Atypical glandular cells: New Bethesda terminology and management guidelines

Although Pap tests have enabled early detection of premalignant lesions, the introduction of new collecting devices has significantly improved the detection of lesions hidden in the endocervical canal, such as adenocarcinoma in situ (AIS). The term "atypical glandular cells of undetermined significance" (AGUS) was introduced at the 1988 Bethesda Conference and defined as morphologic changes in glandular cells beyond those that are suggestive of the benign reactive process, but insufficient for the diagnosis of adenocarcinoma in situ (AIS). In the new 2001 Bethesda System, the term has been eliminated and replaced with the term "atypical glandular cells" (AGC), with the following subclassifications: not otherwise specified (NOS), favor neoplasia, endocervical AIS, and adenocarcinoma. The risks of premalignant or malignant disease associated with the AGC favor neoplasia category are substantially higher than in the AGC NOS category (96% vs. 9-41%, respectively). Patients diagnosed with AGC NOS or AGC favor neoplasia will require colposcopy, endocervical sampling, and, for patients over 35 years of age, endometrial biopsy. If all of these tests are negative, the Pap test should be repeated in 4-6 month intervals until 4 consecutive normal tests are obtained. Positive results in one of the tests will require management according to ASCCP guidelines. The AGC favor neoplasia diagnosis also requires cervical conization and/or other testing, as the incidence of premalignant or malignant lesions in patients with this diagnosis is high. The role of HPV testing in this setting is unknown at this time.