Atypical Glandular Cells of Undetermined Significance

Abstract & Commentary

Synopsis: Atypical glandular cells of undetermined significance on Pap smears were correlated with significant findings in 45% of patients.

Source: Veljovich DS, et al. Am J Obstet Gynecol 1998; 179:382-390.

Veljovich and associates conducted a five-year retrospective review of screening cervical cytologic examinations diagnosed as atypical glandular cells of undetermined significance (AGCUS) to ascertain the types and frequency of pathologic conditions associated with this diagnosis. Three hundred forty-five evaluable patients were identified. The incidence of AGCUS was 0.53%. Pathologic findings for the respective Pap smears with the diagnosis of AGCUS—not otherwise specified—favor benign, squamous intraepithelial lesions, and favor neoplasia through the follow-up interval were as follows: squamous intraepithelial lesions in 11%, 8%, 38%, and 20%; adenocarcinoma in situ in 3%, 0%, 0%, and 10%; endometrial hyperplasia in 3%, 5%, 1%, and 2%; and cancer in 8%, 3%, 1%, and 7%. Overall, 63 patients (32%) had preinvasive or invasive lesions. Veljovich et al conclude that AGCUS on Pap smears were correlated with significant findings in 45% of patients (32% with preinvasive or invasive lesions and 13% with benign lesions). A prompt and aggressive workup was recommended.

Comment by David M. Gershenson, MD

The classification of AGCUS was proposed as part of the Bethesda system in 1988. Not only do Veljovich et al place their findings in perspective, they also review the published reports on the subject. In seven other studies, the incidence of AGCUS was 0.48%, a figure similar to that found in the present study. In addition, the incidence of squamous intraepithelial lesions, adenocarcinoma in situ, endometrial hyperplasia, and cancer in these studies was 29.1%, 3.6%, 5.4%, and 5.8%, respectively. Recently, the American Society for Colposcopy and Cervical Pathology published guidelines for management of women with AGCUS on Pap smear. According to their recommendations, all women with AGCUS should undergo colposcopy of the cervix and vagina as well as endocervical curettage (ECC). Colposcopic-directed biopsies of abnormal areas should be performed. Patients with unqualified AGCUS who have negative colposcopy and ECC should have a repeat Pap smear every 4-6 months until four normal smears are reported. Patients with either AGCUS favoring neoplasia or unqualified AGCUS with positive ECC should undergo cervical conization. If cells appear to be of endometrial origin, endometrial biopsy, hysteroscopy, or curettage is recommended. In summary, the message is clear: the finding of AGCUS on Pap smear should be taken very seriously since the associated incidence of both preinvasive and invasive lesions is relatively high. Appropriate workup should be performed and physicians need to counsel their patients regarding the significance of this finding.