What is the best course of action for an elderly woman with postmenopausal (postmenopausal) vaginal bleeding and abdominal cramping, an enlarged uterus, and thin friable vaginal mucosa?

Management of Postmenopausal Bleeding with Enlarged Uterus

This elderly woman requires immediate endometrial tissue sampling via office endometrial biopsy to rule out endometrial cancer, which is the most likely diagnosis given her postmenopausal bleeding and enlarged uterus. 1

Immediate Diagnostic Workup

Primary Tissue Diagnosis

• Office endometrial biopsy is the standard first-line diagnostic procedure for obtaining histological assessment in this clinical scenario, with sensitivity of 99.6% for detecting endometrial carcinoma. 1, 2
• The false-negative rate of office endometrial biopsy is approximately 10%, which is critical to recognize in symptomatic patients. 1
• If the initial office biopsy is negative but bleeding persists, fractional dilation and curettage (D&C) under anesthesia must be performed to avoid missing the diagnosis. 1, 2

Complementary Imaging

• Transvaginal ultrasound (TVUS) should be performed to measure endometrial thickness and identify structural abnormalities, though tissue diagnosis remains mandatory given her symptoms. 2
• Endometrial thickness >4 mm on TVUS in a postmenopausal woman with bleeding warrants endometrial biopsy regardless. 2
• The enlarged uterus raises concern for both endometrial cancer and uterine sarcoma, which must be ruled out even if fibroids are present, as the risk of unexpected uterine sarcoma increases with age (up to 10.1 per 1,000 in patients 75-79 years). 2

Additional Diagnostic Considerations

When Initial Biopsy is Non-Diagnostic

• Hysteroscopy with directed biopsy should be performed if bleeding persists or recurs after a negative or inadequate endometrial biopsy, as it can identify focal lesions such as polyps that blind sampling may miss. 1, 2
• Hysteroscopy is particularly valuable for evaluating the endometrium when office biopsy fails to provide adequate tissue or when focal pathology is suspected. 1

Baseline Studies

• Complete blood count should be obtained to assess for anemia from chronic bleeding. 3
• Chest imaging (chest X-ray) is recommended as part of the initial workup. 1
• Consider CA-125 if extrauterine disease is suspected, though it may be falsely elevated with peritoneal inflammation and normal with isolated vaginal metastases. 1

Critical Clinical Context

High-Risk Features Present

• Postmenopausal bleeding occurs in approximately 90% of endometrial cancer cases, making this the cardinal presenting symptom. 1
• The enlarged uterus in a postmenopausal woman is particularly concerning and increases suspicion for malignancy. 1
• Thin, friable vaginal mucosa reflects hypoestrogenic state typical of menopause but does not exclude malignancy. 1

Common Pitfall to Avoid

• Never rely solely on a single negative endometrial biopsy in a symptomatic patient - the 10% false-negative rate mandates repeat sampling via D&C if symptoms persist. 1, 2
• Do not assume fibroids or benign pathology explain the enlarged uterus without tissue diagnosis, as endometrial cancer and uterine sarcoma must be definitively excluded in elderly patients with postmenopausal bleeding. 2

Genetic Screening Consideration

• If endometrial cancer is diagnosed, universal tumor testing for DNA mismatch repair (MMR) deficiencies should be performed to identify Lynch syndrome, which accounts for approximately 5% of endometrial cancers. 1
• MLH1 loss should be further evaluated for promoter methylation to distinguish somatic from germline mutations. 1