Negative Predictive Value and Significance of Benign-Appearing Endometrial Cells in Papanicolaou Tests

Reporting benign-appearing endometrial cells (nEMCs) in Papanicolaou (Pap) smears of women 40 years and older, introduced in The Bethesda System 2001, may be interpreted as an abnormal finding and lead to unnecessary endometrial biopsies. To our knowledge, this is the first study on the negative predictive value (NPV) of this cytology finding.

An 11-year database with 1,036,629 Pap test reports and 121,079 surgical pathology reports identified reports of nEMCs in women 40 years and older with follow-up endometrial histopathology within 6 months. Endometrial carcinoma and atypical endometrial hyperplasia were chosen as relevant outcomes. NPVs were calculated. Bayesian modeling assessed the impact of age, bleeding, and postmenopausal status on risk.

NPVs for patients aged 40 to 44 years and 45 to 49 years (99.5% and 99.3%, respectively) were not significantly different. NPVs for patients aged 50 to 54 years, 55 to 59 years, and 60 years and older (97.1%, 95.3%, and 94.5%, respectively) were lower than the NPV for patients aged 40 to 49 years. Bayesian modeling indicated that asymptomatic patients in all age groups 40 years and older have very low risk. Bleeding history increased risk in all age groups, especially in women 50 years and older.

nEMCs in Pap test reports of women 40 years and older are a normal cytology finding in premenopausal women, which may result in unnecessary endometrial biopsies. The NPV associated with this finding for women aged 40 to 49 years exceeded 99%.