Outcome of Thyroid Nodules Characterized as Atypia of Undetermined Significance or Follicular Lesion of Undetermined Significance and Correlation With Ultrasound Features and BRAFV600E Mutation Analysis

Abstract

We aimed to establish the malignancy rate of thyroid nodules initially characterized as atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) and whether they differ according to histologic subcategory. We also investigated the value of ultrasound features that predict malignancy and BRAF(V600E) mutation analysis and suggest strategies for the management of AUS/FLUS nodules. A total of 165 AUS/FLUS nodules were investigated. There are nine histologic subcategories of AUS/FLUS nodules. We compared the risk of malignancy in thyroid nodules according to the histologic subcategory using ultrasound findings and of those exhibiting the BRAF(V600E) mutation. The malignancy rate of nodules with an initial diagnosis of AUS/FLUS was 55.2% (91/165). The malignancy rates by histologic subcategory were 0% in groups 1 (0/2), 2 (0/3), 4 (0/3), 7 (0/3), and 8 (0/1); 76.5% (13/17) in group 3; 83.1% (59/71) in group 5; and 29.2% (19/65) in group 9. The malignancy rate of nodules with suspicious ultrasound features was 79.3% (73/92), and the malignancy rate of nodules with indeterminate ultrasound features was 24.7% (18/73). AUS/FLUS nodules exhibiting taller-than-wide shape, illdefined margins, and microcalcifications or macrocalcifications showed significantly higher odds ratios. The likelihood of BRAF(V600E) mutation-positive nodules showing malignancy was 97.5% (39/40), whereas 39.7% (25/63) of BRAF(V600E) mutation-negative nodules were malignant (p < 0.05). The malignancy rate of AUS/FLUS nodules in our study cohort was higher than previously reported. Nodules with suspicious features on ultrasound had a higher malignancy rate than did those with indeterminate features on ultrasound. The malignancy rate differed according to histologic subcategory; therefore, management of AUS/FLUS nodules should be tailored according to histologic subcategory.