Molecular landscape and therapeutic strategies in pediatric differentiated thyroid carcinoma

There has been significant progress in understanding the molecular landscape of pediatric differentiated thyroid carcinoma over the past two decades. Classification of pediatric differentiated thyroid carcinoma into three-tiers, RAS-like mutant, BRAF-mutant, and kinase-fusions, accurately reflects an increasing risk for invasive behavior, including regional and distant metastasis. In clinical practice, somatic oncogene testing for nodules with indeterminate cytology per the Bethesda System for Reporting Thyroid Cytopathology provides objective data to optimize surgical planning. In addition, knowledge of the somatic oncogene for widely invasive carcinomas allows for incorporation of oncogene-specific inhibitory therapy both in the adjuvant and neoadjuvant setting. In the present review, we review the risk factors, clinical presentation, and evaluation of pediatric DTC, highlighting the correlation among ultrasound features, cytology, and oncogenic driver of the tumor. We subsequently propose an integrated, multi-modal approach that can be used to improve diagnostic accuracy and reliability for pre-operative planning as well as identify and discuss which pediatric patients may benefit from systemic oral targeted therapy.