Are we really at the dawn of understanding sporadic pediatric thyroid carcinoma?

Abstract

Data from the National Cancer Institute and from the literature have disclosed an increasing incidence of thyroid cancer in children, adolescents and adults. Although children and adolescents with thyroid cancer tend to present with more advanced disease than adults, their overall survival rate is excellent; however, there is no clear explanation for the differences observed in the clinicopathological outcomes in these age groups. There has been an ongoing debate regarding whether the clinicopathological differences may be due to the existence of distinct genetic alterations. Efforts have been made to identify these acquired genetic abnormalities that will determine the tumor's biological behavior and ultimately allow molecular prognostication. However, most of the studies have been performed in radiation-exposed pediatric thyroid carcinoma. Therefore, our understanding of the role of these driver mutations in sporadic pediatric differentiated thyroid cancer development is far from complete, and additionally, there is a strong need for studies in both children and adolescents. The aim of this review is to present an extensive literature review with emphasis on the molecular differences between pediatric sporadic and radiation-exposed differentiated thyroid carcinomas and adult population. Key Words" sporadic pediatric papillary thyroid carcinomas " radiation-exposed papillary thyroid carcinomas " RET/PTC

Differentiated thyroid cancer in children: Heterogeneity of predictive risk factors

“…Differentiated thyroid cancers occurring in children and adolescents often show significant differences in clinical presentation, pathology and molecular alterations as compared with DTCs occurring in adulthood . Our results confirm that DTCs in young patients present at diagnosis with a more aggressive disease than in adults: extrathyroidal extension was found in about 30% of young patients, who also exhibited a higher rate of distant and regional metastases (approximately 10% and 50% of cases, respectively).…”

AGK‐BRAF is associated with distant metastasis and younger age in pediatric papillary thyroid carcinoma

“…On the other hand, some of the most common genetic alterations of adult PTC are rare or absent in pediatric PTC, supporting the hypothesis that biological features of PTC may differ by patient age . For instance, BRAF V600E mutation represents the most prevalent event in PTC reported in adults (23–63%) but the prevalence is lower (3–48%) in pediatric PTC patients in most studies .…”

Thyroid Cancer in the Pediatric Age in Sicily: Influence of the Volcanic Environment

“…Similar differences were found when DTCs in the 15-to 19-year-old group were compared to DTCs occurring in adults in Sicily (Tables I and II) and confirm that thyroid cancer characteristics at presentation in children are more aggressive, with an inverse relationship with patient age. These differences in pediatric vs. adult features of DTC may be the consequence of differences in the genetic background, causing earlier clinical presentation because of a more aggressive malignant genotype (33), but may also be due to the endocrine and immune characteristics of the individual. For instance, in our pediatric series, the presence of chronic lymphatic thyroiditis associated with DTC was very high (46.5%) suggesting a potential role of autoimmunity in determining DTC evolution in younger patients.…”

“…The mechanism is unknown but the present observation of a carcinogenic effect already present at an early age suggests that the effect of unidentified volcanic factor(s) is rapid, occurring within 5-15 years of exposure, a time interval similar to that of exposure to radiation. After radiation exposure,the excess relative risk of thyroid cancer depends on the dose and is higher in younger patients (aged 0-4 years at the time of exposure), while it is not significant when exposed individuals are older than 20 years of age (33,40,41). At variance with radiation, however, exposure to putative volcanic carcinogens in the volcanic area is chronic and begins during fetal life, when mothers are contaminated.…”