What is papillary thyroid cancer?

Papillary Thyroid Cancer: Overview and Management

Papillary thyroid cancer (PTC) is the most common type of thyroid malignancy, representing approximately 80% of all thyroid cancers, with an excellent prognosis characterized by 10-year survival rates exceeding 90-95%. 1

Definition and Epidemiology

Papillary thyroid cancer derives from the follicular epithelial cells of the thyroid gland and is characterized by distinctive nuclear features visible under microscopy. Key epidemiological features include:

• Incidence of 5.7 per 100,000 person-years, with higher rates in women (8.8 per 100,000) than men (2.7 per 100,000) 1
• Racial/ethnic variations with higher rates among Asian women and white men 1
• Increasing incidence over recent decades, particularly for micropapillary carcinomas (<1 cm) 1
• Accounts for 80-90% of all thyroid malignancies 1

Risk Factors

• Exposure to ionizing radiation is the most established environmental risk factor, particularly in younger individuals 1
• History of childhood radiation exposure significantly increases risk (as demonstrated by the Chernobyl accident) 1
• Other potential risk factors include:
  • Dietary iodine levels
  • Obesity
  • Hormonal factors
  • Environmental pollutants 2
• Approximately 5% of cases occur in familial settings with identifiable germline mutations 2

Molecular Characteristics

PTC is characterized by two major molecular signatures:

• BRAF-predominant pathway:

  • BRAF V600E mutation occurs in 45-50% of cases, most commonly in classical/conventional PTC (51%) 3
  • Associated with more aggressive features including lymph node metastasis, extrathyroidal extension, and higher recurrence rates 3
  • More common in aggressive histologic variants (tall cell, columnar, solid, hobnail) 3

• RAS-predominant pathway:

  • More common in follicular variant PTC
  • Associated with less aggressive behavior compared to BRAF-mutated tumors
  • Mutually exclusive with BRAF mutations 3

Clinical Presentation and Diagnosis

PTC typically presents as:

• Thyroid nodule(s) detected on physical examination or incidentally on imaging
• Occasionally with cervical lymphadenopathy
• Rarely with symptoms of compression or invasion of surrounding structures

Diagnostic workup includes:

• Ultrasound (US) of the thyroid and neck - primary imaging modality
• Fine-needle aspiration cytology (FNAC) for nodules >1 cm or <1 cm with suspicious features 1
• Molecular testing may be performed on cytology specimens to aid diagnosis in indeterminate cases 1
• Measurement of serum calcitonin (to rule out medullary thyroid cancer) 1

Treatment Approach

Treatment should be tailored based on risk stratification:

1. Surgery:

   • Total or near-total thyroidectomy for tumors ≥1 cm or multifocal/familial disease 1
   • Lobectomy may be considered for unifocal, small (<1 cm), intrathyroidal tumors of favorable histology 1
   • Central neck dissection for clinically evident nodal disease; prophylactic central neck dissection remains controversial 1
   • Lateral neck dissection for clinically positive lateral neck nodes 1

2. Radioactive Iodine (RAI) Ablation:

   • Administered after surgery to ablate remnant thyroid tissue and potential microscopic disease
   • Decreases risk of locoregional recurrence and facilitates long-term surveillance 1
   • Decision based on risk stratification (tumor size, extrathyroidal extension, lymph node involvement)

3. TSH Suppression Therapy:

   • Levothyroxine to suppress TSH and reduce risk of recurrence 1
   • Degree of suppression based on risk of recurrence and patient factors

Follow-up and Surveillance

• Serum thyroglobulin (Tg) measurement - sensitive marker for persistent/recurrent disease 4
• Neck ultrasound - highly sensitive for detecting local recurrence 5
• Whole-body radioiodine scanning may be performed in higher-risk patients
• Recombinant human TSH can be used to stimulate Tg production without requiring thyroid hormone withdrawal 4

Prognosis and Recurrence

• Overall excellent prognosis with disease-specific mortality <5% at 20 years 6
• Recurrence rates approximately 5-20%, with most occurring within the first 5 years 5
• Independent prognostic factors include:
  • Age at diagnosis (worse prognosis in older patients)
  • Tumor size
  • Extrathyroidal extension
  • Completeness of surgical resection 7
  • Presence of distant metastases

Special Considerations

• Micropapillary thyroid carcinomas (<1 cm) have excellent prognosis with >99% disease-specific survival 1
• Aggressive variants (tall cell, columnar cell, hobnail) have worse prognosis
• BRAF V600E mutation is associated with more aggressive disease and higher recurrence rates 3
• Targeted therapies are available for advanced, radioiodine-refractory disease 1, 3

PTC generally has an excellent prognosis with appropriate treatment, but lifelong surveillance is recommended due to the potential for late recurrence.