Endometrial Biopsy is Essential to Establish the Diagnosis
In this 65-year-old postmenopausal woman with multiple risk factors for endometrial cancer (obesity, diabetes, hypertension, hormone replacement therapy) presenting with 8 months of intermittent vaginal bleeding, endometrial biopsy (Option C) is the essential investigation to establish the diagnosis.
Rationale for Endometrial Biopsy
This patient presents with the classic presentation of endometrial cancer—abnormal uterine bleeding occurs in 90% of endometrial cancer cases, particularly in postmenopausal women 1. Her constellation of risk factors is particularly concerning:
- Obesity (BMI 37 kg/m²) increases endometrial cancer risk 3-4 fold 1
- Diabetes mellitus and hypertension are established risk factors 1
- Hormone replacement therapy represents unopposed or inadequate progestational protection 2
- Age >60 years places her in the peak incidence range for endometrial carcinoma 1
Endometrial biopsy using Pipelle or Vabra devices has extremely high sensitivity (99.6% and 97.1% respectively) for detecting endometrial carcinoma 1, 2. This makes it the most direct and accurate method to establish whether malignancy is present.
Why Not the Other Options?
Pelvic Ultrasonography (Option B) - Insufficient Alone
While transvaginal ultrasound is valuable as an initial screening tool, it cannot provide a definitive histological diagnosis 1, 2. The diagnostic algorithm recommended by ESMO guidelines suggests that endometrial thickness measurement (using a cut-off of 3-4 mm) should be followed by endometrial sampling 1.
Ultrasonography has limited diagnostic accuracy: sensitivity of 95-98% but specificity of only 35-47% at standard cut-offs 1. More importantly, ultrasound cannot distinguish between hyperplasia, polyps, and malignancy—it only identifies that further investigation is needed 1, 2.
In this symptomatic patient with multiple risk factors and 8 months of bleeding, proceeding directly to tissue diagnosis is appropriate and avoids unnecessary delay 1, 2.
Cervical Biopsy (Option A) - Wrong Target
Cervical biopsy evaluates cervical pathology, not endometrial pathology. This patient's presentation is classic for endometrial, not cervical, disease 1. While cervical cancer can cause postmenopausal bleeding, the risk factor profile (obesity, diabetes, HRT) specifically points to endometrial pathology.
Tumor Markers (Option D) - Not Diagnostic
Tumor markers like CA-125 have no role in the initial diagnosis of endometrial cancer 2. CA-125 may be helpful in monitoring clinical response in patients with extrauterine disease, but has significant limitations and cannot establish the diagnosis 2.
Critical Clinical Pitfalls to Avoid
Never accept inadequate or negative endometrial biopsy as reassuring in a symptomatic postmenopausal woman—office endometrial biopsies have a false-negative rate of approximately 10% 2, 3. If the initial biopsy is negative, non-diagnostic, or inadequate and symptoms persist, fractional D&C under anesthesia or hysteroscopy with directed biopsy must be performed 1, 2, 3.
Do not delay tissue diagnosis with imaging studies alone—preoperative pathological information is crucial for establishing the surgical plan, and all patients with risk of cancer should be investigated with endometrial biopsy or curettage to avoid inadequate surgery 1, 2.
Recommended Diagnostic Algorithm
Perform endometrial biopsy immediately using Pipelle or Vabra device in the office setting 1, 2
If biopsy is adequate and shows benign pathology but bleeding persists, escalate to hysteroscopy with directed biopsy 1, 2
If biopsy shows atypical hyperplasia or malignancy, refer immediately to gynecologic oncology for definitive surgical management 1, 4
Pelvic ultrasonography can be performed concurrently to evaluate tumor size, myometrial invasion, cervical involvement, and ovarian pathology, but should not replace tissue diagnosis 1
The answer is C: Endometrial biopsy.