Diagnostic Accuracy of Combined Fine-Needle Aspiration Biopsy and Ultrasonography for Malignancy in Bethesda III–IV Thyroid Nodules

Background: Management of Bethesda III–IV thyroid nodules remains challenging because of diagnostic uncertainty and variable malignancy risk. This study evaluated the diagnostic performance of fine-needle aspiration biopsy (FNAB) and ultrasonographic (USG) features separately and in combination. Methods: This retrospective cohort study included 1800 patients with Bethesda III–IV thyroid nodules who underwent thyroidectomy between 2017 and 2025. FNAB results and USG features, including hypoechogenicity, microcalcifications, and irregular margins, were analyzed. Logistic regression and ROC curve analyses were performed to determine predictors of malignancy and diagnostic performance. Results: The overall malignancy rate was 25%. Malignancy rates were 19.1% in Bethesda III and 37.4% in Bethesda IV nodules (p < 0.001). In multivariable analysis, Bethesda IV category, microcalcifications, irregular margins and hypoechogenicity were independent predictors of malignancy (all p < 0.001). FNAB and USG alone showed limited discrimination (AUC 0.60 and 0.61, respectively), whereas the combined model demonstrated significantly improved performance (AUC 0.78). The combined model achieved 82.4% sensitivity, 70.1% specificity and 92.1% negative predictive value. Conclusions: USG features provide significant additional diagnostic value beyond cytology in Bethesda III–IV thyroid nodules. Combining USG findings with FNAB improves risk stratification and may support clinical decision-making in indeterminate thyroid nodules.