Molecular Genetic Findings in Pediatric Thyroid Fine Needle Aspirations: Experience from a Large Academic Medical Center
Sara E Monaco, Liron Pantanowitz, Walid E Khalbuss, Vanessa Benkovich, John Ozolek, Jeffrey Simons, Yuri E Nikiforov. University of Pittsburgh Medical Center, Pittsburgh, PA; Children's Hospital of the University of Pittsburgh Medical Center, Pittsburgh, PA
Background: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) and its management guidelines for thyroid fine-needle aspiration (FNA) are largely based on data from studies with adult populations. Although thyroid nodules are more commonly identified in adults, the rate of malignancy in thyroid nodules in children is higher. Thus, our aim was to analyze the mutational profiles of pediatric thyroid cancer detected by molecular analysis of thyroid FNAs, and to examine its diagnostic use in thyroid nodules from children.
Design: FNAs from children (ages ≤ 21 years) were identified from our pathology archive during a 4.5 year period (2007-2011). Cases were categorized based on the diagnostic categories from TBSRTC and the findings were correlated with histological follow-up and molecular analysis performed for the following mutations: BRAF, NRAS61, HRAS61, KRAS12/13, RET/PTC and PAX8/PPARγ.
Results: A total of 179 cases from 142 patients were identified, including 96 cases (54%) with histological follow-up and 66 cases (37%) with molecular data. Of the 66 FNAs with molecular data, there were 47 (71%) negative, 8 (12%) indeterminate, and 11 (17%) positive for mutations. The FNA samples with molecular testing positive for any mutation were all papillary thyroid carcinomas (PTCs) on resection. The molecular findings in these FNA cases included 4 RAS mutations (36.5%; 1 HRAS, 2 NRAS, and 1 with HRAS and NRAS), 3 RET/PTC rearrangements (27.5%), 2 BRAF mutations (18%), and 2 PAX8/PPARg rearrangements (18%). The FNA diagnoses in these positive cases included atypia of undetermined significance (2 cases), suspicious for follicular or oncocytic neoplasm (5 cases), suspicious for PTC (1 case), and positive for PTC (3 cases).
Conclusions: To our knowledge, this is the first report of molecular testing for a panel of mutations performed in FNA samples from pediatric thyroid nodules. These data reveal 17% positivity for mutations in this population, which is higher than that seen in adult populations. The presence of any mutation in this study correlated with malignancy in 100% of cases, including nodules with indeterminate cytology. Our findings also demonstrate a higher prevalence of RAS and RET/PTC mutations and lower prevalence of BRAF mutations as compared to adult populations, which correlates with the less aggressive nature of PTCs in young individuals.
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 54, Wednesday Afternoon