Clinicopathological significance of atypical glandular cells on cervicovaginal Pap smears

Objective: To evaluate the histologic correlation and clinical significance of atypical glandular cells (AGC) detected on Pap tests. Methods: Pap tests interpreted as AGC were retrieved from an institutional cytopathology database. The AGC subcategories according to the Bethesda system 2001 include atypical glandular cells, not otherwise specified (AGC-NOS), atypical endometrial cells (AEM), and atypical endocervical cells (AEC). Clinicopathologic variables were collected from medical records retrospectively, and histologic follow-up diagnoses were correlated with AGC subcategories. Results: From January 2009 to December 2014, 741 (0.17%) of 435 778 cervical smears were interpreted as AGC. Of 713 cases included in the study analysis, the distribution of AGC subcategories was as follows: AGC 15.3%, AEM 59.6%, and AEC 25.1%. Of 508 cases with histologic follow-up results, 33.9% of cases were diagnosed to have clinically significant lesions, which include cervical squamous or glandular neoplasia (1.4% and 10.0%), endometrial neoplasia (21.5%), and other metastatic carcinoma (1.0%). Endometrial neoplasia was the most common significant pathology in women aged ≥40 years (28.4%), whereas cervical glandular neoplasia was the most commonly diagnosed lesion in women aged <40 years (14.5%, P < 0.001). When considering past histories which could affect the Pap results, IUD use (10.3%) and pregnancy (7.3%) were most frequently documented. Although IUD users showed low prevalence of significant pathology (2.6%), AGC cases related with pregnancy preceded significant pathologic lesions in 14.3%. Conclusions: The relatively high incidence of significant neoplasia linked to AGC emphasizes the importance of adherence to the AGC management guidelines which recommend early and intensive investigation using multiple testing modalities.