EIF1AX Mutations in thyroid nodules and advanced thyroid carcinoma: a systematic review and meta-analysis
In brief
EIF1AX appears in 4.8% of indeterminate nodules; 41% of positive nodules were malignant
Across three cohorts, EIF1AX alterations were found in 92 of 1,935 Bethesda III/IV nodules; among 117 positive nodules with tissue results, 50 were malignant. The alteration was also found in 15% of anaplastic thyroid cancers, but its presence alone cannot establish cancer: variant type, co-alterations and histology all matter.
- Journal
- Virchows Archiv : an international journal of pathology (Q1)
- Published
- 30 September 2026
- Study design
- Systematic review of cohort studies
- Evidence level
- Level 2, Moderate (CEBM 2a)
- Authors
- Vincenzo Fiorentino, Patrizia Straccia, Esther Diana Rossi
- PMID
- 42814126
- DOI
- 10.1007/s00428-026-04708-7
Why clinicians should know about it
- Picked for Pathology and Forensic Medicine (paper of the day, 3 October 2026): EIF1AX mutations in thyroid nodules and carcinoma
Abstract
EIF1AX alterations occur across benign, borderline, differentiated, and high-grade thyroid neoplasia, requiring contextual interpretation. PubMed/MEDLINE, Scopus, and Embase were searched through 6 May 2026; complementary genomic, citation, and supplementary-data searches continued through 19 July 2026. Analyses addressed prevalence in strict Bethesda III/IV nodules, tissue-verified outcomes in EIF1AX-positive Bethesda III/IV nodules, and prevalence in WHO- or Turin-defined poorly differentiated thyroid carcinoma (PDTC) and histology-defined anaplastic thyroid carcinoma (ATC) cohorts not molecularly preselected. Proportions were pooled with binomial-normal generalized linear mixed models; study intervals were exact Clopper-Pearson intervals and heterogeneity was τ² on the logit scale. Among 43 reports, 13 contributed to a primary estimate and 17 to a primary or sensitivity analysis. EIF1AX prevalence in three strict Bethesda III/IV cohorts was 4.75% (92/1935; 95% CI, 3.89%-5.80%; τ²=0.000). Malignant histology occurred in 50/117 tissue-verified nodules (40.77%; 95% CI, 24.59%-59.24%; τ²=0.413). Including noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)/borderline outcomes and compatible Desai and Connelly data yielded 64/124 (48.16%; 95% CI, 30.69%-66.10%; τ²=0.497). Prevalence was 6.15% in PDTC (11/136; 95% CI, 2.04%-17.12%; τ²=0.455) and 15.06% in ATC (25/162; 95% CI, 9.19%-23.70%; τ²=0.154). EIF1AX is uncommon in indeterminate cytology and is not a stand-alone rule-in marker. Interpretation requires variant class, co-alterations, assay, verification, and histologic context.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.