| Abstrakt: |
Background: The EIF1AXmutation has been identified in various benign and malignant thyroid lesions, with a higher prevalence in poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma, especially when combined with RASor TP53mutation. However, data and clinical significance of EIF1AXmutations in thyroid nodules is still limited. We investigated the prevalence of EIF1AXmutations and co-mutations in cytologically indeterminate thyroid nodules at our institution. Methods: A 5-year retrospective analysis was performed on surgically resected thyroid nodules with identified EIF1AXmutations on molecular testing with ThyroseqV3®. Mutation type and presence of co-mutations were correlated with histopathologic diagnosis and clinical characteristics. Histopathology diagnoses were subsequently categorized as benign, borderline, malignant or aggressive malignant (≥ 10% PDTC component). Chi-square test was used to compare the malignancy associations of the: 1) A113_splice mutation compared to non-A113_splice mutations 2) singular A113_splice mutations compared to singular non-A113_splice mutations. Fisher’s Exact Test was used to determine the association of A113_splice mutation with aggressive malignancies compared to non-A113_splice mutations. A pvalue of 0.05 or less was considered statistically significant. Results: Out of 1583 patients who underwent FNA, 621 had further molecular testing. 31 cases (5%) harbored EIF1AXmutations. Of these cases, 12 (38.7%) were malignant, 2 (6.5%) were borderline, and 17 (55%) were benign. 4/31 cases (13%) were aggressive malignant (≥ 10% PDTC component). The most prevalent mutation was the A113_splice mutation at the junction of intron 5 and exon 6 (48%). All other mutations, except one, were located at the N-terminal in exon 2. 7/31 cases (22.6%) harbored ≥ 1 co-mutation(s), including 4 RAS, 3 TP53, 1 TERT and 1 PIK3CA,with 86% of them being malignant. All 4 nodules with RASco-mutations were malignant including one PDTC. Conclusion: Our study reports the largest cohort of EIF1AXmutations in Bethesda III/IV FNA samples with surgical follow-up to our knowledge. The presence of the EIF1AXmutation confers a 45.2% risk of malignancy (ROM) or borderline after surgery. However, the coexistence of EIF1AXmutations with other driver mutations such as RAS, TERTor TP53conferred an 86% ROM. While 55% of thyroid nodules were benign at the time of surgery, the possible malignant transformation of these nodules, had they not been resected, is unknown. Finally, 13% of the nodules with EIF1AXmutations were aggressive with a significant PDTC component. These findings can further aid in clinical decisions for patients with thyroid nodules. Graphic Abstract: ![]() |
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