Atypical cells thought to be of endocervical glandular origin often cause diagnostic uncertainty in cervicovaginal smears. For this reason consecutive cases of endocervical glandular atypia diagnosed in smears were correlated with subsequent biopsy diagnoses and then retrospectively reviewed. Smears were originally diagnosed as "mild glandular atypia, probably reactive" or "severe glandular atypia, suggestive of adenocarcinoma in situ" (AIS). Biopsy follow-up was obtained on 34 of 58 patients diagnosed with severe endocervical glandular atypia. Nine patients (26%) had AIS, three with concomitant high-grade squamous intraepithelial lesions (HSIL) and tow with invasive adenocarcinoma. Eighteen patients (53%) had HSIL only. Seven had benign changes. Of 152 patients diagnosed with mild glandular atypia, biopsy follow-up was obtained on 40. One patient had AIS; 14 (35%) had HSIL; one had low-grade SIL (LSIL); and 24 (60%) had benign changes. Blinded review of these smears yielded results similar to those in the biopsy follow-up, that is, the prediction of AIS on smears included most cases of AIS, some invasive adenocarcinomas, a significant number of HSIL, cases and a few benign lesions. A review diagnosis of "reactive glandular cells" proved to be HSIL in 31% of cases and AIS in one case. We conclude that patients with a diagnosis of severe glandular atypia in smears may prove to have AIS or invasive adenocarcinoma, but often have HSIL without concomitant AIS. In addition, although "reactive" glandular atypia in smears usually reflects a benign condition, a significant minority of such patients prove to have HSIL.
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