ESPE Yearbook of Paediatric Endocrinology

Brief summary: In 2021 and 2022, two important publications on pediatric thyroid carcinomas revealed a distinct molecular landscape compared to adult thyroid carcinomas (1,2). Pediatric differentiated thyroid carcinoma was mainly caused by fusion oncogenes, especially in children younger than 10 years (93%), compared to children aged 10–15 years (28%) and 15–20 years old patients (14%). In contrast, PTC due to BRAF mutations showed increasing frequency with age (7%, 30%, and 65%, respectively in children <10 years, 10–15 years, and 15–20 years. The major clinical consequence of these results was that pediatric thyroid carcinomas caused by fusion oncogenes could successfully be treated with fusion targeted therapies in patients after molecular diagnosis (1). These results were confirmed in a second large study (2).

The presented retrospective monocenter case series by Gallant et al. investigated n=95 patients with a median age of 16.3 years (range: 4.8–21.1 years) who underwent thyroidectomy for thyroid nodule. Surgical samples were analyzed by a commercially available DNA/RNA next generation sequencing genomic classification test used for adult thyroid tumors. The molecular analyses confirmed the results of the two papers presented in the 2022 Yearbook that fusion oncogenes and DICER1 variants were more frequent in the pediatric cohort than in published adult series and showed that genomic classifiers are useful for molecular diagnosis.

In summary, these results first confirm recent data on different molecular landscape of pediatric thyroid carcinomas, and second show that genomic classifiers established for adult thyroid tumors are amendable in pediatric thyroid tumor patients for better molecular diagnosis. Better molecular diagnosis is the key for targeted therapies in patients with unfavourable outcome.

References: 1. NTRK and RET fusion-directed therapy in pediatric thyroid cancer yields a tumor response and radioiodine uptake. Lee YA, Lee H, Im SW, Song YS, Oh DY, Kang HJ, Won JK, Jung KC, Kwon D, Chung EJ, Hah JH, Paeng JC, Kim JH, Choi J, Kim OH, Oh JM, Ahn BC, Wirth LJ, Shin CH, Kim JI, Park YJ. NTRK and RET fusion-directed therapy in pediatric thyroid cancer yields a tumor response and radioiodine uptake. J Clin Invest. 2021 Sep 15;131(18):e144847. doi: 10.1172/JCI144847. PMID: 34237031. 2. Fusion Oncogenes Are Associated With Increased Metastatic Capacity and Persistent Disease in Pediatric Thyroid Cancers. Franco AT, Ricarte-Filho JC, Isaza A, Jones Z, Jain N, Mostoufi-Moab S, Surrey L, Laetsch TW, Li MM, DeHart JC, Reichenberger E, Taylor D, Kazahaya K, Adzick NS, Bauer AJ. Fusion oncogenes are associated with increased metastatic capacity and persistent disease in pediatric thyroid cancers. J Clin Oncol. 2022 Apr 1;40(10):1081–1090. doi: 10.1200/JCO.21.01861. Epub 2022 Jan 11. PMID: 35015563.