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A nomogram for preoperative risk evaluation of Bethesda III thyroid nodules
Riying Liang1, Yue Jie1, Shan Xu1
1Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No.107 Yanjiang West Road, Yuexiu District, Guangzhou 510120, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No.107 Yanjiang West Road, Yuexiu District, Guangzhou 510120, China.
Background:
Bethesda Category III thyroid nodules (AUS/FLUS) pose a diagnostic challenge due to their malignancy rate of 15-30%. This study aimed to develop and validate a preoperative nomogram combining ultrasonographic features and BRAF V600E mutation status to enhance individualized risk assessment.
Methods:
We analyzed 173 surgically resected Bethesda III nodules (50 benign, 123 malignant) from a tertiary referral center (2020-2025). Standardized ultrasound characteristics and BRAFV600E status were evaluated. Multivariable logistic regression identified malignancy predictors. Diagnostic performance was assessed using ROC analysis with DeLong's test.
Results:
Malignant nodules were significantly smaller than benign ones (8.0 ± 6.0 vs 21.0 ± 13.2 mm, P < 0.001), with higher rates of hypoechogenicity (84.6% vs 50.0%), taller-than-wide shape (47.2% vs 12.0%), and punctate echogenic foci (30.1% vs 12.0%). BRAFV600E positivity occurred in 72.4% of malignancies and correlated with hypoechogenicity (P < 0.001) and taller-than-wide morphology. Multivariable analysis identified four independent predictors: BRAFV600E (aOR 8.56, 95% CI 3.92-18.71), TI-RADS 5 (aOR 4.23, 2.15-8.32), taller-than-wide shape (aOR 6.75, 2.57-17.72), and size ≤ 15 mm (aOR 3.94, 1.92-8.08). The nomogram achieved superior performance (AUC 0.95 vs 0.71 ultrasound alone, ΔAUC + 0.24, P < 0.001) with excellent calibration.
Conclusions:
This nomogram combines BRAFV600E status with key ultrasound features to refine preoperative malignancy risk prediction for Bethesda III nodules.
