Value of BRAF V600E in High-Risk Thyroid Nodules with Benign Cytology Results

Limitations of ultrasound-guided fine-needle aspiration include nondiagnostic, indeterminate cytology and false-negative results. The BRAF V600E mutation is a specific biomarker for papillary thyroid carcinoma. This study aimed to investigate the additional diagnostic role of the BRAF V600E mutation in high-risk thyroid nodules with benign cytology results.

A total of 787 high-risk nodules in 720 patients underwent ultrasound-fine-needle aspiration. A subsequent BRAF V600E mutation test was performed on thyroid nodules with benign cytology. Final pathology confirmed thyroid nodules with benign cytology that were positive for the BRAF V600E mutation. Ultrasound was performed on thyroid nodules with benign cytology results that were negative for the BRAF V600E mutation. Fine-needle aspiration was repeated on thyroid nodules with enlarged size or changed ultrasound features.

Among the 787 nodules, 292 thyroid nodules had benign cytology results with 256 nodules negative for the BRAF V600E mutation and 36 nodules positive for the BRAF V600E mutation. Thirty-one nodules positive for the BRAF V600E mutation were confirmed malignant, and 5 nodules were confirmed benign by pathology. Fine-needle aspiration was repeated on 11 enlarged thyroid nodules with benign cytology findings that were negative for the BRAF V600E mutation. The results of repeat fine-needle aspiration were 4 benign nodules, 2 follicular neoplasms or suspected follicular neoplasms, 3 suspected malignancies, and 2 malignant nodules. Among the 36 thyroid nodules positive for the BRAF V600E mutation, 25 (69.4%) had ≥2 suspicious ultrasound features and 11 (30.6%) nodules had 1 suspicious ultrasound feature.

The BRAF V600E mutation test can detect papillary thyroid carcinomas that might be missed by fine-needle aspiration. We recommend that fine-needle aspiration be routinely accompanied by the BRAF V600E mutation test in high-risk thyroid nodules with ≥2 suspicious ultrasound features.