"Atypical Glandular Cells" on Cervical Cytology: Correlation Between Glandular Cell Component Volume and Histological Follow-Up

Abstract

Background: Atypical glandular cells (AGC) in cervical cytology, as defined by the Bethesda System, indicate nuclear atypia beyond reactive changes but without definitive features of malignancy. Although clinically significant because it prompts follow-up procedures, no quantitative threshold exists for AGC diagnosis. This study evaluated whether the volume of glandular cell clusters (GCC), regardless of atypia, influences AGC interpretation and may contribute to unnecessary sampling.

Methods: Following IRB approval, all cervical cytology cases diagnosed as AGC between January 2014 and June 2024 were retrieved, along with 100 random negative for intraepithelial lesion or malignancy (NILM) cases, and were manually re-screened with quantification of glandular cell clusters (GCC) defined as a group of ≥ 6 cohesive glandular cells irrespective of origin (endocervical versus endometrial) and the results were correlated with follow-up findings including endocervical and endometrial sampling.

Results: Of 301 AGC cases, 186 cases had slides available for review and follow-up data; two were excluded due to unsatisfactory quality. Eight cases were reclassified as unsatisfactory because of insufficient squamous cells and absence of atypia, most of which exhibited high GCC (mean 59). Notably, 140 cases (76.6%) showed no significant glandular pathology on follow-up, and in 111 cases (60.6%) the follow-up was negative. Overall, increased GCC correlated significantly with AGC interpretation compared to NILM cases (p = 0.01), even when histologic follow-up was negative.

Conclusion: Higher GCC volumes may influence AGC diagnoses, even in cases lacking true cytologic atypia, potentially leading to unnecessary interventions. Greater awareness of this tendency and adherence to established cytologic criteria may improve diagnostic precision within the AGC category.

Keywords: Pap smear; atypical glandular cells; cut‐off; cyto‐histo correlation; number; quantity.