Diagnostic Efficacy of Ultrasound, Cytology, and BRAF(V600E) Mutation Analysis and Their Combined Use in Thyroid Nodule Screening for Papillary Thyroid Microcarcinoma

BACKGROUND: Ultrasound, cytology, and BRAF(V600E) mutation analysis were applied as valuable tools in the differential diagnosis of thyroid nodules. The aim of the present study was to evaluate the diagnostic efficiency of the three methods and their combined use in screening for papillary thyroid microcarcinoma (PTMC). METHODS: A total of 1,081 patients with 1,157 thyroid nodules (0.5–1 cm in maximum diameter) classified as thyroid imaging reporting and data system (TIRADS) 4–5 were recruited. All patients underwent ultrasound, fine-needle aspiration (FNA) examination, and an additional BRAF(V600E) mutation test. TIRADS and Bethesda System for Reporting Thyroid Cytopathology (BSRTC) were adopted to judge the ultrasound and cytological results. The receiver operating characteristic (ROC) curve was established to assess the diagnostic values of different methods. RESULTS: Of the 1,157 nodules, 587 were benign and 570 were PTMCs. BRAF(V600E) mutation test had highest sensitivity (85.4%), specificity (97.1%), accuracy (91.4%), and area under the ROC curve (Az) value (0.913) among the three methods. The combination of BSRTC and BRAF(V600E) mutation analysis yielded a considerably high sensitivity (96.0%), accuracy (94.3%), and negative predictive value (95.9%) than either BSRTC or BRAF(V600E) mutation alone (P < 0.0001 for all comparisons). Of all the methods, the combined use of the three methods produced the best diagnostic performance (Az = 0.967), which was significantly higher than that (Az = 0.943) for the combination of BSRTC and BRAF(V600E) mutation (P < 0.0001). The diagnostic accuracy of the molecular method in the 121 nodules with indeterminate cytology was 90.1% (109/121), which was significantly higher than that of TIRADS classification, 74.4% (90/121) (P = 0.002). CONCLUSION: The combined use of ultrasound, cytology, and BRAF(V600E) mutation analysis is the most efficient and objective method for diagnosing PTMC. Both BRAF(V600E) mutation and TIRADS classification are potentially useful adjuncts to differentiate thyroid nodules, especially indeterminate samples classified as BSRTC III.