The Value of Multimodal Ultrasound in Differentiating Benign from Malignant Cytologically Indeterminate Thyroid Nodules

Aim: To evaluate the diagnostic value of conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) features in differentiating benign from malignant Bethesda III/IV thyroid nodules, and to identify independent predictors of malignancy. Methods: We retrospectively analyzed 164 surgically confirmed Bethesda III/IV thyroid nodules. CUS and CEUS features were evaluated by two experienced radiologists blinded to pathological outcomes. Univariate analysis compared features between benign and malignant groups. Multivariate logistic regression was used to identify independent predictors. Diagnostic models were constructed based on CUS alone, CEUS alone, and their combination, with performance evaluated using receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each model. Results: The malignancy rate was 48.8% (80/164). Multivariate analysis identified microcalcifications (OR = 4.815, p < 0.001), aspect ratio >1 (OR = 2.499, p = 0.028), and irregular shape (OR = 2.465, p = 0.035) as independent risk factors, while older age (OR = 0.926 per year, p < 0.001) was protective. The CUS model achieved an AUC of 0.815 with high sensitivity (91.3%) and NPV (87.7%). The CEUS model performed poorly (AUC = 0.609). The combined model (AUC = 0.823) showed no significant improvement over CUS alone (p > 0.05). Physician subjective diagnosis based on CEUS TI-RADS yielded an AUC of 0.775. Conclusions: Conventional ultrasound features provide good diagnostic value for Bethesda III/IV nodules, with high sensitivity and NPV suitable for clinical screening. The addition of CEUS offered limited incremental benefit in this specific population, suggesting that the diagnostic value of CEUS for differentiating benign from malignant cytologically indeterminate thyroid nodules (ITNs) may be limited.