Thyroid Cancer

Background

• Thyroid carcinomas are thyroid malignancies that can develop from the two cell types present in the thyroid gland (follicular and parafollicular cells)
• Thyroid carcinomas are more common in women (peaking in the third and fourth decades of life)
• Radiation exposure significantly increases the risk for malignancies arising from thyroid follicular cells; particularly papillary thyroid carcinoma
• Diagnosis is achieved through Fine needle aspiration (FNA) in most cases except in the case of follicular carcinoma
• Definitive management is achieved through thyroidectomy

Version 2

• Definition: Malignant tumors arising from thyroid follicular cells (papillary, follicular, anaplastic) or parafollicular C cells (medullary)
• Epidemiology:
  • Incidence: ~13.5 cases per 100,000 per year
  • Female predominance (3:1) for differentiated carcinomas
  • Peak incidence: 30-50 years for papillary, 40-60 years for follicular
  • Most common endocrine malignancy
• Risk factors:
  • Radiation exposure (especially childhood) - strongest risk factor for papillary carcinoma
  • Family history and genetic syndromes (MEN 2A/2B for medullary)
  • Pre-existing thyroid disease (Hashimoto's for lymphoma)
  • Female gender
• Prognosis varies by type: Papillary (>90% 5-year survival) to anaplastic (5-14% 5-year survival)

Types

Version 2

Clinical features

• Symptoms
  • Dysphagia and hoarseness (secondary to direct compression by the tumor)
• Physical exam
  • Neck mass or palpable thyroid nodule (painless)
  • Cervical lymphadenopathy might be present

Version 2

• Symptoms:
  • Usually asymptomatic (incidental finding)
  • Dysphagia (compression of esophagus)
  • Hoarseness (recurrent laryngeal nerve involvement)
  • Dyspnea (tracheal compression)
  • Horner syndrome (rare - sympathetic chain involvement)
• Physical exam:
  • Thyroid nodule: Firm to hard, fixed, painless
  • Cervical lymphadenopathy (especially papillary)
  • Pemberton sign (facial plethora with arm elevation - SVC obstruction)
• Red flags for malignancy:
  • Fixed, hard nodule
  • Rapid growth
  • Associated lymphadenopathy
  • Voice changes
  • Age <20 or >60 years
  • Male gender
  • History of radiation exposure

Diagnosis

• Imaging
  • Radioactive iodine uptake test
    

    	Radioactive Iodine Uptake Findings & Clinical Implications
    Hot thyroid nodules	Benign Do not require fine needle aspiration (FNA)
    Cold thyroid nodules	Suspicion for malignancy Require fine needle aspiration (FNA)

  • Ultrasonography (required for all thyroid nodules): hypoechoic lesions are concerning for malignancy
• Serum labs
  • TSH levels (low TSH levels are more concerning for malignancy)
  • Serum calcitonin (tumor marker for medullary thyroid cancer)
  • Fine needle aspiration (FNA) is required for all cold nodules on radioactive iodine uptake scan

Version 2

• Initial evaluation:
  • TSH: Usually normal; if low, perform radioiodine scan
  • Thyroid ultrasound (all nodules):
    • Suspicious features: Solid, hypoechoic, irregular margins, microcalcifications, taller than wide, extrathyroidal extension
  • Radioiodine scintigraphy (if TSH low):
    • Cold nodules: Higher malignancy risk → require FNA
    • Hot nodules: Rarely malignant → usually no FNA needed
• Confirmatory test:
  • Fine needle aspiration (FNA): Gold standard for diagnosis
    • Exception: Cannot distinguish follicular adenoma from carcinoma
  • Bethesda classification system for cytology reporting
• Tumor markers:
  • Thyroglobulin: For differentiated thyroid cancer (post-treatment monitoring)
  • Calcitonin: For medullary carcinoma (diagnosis and monitoring)
  • CEA: Additional marker for medullary carcinoma
• Staging: CT/MRI neck, chest imaging for metastases

Differential diagnosis

• Benign thyroid nodule (typically a hot nodule on radioactive iodine uptake test)

Version 2

• Benign thyroid nodule (80-95% of all nodules)
• Thyroid cyst
• Multinodular goiter
• Thyroiditis (subacute, chronic)
• Riedel's thyroiditis (hard, fixed gland)
• Metastases to thyroid (rare)

Treatment

• Medical management
  • Iodine radiotherapy (possibly for cases of papillary thyroid cancer)
• Surgical management
  • Thyroidectomy

Version 2

• Surgical management:
  • Total thyroidectomy:
    • Tumors ≥4 cm
    • Extrathyroidal extension
    • Nodal/distant metastases
    • Medullary carcinoma
    • Anaplastic carcinoma (if resectable)
  • Hemithyroidectomy:
    • Low-risk tumors <4 cm
    • No extrathyroidal extension
    • No metastases
  • Neck dissection: As needed for nodal involvement
• Adjuvant therapy:
  • Radioactive iodine ablation (RAI):
    • For differentiated thyroid cancer post-thyroidectomy
    • NOT effective for medullary or anaplastic carcinoma
  • TSH suppression with levothyroxine:
    • For differentiated thyroid cancer
    • Target TSH based on risk stratification
  • External beam radiation: For anaplastic or unresectable disease
  • Chemotherapy: Limited role, mainly for anaplastic carcinoma

Surgical complications

• Dysphagia and persistent hoarseness (due to injury to recurrent laryngeal nerve)
• Hypocalcemia (due to injury or removal of parathyroid glands)
• Loss of tenor; which is noticeable in professional voice users (due to injury to the external branch of the superior laryngeal nerve)

version 2

• Hypocalcemia (hypoparathyroidism from parathyroid injury/removal)
• Voice changes:
  • Hoarseness (recurrent laryngeal nerve injury)
  • Loss of vocal range (external branch of superior laryngeal nerve)
• Bleeding/hematoma
• Thyroid storm (rare)

Supplementary tables

• Table 1: classification of multiple endocrine neoplasia

Table: Multiple Endocrine Neoplasia (MEN) Syndromes