Abstract
We assessed the usefulness of revised Bethesda System reporting of exfoliated benign endometrial cells (EMs) in postmenopausal women. Cervicovaginal cytology specimens with benign EMs in postmenopausal women and "out-of-phase EMs" in premenopausal women 40 years and older were identified. Cases with histologic follow-up within 12 months were selected.
There was tissue follow-up for 130 postmenopausal women: 10 (7.7%) had significant findings (endometrial adenocarcinoma, 6 [2 (33%) in asymptomatic women]; complex atypical endometrial hyperplasia [CAH], 3; leiomyosarcoma, 1); 20 were receiving hormone replacement therapy (HRT; n = 15) or tamoxifen (n = 5); 2 (10%) had significant pathology (endometrial adenocarcinoma, 1; CAH, 1). Eight not taking hormones (7.3%) had significant pathology (adenocarcinoma, 5; CAH, 2; leiomyosarcoma, 1). There were follow-up data for 96 premenopausal women; only 1 (who had vaginal bleeding) had significant pathology (CAH).
The difference in incidence of preneoplastic and neoplastic conditions after a cytologic interpretation of "benign EM" between postmenopausal and premeno-pausal women was significant ( P ≤ .025); There was no difference between postmenopausal women receiving or not receiving HRT ( P > .05). Reporting benign EMs for premenopausal women 40 years and older has no clinical significance but does for postmenopausal women, regardless of HRT and symptoms.
Introduction
Benign-appearing endometrial cells commonly are seen in cervicovaginal cytologic (CV) specimens obtained from women of reproductive age in the proliferative phase (days 1-14) of the menstrual cycle. Historically, the presence of "cytologically benign-appearing" endometrial cells, outside the proliferative phase and in postmenopausal women, was reported to the clinician regardless of patient age. With the inception of the 1991 Bethesda System for the reporting of CV abnormalities, the reporting of benign endometrial cells was modified to state the presence of exfoliated endometrial cells only in postmenopausal women. This revision was based on the findings of several studies that suggested that spontaneously exfoliated benign endometrial cells might indicate endometrial pathology in postmenopausal women, necessitating endometrial sampling. Furthermore, it has been noted that while most women with endometrial adenocarcinoma are symptomatic, in a small portion of women, exfoliated benign endometrial cells in a CV specimen might be the only sign of underlying endometrial pathology; thus, their presence requires further investigation.
In 2001, the reporting of benign endometrial cells was further modified (TBS 2001) to include all women 40 years and older. The rationale behind this change was that an individual woman's risk factors for endometrial adenocarcinoma, the clinical symptoms, hormonal intake history, menopausal status, and the date of the last menstrual period (LMP) often are unclear or unavailable to the cytopathology laboratory. Thus, the significance of exfoliated benign endometrial cells can be interpreted only by the clinician.
A major concern with the reporting of cytologically benign-appearing endometrial cells in all women 40 years and older has been the potential for unnecessary clinical concern and intervention because more recent outcome studies have shown that this finding in premenopausal women has no clinical relevance and, in many cases, creates a management dilemma for clinicians. In addition, many older studies showing the association of exfoliated benign endometrial cells with endometrial adenocarcinoma were based on data obtained before the widespread use of exogenous hormonal replacement therapy (HRT) and hormonal treatment with tamoxifen. Recently, HRT was shown to be associated with an increased prevalence of exfoliated benign endometrial cells on CV specimens and a lower incidence of endometrial pathology in comparison with specimens from women who did not use HRT. The converse was true for patients taking tamoxifen. In this group, the presence of benign endometrial cells on CV smears was associated with an increased risk of the development of endometrial adenocarcinoma.
We studied the clinical significance of modifying the reporting of endometrial cells in TBS 2001 by comparing the outcome in postmenopausal women with premenopausal women 40 years and older. We also evaluated the clinical significance of exfoliated benign endometrial cells in CV specimens in women receiving hormonal therapy.