What is the diagnostic approach for granulosa cell tumors of the ovaries?

Diagnostic Approach for Granulosa Cell Tumors of the Ovaries

The diagnosis of ovarian granulosa cell tumors requires a comprehensive workup including pelvic ultrasound, abdomino-pelvic CT scan, chest X-ray, and PET scan in selected cases, along with specific tumor markers and histopathological confirmation by an expert pathologist. 1

Clinical Presentation

Granulosa cell tumors (GCTs) typically present with:

• Subacute pelvic pain
• Feeling of pelvic pressure due to pelvic mass
• Menstrual irregularities 1
• Postmenopausal bleeding (in older women) due to endometrial hyperplasia 1
• Hormonal manifestations (estrogen excess) 1
• Some patients (approximately 30%) may be asymptomatic 2

Diagnostic Algorithm

Step 1: Imaging Studies

• Transvaginal and transabdominal ultrasound (first-line imaging)

  • Look for characteristic features:
    • Multilocular-solid masses (52%)
    • Purely solid masses (39%)
    • Large tumors (median diameter 102 mm)
    • Multiple small locules (>10) in multilocular tumors
    • Mixed or low-level echogenicity 2
    • Moderate to high vascularity on color Doppler (color score 3-4) 3, 2

• Abdomino-pelvic CT scan - for better characterization and staging 1

• Chest X-ray - to rule out metastatic disease 1

• PET scan - in selected cases for evaluation of metastatic disease 1

Step 2: Laboratory Tests

• Hormone levels:
  • Inhibin B - elevated in 80-90% of cases (key biomarker) 4
  • Estradiol - often elevated 5
• Other tumor markers:
  • CA-125 (may be elevated but non-specific)
• Complete blood count
• Liver and renal function tests 1

Step 3: Endometrial Assessment

• Endometrial curettage/biopsy - must be performed to rule out concomitant uterine cancers, as endometrial pathology is found in up to 54% of patients due to estrogen production by the tumor 1, 2

Step 4: Histopathological Confirmation

• Surgical specimen - definitive diagnosis requires histopathological examination 1
• Expert pathologist review - histological second opinion by an expert pathologist should always be considered 1

Histopathological Diagnosis

• Adult form characteristics:

  • Small uniform cells with scanty cytoplasm
  • Grooved nuclei ("coffee bean" appearance)
  • Small eccentric nucleoli
  • Macrofollicular, microfollicular, solid, insular or trabecular patterns
  • Characteristic Call-Exner bodies 1

• Immunohistochemistry panel:

  • Inhibin alpha (positive)
  • Calretinin (positive)
  • FOXL2 (positive)
  • CD99 and melan A (positive) 1

• Molecular testing:

  • FOXL2 (402C-G) mutation analysis - useful to confirm diagnosis in morphologically ambiguous cases 1

Diagnostic Challenges and Pitfalls

• GCTs can be misdiagnosed as benign or other cystic tumors, especially when presenting as pure cystic lesions 5
• Juvenile GCTs (occurring in patients <20 years) may present differently with sexual precocity 1
• Varying histopathological features can make diagnosis difficult, including tumor cells with luteinization or free cell clusters 5
• Differential diagnosis includes other ovarian tumors, particularly endometrioid carcinoma or carcinoid tumors 1

Follow-up After Diagnosis

• Regular follow-up with transvaginal ultrasound is essential for monitoring recurrence 3
• Inhibin levels should be monitored to detect recurrence 6
• Sonographic features of recurrences are comparable to those of primary tumors 3

Key Points to Remember

• GCTs account for 2-8% of all ovarian malignancies 7
• They are more difficult to diagnose than epithelial ovarian tumors 7
• Most GCTs are unilateral and confined to the ovary at diagnosis 1
• Bilateral presentation is rare, especially with pure cystic features 5
• Tumor stage at diagnosis remains the most important prognostic factor 1

By following this diagnostic approach, clinicians can accurately identify granulosa cell tumors of the ovary and initiate appropriate treatment to improve patient outcomes.