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The annual incidence of thyroid cancers is 2.0 cases per 1 million people per year in children younger than 15 years, accounting for approximately 1.5% of all cancers in this age group. Thyroid cancer incidence is higher in children aged 15 to 19 years (17.6 cases per 1 million people), and it accounts for approximately 8% of cancers arising in this older age group.[1,2] More thyroid carcinomas occur in females than in males.
A retrospective review of the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2011 identified 2,504 cases of papillary thyroid carcinoma in patients aged 20 years and younger. The incidence of papillary thyroid carcinoma increased over this interval by roughly 2% each year. The trend toward larger tumors suggests that diagnostic scrutiny is not the only explanation for the observed results.
An update from the SEER database for the period of 2007 to 2012 identified 1,723 pediatric patients with thyroid cancer. The average age-adjusted incidence of pediatric thyroid cancer was 0.59 cases per 100,000 patients. When the incidence in females was compared with the incidence in males, the ratio of pediatric thyroid cancer was 4.4:1. The incidences of papillary, follicular variant, follicular, and medullary subtypes differ over the pediatric age range (refer to Figure 1).
Figure 1. Incidence of pediatric thyroid carcinoma based on most frequent subtype per 100,000 as a percent of total cohort. Reprinted from International Journal of Pediatric Otorhinolaryngology, Volume 89, Sarah Dermody, Andrew Walls, Earl H. Harley Jr., Pediatric thyroid cancer: An update from the SEER database 2007-2012, Pages 121-126, Copyright (2016), with permission from Elsevier.
There is an excessive frequency of thyroid adenoma and carcinoma in patients who previously received radiation to the neck.[1,2] In the decade following the Chernobyl nuclear incident, there was a tenfold increase in the incidence of thyroid cancer compared with the previous and following decades. In this group of patients with exposure to low-dose radiation, tumors commonly show a gain of chromosome band 7q11.
When occurring in patients with the multiple endocrine neoplasia syndromes, thyroid cancer may be associated with the development of other types of malignant tumors. (Refer to the Multiple Endocrine Neoplasia [MEN] Syndromes and Carney Complex section of the PDQ summary on Unusual Cancers of Childhood Treatment for more information.)
Tumors of the thyroid are classified as adenomas or carcinomas.[1,2,3] Adenomas are benign, well circumscribed and encapsulated nodules that may cause enlargement of all or part of the gland, which extends to both sides of the neck and can be quite large; some tumors may secrete hormones. Transformation to a malignant carcinoma may occur in some cells, which may grow and spread to lymph nodes in the neck or to the lungs. Approximately 20% of thyroid nodules in children are malignant.[1,4]
Various histologies account for the general diagnostic category of carcinoma of the thyroid; papillary and follicular carcinoma are often referred to as differentiated thyroid carcinoma:
Studies have shown subtle differences between the genetic profiling of childhood differentiated thyroid carcinomas and that of adult tumors (refer to Table 1). In one study, a higher prevalence of RET/PTC rearrangements was reported in pediatric papillary thyroid carcinoma (45%-65% in children vs. 3%-34% in adults).BRAF V600E mutations are seen in more than 50% of adults with papillary thyroid carcinoma; although it likely occurs in a similar frequency in pediatric patients, studies have revealed a wide variation in frequency of this mutation.[1,2,3,4] In children, the correlation between the genomic alteration and stage or prognosis has not been well defined. While two studies failed to show a correlation,[3,4] one study that included 55 pediatric thyroid carcinoma cases demonstrated a significant correlation between the presence of a BRAF V600E mutation and an increased risk of recurrence. Differentiated thyroid carcinoma has been associated with germline DICER1 mutations and it is considered part of the DICER1 syndrome.
Patients with thyroid cancer usually present with a thyroid mass with or without painless cervical adenopathy.[1,2,3] On the basis of medical and family history and clinical constellation, the thyroid cancer may be part of a tumor predisposition syndrome such as multiple endocrine neoplasia or DICER1 syndrome.
Younger age is associated with a more aggressive clinical presentation in differentiated thyroid carcinoma. Children have a higher proportion of nodal involvement (40%-90% in children vs. 20%-50% in adults) and lung metastases (20%-30% in children vs. 2% in adults) than do adults.[5,6] Larger tumor size (>1 cm), extrathyroidal extension, and multifocal disease are associated with increased risk of nodal metastases. Likewise, when compared with pubertal adolescents, prepubertal children have a more aggressive presentation with a greater degree of extrathyroid extension, lymph node involvement, and lung metastases. However, outcome is similar in the prepubertal and adolescent groups.
In well-differentiated thyroid cancer, male sex, large tumor size, and distant metastases have been found to have prognostic significance for early mortality; however, even patients in the highest risk group who have distant metastases had excellent survival at 90%. A French registry analysis found similar outcomes in children and young adults who developed papillary thyroid carcinoma after previous radiation therapy compared with children and young adults who developed spontaneous papillary thyroid carcinoma; patients with previous thyroid irradiation for benign disease, however, presented with more invasive tumors and lymph node involvement.
Initial evaluation of a child or adolescent with a thyroid nodule includes the following:
Tests of thyroid function are usually normal, but thyroglobulin can be elevated.
Fine-needle aspiration as an initial diagnostic approach is sensitive and useful. However, in doubtful cases, open biopsy or resection should be considered.[1,2,3,4] Open biopsy or resection may also be preferable for young children (refer to Table 2).
Treatment options for papillary and follicular (differentiated) thyroid carcinoma may include the following:
The management of differentiated thyroid cancer in children has been reviewed in detail.[1,2] In 2015, the American Thyroid Association (ATA) Task Force on Pediatric Thyroid Cancer published guidelines for the management of thyroid nodules and differentiated thyroid cancer in children and adolescents. These guidelines (summarized below) are based on scientific evidence and expert panel opinion, with a careful assessment of the level of evidence.
Pediatric thyroid surgery should ideally be performed by a surgeon who performs at least 30 or more cervical endocrine procedures annually in a hospital with the full spectrum of pediatric specialty care.
For patients with papillary or follicular carcinoma, total thyroidectomy is the recommended treatment of choice. The ATA expert panel recommendation is based on data showing an increased incidence of bilateral (30%) and multifocal (65%) disease.
In patients with a small unilateral tumor confined to the gland, a near-total thyroidectomy-whereby a small amount of thyroid tissue (<1%-2%) is left in place at the entry point of the recurrent laryngeal nerve or superior parathyroid glands-might be considered to decrease permanent damage to those structures.
Total thyroidectomy also optimizes the use of radioactive iodine for imaging and treatment.
Despite the limited data in pediatrics, the ATA Task Force recommends the use of the tumor-node-metastasis (TNM) classification system to categorize patients into one of three risk groups. (Refer to the Stage Information for Thyroid Cancer section in the PDQ summary on Thyroid Cancer Treatment [Adult] for more information about the TNM system.) This categorization strategy is meant to define the risk of persistent cervical disease and help determine which patients should undergo postoperative staging for the presence of distant metastasis.
Initial staging should be performed within 12 weeks after surgery; the purpose is to assess for evidence of persistent locoregional disease and to identify patients who are likely to benefit from additional therapy with iodine I 131 (131I). The ATA Pediatric Risk Level (as defined above) helps determine the extent of postoperative testing.
For patients with anti-thyroglobulin antibodies, consideration can be given to deferred postoperative staging to allow time for antibody clearance, except in patients with T4 or M1 disease.
The goal of 131I therapy is to decrease the risks of recurrence and to decrease mortality by eliminating iodine-avid disease.
While rare, late effects of 131I treatment include salivary gland dysfunction, bone marrow suppression, pulmonary fibrosis, and second malignancies.
Patients with differentiated thyroid cancer generally have an excellent survival with relatively few side effects.[1,2,3] However, recurrence is common (35%-45%) and is seen more often in children younger than 10 years and in those with palpable cervical lymph nodes at diagnosis.[4,5] Even patients with a tumor that has spread to the lungs may expect to have no decrease in life span after appropriate treatment. Of note, the sodium-iodide symporter (a membrane-bound glycoprotein cotransporter), essential for uptake of iodide and thyroid hormone synthesis, is expressed in 35% to 45% of thyroid cancers in children and adolescents. Patients with expression of the sodium-iodide symporter have a lower risk of recurrence.
Recurrent papillary thyroid cancer is usually responsive to treatment with radioactive iodine ablation.
Tyrosine kinase inhibitors (TKIs) such as sorafenib have been shown to induce responses in up to 15% of adult patients with metastatic disease. Response to sorafenib has also been documented in a pediatric case.
TKIs approved for the treatment of adults include the following:
Given the high incidence of BRAF mutations in patients with papillary thyroid carcinoma, the use of selective RAF/MEK inhibitors is being investigated.[9,14,15]
(Refer to the PDQ summary on Thyroid Cancer Treatment [Adult] for more information.)
Treatment Options Under Clinical Evaluation for Recurrent Papillary and Follicular Thyroid Carcinoma
Information about National Cancer Institute (NCI)-supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.
The following is an example of a national and/or institutional clinical trial that is currently being conducted:
Tumor tissue from progressive or recurrent disease must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the ClinicalTrials.gov website for APEC1621 (NCT03155620).
Medullary thyroid carcinomas are commonly associated with the multiple endocrine neoplasia 2 (MEN2) syndrome (refer to the Multiple Endocrine Neoplasia [MEN] Syndromes and Carney Complex section of the PDQ summary on Unusual Cancers of Childhood Treatment for more information). They present with a more aggressive clinical course; 50% of the cases have hematogenous metastases at diagnosis. Patients with medullary carcinoma of the thyroid have a guarded prognosis, unless they have very small tumors (microcarcinoma, defined as <1.0 cm in diameter), which carry a good prognosis. A natural history study of children and young adults with medullary thyroid cancer is being conducted by the National Cancer Institute (NCT01660984). For patients with de novo RET mutations and no familial history, nonendocrine manifestations, such as intestinal ganglioneuromatosis or skeletal or ocular stigmata, may facilitate early diagnosis and result in better outcomes.
Treatment options for medullary thyroid carcinoma include the following:
Most cases of medullary thyroid carcinoma occur in the context of the MEN2A and MEN2B syndromes. In those familial cases, early genetic testing and counseling is indicated, and prophylactic surgery is recommended for children with the RET germline mutation. Strong genotype-phenotype correlations have facilitated the development of guidelines for intervention, including screening and age at which prophylactic thyroidectomy should occur.
Children with locally advanced or metastatic medullary thyroid carcinoma were treated with vandetanib in a phase I/II trial. Of 16 patients, only 1 had no response, and 7 had a partial response, for an objective response rate of 44%. Disease in three of those patients subsequently recurred, but 11 of 16 patients treated with vandetanib remained on therapy at the time of the report. The median duration of therapy for the entire cohort was 27 months, with a range of 2 to 52 months.
(Refer to the Multiple Endocrine Neoplasia [MEN] Syndromes and Carney Complex section of the PDQ summary on Unusual Cancers of Childhood Treatment and the Treatment for those with MTC section in the PDQ summary on Genetics of Endocrine and Neuroendocrine Neoplasias for more information.)
Treatment Options Under Clinical Evaluation for Medullary Thyroid Carcinoma
Cancer in children and adolescents is rare, although the overall incidence of childhood cancer has been slowly increasing since 1975. Referral to medical centers with multidisciplinary teams of cancer specialists experienced in treating cancers that occur in childhood and adolescence should be considered for children and adolescents with cancer. This multidisciplinary team approach incorporates the skills of the following health care professionals and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life:
(Refer to the PDQ Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.)
Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics. At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate in these trials is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with therapy that is currently accepted as standard. Most of the progress made in identifying curative therapy for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.
Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%. Childhood and adolescent cancer survivors require close monitoring because cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)
Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years. The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 persons and, by definition, all pediatric cancers are considered rare. The designation of a pediatric rare tumor is not uniform among international groups, as follows:
These rare cancers are extremely challenging to study because of the low incidence of patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the lack of clinical trials for adolescents with rare cancers.
Information about these tumors may also be found in sources relevant to adults with cancer such as the PDQ summary on Thyroid Cancer Treatment (Adult).
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Clinical Presentation and Outcome
Added Al-Qurayshi et al. as reference 6.
This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood thyroid cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Childhood Thyroid Cancer Treatment are:
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
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The preferred citation for this PDQ summary is:
PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Thyroid Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/thyroid/hp/child-thyroid-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389315]
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Last Revised: 2018-02-02
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