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Pediatric Thyroid Cancer

  • Author: Mark E Gerber, MD; Chief Editor: Arlen D Meyers, MD, MBA  more...
 
Updated: Apr 30, 2015
 

Background

Although a review of the literature contains numerous reports on the subject of pediatric thyroid carcinoma, the low incidence and subsequent lack of prospective randomized trials make drawing absolute conclusions regarding the definitive workup, management, and treatment of this disease difficult. In 2015, however, a task force commissioned by the American Thyroid Association (ATA), following an extensive literature search, issued the first guidelines on the management of pediatric thyroid nodules and differentiated thyroid cancer.[1, 2]

A detailed understanding of how to perform a comprehensive evaluation of the pediatric thyroid nodule and persistent cervical adenopathy is necessary in order to establish the diagnosis of pediatric thyroid cancer. The incidence of head and neck malignancies, including those of the thyroid, has increased 25% during the past 30 years.[3] Based on retrospective series, the prevalence of thyroid nodules in children ranges from 0.2-5%, compared with approximately 30% in adults. However, pediatric thyroid nodules carry a far greater risk of harboring malignancy compared with adults, at approximately 26.4%. Some authors have reported an incidence of as high as 36%.[4] Because pediatric thyroid nodules carry this increased risk of malignancy, physicians should perform an expeditious workup.[5, 6]

The recommended diagnostic protocol of thyroid nodules consists of the following steps:

  1. Child's history, including familial history and radiation exposure
  2. Clinical examination
  3. Laboratory tests
  4. Thyroid ultrasonography
  5. Fine-needle aspiration biopsy (FNAB)

The beneficial role of scintigraphy is limited.[7, 8] However, molecular marker analysis of FNAB samples is proving to be beneficial in determining surgical plans.

Most childhood thyroid nodules are asymptomatic and are detected by parents or by physicians during routine examination. Only about 50% of children with thyroid carcinoma present with nodular thyroid enlargement as the presenting symptom. Follicular adenoma is the most common cause of solitary thyroid nodules in the pediatric population; however, solitary nodules in children reportedly have a 20-73% incidence of malignancy.[9, 10, 11] A painless noninflammatory metastatic cervical mass is the presenting symptom in 40-80% of patients.[12] Malignant lesions are usually papillary and follicular carcinomas. Radiation exposure, which is still used either as therapy prior to bone marrow transplantation or as a treatment of Hodgkin disease, remains a major risk factor.[13]

The subsequent diagnostic workup is aimed at determining whether the lesion represents a malignancy. Collected data can be useful in preoperative planning if surgery is indicated. Pediatric and adult thyroid cancers have differing biological behaviors. Despite the fact that pediatric thyroid cancer usually presents at an advanced stage, it carries an excellent prognosis, with long-term survival rates greater than 95%.

An image depicting thyroid cancer can be seen below.

A monomorphous cell population of Hürthle cells ar A monomorphous cell population of Hürthle cells arranged in loosely cohesive clusters and single cells. The cells are polyhedral and have abundant granular cytoplasm with well-defined cell borders. The nuclei are enlarged and have a central prominent macronucleolus.

Guidelines

As mentioned, in 2015 the American Thyroid Association (ATA) issued guidelines for the management of children with thyroid nodules and differentiated thyroid cancer. The guidelines’ 34 recommendations include the following, which have a recommendation rating of A[1, 2] :

  • For pediatric patients with a suppressed thyroid-stimulating hormone (TSH) associated with a thyroid nodule, thyroid scintigraphy should be pursued
  • A comprehensive neck ultrasonogram to interrogate all regions of the neck is required in order to optimize the preoperative surgical plan in children with a newly diagnosed papillary thyroid cancer
  • For the majority of children with papillary thyroid cancer, total thyroidectomy is recommended
  • In order to facilitate iodine-131 ( 131 I) uptake by residual iodine-avid cancer, the TSH should be above 30 mIU/L
  • Neck ultrasonography is recommended in the follow-up of children with papillary thyroid cancer; it should be performed at least 6 months after initial surgery and then at 6-12 month intervals for ATA pediatric intermediate- and high-risk patients and at annual intervals for ATA pediatric low-risk patients; follow-up beyond 5 years should be individualized based on recurrence risk
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Epidemiology

Frequency

United States

Thyroid cancer, the most common pediatric endocrine neoplasm, represents 3% of all pediatric malignancies and 5-5.7% of malignancies in the head and neck. Only 5% of all thyroid cancers occur in children and adolescents.[14] Thyroid nodules occur in up to 35% of the general adult population and in only 1-2% of the pediatric population. These numbers are estimated using a compilation of data from multiple reports.[13, 15, 16]

Paradoxically, despite the lower incidence of thyroid nodules in children, a pediatric thyroid nodule has a greater risk of containing or developing a malignancy. Whereas 5% of nodules in adults are malignant, in the pediatric population, the percentage of malignant nodules is 26.4%.[17] The incidence of malignancy in multinodular goiter is 1-7% and 10-25% in solitary nodules.[13] Pediatric thyroid cancer (3% prevalence) in adolescents is also associated with juvenile autoimmune thyroiditis.[18]

Papillary thyroid cancer is by far the common thyroid malignancy in children, constituting 83% of all pediatric thyroid malignancies.[19] Although papillary carcinoma is more aggressive in children than in adults, pediatric papillary cancer carries a much better prognosis that adult thyroid cancer.[20]

Medullary thyroid cancer (MTC), which constitutes 5% of pediatric thyroid malignancies, is usually associated with multiple endocrine neoplasia type 2 (MEN2) in the pediatric population. The inheritance pattern occurs either sporadically or as familial MTC without other associated endocrine abnormalities. MEN2 consists of MTC and pheochromocytoma and either hyperparathyroidism (2A) or mucosal neuromas (2B). MTC associated with MEN2B is more virulent and may occur and metastasize early in infancy.

International

After the Chernobyl nuclear power plant disaster, individuals living in Russia, Ukraine, and Eastern Europe were exposed to significant levels of radioactive iodines, primarily iodine 131 (131 I). This radioactivity, which is concentrated in the thyroid gland, has resulted in a substantial increase in pediatric thyroid cancer rates among this cohort of children.[21, 22]

Mortality/Morbidity

Pediatric thyroid malignancies are usually a well-differentiated papillary subtype or the papillary-follicular subtype, but all histologic types have been observed. Children commonly present with advanced disease. At presentation, 70% of patients have extensive regional nodal involvement, and 10-20% of patients have distant metastasis.[23] The lungs are the most common sites of metastasis.

Pediatric patients seem to have higher local and distant recurrence rates than adults, but they tend to respond rapidly to therapy. The prognosis for children is excellent, with mortality rates of less than 10%.[24] Benign tumors such as follicular adenomas should be considered at risk for tumor progression toward follicular thyroid carcinoma, and they must be surgically addressed.[17]

Sex

Thyroid carcinoma is 2-3 times more common in females.[25]

The gender distribution of thyroid carcinoma differs between adults and children. Thyroid cancer is 4 times as common in women as in men. This difference is not seen in individuals younger than 15 years; the girl-boy ratio is as low as 1.5:1. However, in individuals aged 15–20 years, the female-to-male ratio is 3:1.[26] This implies that female sex hormones, especially during puberty, play a significant yet still undefined role in the increased incidence of thyroid cancer in females.[14]

Age

Age is a major determinant of both the incidence and recurrence of pediatric thyroid carcinoma. Pediatric thyroid carcinoma occurs more frequently in adolescents, although it has been reported in the neonatal period.[27] In children younger than 10 years, identified thyroid lesions are more likely to be malignant.[28] Children younger than 10 years are also more likely to have recurrent cancer.[24]

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Contributor Information and Disclosures
Author

Mark E Gerber, MD Clinical Associate Professor of Surgery, University of Chicago Pritzker School of Medicine; Division Head, Otolaryngology-Head and Neck Surgery; Director, Pediatric Otolaryngology-Head and Neck Surgery, NorthShore University Health System

Mark E Gerber, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Bronchoesophagological Association, American Society of Pediatric Otolaryngology, Society for Ear, Nose and Throat Advances in Children, American Academy of Pediatrics, American Rhinologic Society

Disclosure: Nothing to disclose.

Coauthor(s)

Brian Kip Reilly, MD Assistant Professor of Otolaryngology and Pediatrics, Department of Otolaryngology, Children's National Medical Center, George Washington University School of Medicine

Brian Kip Reilly, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery

Disclosure: Nothing to disclose.

Mihir K Bhayani, MD Clinical Assistant Professor, Department of Surgery, University of Chicago Division of the Biological Sciences, The Pritzker School of Medicine; Consulting Surgeon, Head and Neck Surgical Oncology Section, Department of Otolaryngology, NorthShore University Health System

Mihir K Bhayani, MD is a member of the following medical societies: American Head and Neck Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Nader Sadeghi, MD, FRCSC Professor, Otolaryngology-Head and Neck Surgery, Director of Head and Neck Surgery, George Washington University School of Medicine and Health Sciences

Nader Sadeghi, MD, FRCSC is a member of the following medical societies: American Head and Neck Society, American Thyroid Association, American Academy of Otolaryngology-Head and Neck Surgery, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA Professor of Otolaryngology, Dentistry, and Engineering, University of Colorado School of Medicine

Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cerescan;RxRevu;SymbiaAllergySolutions<br/>Received income in an amount equal to or greater than $250 from: Symbia<br/>Received from Allergy Solutions, Inc for board membership; Received honoraria from RxRevu for chief medical editor; Received salary from Medvoy for founder and president; Received consulting fee from Corvectra for senior medical advisor; Received ownership interest from Cerescan for consulting; Received consulting fee from Essiahealth for advisor; Received consulting fee from Carespan for advisor; Received consulting fee from Covidien for consulting.

Acknowledgements

Russell A Faust, MD, PhD Consulting Staff, Department of Otolaryngology, Columbus Children's Hospital

Disclosure: Nothing to disclose.

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A monomorphous cell population of Hürthle cells arranged in loosely cohesive clusters and single cells. The cells are polyhedral and have abundant granular cytoplasm with well-defined cell borders. The nuclei are enlarged and have a central prominent macronucleolus.
 
 
 
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