LAUSR

EIF1AX gene mutations are reported in both benign and malignant thyroid tumors, with unclear outcomes when detected preoperatively. The aim of this study was to determine the features and outcomes of thyroid nodules with various types of EIF1AX mutation identified in cytologic (FNA) samples on preoperative ThyroSeq testing and with surgical outcomes. In this single-institution retrospective study of 31 consecutive patients, 77% were female and nodule size ranged from 1.5-9.4 cm with widely varying cytologic and TIRADS ultrasound categorizations Among two main EIF1AX mutational hotspots, 55% were located in exon 2 and 45% at the intron 5/exon 6 splice site. On histology, 45% of EIF1AX-positive nodules were cancer/NIFTP including 19% encapsulated FVPTC, 10% follicular carcinoma, 10% anaplastic carcinoma (ATC), and 7% NIFTP. Almost half (48%) of patients had one or more co-existing mutation, most frequently RAS. The prevalence of cancer/NIFTP was 80% for EIF1AX mutation with coexisting molecular alteration versus 13% with an isolated EIF1AX mutation (p =0.0002). Cancer probability was associated with EIF1AX mutation type and was 64% for splice-site mutation and 29% for non-splice mutation (p=0.075). All 3 nodules with EIF1AX+RAS+TERT+TP53 mutations were ATC. In summary, in this study all nodules with an isolated non-splice EIF1AXmutation were benign, one-third of those with an isolated splice mutation were cancer, and most nodules with EIF1AX co-existing with RAS or other alterations were malignant. These findings suggest that clinical management decisions for patients with EIF1AX-mutantnodules should consider both the type ofmutation and its co-occurrence with other genetic alterations.