BRAFV600E and TERT promoter mutations in paediatric and young adult papillary thyroid cancer and clinicopathological correlation

Objectives: The primary objective of this study was to determine the prevalence of BRAF(V600E) and TERT promoter mutations in paediatric and young adult patients with papillary thyroid carcinoma (PTC) and the secondary objective, to assess their association with clinicopathological features. Methods: Patients <= 20 years who underwent surgery for differentiated thyroid cancer (DTC) from 2005 to 2018 were consecutively enrolled for BRAF(V600E) and TERT promoter mutations analysis and records analysed for the association of aggressive features. Univariate analysis and multivariate logistic regression were used to identify the independent predictors of BRAF(V600E) mutations. Results: Among 100 patients with DTC, 68 patients were <= 18 years and the remaining 30 patients were >18 years of age with a median age of 17 years (IQR 14-19 years) 98 patients had PTC and 2 had FTC. BRAF v600E mutation was present in 14/98 (14.3%) PTC and TERT promoter mutation noted in none. Multivariate analysis identified RAI refractoriness (OR:10.57, 95% CI: 2.6 to 41.6, P-0.0008) as an independent factor associated with BRAF(V600E) mutation. 17 patients with distant metastases were negative for both BRAF(V600E) or TERTpromoter mutation. No significant association was observed between age, gender, PTC variants, extra-thyroidal extension, lymphovascular invasion, multifocality, RAI administration and event rate with BRAF(V600E)mutation. Irrespective of BRAF(V600E) mutation, radioiodine refractory status (p-0.0001) had a reduced EFS probability. Conclusion: In paediatric & young adult PTC, TERT promoter mutation is absent and BRAF(V600E) mutation is not associated with distant metastasis. The prevalence rate of the BRAF(V600E) mutation is much lower compared to adult PTC patients.