Thyroid Tumors in Pediatric Age

Thyroid tumors in children and adolescents are rare but significant neoplasms that require careful management. While most pediatric thyroid nodules are benign, the risk of malignancy is higher in children compared to adults. This comprehensive overview covers key aspects of pediatric thyroid tumors, essential for pediatricians and medical students.

Epidemiology

• Incidence: 0.54 cases per 100,000 children per year
• Age distribution: Increases with age, rare before age 10, peak in adolescence
• Sex predilection: Female predominance (F:M ratio 3:1)
• Proportion of pediatric cancers: 1.5-3% of all childhood malignancies
• Malignancy risk: 20-26% of thyroid nodules in children are malignant (compared to 5-10% in adults)

Etiology and Risk Factors

• Radiation exposure: Significant risk factor, especially in young children
• Genetic predisposition:
  • Familial syndromes: Multiple Endocrine Neoplasia (MEN) 2, Familial Adenomatous Polyposis (FAP)
  • DICER1 syndrome
  • PTEN hamartoma tumor syndrome
• Iodine deficiency or excess
• Pre-existing thyroid conditions: Hashimoto's thyroiditis
• Environmental factors: Certain chemical exposures

Classification

Pediatric thyroid tumors are classified as follows:

1. Benign tumors:
   • Follicular adenomas
   • Hurthle cell adenomas
2. Malignant tumors:
   • Differentiated thyroid carcinoma (DTC):
     • Papillary thyroid carcinoma (PTC) - most common, 90% of cases
     • Follicular thyroid carcinoma (FTC)
   • Medullary thyroid carcinoma (MTC)
   • Poorly differentiated thyroid carcinoma
   • Anaplastic thyroid carcinoma (extremely rare in children)

Clinical Presentation

Symptoms and signs may include:

• Thyroid nodule: Usually painless, may be single or multiple
• Cervical lymphadenopathy: Common in pediatric thyroid cancer
• Hoarseness or voice changes: Indicates recurrent laryngeal nerve involvement
• Dysphagia or dyspnea: In cases of large tumors causing compression
• Hyperthyroidism symptoms: Rarely, in cases of toxic adenomas
• Incidental finding: On imaging studies performed for other reasons

Note: Many children are asymptomatic, and the nodule is often discovered during routine physical examination or unrelated imaging studies.

Diagnosis

Diagnostic approach includes:

1. Physical examination:
   • Careful neck palpation
   • Assessment of cervical lymph nodes
2. Imaging studies:
   • Ultrasound: First-line imaging modality
   • CT or MRI: For evaluating extent of disease and metastases
   • Nuclear medicine scans: Radioiodine scans for functional status and metastases
3. Laboratory tests:
   • Thyroid function tests (TSH, free T4)
   • Thyroglobulin (Tg) and anti-Tg antibodies
   • Calcitonin (for suspected medullary thyroid carcinoma)
4. Fine-needle aspiration (FNA) biopsy:
   • Gold standard for diagnosis
   • Interpreted using the Bethesda System for Reporting Thyroid Cytopathology
5. Molecular testing:
   • BRAF, RAS mutations
   • RET/PTC and PAX8/PPARγ rearrangements

Treatment

Treatment is multimodal and depends on the tumor type and stage:

1. Surgery:
   • Primary treatment for most thyroid tumors
   • Total thyroidectomy: Standard for malignant tumors
   • Lobectomy: May be considered for small, low-risk tumors
   • Lymph node dissection: Central and/or lateral neck dissection as indicated
2. Radioactive iodine (RAI) therapy:
   • Used for ablation of residual thyroid tissue and treatment of metastases in DTC
   • Dose determined based on disease extent and risk stratification
3. Thyroid hormone therapy:
   • Lifelong levothyroxine replacement
   • TSH suppression in cases of DTC
4. Targeted therapies:
   • Tyrosine kinase inhibitors (e.g., sorafenib, lenvatinib) for advanced, RAI-refractory DTC
   • RET inhibitors for MTC with RET mutations
5. External beam radiation therapy:
   • Rarely used in pediatric thyroid cancer
   • May be considered for unresectable disease or palliation

Prognosis and Follow-up

Prognosis is generally excellent for pediatric thyroid tumors, but long-term follow-up is crucial.

• Survival rates:
  • Differentiated thyroid carcinoma: >95% 20-year survival rate
  • Medullary thyroid carcinoma: Variable, depends on stage and genetic factors
• Prognostic factors:
  • Age at diagnosis: Younger age may be associated with more extensive disease but excellent response to therapy
  • Tumor size and extrathyroidal extension
  • Presence of distant metastases
  • Completeness of surgical resection
• Follow-up:
  • Regular physical examinations
  • Serum thyroglobulin monitoring
  • Neck ultrasound
  • Whole-body radioiodine scans as indicated
  • Lifelong thyroid hormone replacement and monitoring
• Long-term considerations:
  • Risk of recurrence: Can occur decades after initial treatment
  • Secondary malignancies: Particularly in patients treated with radioiodine
  • Fertility and pregnancy planning
  • Psychosocial support and quality of life