Molecular Abnormalities Common in Pediatric Thyroid Lesions

Thyroid lesions identified in pediatric patients were often found to have one of the molecular abnormalities commonly seen in adults with thyroid lesions, a new study has found.

Researchers led by Leomar Y. Ballester, MD, PhD, of Baylor College of Medicine, screened pediatric thyroid lesions for molecular abnormalities and found that 67% had a genetic alteration.

“Molecular testing may be crucial to identifying therapeutic targets that may be useful for patients with non-resectable or metastatic tumors and for disease monitoring in these young patients,” Ballester and colleagues wrote in Pediatric and Developmental Pathology. “Although prospective and larger studies evaluating the benefits of molecular testing in pediatric thyroid lesions are needed, our data suggest that molecular testing may be a useful tool to optimize the diagnosis and management of pediatric patients with thyroid lesions.”

According to the study, thyroid nodules occur in 1% to 2% of children. Identification of malignant nodules can be difficult, and, at times, can require multiple surgeries to first, biopsy the mass, and then remove it if it is found to be malignant.

In this study, Ballester and colleagues sought to identify common genetic alterations in thyroid lesions that could help to determine which cases are malignant. To do that, they looked at 27 thyroid carcinomas taken from patients aged 10 to 19. These samples were tested for several mutations commonly seen in adult thyroid lesions including BRAF V600E, RET fusions, and TERT promoter mutations.

Among the patients in the study, 12 patients had classic papillary thyroid carcinoma (PTC), 13 had follicular variants of PTC, 1 patient had medullary thyroid carcinoma, and 1 had follicular carcinoma.

Testing revealed that 10 of the samples included had a BRAF V600E mutation and 6 had RET fusions. Of those samples with BRAF V600E mutations, 3 were in follicular variants of PTC and 7 were in classic PTC. Additionally, 5 out of 6 cases with RET fusions were in classic PTC.

No TERT promoter mutations were found in any of the samples tested, a finding that is in agreement with a prior study from The Cancer Genome Atlas that found strong associations with TERT mutations and older age.

No RAS mutations were identified in these tumors samples, which the researchers wrote was “unexpected” given that prior studies have shown RAS mutations in about 36% of pediatric thyroid carcinomas.

“Interestingly, our results agree with those of some prior studies reporting a similarly low frequency of RAS mutations in children,” the researchers wrote. “Whether age may play a role in the frequency discrepancies of RAS mutations in pediatric thyroid cancers, or if this finding is simply incidental, will have to be determined in future studies.”

Finally, the researchers concluded that “mutation frequency is important when considering the utility and cost benefit of implementing a diagnostic algorithm including molecular testing. The clinical utility of molecular testing in the pediatric population will be greatly affected by the frequency at which mutations are detected.”