What is the diagnostic approach for endometrial cancer?

Diagnostic Approach for Endometrial Cancer

Endometrial biopsy using an office-based Pipelle or Vabra device is the definitive diagnostic test for endometrial cancer, achieving sensitivities of 99.6% and 97.1% respectively for detecting carcinoma. 1

Initial Clinical Assessment

Key Presenting Symptoms

• Abnormal uterine bleeding is present in approximately 90% of endometrial cancer cases, particularly postmenopausal bleeding, which mandates immediate evaluation. 1, 2, 3
• Any postmenopausal bleeding—even a single episode—requires prompt diagnostic workup to exclude malignancy. 4, 3

Risk Factor Identification

• High-risk features include: obesity (3–4-fold increased risk), diabetes mellitus, hypertension, age >60 years, unopposed estrogen exposure, tamoxifen therapy, nulliparity, polycystic ovary syndrome, and Lynch syndrome. 1, 2
• Women with Lynch syndrome carry a 30–60% lifetime risk of endometrial cancer and require annual endometrial biopsy starting at age 30–35 years. 1

Diagnostic Algorithm

Step 1: Transvaginal Ultrasound (TVUS)

• TVUS is the recommended first-line imaging modality to assess endometrial thickness and identify structural abnormalities. 1, 4, 3
• Endometrial thickness ≤4 mm in postmenopausal women has a negative predictive value approaching 100% for endometrial cancer. 5, 4, 3
• Endometrial thickness ≥5 mm warrants tissue sampling regardless of symptoms. 5
• TVUS should be combined with transabdominal ultrasound when possible for complete pelvic assessment. 5

Critical caveat: Ultrasound cannot provide histologic diagnosis or reliably differentiate between hyperplasia, polyps, and malignancy—it only signals the need for tissue sampling. 1

Step 2: Endometrial Biopsy (Primary Diagnostic Test)

• Office endometrial sampling with Pipelle or Vabra device is the first-line tissue diagnosis method, with sensitivities of 99.6% and 97.1% respectively. 1, 6
• Biopsy is indicated for:
  • Postmenopausal bleeding with endometrial thickness ≥3–4 mm 1, 5
  • Any persistent or recurrent abnormal bleeding 1
  • Premenopausal women ≥35 years with risk factors and abnormal bleeding 1
  • All women ≥35 years with atypical glandular cells on cervical cytology 1

Important limitation: Office endometrial biopsy has a 10% false-negative rate. 1, 6

Step 3: Escalation for Inadequate or Negative Sampling

• If initial biopsy is inadequate, non-diagnostic, or negative but symptoms persist, proceed immediately to hysteroscopy with directed biopsy or fractional dilation and curettage (D&C) under anesthesia. 1, 4, 3, 6
• Hysteroscopy is the definitive diagnostic step, allowing direct visualization of the endometrium and targeted biopsy of focal lesions such as polyps. 1, 6
• Hysteroscopy achieves the highest diagnostic accuracy and should be used when blind sampling fails. 1

Step 4: Advanced Imaging (When Indicated)

• Saline infusion sonohysterography (SIS) demonstrates 96–100% sensitivity for endometrial pathology and should be employed when focal lesions are suspected or TVUS inadequately visualizes the endometrium. 1
• MRI is reserved for preoperative staging to assess myometrial invasion, cervical involvement, and lymph node status—not for initial diagnosis. 7
• CT and PET scans are used only for evaluating extrauterine disease spread, not for primary diagnosis. 1, 7

Critical Pitfalls to Avoid

Never Accept Reassurance Without Tissue Diagnosis

• Do not accept a negative or inadequate endometrial biopsy as reassuring in a symptomatic postmenopausal woman—the 10% false-negative rate mandates escalation to hysteroscopy or D&C. 1, 6
• Persistent bleeding after benign biopsy requires further evaluation regardless of initial results. 1, 4

Pap Smear Is Not a Diagnostic Tool

• Pap smear is designed to screen for cervical cancer, not endometrial pathology, and is inadequate for evaluating postmenopausal bleeding or suspected endometrial cancer. 1

Ultrasound Alone Is Insufficient

• While TVUS has 95–98% sensitivity at standard thresholds, specificity is only 35–47%. 1
• Ultrasound cannot differentiate benign from malignant pathology—tissue diagnosis is mandatory. 1

Special Populations Require Heightened Vigilance

• Tamoxifen users: Tamoxifen increases endometrial cancer risk 4-fold and uterine sarcoma risk; any bleeding mandates immediate tissue diagnosis before modifying therapy. 1, 8
• Rapidly growing fibroids in postmenopausal women: This pattern is highly suspicious for leiomyosarcoma and requires urgent tissue diagnosis, not observation. 8

Evidence Strength Summary

• The high sensitivities for Pipelle (99.6%) and Vabra (97.1%) devices are derived from large cohort studies (Level I evidence). 1
• The negative predictive value of endometrial thickness ≤4 mm (approaching 100%) is supported by multiple high-quality guidelines including ACOG 2018. 5, 4, 3
• Hysteroscopy as the gold standard for persistent symptoms is consistently recommended across NCCN, ESMO, and ACOG guidelines. 1, 4, 6