What is the most likely diagnosis for an ovarian cyst on transvaginal ultrasound in a 70‑year‑old postmenopausal woman with elevated estrogen and low luteinizing hormone (LH) and follicle‑stimulating hormone (FSH)?

Ovarian Cyst with Elevated Estrogen and Suppressed Gonadotropins in a 70-Year-Old Woman

The most likely diagnosis is an estrogen-producing sex cord-stromal tumor, specifically a granulosa cell tumor or thecoma-fibroma, given the combination of elevated estrogen with suppressed LH and FSH in a postmenopausal woman with an ovarian cyst. 1, 2

Diagnostic Reasoning

Hormonal Pattern Analysis

The hormonal profile is the critical diagnostic clue in this case:

• Elevated estrogen in a postmenopausal woman is pathological and indicates autonomous hormone production, as normal postmenopausal ovaries do not produce significant estrogen 1
• Suppressed LH and FSH with elevated estrogen represents negative feedback, confirming that the estrogen elevation is physiologically active and not a laboratory artifact 1
• This specific pattern (high estrogen, low gonadotropins) is characteristic of estrogen-secreting ovarian tumors rather than functional cysts, which should not occur in postmenopausal women 3, 1

Most Likely Tumor Types

Sex cord-stromal tumors (SCSTs) are the primary consideration:

• Granulosa cell tumors are the most common estrogen-producing ovarian tumors in postmenopausal women, accounting for 12.9% of all SCSTs 2
• Thecoma-fibroma group tumors are sex cord-stromal neoplasms most commonly seen in postmenopausal patients, appearing as solid hypoechoic masses with smooth margins, acoustic shadowing, and minimal Doppler flow 4
• SCSTs occur significantly more frequently in postmenopausal women (9.5% vs 2.1% in premenopausal women, p<0.0001) 2

Estrogen-producing endometrioid adenocarcinoma is a less common but important differential:

• This variant of ovarian cancer can mimic sex cord-stromal tumors both clinically and on imaging, presenting with elevated estrogen (48.7-83.0 pg/mL) and suppressed FSH in postmenopausal women 1
• These tumors often appear as predominantly solid masses with homogeneous yellow coloration and may be misdiagnosed as granulosa cell tumors or thecomas on preoperative MRI 1

Clinical Manifestations to Assess

Look for these specific estrogenic manifestations:

• Postmenopausal vaginal bleeding is the most common presenting symptom, occurring due to endometrial stimulation 1, 5
• Cervicovaginal cytology showing maturation of squamous epithelium and active endometrial proliferation 1
• Endometrial thickening on imaging or endometrial hyperplasia/cancer on biopsy (estrogen stimulation effect) 1
• Less commonly, hirsutism or virilization if the tumor produces androgens (seen in approximately 10% of granulosa cell tumors) 5

Imaging Characteristics

Transvaginal ultrasound with color Doppler findings:

• Solid hypoechoic masses with smooth margins and acoustic shadowing suggest thecoma-fibroma 4
• Predominantly solid growth pattern with homogeneous appearance may be seen 1
• Minimal Doppler flow is characteristic of thecoma-fibroma group tumors 4
• Complex masses with both solid and cystic components can occur 1

MRI pelvis with IV contrast is the next appropriate step:

• MRI is the modality of choice for indeterminate adnexal masses to determine organ of origin and characterize solid components 4
• MRI can help distinguish between sex cord-stromal tumors and epithelial malignancies, though preoperative imaging may misdiagnose estrogen-producing endometrioid adenocarcinoma as SCST in up to 75% of cases 1

Critical Management Algorithm

Step 1: Confirm the hormonal pattern

• Repeat estradiol, LH, and FSH measurements to verify the pattern 1
• Obtain testosterone and DHEA-S if any signs of virilization are present 5

Step 2: Perform endometrial assessment

• Transvaginal ultrasound to measure endometrial thickness 1
• Endometrial biopsy if endometrial thickness >4-5 mm or any postmenopausal bleeding, as estrogen-producing tumors carry risk of concurrent endometrial hyperplasia or cancer 1

Step 3: Advanced imaging

• Obtain MRI pelvis with IV contrast for definitive characterization of the mass 4
• Do NOT rely on CT for characterization, as it has poor soft-tissue discrimination for adnexal masses 4

Step 4: Tumor marker assessment

• CA-125 should be obtained, though it may be normal in sex cord-stromal tumors and low-grade malignancies 4
• Inhibin A and B are more specific markers for granulosa cell tumors but are not routinely available 6

Step 5: Surgical referral

• Immediate gynecologic oncology consultation is mandatory for any postmenopausal woman with a solid or complex ovarian mass and hormonal abnormalities 7
• Surgical exploration with frozen section is required for definitive diagnosis, as imaging cannot reliably distinguish between benign and malignant SCSTs or exclude estrogen-producing epithelial cancer 1

Important Caveats and Pitfalls

Do not assume benignity based on imaging alone:

• Even small, solid-appearing masses with benign imaging features can harbor malignancy in postmenopausal women with hormonal abnormalities 1
• Conservative management with serial ultrasound is NOT appropriate when there is biochemical evidence of hormone production 4, 1

Do not delay surgical evaluation:

• The combination of an ovarian mass with elevated estrogen and suppressed gonadotropins in a postmenopausal woman requires surgical diagnosis, as this pattern indicates a functioning tumor that will not resolve spontaneously 1, 2
• Approximately 10-20% of granulosa cell tumors are malignant, and estrogen-producing endometrioid adenocarcinomas are by definition malignant 1, 2

Recognize that CA-125 has limited utility:

• CA-125 performs worse than ultrasound in distinguishing benign from malignant lesions and may be normal in sex cord-stromal tumors and borderline malignancies 4, 3
• Normal CA-125 does NOT exclude malignancy in this clinical scenario 3, 1