Introduction
Thyroid cancer is relatively rare in children and adolescents, accounting for only 1.8% of the total thyroid cancers diagnosed in the United States annually, but the incidence is increasing.1-4 Female predominance of thyroid cancer increases with age, approximating a 6:1 female to male ratio by age 15 to 19 years, making thyroid cancer the second most common malignancy in this age/gender group.1,5 In children, thyroid cancer may be asymptomatic and discovered incidentally at imaging for another purpose, or may present as a painless palpable thyroid mass, neck mass related to cervical lymphadenopathy, difficulty breathing, and/or hoarseness6
Thyroid cancer in children is classified into differentiated, poorly differentiated, and medullary subtypes. Subtypes of differentiated thyroid cancer include papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) subtypes. PTC is most common, accounting for up to 90%, and is further subdivided into classical, follicular, solid, and diffuse sclerosing variants.1,2 FTC accounts for up to 10% of thyroid cancer.2
Risk factors for developing PTC and FTC include autoimmune thyroid disease (i.e. Hashimoto’s thyroiditis and Graves’ disease), iodine deficiency, and prior therapeutic radiation exposure.6,7 Genetic predisposition syndromes including APC-associated polyposis, DICER1 syndrome, Carney Complex, PTEN hamartoma syndrome, and Werner syndrome may account for up to 5% of differentiated thyroid cancers.6,7Additionally, Li-Fraumeni, Peutz-Jeghers, familial paraganglioma, McCune-Albright, and Beckwith-Wiedemann syndromes are also associated with an increased risk of differentiated thyroid cancer.7 Genetic mutations of the BRAF, RET/PTC, ALK , RAS, and PAX8/PPARγ genes play a role in thyroid cancer pathogenesis.4,8 TheRET/PTC genetic rearrangement is relatively more common in children compared to adult thyroid cancers, while BRAF mutations are less commonly encountered in children than adults with PTC.6,9 Finally, thyroid cancer is one of the most common secondary malignancies in childhood cancer survivors.7,10
Poorly differentiated and medullary thyroid cancers are rare in the pediatric population.7 Most medullary thyroid carcinomas are hereditary, related to germline RET mutations causing multiple endocrine neoplasia (MEN) type 2A, MEN 2B, or familial medullary thyroid carcinoma (FMTC) and incidence is highest in the 0 to 4 year age group.1,2,7
In children, thyroid nodules occur in 0.5-5% of the population, however, there is a 19-25% rate of malignancy, highlighting the importance of nodule identification.11-13 Compared to adults, children with thyroid cancer are more likely to present with larger tumor size and extrathyroidal extension.9,14Children also have increased rates of regional lymph node and pulmonary metastasis compared to adults, at 60-80% and 10-25% respectively.9,14 However, despite more extensive disease at presentation, the mortality rate from thyroid cancer is lower in children than adults, with overall survival of 95% at 20 years in children.9,14