Integration of BRAF V600E mutation with contrast-enhanced ultrasound parameters provides complementary diagnostic value for malignant thyroid nodules.

Objective: To evaluate the diagnostic efficacy of a combined model integrating the BRAF V600E mutation and quantitative contrast-enhanced ultrasound (CEUS) parameters for differentiating benign from malignant thyroid nodules(TNs). Design: A retrospective diagnostic study. Setting and participants: A total of 66 patients with TNs confirmed by surgical resection or core needle biopsy at our hospital between January 2023 and August 2025 were enrolled. Primary and secondary outcome measures: The primary outcome was the diagnostic performance, measured by the area under the receiver operating characteristic (ROC) curve, of the combined model compared to either the BRAF V600E mutation or CEUS parameter time to peak (TTP) alone. Secondary measures included the detection rate of BRAF V600E and the independent predictive value of each variable via multivariate logistic regression. Results: Among 66 patients (37 malignant, 29 benign), the BRAF V600E mutation was significantly more frequent in the malignant group (64.9% vs. 3.4%; P < 0.001). In a regression model containing only CEUS parameters, TTP was an independent predictor of malignancy (OR = 1.075, P = 0.013). However, with BRAF V600E added, TTP lost significance (P > 0.05), while BRAF V600E remained a significant predictor (OR = 38.380, P = 0.001). ROC analysis showed the combined model of TTP and BRAF V600E achieved the highest area under the curve (AUC) of 0.855, which was higher than using TTP alone (AUC = 0.681) or BRAF V600E alone (AUC = 0.807) (P < 0.05 for both comparisons).Notably, exploratory analysis suggested that CEUS parameters may provide complementary value in BRAF V600E-negative nodules, a clinically important subgroup where molecular testing alone is less informative. Compared with TI-RADS, the combined model achieved a higher specificity (64.9% vs. 24.1%) while maintaining comparable sensitivity (96.6% vs. 94.6%), indicating fewer false-positives. Conclusion: The BRAF V600E mutation is a strong independent predictor of thyroid nodule malignancy. Adding the quantitative CEUS parameter TTP to BRAF V600E yielded modest but significant diagnostic improvement vs BRAF V600E alone. Although validation in larger cohorts is needed, the integration of BRAF V600E mutation status with quantitative CEUS parameters may contribute to improved preoperative risk stratification, particularly in BRAF V600E-negative cases.