Atypical Glandular Cells and Endocervical Adenocarcinoma in Situ of the Uterine Cervix

Abstract

Since its introduction in 1988 as a part of the Bethesda System (TBS) for reporting cervical/vaginal diagnoses in gynecologic Papanicolaou tests, the interpretation category of "atypical glandular cells of undetermined significance" has been a source of much discussion and controversy. Although the category is reported in a very small percentage of all Papanicolaou test results (Ͻ1%), these cases harbor a high percentage of significant cervical neoplasia. Problems of sampling and poor interobserver agreement of cytologic interpretations have resulted in difficulties in the differential diagnosis of early cervical glandular lesions. Revisions in the 2001 Bethesda System resulted in changes to the cytologic reporting of abnormalities observed in glandular cells, which endeavor to reflect the current knowledge and understanding of glandular neoplasia in the uterine cervix. This paper provides case examples and an overview of the category of "atypical glandular cells" originating in the uterine cervix and its associated pathology. CASE REPORTSTwo cases are presented to illustrate abnormal glandular cells seen on Papanicolaou tests and their follow-up. Case Report 1A 35-year-old woman who was 2 years postcervical conization for moderate dysplasia (CIN II) was referred by her local physician for workup of an abnormal Papanicolaou test. The original outside Papanicolaou test slide was reviewed and a repeat Papanicolaou test (ThinPrep Pap Test, Cytyc Corporation) was performed at the time of her referral visit.Cytologic evaluation of the Papanicolaou test slides showed clusters of normal-appearing endocervical cells and scattered groups of atypical glandular cells (AGC) with enlarged round, oval, or rarely elongated hyperchromatic nuclei, granular but evenly distributed chromatin, and inconspicuous nucleoli (Figs. 1-2). The atypical cells demonstrated some crowding and pseudostratification, with a rare suggestion of lumen formation. Moderate amounts of cytoplasm were seen, but nuclear/cytoplasmic ratios were increased. Mitotic figures were not identified, and the specimen background was clean. Both Papanicolaou tests were interpreted as AGC of endocervical origin (atypical endocervical cells, AEC). Given her prior history of cervical dysplasia, clinical concern was high for residual or recurrent neoplasia. Highrisk human papillomavirus testing by the Hybrid Capture II method (Digene Corporation) was positive on a residual sample from the current Papanicolaou test.On colposcopy, the T zone was just inside the canal and seen fleetingly. A 3-mm lesion was noted at 8 o'clock that could not be adequately biopsied. A cervical conization was performed, which revealed a microscopic focus of endocervical adenocarcinoma in situ (AIS) characterized by rare glands with crowded, pseudostratified cells, mitotic activity and apoptotic bodies (Fig. 3). The cell nuclei were enlarged and hyperchromatic with granular chromatin. All margins were free of neoplastic involvement. No evidence of squamous dysplasia was identified on multiple sec...

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