Preoperative detection of RAS mutation may guide extent of thyroidectomy

Background. Preoperative detection of RAS mutations can contribute to cancer risk assessment in indeterminate thyroid nodules, although RAS is not always associated with malignancy. Methods. Fine-needle aspiration samples classified in 1 of 3 indeterminate cytology categories were prospectively tested for N-, H-, and K-RAS mutations using next-generation sequencing assay. Results. In the study, 93 patients with 94 nodules had preoperative RAS detected, of whom 86 patients had an operation (69% total thyroidectomy, 29% lobectomy). In total, 76% of RAS-positive nodules were malignant and follicular variant papillary thyroid cancer was the most common cancer type (83 %). HRAS mutations had the greatest risk of cancer (92%) followed by NRAS (74 %) and KRAS (64 %; P=.05). No preoperative variables were associated with malignancy including age (P=.07), sex (P=.49), RAS isoform (P=.05), mutational allelic frequency (P=.49), nodule size (P=.14), cytology category (P=.63), or ultrasound bilaterality (P=.24), multifocality (P=.23), or presence of >= 1 suspicious feature (P=.86). Only 60% of patients with a unifocal nodule on ultrasound had single focus low-risk encapsulated follicular variant papillary thyroid cancer or benign disease. Conclusion. Preoperative RAS mutation detection in thyroid nodules carries a substantial risk of cancer with a greater risk associated with HRAS and NRAS. Most RAS malignancies are follicular variant papillary thyroid cancer, which may inform the extent of operation.