What is the most likely diagnosis and recommended management for a patient presenting with a thickened endometrium with negative biopsy, a septated cystic adnexal mass, and elevated inhibin‑B levels?

Granulosa Cell Tumor Until Proven Otherwise

This clinical triad—thickened endometrium with negative biopsy, septated cystic adnexal mass, and elevated inhibin B—is highly suggestive of a granulosa cell tumor (GCT) of the ovary, and you should proceed with gynecologic oncology referral for surgical evaluation and staging.

Why This Diagnosis is Most Likely

Elevated inhibin B is the critical diagnostic clue here. Inhibin B is a highly sensitive and specific marker for granulosa cell tumors, with a sensitivity of 98.8% and specificity of 88.9% at a cut-off of 7 pg/mL 1. In healthy postmenopausal women, inhibin B becomes unmeasurable 2, making any elevation pathologically significant. The combination of:

• Elevated inhibin B (essentially pathognomonic for GCT in this context)
• Septated cystic adnexal mass (GCTs characteristically present as complex cystic masses)
• Thickened endometrium (from estrogen production by the tumor causing endometrial stimulation)
• Negative endometrial biopsy (the endometrium itself is not malignant; it's responding to hormonal stimulation)

This constellation strongly points to a hormone-secreting ovarian sex cord-stromal tumor, most commonly adult-type granulosa cell tumor.

Immediate Management Algorithm

Step 1: Confirm Menopausal Status

• If postmenopausal: Any inhibin B elevation is abnormal and highly concerning 2
• If premenopausal: Interpret inhibin B in context of menstrual cycle, though marked elevation remains concerning

Step 2: Complete Imaging Characterization

MRI pelvis with and without IV contrast is the next appropriate imaging study 3, 4. The septated cystic mass needs full characterization because:

• MRI provides superior tissue characterization for indeterminate adnexal masses 3
• It can assess for solid components, enhancement patterns, and extraovarian disease
• CT abdomen/pelvis with contrast should also be considered if there's concern for metastatic disease 5

Step 3: Risk Stratification Using O-RADS

Based on the septated cystic nature, this mass likely falls into O-RADS 4 or 5 category (10-50% or >50% malignancy risk) 4. Key features that increase malignancy risk:

• Multilocular-solid components
• Irregular walls or septations
• Size >10 cm
• Presence of solid tissue with color flow on Doppler

Step 4: Urgent Gynecologic Oncology Referral

Do not attempt initial surgical management without gynecologic oncology involvement 6, 5. Granulosa cell tumors require:

• Comprehensive surgical staging with lymphadenectomy for accurate staging 5
• Frozen section analysis during surgery 5
• Expertise in fertility-sparing surgery if the patient desires future fertility (unilateral salpingo-oophorectomy may be appropriate for stage IA disease) 5

Critical Pitfalls to Avoid

Don't Dismiss the Negative Endometrial Biopsy

The negative biopsy doesn't rule out malignancy—it simply confirms the endometrium itself isn't the source. The thickened endometrium is a secondary effect of estrogen hypersecretion from the ovarian tumor. In postmenopausal women, endometrial thickness >11 mm warrants evaluation 7, but here the pathology is ovarian, not endometrial.

Don't Delay Based on "Benign-Appearing" Cystic Features

Granulosa cell tumors characteristically appear as complex cystic masses that can mimic benign lesions like endometriomas or hemorrhagic cysts. The elevated inhibin B overrides any reassuring imaging features 1.

Don't Perform Laparoscopic Cystectomy Without Oncology Input

If malignancy is confirmed, inadequate initial surgery (cyst rupture, incomplete staging) significantly worsens prognosis and may necessitate reoperation 5. Laparoscopy is acceptable only if comprehensive staging can be achieved and a gynecologic oncologist is involved 5.

Role of Inhibin B in Ongoing Management

If GCT is confirmed surgically, inhibin B becomes your primary surveillance tool 1:

• Levels correlate with tumor burden and lesion size
• Inhibin B >15.6 pg/mL corresponds to 25% probability of abnormal imaging
• Inhibin B >73.6 pg/mL corresponds to 75% probability of recurrence 1
• Serial measurements guide timing of imaging, avoiding unnecessary scans when levels are undetectable

Alternative Considerations (Less Likely)

While the elevated inhibin B makes GCT most likely, other sex cord-stromal tumors (thecomas, Sertoli-Leydig cell tumors) can present similarly but are far less common. The negative endometrial biopsy also excludes primary endometrial pathology as the driver, though simple endometrial hyperplasia can coexist with other conditions 8.

Bottom line: Treat this as ovarian malignancy until surgical pathology proves otherwise. The inhibin B elevation demands aggressive evaluation and specialist involvement.