eMedicine Specialties > Otolaryngology and Facial Plastic Surgery > Head & Neck Surgery

Thyroid Cancer in Children

Author: Mark E Gerber, MD, Assistant Professor, Section Head, Pediatric Otolaryngology-Head and Neck Surgery, Evanston Northwestern Healthcare
Coauthor(s): Brian Reilly, MD, Staff Physician, Department of Otolaryngology, McGaw Medical Center of Northwestern University
Contributor Information and Disclosures

Updated: Sep 26, 2008

Introduction

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.

A detailed understanding of how to perform a comprehensive evaluation of the pediatric thyroid nodule 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.1 Although the incidence of thyroid nodules in children is rare before adolescence (1.5%), pediatric thyroid nodules have a 26.4% mean risk of cancer. Moreover, pediatric thyroid nodules are 4 times more likely to carry a diagnosis of thyroid cancer than adult nodules.2 Because pediatric thyroid nodules carry this increased risk of malignancy, physicians should perform an expeditious workup.3,4

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

  1. Child's history, including the prior existence and treatment of a benign thyroid disease
  2. Clinical examination
  3. Laboratory tests
  4. Thyroid ultrasonography
  5. Fine-needle aspiration biopsy (FNAB)

The beneficial role of scintigraphy is limited, and molecular marker analysis is currently more beneficial in a clinical research setting.5,6

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.7,8,9 A painless noninflammatory metastatic cervical mass is the presenting symptom in 40-60% of patients.10 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.11

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.

Frequency

United States

Thyroid cancer, the most common pediatric endocrine neoplasm, represents 1-1.5% 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.12 Thyroid nodules occur in 4-7% 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.11,13,14

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%.15 The incidence of malignancy in multinodular goiter is 1-7% and 10-25% in solitary nodules.11   Pediatric thyroid cancer (3% prevalence) in adolescents is also associated with juvenile autoimmune thyroiditis.16

Papillary thyroid cancer is by far the common thyroid malignancy in children. Although papillary carcinoma is more aggressive in children than in adults, pediatric papillary cancer carries a much better prognosis that adult thyroid cancer.17

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 Belarus were exposed to significant levels of radioactive iodines, primarily 131I. 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.18,19

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.20 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%.21 Benign tumors such as follicular adenomas should be considered at risk for tumor progression toward follicular thyroid carcinoma, and they must be surgically addressed.15

Sex

  • Thyroid carcinoma is 2-3 times more common in females.22
  • 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 3:1.23 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.12

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.24 In children younger than 10 years, identified thyroid lesions are more likely to be malignant.25 Children younger than 10 years are also more likely to have recurrent cancer.21

Clinical

History

  • Thyroid carcinoma in pediatric patients usually manifests as an asymptomatic neck mass, with a reported incidence of cervical lymphadenopathy that ranges from 35-83%.26 The neck masses are typically discovered incidentally by parents, patients, or physicians during routine physical examination.
  • Focal fold paralysis in children with thyroid malignancy is much less common than in adults with thyroid malignancy.15 Niedziela and Korman (2002) studied 37 children in Poland with thyroid cancer, none of whom presented with vocal cord paralysis or associated hoarseness.5
  • Additionally, unlike adults, young patients with thyroid nodules often do not report pain, tenderness, compression of the respiratory tract, problems with swallowing, or inappropriate fixation of the neck. Even young patients who have lung metastases usually do not report pulmonary symptoms.6 However, 10-20% of patients present with distant metastasis (most commonly to the lungs) and 70% of patients present with extensive regional nodal involvement.20
  • Many young patients have a family history of thyroid cancer. For example, 25% of medullary thyroid cancer (MTC) cases are hereditary, while over 75% are sporadic. A family history of MTC, pheochromocytoma, or hyperparathyroidism may indicate multiple endocrine neoplasia 2A (MEN2A) or multiple endocrine neoplasia 2B (MEN2B), both of which are inherited in an autosomal dominant fashion. All family members should be genetically screened for this mutation, especially given its autosomal dominant mode of inheritance. A history of Graves disease, hypothyroidism, or goiter should suggest a benign thyroid disease process, although long-term suppression of Graves Disease with antithyroid drugs may lead to increased risk of malignant thyroid transformation.15
  • Finally, patients who report a rapid growth rate of cancer may have a poorer prognosis, although that observation is controversial. Pain is rarely associated. Local tenderness is attributed to either thyroid cyst formation or hemorrhage into a rapidly growing nodule. Autoimmune disease, which often results in rapidly enlarging thyroid glands, confounds any associated glandular nodularity for which malignancy must be excluded.6

Physical

  • Thyroid carcinoma usually presents with one or more painless firm neck nodules. Most malignant nodules detected in children were 1.5 cm or larger in size.27 Tenderness of the nodule suggests hemorrhage into a nodule, a cyst, or an inflammatory process. For instance, if the skin is warm, erythematous, and diffusely tender, a diagnosis of acute suppurative thyroiditis is most likely and an inflammatory workup should be pursued.28
  • A soft compressible nodule is less likely to be malignant than a firm one.
  • Fixation of the mass to surrounding tissues and vocal fold paralysis suggest malignancy, although this process is rare.5 Lymphadenopathy further increases the likelihood of malignancy.
  • Diffuse thyroid enlargement or multiple nodules are more suggestive of a benign process. Mucosal neuromas of the tongue, palpebral conjunctiva, and lips with marfanoid body habitus may suggest MEN2B syndrome with medullary carcinoma, which often manifests in infancy.6

Causes

  • Thyroid carcinoma is a known sequela of radiation exposure. From the 1920s to the 1960s, external beam radiation was used for treatment of benign lesions (eg, tinea capitis, tonsillar hypertrophy, acne, thymic enlargement, hemangiomas) prior to recognition of its carcinogenic effects.29,30,31,32,33 The Chernobyl disaster in 1986 caused up to a 100-fold increase in the incidence of pediatric thyroid carcinoma in the exposed population. Cases associated with radiation exposure are mostly papillary carcinoma, and those associated iodine-deficient areas are more likely follicular.32,34,6
  • Radiation and chemotherapy for other pediatric malignancies also have been implicated in thyroid malignancy. Children who undergo pretreatment radiation therapy prior to bone marrow transplant and children who undergo primary radiation treatments for Hodgkin lymphoma are at increased risk for thyroid cancer. The risk for thyroid cancer is dose dependent.35
  • Congenital hypothyroidism (CH), due to either dyshormonogenesis or an iodine transporter defect, increases the risk of thyroid nodules. Chronic thyroid-stimulating hormone (TSH) elevation increases the risk of neoplastic transformation of thyroid. The benign nodules usually respond to thyroxine treatment. Those that remain or enlarge despite suppression therapy should undergo biopsy.5
  • Thyroglossal duct cysts, the most common developmental thyroid anomaly, carry an increased, albeit small, risk of malignant transformation. This is one of the reasons excision with the Sistrunk procedure (removal of cyst, central hyoid bone, and core from the base of the tongue) is recommended. However, only 8 cases of malignant thyroglossal duct transformation have been reported in the literature.36

More on Thyroid Cancer in Children

Overview: Thyroid Cancer in Children
Differential Diagnoses & Workup: Thyroid Cancer in Children
Treatment & Medication: Thyroid Cancer in Children
Follow-up: Thyroid Cancer in Children
References
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Further Reading

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Keywords

thyroid cancer in children, thyroid, thyroid cancer, pediatric thyroid carcinoma, thyroid nodule, thyroid enlargement, papillary carcinoma, follicular carcinoma, familial medullary thyroid carcinoma, MTC, familial MTC, endocrine disorder, endocrine abnormality, multiple endocrine neoplasia type 2, MEN2, MEN2A, MEN2B, pheochromocytoma, hyperparathyroidism, mucosal neuromas

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Contributor Information and Disclosures

Author

Mark E Gerber, MD, Assistant Professor, Section Head, Pediatric Otolaryngology-Head and Neck Surgery, Evanston Northwestern Healthcare
Mark E Gerber, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Academy of Pediatrics, American Cleft Palate/Craniofacial Association, American College of Surgeons, American Medical Association, American Rhinologic Society, Chicago Medical Society, and Illinois State Medical Society
Disclosure: Nothing to disclose.

Coauthor(s)

Brian Reilly, MD, Staff Physician, Department of Otolaryngology, McGaw Medical Center of Northwestern University
Brian Reilly, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery
Disclosure: Nothing to disclose.

Medical Editor

Russell A Faust, MD, PhD, Consulting Staff, Department of Otolaryngology, Columbus Children's Hospital
Russell A Faust, MD, PhD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American College of Legal Medicine, American Laryngological Rhinological and Otological Society, American Rhinologic Society, American Society for Head and Neck Surgery, and American Society of Law Medicine and Ethics
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Nader Sadeghi, MD, FRCS(C), Associate Professor of Surgery, Director of Head and Neck Surgery, Division of Otolaryngology, George Washington University
Nader Sadeghi, MD, FRCS(C) is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society, Federation of Medical Specialists in Quebec, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

CME Editor

Christopher L Slack, MD, Otolaryngology-Facial Plastic Surgery, Private Practice, Associated Coastal ENT; Medical Director, Treasure Coast Sleep Disorders
Christopher L Slack, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA, Professor, Department of Otolaryngology-Head and Neck Surgery, 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, and American Head and Neck Society
Disclosure: Covidien Corp Consulting fee Consulting; US Tobacco Corporation unstricted gift unknown

 
 
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