ReviewVirchows Archiv : an international journal of pathology2026
EIF1AX Mutations in thyroid nodules and advanced thyroid carcinoma: a systematic review and meta-analysis.
Review in Virchows Archiv : an international journal of pathology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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.
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