Histologic follow-up of patients with the Bethesda system cervicalvaginal diagnosis of atypical glandular cells of undetermined significance (AGUS), "favor endocervical origin", or "not otherwise specified" (NOS) shows a high percentage of clinically significant (neoplastic or preneoplastic) lesions. Using the criteria of atypical single cells, irregular nuclear membranes, and decreased cytoplasm, eight observers retrospectively reclassified 88 AGUS, "favor endocervical", or NOS smears using a probabilistic scheme. Follow-up showed 46 clinically significant and 42 benign lesions. The mean accuracy for all observers and the experienced observers was 65% and 72%, respectively. For the experienced observers, the mean specificity of a "favor clinically significant" category was 72%; the mean sensitivity of a "favor benign" category was 90%. For the less experienced observers, subclassification had poor predictive value. We conclude that experienced observers may use specific criteria to correctly subclassify AGUS lesions, and this may aid in patient management. (Key words: Cytology; Accuracy; Cervical-vaginal smear; Dysplasia; Probability; Carcinoma) Am J Clin Pathol 1997,107:299-307.The Bethesda system diagnostic category of atypical glandular cells of undetermined significance (AGUS) is important for two reasons: (1) AGUS has a relatively high incidence that reportedly ranges from 0.46% to 2.5% of all cervical-vaginal smears 1-3 ; and (2) a high percentage (42%-83%) of patients with an AGUS diagnosis have a clinically significant lesion. [1][2][3][4][5][6][7][8] Surprisingly, histologic follow-up has shown that some of the clinically significant lesions are pure squamous dysplasias without glandular neoplasia.Problems with the AGUS diagnosis are that its defining criteria are somewhat nebulous, and it is used as a wastebasket for lesions that cannot be definitely classified as reactive or neoplastic.9-11 The Bethesda system recommends subclassification of AGUS into the categories of "favor endocervical origin", "favor endometrial origin", and "not otherwise specified" (NOS); "favor endocervical origin" lesions are further classified into the categories of "favor neoplastic" and "favor reactive". [9][10][11] This classification scheme is supposed to aid in patient triage, which, given the AGUS incidence and the high rate of clinically significant lesions, is exceedingly important. However, subclassification of AGUS has yet to be proved clinically effective, and although the Bethesda Committee and many others have studied cytologic criteria important in subclassification, these criteria have not been tested rigorously. This has resulted in the AGUS category being confusing for the pathologist and the clinician.To more thoroughly investigate the utility of AGUS subclassification, our laboratory used a rigorous statistical technique known as logistic regression analysis to identify cytologic criteria important in differentiating a clinically significant AGUS lesion from a benign AGUS lesion.3 The presence of the crit...

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