of retroperitoneal metastases in early-stage disease, this adds morbidity without benefit 1, 4
Do not forget endometrial evaluation in granulosa cell tumors - concurrent endometrial pathology occurs in over one-third of cases 1, 5