What is the role of endometrial biopsy in diagnosing Lynch syndrome (Hereditary Nonpolyposis Colorectal Cancer, HNPCC)?

From the Guidelines

Endometrial biopsy is recommended as a screening tool for women with Lynch syndrome starting between ages 30-35 years. This procedure involves sampling the uterine lining to detect early endometrial cancer or precancerous changes. For women with Lynch syndrome, annual endometrial biopsies are typically performed alongside transvaginal ultrasound as part of comprehensive gynecologic surveillance. The procedure is usually done in an outpatient setting, takes about 10-15 minutes, and may cause mild cramping. No specific preparation is needed, though timing it after menstruation is preferable.

Importance of Screening

This screening is crucial because women with Lynch syndrome have a 40-60% lifetime risk of developing endometrial cancer compared to the general population's 3% risk 1. Lynch syndrome causes DNA mismatch repair defects that lead to microsatellite instability, which can be detected in endometrial tissue before cancer develops. While prophylactic hysterectomy offers definitive risk reduction after childbearing is complete, regular endometrial biopsies remain an important surveillance option for those wishing to preserve fertility or avoid surgery.

Recommendations

Key points to consider include:

• Screening via endometrial biopsy every 1–2 years starting at age 30–35 years can be considered 1.
• Transvaginal ultrasound to screen for endometrial cancer in postmenopausal patients has not been shown to be sufficiently sensitive or specific, but may be considered at the clinician’s discretion 1.
• The decision to have a risk-reducing hysterectomy or bilateral salpingo-oophorectomy (BSO) should be individualized based on whether childbearing is complete, menopause status, comorbidities, family history, and the specific Lynch syndrome gene, as risks for endometrial and ovarian cancer vary by gene 1.

Clinical Considerations

Given the higher risks of early endometrial and ovarian cancer in certain Lynch syndrome genes, hysterectomy with BSO may be considered starting at age 40 years 1. As premature menopause due to oophorectomy can cause detriments to bone health, cardiovascular health, and generalized quality of life, estrogen replacement therapy should be considered. The value of endometrial biopsy as a diagnostic procedure is high, being both highly sensitive and highly specific, which supports its use in screening for endometrial cancer in women with Lynch syndrome 1.

From the Research

Endometrial Biopsy for Lynch Syndrome

• Endometrial biopsy is a screening method for endometrial cancer in women with Lynch syndrome, with a sensitivity of 57.1% and a number needed to screen of 23-380 (median 78) 2.
• The incidence of endometrial cancer in women with Lynch syndrome is 3.9% at the time of screening, with most (64.1%) endometrial cancers detected through screening 2.
• Combined colonoscopy and endometrial biopsy screening is a feasible and less painful approach for women with Lynch syndrome, with a high level of patient satisfaction and acceptability 3, 4.
• The lifetime cumulative risk of endometrial cancer for women with Lynch syndrome is 40% to 60%, with a median age of 49 years 5, 6.
• Screening guidelines for women with Lynch syndrome include annual endometrial sampling and transvaginal ultrasonography beginning at age 30 to 35 years 5.
• Prevention options for endometrial and ovarian cancer in women with Lynch syndrome include the use of oral contraceptives and prophylactic surgery to remove the uterus and ovaries 6.

Screening and Prevention

• Endometrial biopsy every 1-2 years is effective in the early detection of (pre)cancerous lesions, leading to prompt definitive management and potential reduction in endometrial cancer 4.
• Transvaginal ultrasound has a sensitivity of 34.4% and a number needed to screen of 35-973 (median 170) for endometrial cancer in women with Lynch syndrome 2.
• Ovarian cancer risk in women with Lynch syndrome is 6-8%, with a variety of histopathological subtypes 6.
• Risk-reducing surgery remains the most reliable way to reduce endometrial and ovarian cancer risk in Lynch syndrome 2.