Integrated Ultrasound Features, Cytologic Subclassification, and Systemic Inflammatory Markers for Predicting Malignancy in Bethesda III Thyroid Nodules

Background/Objectives: Bethesda category III (atypia of undetermined significance/follicular lesion of undetermined significance; AUS/FLUS) thyroid nodules represent a heterogeneous group with variable malignancy risk, creating challenges in clinical management. This study aimed to evaluate the associations of preoperative ultrasonographic findings, inflammation-based hematological markers, and cytological atypia subtypes with final histopathological outcomes in surgically treated Bethesda III thyroid nodules. Methods: This retrospective study included 72 adult patients with Bethesda III thyroid nodules who underwent thyroid surgery between January 2020 and December 2025. Demographic characteristics, ultrasonographic findings, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), cytological atypia subtypes, and final histopathological diagnoses were analyzed. Univariate and multivariable logistic regression analyses were performed to identify predictors of malignancy. Results: Final histopathological examination revealed benign lesions in 49 patients (68.1%) and malignant lesions in 23 patients (31.9%). Age, sex, nodule size, multinodular goiter, Hashimoto thyroiditis, microcalcifications, hypoechogenicity, suspicious margins, and TI-RADS category were not significantly associated with malignancy (all p > 0.05). Similarly, NLR and PLR did not differ significantly between benign and malignant nodules (NLR: 1.80 vs. 1.98, p = 0.319; PLR: 117.9 vs. 135.0, p = 0.398). Among cytological atypia subtypes, nuclear atypia demonstrated the highest malignancy rate (50.0%) and was significantly associated with malignant histopathological outcomes (OR = 3.364, 95% CI: 1.182–9.570, p = 0.023). After adjustment for age and biopsied nodule size, nuclear atypia remained an independent predictor of malignancy (adjusted OR = 3.963, 95% CI: 1.298–12.094, p = 0.016). Conclusions: In surgically treated Bethesda III thyroid nodules, nuclear atypia was the only independent predictor of malignancy, whereas ultrasonographic characteristics, NLR, and PLR showed limited predictive value. Subclassification of Bethesda III nodules according to cytological atypia may improve preoperative risk stratification and support clinical decision-making. Because the study included only surgically treated patients, the findings should be interpreted in the context of a surgically selected cohort and may not be generalizable to the overall Bethesda III population.