Multiplatform Molecular Testing as an Adjunct to Fine Needle Aspiration in the Evaluation of Pediatric Thyroid Nodules

Abstract Context Molecular analysis of thyroid cytopathology derived from fine needle aspiration (FNA) improves diagnostic yield and informs presurgical treatment stratification of adults with thyroid nodules. Its use is limited in pediatrics, but it has the potential to guide clinical management for these patients. Objective To report on the results of oncogene sequencing and microRNA (miRNA)-based risk classification of thyroid FNA cytopathology in a pediatric cohort. Design Retrospective analysis of archived FNA samples collected from patients seen at Lurie Children's Hospital between October 2020 and March 2023; 39 cases were included in the study. Setting Referral center. Patients Thirty-seven patients ages 7 to 20 years (mean age 13.9 years). Interventions Interpace Diagnostics®’ multiplatform testing including ThyGeNEXT® (oncogene panel) and ThyraMIR® (miRNA risk classifier) was performed on FNA samples. Molecular results were compared to final surgical pathology or repeat FNA results. Main Outcome Measures Description of cohort molecular characteristics; test sensitivity and specificity. Results The most common oncogenic alterations among malignant cases were the BRAFV600E variant (38%), RET-PTC1 fusions (14%), and NRAS variants (14%). Nineteen of 21 malignant samples had positive (high-risk) miRNA expression profiles. Fifteen of 18 benign cases had negative (low-risk) miRNA profiles. Multiplatform molecular testing demonstrated 90.5% sensitivity and 88.9% specificity in detecting malignant pathology. Conclusion This is the first study to report on the use of combined oncogene and miRNA analysis of FNA cytopathology in a pediatric cohort. Multiplatform molecular testing is a potentially useful adjunct to FNA as a presurgical diagnostic tool in the evaluation of pediatric thyroid nodules.