What is the appropriate workup and treatment for a postmenopausal woman presenting with abnormal vaginal bleeding suspected of having uterine cancer?

Workup for Uterine Cancer

Any postmenopausal woman with vaginal bleeding requires immediate evaluation with transvaginal ultrasound followed by endometrial biopsy, as approximately 10% of these patients will have endometrial cancer. 1, 2

Initial Diagnostic Algorithm

Step 1: Clinical Assessment

• Document bleeding characteristics to confirm the source is vaginal (not urologic or rectal), assess timing, duration, and severity 3
• Identify high-risk features including age >50 years (>90% of cases occur in this group), obesity (BMI >30), unopposed estrogen exposure, tamoxifen use, nulliparity, diabetes mellitus, hypertension, and Lynch syndrome (30-60% lifetime risk) 1, 4
• Perform pelvic examination with speculum to exclude cervical cancer, polyps, or vaginal atrophy as bleeding sources, and obtain Pap smear 3

Step 2: Transvaginal Ultrasound (First-Line Imaging)

• Measure endometrial thickness using a cut-off of 3-4mm; thickness ≤4mm has >99% negative predictive value for endometrial cancer 1, 5, 6
• Assess for structural abnormalities including polyps, fibroids, and ovarian masses 4, 3
• If endometrial thickness >4mm or not measurable, proceed immediately to endometrial sampling 1, 3
• If endometrial thickness ≤4mm and bleeding has stopped, observation with repeat ultrasound in 3 months is acceptable 3

Step 3: Endometrial Biopsy (Tissue Diagnosis)

• Office endometrial biopsy using Pipelle or Vabra devices has 99.6% and 97.1% sensitivity respectively for detecting endometrial carcinoma 1, 5
• Critical limitation: Office biopsy has a 10% false-negative rate 1, 5
• If initial biopsy is negative but bleeding persists, you must proceed to fractional dilation and curettage (D&C) under anesthesia—never accept a negative biopsy as reassuring in a symptomatic patient 1, 5, 7

Step 4: Advanced Evaluation When Needed

• Hysteroscopy with directed biopsy should be performed when initial sampling is inadequate, non-diagnostic, or if focal lesions (polyps) are suspected 1, 5
• Saline infusion sonohysterography can distinguish focal from diffuse pathology with 96-100% sensitivity when ultrasound findings are equivocal 5, 3

Special Population Considerations

Lynch Syndrome Patients

• Annual endometrial biopsy starting at age 30-35 years is mandatory due to 30-60% lifetime risk 1, 5
• Prophylactic hysterectomy with bilateral salpingo-oophorectomy should be offered after childbearing is complete 1

Tamoxifen Users

• Any vaginal spotting requires immediate endometrial sampling, as tamoxifen increases endometrial cancer risk to 2.20 per 1,000 women-years versus 0.71 for placebo 4
• Never stop tamoxifen before establishing tissue diagnosis—you must rule out malignancy first 5
• Hysteroscopy is particularly valuable in tamoxifen users due to increased polyp formation 5

Premenopausal Women with Risk Factors

• Endometrial biopsy is indicated for women with long-standing unopposed estrogen exposure, polycystic ovary syndrome, chronic anovulation, or age ≥35 years with atypical glandular cells on Pap smear 5

Additional Workup for Confirmed or Suspected Cancer

• CT, MRI, and PET scans are reserved for evaluating extrauterine disease based on clinical symptoms, physical findings, or abnormal laboratory results—not for initial diagnosis 1
• Serum CA-125 may be helpful for monitoring clinical response in patients with extrauterine disease, but has limitations (falsely elevated with peritoneal inflammation, normal with isolated vaginal metastases) 1
• Universal tumor testing for Lynch syndrome (immunohistochemistry and/or microsatellite instability testing for MLH1, MSH2, MSH6) should be performed on all endometrial cancer specimens 1

Critical Pitfalls to Avoid

• Never accept inadequate tissue sampling as definitive—the 10% false-negative rate of office biopsy mandates escalation to D&C or hysteroscopy if symptoms persist 1, 5
• Never proceed to hysterectomy without tissue diagnosis—this exposes patients to unnecessary surgical risk if pathology is benign 5
• Never assume fibroids explain postmenopausal bleeding—uterine sarcoma and endometrial cancer must be excluded, with sarcoma risk reaching 10.1 per 1,000 in women aged 75-79 years 4
• Never use transvaginal ultrasound as a screening tool in asymptomatic postmenopausal women without bleeding—it is not validated for this purpose 6