To evaluate the value of BRAF V600E mutation and American College of Radiology (ACR) thyroid imaging reporting and data system (TI-RADS) classification in risk assessment of Bethesda Ⅲ thyroid nodules.

A retrospective analysis was conducted on 127 Bethesda category Ⅲ nodules in patients who underwent fine needle aspiration cytology (FNA) and subsequent surgical pathology examination at China-Japan Friendship Hospital from April 2019 to April 2022. According to pathological findings, the nodules were divided into either a benign group (n=19) or a malignant group (n=108). The Chi-square test was used to compare the differences in the BRAF gene test results and ACR TI-RADS classification between benign and malignant groups of Bethesda category Ⅲ nodules. The diagnostic efficacy of BRAF gene mutation and ACR TI-RADS classification, individually and combined, for Bethesda category Ⅲ nodules was compared, and a malignancy risk stratification for Bethesda category Ⅲ nodules was performed using the BRAF gene muatation and ACR TI-RADS classification.

The sensitivity, specificity, and accuracy of BRAF V600E mutation for diagnosing Bethesda category Ⅲ nodules were 47.2%, 100%, and 55.1%, respectively. The corresponding values for ACR TI-RADS classification were 81.5%, 68.4%, and 79.5%, respectively. The sensitivity, specificity, and accuracy of BRAF V600E mutation combined with ACR TI-RADS classification were 92.6%, 68.4%, and 89.0%, respectively. The combined method showed statistically significant higher sensitivity and accuracy compared to ACR TI-RADS classification alone (χ²=10.08 and 4.27; P=0.002 and 0.039, respectively). Bethesda category Ⅲ nodules with positive BRAF gene results had a 100% risk of malignancy and were recommended for surgical treatment. For BRAF-negative Bethesda category Ⅲ nodules, those with ACR TI-RADS 3 classification had a 0% malignancy rate and were recommended for follow-up observation, ACR TI-RADS 4 nodules had a 44.4% malignancy rate and were suggested for repeat FNA, and ACR TI-RADS 5 nodules had an 89.1% malignancy rate and were recommended for surgical treatment.

The combination of BRAF V600E mutation with ACR TI-RADS classification improves the diagnostic sensitivity and accuracy for Bethesda category Ⅲ nodules and facilitates risk stratification and clinical management of these nodules.