Definitions of PMB, VUS, and EMB in Women's Health
PMB stands for Postmenopausal Bleeding, VUS stands for Variant of Unknown Significance (a genetic/molecular term not specific to women's health), and EMB stands for Endometrial Biopsy—a critical diagnostic procedure for evaluating abnormal uterine bleeding.
Postmenopausal Bleeding (PMB)
PMB is defined as any uterine bleeding occurring after permanent cessation of menstruation due to loss of ovarian follicular activity. 1
Clinical Significance
- PMB is present in approximately 91% of women with endometrial cancer, making it the cardinal warning sign for endometrial malignancy. 2
- Despite this high sensitivity, only 9% of women presenting with PMB will actually have endometrial cancer, meaning most cases have benign etiologies. 2
- The risk varies by geographic region (5-13%) and hormone therapy use (7-12%). 2
Types of PMB
- Spontaneous PMB: Bleeding unrelated to hormone therapy 1
- Hormone-related PMB: Associated with hormone replacement therapy or selective estrogen receptor modulators like tamoxifen 1
Common Etiologies
- Endometrial cancer (most serious, must be excluded first) 3
- Endometrial polyps 3
- Endometrial hyperplasia 3
- Endometrial atrophy (most common benign cause) 3
- Hormone-producing ovarian tumors 3
- Cervical stenosis with hematometra 3
Endometrial Biopsy (EMB)
EMB is an office-based tissue sampling procedure used to obtain endometrial tissue for histological diagnosis, serving as the primary method for excluding endometrial cancer in women with abnormal bleeding. 4
Indications for EMB
- Postmenopausal bleeding with endometrial thickness ≥4-5 mm on transvaginal ultrasound 4, 3
- Any postmenopausal bleeding when ultrasound is inadequate or unavailable 4
- Premenopausal women ≥35 years with risk factors for endometrial cancer (unopposed estrogen, PCOS, tamoxifen therapy, obesity, diabetes) 4
- Women with Lynch syndrome (annual screening starting age 30-35 years) 4
- All women ≥35 years with atypical glandular cells on cervical cytology 4
- Persistent or recurrent bleeding even after initial negative biopsy 4
Diagnostic Performance
- Pipelle and Vabra devices have sensitivities of 99.6% and 97.1% respectively for detecting endometrial carcinoma 4
- Critical limitation: EMB has a false-negative rate of approximately 10% 4, 5
- Blind sampling techniques may miss focal lesions like polyps 4
When EMB is Insufficient
- If EMB is negative but bleeding persists, fractional dilation and curettage (D&C) under anesthesia must be performed 4, 3
- Hysteroscopy with directed biopsy has the highest diagnostic accuracy and should be used when initial sampling is inadequate or focal lesions are suspected 4, 6
Critical Pitfall to Avoid
- Never accept a negative or inadequate EMB as reassuring in a symptomatic postmenopausal woman—the 10% false-negative rate mandates escalation to D&C or hysteroscopy if bleeding persists 4, 5
Variant of Unknown Significance (VUS)
VUS is a genetic/molecular pathology term referring to genetic variants whose clinical significance cannot be definitively determined. While not specific to women's health, VUS may appear in genetic testing for hereditary cancer syndromes (like Lynch syndrome, which increases endometrial cancer risk 30-60%) or in molecular profiling of gynecologic tumors. 4 This term is used across all medical specialties when genetic sequencing identifies variants that cannot be classified as clearly pathogenic or benign.
Diagnostic Algorithm for PMB
Step 1: Initial Evaluation
- Transvaginal ultrasound (TVUS) is the first-line test for PMB 7, 3
- Measure endometrial thickness: ≤4 mm has nearly 100% negative predictive value for cancer 7, 3, 8