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