Broad genomic analyses among thyroid histologies have been described from relatively small cohorts.Investigate the molecular findings across a large, real-world cohort of thyroid fine needle aspiration (FNA) samples.Retrospective analysis of RNA sequencing data files.CLIA laboratory performing Afirma Genomic Sequencing Classifier (GSC) and Xpression Atlas (XA) testing.50,644 consecutive Bethesda III-VI nodules.none.Molecular test 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.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.
Mimi I Hu, Steven G Waguespack, Chrysoula Dosiou, Paul W Ladenson, Masha J Livhits, Lori J Wirth, Peter M Sadow, Jeffrey F Krane, Brendan C Stack, Mark E Zafereo, Syed Z Ali, Steven P Weitzman, Yangyang Hao, Joshua E Babiarz, Giulia C Kennedy, Richard T Kloos