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Background  We evaluated the usefulness of follow-up BRAF V600E  mutation analysis using ultrasonography-guided fine-needle aspiration (US-FNA) in diagnosis of thyroid nodules showing negative BRAFV600E mutation on prior analysis.    Methodology/Principal Finding  A total of 49 patients (men: 6, women: 43, mean age: 50.4 years) with 49 thyroid nodules were included. Patients had undergone initial and follow-up US-FNA and subsequent BRAF V600E  mutation analysis from US-FNA aspirates. All patients had negative results on initial BRAF V600E  mutation analysis. Clinicopathologic findings, US assessment, and BRAF V600E  mutation results were analyzed according to the final pathology. Of the 49 nodules, 12 (24.5%) were malignant and 37 (75.5%) were benign. Seven (58.3%) of the 12 malignant nodules were positive for BRAF V600E  mutation on follow-up, all showing suspicious US features. Initial US-FNA cytology of the 7 nodules were non-diagnostic (n = 2), benign (n = 2), or atypia (n = 3), while follow-up were benign (n = 1), indeterminate (n = 1), suspicious for malignancy (n = 4), and malignancy (n = 1).    Conclusions/Significance  Follow-up BRAF V600E  mutation analysis may be helpful in the diagnosis of selected thyroid nodules negative for BRAF V600E  mutation on initial analysis, which are assessed as suspicious malignant on US, diagnosed as non-diagnostic, benign or atypia on follow-up US-FNA.

Is Follow-up BRAFV600E Mutation Analysis Helpful in the Differential Diagnosis of Thyroid Nodules with Negative Results on Initial Analysis?