Somatic mutations in 33 benign and malignant hot thyroid nodules in children and adolescents

Abstract

Hot thyroid nodules (HTNs) in children are rare. Their reported malignancy rate is higher than in adults. However molecular data are rare. We present clinical and molecular data for 33 consecutive (29 benign and 4 malignant) HTNs. 17/29 Benign HTNs (59%) harbored somatic TSHR mutations. The most commonly observed mutation was M453T (in 8/29 samples). T632I and D633Y mutations were each detected twice. All other TSHR mutations were each found in one sample, including the new A538T mutation. One NRAS mutation was detected in a benign HTN with a M453T mutation. A PAX8/PPARG rearrangement was found in one malignant HTN. A T632I mutation was detected in one hot papillary thyroid carcinoma. The percentage of TSHR mutation positive HTNs in children and adolescents is within the range observed in adults. Contrary to adults, the M453T mutation is the predominant TSHR mutation in HTNs of children and adolescents. The increased malignancy rate of HTNs of children does not appear to be associated with RAS, BRAF, PAX8/PPARG and RET/PTC mutations.

Keywords: Hyperthyroidism; Thyroid cancer; Thyroid nodule.