Cytomorphological and immunohistochemical predictors of neoplastic pathology in atypical glandular cells detected in cervical cytology: a 10-year retrospective cohort study.

INTRODUCTION: To evaluate histopathological outcomes following a diagnosis of atypical glandular cells (AGC) and identify independent predictors of neoplastic pathology. MATERIALS AND METHODS: This retrospective cohort study included patients diagnosed with AGC on cervical cytology between January 2013 and December 2023 at a tertiary gynecologic oncology center. Cases with histopathological follow-up within 12 months were included. Cytology slides were rereviewed according to the 2014 Bethesda System. Clinical characteristics, cytomorphological features, p16/Ki67 immunohistochemical status on follow-up tissue specimens, and histopathological outcomes were analyzed. Multivariable logistic regression and receiver operating characteristic analyses were performed. RESULTS: AGC was identified in 141 of 128,022 cytology specimens (0.11%). After exclusions, 119 patients were analyzed. Neoplastic pathology was detected in 28 cases (23.5%), including endometrial carcinoma (39.3%), cervical neoplasia (35.7%), metastatic malignancies (17.9%), and ovarian high-grade serous carcinoma (7.1%). Neoplastic outcomes were significantly associated with increasing age, postmenopausal status, p16/Ki67 positivity, increased nuclear-to-cytoplasmic ratio, nuclear enlargement, and loss of polarity. Multivariable analysis identified increasing age (odds ratio [OR]: 1.141, 95% confidence interval [CI]: 1.072-1.214; P < 0.001), p16/Ki67 positivity (OR: 7.321, 95% CI: 1.828-29.318; P = 0.005), and loss of polarity (OR: 16.873, 95% CI: 4.012-70.953; P < 0.001) as independent predictors of neoplastic pathology. The predictive model demonstrated excellent discrimination (area under the curve = 0.918). CONCLUSIONS: Nearly one-quarter of AGC cases harbored neoplastic pathology. Increasing age, p16/Ki67 positivity, and loss of polarity independently predicted neoplastic outcomes. Integration of these parameters with thorough clinical history may improve risk stratification and clinical management of patients with AGC.