Though thyroid tumors possessing isolated RAS mutations are generally considered to be indolent, the oncologic outcomes of tumors evaluated with comprehensive molecular testing have not been well characterized. We performed a retrospective cohort study of 368 consecutive patients with Bethesda III - VI thyroid nodules at a single institution (2016 to 2021) who underwent molecular testing with Thyroseq v3. Patients with isolated RAS mutations were identified, and those with isolated BRAF V600E-mutated cancers were used as comparators. Outcomes of interest included rate of malignancy, high-risk histopathologic features, and structural disease recurrence. A total of 50 (14%) patients had an isolated RAS-mutated nodule, of which 41 underwent surgery (median age 43 years, 83% female). The malignancy rate on final pathology was 46%, while 32% of patients had NIFTP and 22% of patients had benign histopathology. In comparison, the isolated BRAF-mutated cohort (86 [24%] patients, median age 45 years, 68% female) had a 100% rate of malignancy. Only 2 (11%) of the isolated RAS patients with malignant histopathology had lymph node metastasis, compared to 34 (39%) of the BRAF cohort (p=0.016). Over a median follow up of 5 years, no patients with isolated RAS mutations had a structural recurrence compared to 5 (6%) patients in the isolated BRAF cohort. Bethesda III-VI thyroid nodules with isolated RAS mutations have a low rate of aggressive histopathologic features and are unlikely to recur. Thyroid lobectomy may be sufficient treatment for these tumors.
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