Integrating Molecular Testing in the Diagnosis and Management of Children with Thyroid Lesions

Leomar Y. Ballester, Stephen F. Sarabia, Hadi Sayeed, Nimesh Patel, Joshua Baalwa, Ioanna Athanassaki, Jose A. Hernandez, Erica Fang, Norma M. Quintanilla, Angshumoy Roy, Dolores H. López-Terrada

Thyroid nodules occur in 1-2% of children and identifying which nodules are malignant is often challenging. Cytologic evaluation facilitates the diagnosis of thyroid lesions (TL) but in 10-40% of cases the interpretation is indeterminate. Patients with indeterminate diagnoses are often treated with hemi-thyroidectomy followed by completion thyroidectomy, if cancer is found in the initial specimen. Exposing patients to multiple surgeries increases costs and morbidity. The American Thyroid Association states that that a combination of molecular markers is likely to optimize the management of patients with indeterminate cytology. However, few studies have addressed the molecular alterations present in pediatric TL. Twenty-seven thyroid carcinomas from pediatric patients were tested for alterations common in adult TL including BRAF V600E mutation, RET fusions, and TERT promoter mutations. Mutation-negative cases were subsequently analyzed with a next generation sequencing (NGS) mutation panel to search for additional targets. Histologic diagnoses included 12 classic papillary thyroid carcinomas (PTC), 13 follicular variant PTC, 1 medullary thyroid carcinoma, and 1 follicular carcinoma. Fourteen cases showed lymph node involvement and 13 cases demonstrated lymphovascular invasion. The BRAF V600E mutation was detected in 10/27 cases, and RET fusions were detected in 6/27 cases. No TERT promoter mutations were identified in any of the cases. The NGS panel revealed additional RET and CTNNB1 pathogenic missense mutations. Our results demonstrate that molecular abnormalities are common in pediatric TLs and suggest that incorporation of molecular testing will be helpful in optimizing patient management.