Thyroid Cancer

🦋 Thyroid Cancer – Classification, Risk Factors, Staging, Investigations & Treatment

Thyroid cancer accounts for about 1% of all cancers in the body and has a higher incidence in females.

• Sex ratio: Female : Male = 3 : 1

• Peak incidence: 3rd–4th decades of life

📑 Classification of Thyroid Tumors

1. WHO Classification (comprehensive list):

• Follicular adenoma
• Hyalinizing trabecular tumor
• Other encapsulated follicular pattern thyroid tumors
• Papillary thyroid carcinoma
• Follicular thyroid carcinoma
• Hürthle cell tumor
• Poorly differentiated thyroid carcinoma
• Anaplastic carcinoma
• Squamous cell carcinoma
• Medullary thyroid carcinoma
• Mixed medullary + follicular carcinoma
• Mucoepidermoid carcinoma (± with eosinophilia)
• Mucinous carcinoma
• Ectopic thymoma
• Spindle epithelial tumor
• Intrathyroid thymic carcinoma
• Paraganglioma
• Mesenchymal stromal tumors
• Hematolymphoid tumors
• Germ cell tumors
• Secondary tumors

2. Simplified Classification:

• Benign: Follicular adenoma, Hürthle cell adenoma, microfollicular adenoma, embryonal adenoma

• Malignant:

a. Primary:

• From follicular epithelium:

  • Papillary carcinoma
  • Follicular carcinoma
  • Anaplastic carcinoma

• From parafollicular C cells: Medullary carcinoma

• From lymphoid tissue: Lymphoma

b. Secondary:

• Metastasis (kidney, lung, colon, breast)

• Direct spread (larynx, post-cricoid carcinoma)

What is the most common Benign thyroid tumor?

What is the most common malignant thyroid tumor?

⚠️ Risk Factors for Thyroid Cancer

• Age: 30–40 years most common; >65 yrs → risk of anaplastic carcinoma
• Sex: Females > males
• Family history Gardner syndrome, Cowden syndrome
• Genetic:
  • Medullary carcinoma → MEN2A, MEN2B
  • Papillary carcinoma → Gardner & Cowden syndromes
• Radiation exposure: Strongest risk factor
• Other risks: Endemic goiter, Graves’ disease, inborn errors of metabolism

What are the features of MEN2A and MEN2B syndrome?

What are the mutations associated with Papillary, Follicular and Medullary Thyroid Cancer?

🩺 Clinical Features of Thyroid Cancer

• Thyroid nodule:
  • Usually painless
  • Hard, fixed
  • Solitary or multiple

What are red flag signs in Thyroid nodule that point towards malignancy?

• Other features:
  • Cervical lymphadenopathy
  • Pressure symptoms:
    • Hoarseness (RLN involvement)
    • Dysphagia (esophagus compression)
    • Dyspnea (tracheal compression)
  • Horner’s syndrome: Miosis, ptosis, anhidrosis (sympathetic chain compression)
  • Constitutional: Weight loss, fatigue, fever, night sweats
  • Rapidly enlarging pre-existing goiter

🧾 TNM Staging of Thyroid Cancer

T Staging:

• T1: ≤2 cm, confined to thyroid
  • T1a: ≤1 cm
  • T1b: >1–2 cm
• T2: >2–4 cm, confined to thyroid
• T3:
  • T3a: >4 cm confined to thyroid
  • T3b: any size with extrathyroid extension to strap muscles
• T4: Gross extrathyroid extension
  • T4a: Invades subcutaneous tissue, larynx, trachea, esophagus, RLN
  • T4b: Invades prevertebral fascia, mediastinal vessels, carotid artery

N Staging:

• Nx: Cannot assess
• N0: No Lymph Node involvement
• N1a: Level VI (pretracheal, paratracheal, prelaryngeal, superior mediastinal)
• N1b: Unilateral, bilateral, or contralateral cervical Lymph Nodes (levels I–V) or retropharyngeal Lymph Nodes

M Staging:

• M0: No distant metastasis
• M1: Distant metastasis present

Residual Tumor Status:

• R0: No residual tumor
• R1: Microscopic residual
• R2: Macroscopic residual

🎯 Stage Grouping

Medullary Thyroid Carcinoma:

• Stage I: T1a/b, N0
• Stage II: T2/T3, N0
• Stage III: T1–T3, N1a
• Stage IVA: T1–T3, N1b or T4a
• Stage IVB: T4b
• Stage IVC: Any T, Any N, M1

Papillary & Follicular Carcinoma:

< 55 years:

• Stage I: Any T, Any N, M0
• Stage II: Any T, Any N, M1

≥ 55 years:

• Stage I: T1–T2, N0
• Stage II: T1–T3, N1 or T3 N0
• Stage III: T4a
• Stage IVA: T4b
• Stage IVB: Any M1

🧪 Investigations in Thyroid Cancer

• Blood tests:
  • ESR ↑
  • Thyroid function tests (T3, T4, TSH)
  • Anti-thyroid antibodies
  • Serum thyroglobulin
  • Serum calcitonin

Which is the biochemical marker of medullary thyroid cancer?

• Imaging:
  • Ultrasound (first-line)

What are the suspicious features in ultrasound suggesting thyroid malignancy?

• FNAC (gold standard): Except follicular carcinoma (can’t differentiate adenoma vs carcinoma) → use Bethesda system

• CT/MRI: Extent, cartilage invasion, retrosternal spread, lymph node assessment

• CT Abdomen: If lymphoma suspected or MEN syndrome evaluation

• Thyroid scintigraphy:

  • Tc-99m scan → Cold nodule (20% risk of malignancy) vs Hot nodule (unlikely malignant)
  • MIBG scan → MEN syndrome (pheochromocytoma + medullary carcinoma)
  • Gallium citrate → Thyroid lymphoma
  • I-131 scan → Post-surgical ablation

• Special tests:

  • Serum calcitonin + CEA (medullary carcinoma)
  • RET mutation analysis (MEN syndrome)
  • Core biopsy (anaplastic carcinoma)
  • Laryngoscopy (pre-op baseline RLN function)

💊 Treatment of Thyroid Cancer

1. Surgery (Primary Treatment):

• Thyroidectomy types:

  • Hemithyroidectomy (1 lobe + isthmus)
  • Subtotal thyroidectomy (>50% both lobes + isthmus)
  • Near-total thyroidectomy (1 complete lobe + isthmus + >90% opposite lobe)
  • Total thyroidectomy (both lobes + isthmus)
  • Completion thyroidectomy (convert lesser operation to total)

• Neck Dissection: If nodal involvement present

2. Radioiodine Ablation (I-131):

• For residual tissue/microscopic disease

What is the indication of Radioiodine ablation in Thyroid malignancy?

3. External Beam Radiotherapy (EBRT):

• Unresectable tumors
• Residual disease not responsive to I-131
• Palliative (bone/brain mets)

4. Thyroid Hormone Suppression Therapy:

• Levothyroxine to suppress TSH
• High risk → TSH < 0.1 mIU/L
• Low risk → TSH 0.1–0.5 mIU/L

5. Chemotherapy:

• Limited role