SAT522 Validating Molecular Testing As An Adjunct To Fine Needle Aspiration In Pediatric Thyroid Malignancy

Disclosure: A. Aekka: None. N. Arva: None. M. Raval: None. J. Rastatter: None. S.D. Finkelstein: Employee; Self; Interpace Biosciences. J. Levine: Employee; Self; Interpace Biosciences. J. Josefson: None. The standard diagnostic approach for thyroid malignancy includes evaluation of cytopathology derived from thyroid fine needle aspiration (FNA). Nearly 40% of pediatric cases have indeterminate FNA results, and there is no clear consensus regarding the management of these cases. Molecular analysis is beneficial in increasing diagnostic yield and informing treatment stratification in adults, although its use remains limited in pediatrics. This study sought to assess the validity of next-generation sequencing mutational analysis and microRNA (miRNA)-based risk classification of FNA cytopathology derived from a single-center cohort of pediatric patients. The study hypothesized that molecular analyses improve diagnostic performance of FNA for children with thyroid cancer. Interpace Diagnostics’ validated multiplatform tool comprised of ThyGeNEXT (mutational panel capturing 10 oncogene sequence variants and 38 fusions) and ThyraMIR (miRNA risk classifier including 11 miRNA markers) was utilized for this study. Multiplatform testing was performed on 27 archived FNA thyroid samples collected from patients ages 7-20 years (mean age 14.1 years, 78% female). Molecular results were compared with final surgical pathology or repeat FNA results to determine validity. Surgical pathology confirmed papillary thyroid carcinoma in 14 patients and benign pathology in 6 patients. Repeat FNA confirmed benign pathology in 2 patients. Surgical pathology or repeat FNA was unavailable for 5 cases, all of which had benign initial cytopathology. The most common mutational finding was BRAF_V600E (6/14) followed by RET-PTC fusions (3/14). MiRNA findings were as follows: 16 high-risk expression profiles, 3 low-risk expression profiles, and 8 negative profiles. The validation analysis included 22 samples that had corresponding surgical or repeat FNA results. All cases of malignancy demonstrated high-risk miRNA profiles and all benign cases demonstrated negative or low-risk miRNA profiles. Multiplatform molecular testing demonstrated 100% sensitivity, 87.5% specificity, 93.3% positive predictive value, and 100% negative predictive value in detecting malignant versus benign pathology in our population. Molecular analyses appear to be a valid adjunct to FNA in pediatric thyroid cancer evaluation. Incorporation of molecular diagnostics advances precision medicine in pediatric thyroid care and may better inform presurgical treatment stratification, mitigate risks associated with unnecessary procedures, and ultimately improve outcomes for children and adolescents with thyroid nodules. Presentation Date: Saturday, June 17, 2023