RASMutations in Thyroid FNA Specimens Are Highly Predictive of Predominantly Low-Risk Follicular-Pattern Cancers

INTRODUCTION: RAS mutations are common in thyroid tumors and confer a high risk of cancer when detected in fine-needle aspiration (FNA) specimens. Specific characteristics of RAS-positive thyroid cancers are not well described. METHODS: From April 2007 to April 2009, 921 consecutive patients undergoing FNA were evaluated prospectively with a panel of molecular markers. Ultrasonographic, cytological, histological, and surgical outcomes were retrospectively assessed. RESULTS: Sixty-eight aspirates from 66 patients were positive for RAS mutations including 63 cytologically indeterminate (93%), 3 malignant (4%), and 2 benign (3%) specimens. Cancer was histologically confirmed in 52 of 63 aspirates (83%) including the following: 46 papillary thyroid cancers, 4 follicular thyroid cancers, 1 medullary cancer, and 1 anaplastic cancer. All 46 RAS-positive papillary thyroid cancers, including 1 metastatic cancer, had follicular variant histology papillary thyroid cancer; only 11 tumors demonstrated vascular/capsular invasion and 4 had infiltrative growth. Of 48 patients with differentiated thyroid cancer, lymph node metastasis was uncommon and bilateral cancer was present in 48%. Only 33% of malignant nodules were suspicious by preoperative ultrasonography. At a mean follow-up of 22 months, 31 of 35 differentiated thyroid cancer patients (89%) have no evidence of recurrence, 4 patients (9%) have detectable thyroglobulin, 1 patient has bone metastases, and both patients with medullary and anaplastic cancer have died. CONCLUSION: Most RAS-positive thyroid cancers have indeterminate cytology, lack suspicious ultrasound features, and are histologically low-grade follicular variant histology papillary thyroid cancer. Lymph node and distant metastases are uncommon but bilateral disease is frequent. Total thyroidectomy should be considered for initial surgical management of most patients with RAS-positive FNA results. The role of prophylactic lymphadenectomy remains unclear.