Utilizing molecular testing to improve the management of thyroid nodules with indeterminate cytology: an institutional experience with review of molecular alterations

Abstract Introduction Molecular testing has helped clinicians and cytopathologists further categorize indeterminate thyroid fine needle aspiration specimens. The purpose of this study is to evaluate the accuracy of commercially available molecular tests, review their impact on patient management, and correlate molecular alterations with histologic findings. Materials and Methods A Pathology LIS search identified thyroid FNAs performed at our institution between 1/1/2015 and 6/30/2020. Results of surgical follow-up and ancillary molecular testing were collected. We evaluated the accuracy of these tests and whether they could reduce the number of surgeries being performed. Results Our LIS search identified 510 cases reported as AUS, 94 as SFN and 44 as SFN-H. 343 specimens had no ancillary molecular testing while 146 were sent for ThyGenX/ThyraMIR and 136 for ThyroSeq. 50.4% of patients without molecular testing had follow-up surgery compared to 30.8% with ThyGenX/ThyraMIR and 38.2% with ThyroSeq. This corresponds to 38.9% and 24.2% fewer surgeries and ORs of 0.04 (95% CI 0.00-0.33) and 0.14 (95% CI 0.01-0.95), respectively. For ThyGenX/ThyraMIR testing, the risk of malignancy for high and moderate-high risk alterations was 80%, 28.6% for moderate and low-moderate risk alterations, and 23.1% for low risk alterations. For ThyroSeq, the risk of malignancy was 87.5% for high risk alterations, 36.8% for intermediate-high risk alterations, 27.3% for intermediate risk alterations and 0% for low risk alterations. The AUCs for ThyGenX/ThyraMIR and ThyroSeq testing were 0.65 and 0.85, respectively. Conclusions These findings suggest that, at our institution, both ThygenX/ThyraMIR and ThyroSeq effectively stratify cytology specimens based on risk of malignancy and reduce the number of surgeries performed at our institution.