CONTEXT: Broad genomic analyses among thyroid histologies have been described from relatively small cohorts.OBJECTIVE: Investigate the molecular findings across a large, real-world cohort of thyroid fine needle aspiration (FNA) samples.DESIGN: Retrospective analysis of RNA sequencing data files.SETTING: CLIA laboratory performing Afirma Genomic Sequencing Classifier (GSC) and Xpression Atlas (XA) testing.PARTICIPANTS: 50,644 consecutive Bethesda III-VI nodules.INTERVENTION: none.MAIN OUTCOME MEASURES: Molecular test results.RESULTS: Of 48,952 Bethesda III/IV FNAs studied, 66% were benign by Afirma GSC. The prevalence of BRAF V600E was 2% among all Bethesda III/IV FNAs and 76% among Bethesda VI FNAs. Fusions involving NTRK, RET, BRAF, and ALK were most prevalent in Bethesda V (10%), and 130 different gene partners were identified. Among small consecutive Bethesda III/IV sample cohorts with one of these fusions and available surgical pathology excision data, the positive predictive value of an NTRK or RET fusion for carcinoma or non-invasive follicular thyroid neoplasm with papillary-like nuclear features was >95%, while for BRAF and ALK fusions it was 81% and 67%, respectively. At least one genomic alteration was identified by the expanded Afirma XA panel in 70% of Medullary Thyroid Carcinoma Classifier positive FNAs, 44% of Bethesda III or IV Afirma GSC suspicious FNAs, 64% of Bethesda V FNAs, and 87% of Bethesda VI FNAs.CONCLUSIONS: This large study demonstrates that almost half of Bethesda III/IV Afirma GSC suspicious and most Bethesda V/VI nodules had at least 1 genomic variant or fusion identified, which may optimize personalized treatment decisions.
View details for DOI 10.1210/clinem/dgab304
View details for PubMedID 34009369