Overview
Thyroid Cancer
1. Clinical Overview
Summary
Thyroid Cancer is a malignancy arising from the cells of the thyroid gland. The vast majority are Differentiated Thyroid Cancers (DTC) – Papillary (70-80%) and Follicular (10-15%) – which have an excellent prognosis. Medullary Thyroid Cancer (MTC, 5%) arises from parafollicular C-cells and is associated with MEN2 syndrome. Anaplastic Thyroid Cancer (ATC, 1-2%) is an aggressive, undifferentiated malignancy with very poor prognosis. Management of DTC involves Total Thyroidectomy, Radioactive Iodine (RAI) ablation, and TSH suppression with levothyroxine, followed by long-term surveillance with Thyroglobulin levels and ultrasound. [1,2]
Clinical Pearls
"Orphan Annie Eyes": Papillary Thyroid Cancer has characteristic nuclear features on histology – clear, empty-looking ("ground glass") nuclei with grooves and inclusions.
Follicular vs Adenoma: Fine Needle Aspiration (FNA) CANNOT distinguish Follicular Carcinoma from Follicular Adenoma. You need a lobectomy for histological capsular/vascular invasion to diagnose cancer.
Medullary = Calcitonin = MEN2: MTC secretes Calcitonin. Always screen for RET mutation. If MEN2, screen for Phaeochromocytoma BEFORE surgery.
Anaplastic = Emergency: Rapidly growing, locally invasive, usually fatal within months. Often presents with stridor/dysphagia. May require tracheostomy.
2. Epidemiology
Incidence
- Incidence: ~3-4 per 100,000 per year. Increasing (partly due to incidental detection on imaging).
- Age: Varies by type. Papillary – Young to middle-aged. Anaplastic – Elderly.
- Sex: Female > Male (3:1) for DTC. Equal for Anaplastic.
- Prognosis: Excellent for DTC (>95% 10-year survival). Very poor for Anaplastic (less than 10% 1-year survival).
Risk Factors
| Factor | Notes |
|---|---|
| Radiation Exposure | Neck irradiation in childhood. Chernobyl/Fukushima. Strong risk for Papillary. |
| Family History | First-degree relative with DTC. MEN2 for MTC. |
| Hereditary Syndromes | MEN2 (MTC), FAP (Papillary – Cribriform Morular Variant), Cowden Syndrome. |
| Iodine Deficiency | Associated with Follicular Carcinoma (in endemic goitre areas). |
| Age less than 20 or >60 | Higher risk nodules in these age groups. |
3. Classification
Histological Types
| Type | Prevalence | Origin | Features | Prognosis |
|---|---|---|---|---|
| Papillary (PTC) | 70-80% | Follicular cells | "Orphan Annie" nuclei, Psammoma bodies. Lymph node spread (multifocal LN mets common). | Excellent (>95% 10-yr survival). |
| Follicular (FTC) | 10-15% | Follicular cells | Haematogenous spread (Bone, Lung). Cannot diagnose on FNA (needs capsular invasion). | Good (80-90% 10-yr). |
| Medullary (MTC) | 5% | Parafollicular C-cells | Calcitonin secretion. Amyloid on histology. 25% hereditary (MEN2). Screen RET, Pheo. | Moderate (70-80% 10-yr). |
| Anaplastic (ATC) | 1-2% | Undifferentiated | Rapidly growing, locally invasive. Elderly. Stridor, dysphagia. | Very poor (less than 10% 1-yr). |
| Poorly Differentiated (PDTC) | less than 5% | Follicular cells | Behaviour between DTC and ATC. Aggressive. | Poor. |
TNM Staging (For DTC - AJCC 8th Edition)
- Age-Adjusted: Patients less than 55 years with DTC are Stage I (no distant mets) or Stage II (distant mets). Reflects excellent prognosis in young. Older patients staged I-IV based on T, N, M.
4. Differential Diagnosis (Thyroid Nodule)
| Condition | Key Features |
|---|---|
| Thyroid Cancer | Hard, fixed nodule. Rapid growth. Cervical lymphadenopathy. Suspicious FNA (Thy3-5). |
| Benign Thyroid Nodule / Adenoma | Soft, mobile. No worrying features. Thy2 on FNA. Common. |
| Multinodular Goitre | Multiple nodules. Long history. May have compressive symptoms. Evaluate dominant nodule. |
| Thyroid Cyst | Simple cyst on USS. Thy1 (cyst fluid) on FNA. Benign. |
| Thyroiditis (Hashimoto's, De Quervain's) | Diffuse gland changes. Antibodies (Hashimoto's). Painful (De Quervain's). |
| Lymphoma | Rapidly growing. Associated with Hashimoto's. Diagnosed on core biopsy. |
Suspicious Features on Ultrasound (Thy3-5 on BTA Scoring)
- Solid, hypoechoic nodule.
- Microcalcifications ("Psammoma bodies").
- Irregular margins.
- Taller-than-wide shape.
- Absent halo sign.
- Cervical lymphadenopathy.
5. Clinical Presentation
History
Examination
| Finding | Notes |
|---|---|
| Thyroid Nodule | Size, Consistency (hard = concerning), Mobility (fixed = concerning), Tenderness. |
| Cervical Lymph Nodes | Central vs Lateral compartments. |
| Tracheal Deviation | Large goitre. |
| Pemberton's Sign | Facial plethora/SVC obstruction when arms raised (retrosternal goitre). |
| Vocal Cord Function | Hoarseness. Consider indirect laryngoscopy pre-operatively. |
Thyroid Nodule/Lump
Most common presentation. Often asymptomatic, found incidentally.
Neck Swelling
Goitre.
Compressive Symptoms
Dysphagia, Dyspnoea, Stridor (suggests invasion or large goitre).
Hoarseness
Red flag. Suggests Recurrent Laryngeal Nerve involvement.
Cervical Lymphadenopathy
Palpable neck nodes.
Symptoms of Metastases
Bone pain (FTC mets), Respiratory symptoms (Lung mets).
Family History
MEN2 (Phaeochromocytoma, Hyperparathyroidism + MTC).
6. Investigations
Thyroid Function Tests
- Usually Euthyroid (Normal TSH). Thyroid cancer rarely causes hypo/hyperthyroidism.
- Suppressed TSH (if hyperfunctioning nodule) = Usually benign ("Hot" nodule).
Ultrasound Neck
- First-line imaging for thyroid nodule.
- Characterise nodule (solid, cystic, mixed). Look for suspicious features.
- Assess lymph nodes.
- Thy Scoring (BTA): Thy1 (non-diagnostic), Thy2 (benign), Thy3 (indeterminate), Thy4 (suspicious), Thy5 (malignant).
Fine Needle Aspiration Cytology (FNAC)
- Gold Standard for evaluating thyroid nodules.
- Ultrasound-guided FNA of suspicious nodules.
- Bethesda Classification: I-VI.
- Limitation: Cannot distinguish Follicular Adenoma from Follicular Carcinoma.
Tumour Markers
| Marker | Use |
|---|---|
| Thyroglobulin (Tg) | Tumour marker for DTC (Papillary/Follicular) POST-THYROIDECTOMY. Should be undetectable after total thyroidectomy + RAI. Rising Tg = Recurrence. |
| Calcitonin | Marker for Medullary Thyroid Cancer. Screen if MTC suspected or FHx MEN2. |
| CEA | Also elevated in MTC. Used with Calcitonin. |
Genetic Testing
- RET Proto-Oncogene: Screen in ALL MTC patients. If RET +ve = MEN2 syndrome.
- BRAF V600E: Common in Papillary. May have prognostic value.
Staging Imaging (If Cancer Confirmed)
- CT Neck/Chest (without IV contrast if RAI planned soon – iodinated contrast delays RAI uptake).
- MRI: If local invasion suspected (trachea, oesophagus).
- Whole Body Iodine Scan: Post-RAI ablation to detect uptake (metastatic disease).
7. Management
Management Algorithm
THYROID NODULE DETECTED
↓
ULTRASOUND NECK (Characterise Nodule)
↓
FNA IF INDICATED (Thy Scoring)
┌────────────────┴────────────────┐
Thy2 (Benign) Thy3/4/5 (Indeterminate / Suspicious / Malignant)
↓ ↓
SURVEILLANCE SURGERY
(Repeat USS 6-12mo) - Hemithyroidectomy (Thy3) OR
- Total Thyroidectomy (Thy4/5, large tumour, bilateral)
+
- Central +/- Lateral Neck Dissection
(if Lymph Node involvement)
↓
HISTOLOGY CONFIRMS TYPE + STAGE
┌───────────────────────────────┼───────────────────────────────┐
PAPILLARY / FOLLICULAR MEDULLARY ANAPLASTIC
(Differentiated) (C-Cell) (Undifferentiated)
↓ ↓ ↓
RADIOACTIVE IODINE (RAI) NO RAI Palliation (+/- Chemo/RT)
(Ablate remnant thyroid (MTC doesn't take up iodine) - Often inoperable
+ treat mets - I-131) ↓ - BRAF/MEK inhibitors
↓ RET MUTATION SCREEN if targetable
TSH SUPPRESSION (Genetic Counselling) - Tracheostomy if airway
(Levothyroxine to suppress ↓ obstruction
TSH → Reduce recurrence) If RET +ve:
↓ Screen for Pheo + HPTH
SURVEILLANCE Family Screening
- Thyroglobulin Prophylactic Thyroidectomy
- Ultrasound Neck in gene carriers
Surgical Treatment
| Surgery | Indication |
|---|---|
| Hemithyroidectomy (Lobectomy) | Small (less than 1cm), unifocal, low-risk PTC. Indeterminate nodule (Thy3) for diagnosis. |
| Total Thyroidectomy | PTC >4cm, Multifocal, Extrathyroidal extension, Lymph node mets, Follicular, Medullary, Anaplastic. |
| Central Neck Dissection (Level VI) | If central nodes involved (clinically or on imaging). Prophylactic in MTC. |
| Lateral Neck Dissection (Levels II-V) | If lateral nodes involved. |
Radioactive Iodine (RAI) Ablation (I-131)
- Indication: Post-total thyroidectomy for intermediate/high-risk DTC.
- Mechanism: Differentiated thyroid cancer cells take up iodine. RAI destroys residual thyroid tissue and iodine-avid metastases.
- Preparation: TSH stimulation (Stop Levothyroxine or give Recombinant TSH - Thyrogen). Low-iodine diet.
- Not Effective For: MTC, Anaplastic (cells don't take up iodine).
TSH Suppression Therapy
- Levothyroxine (Thyroxine) given at doses to suppress TSH (TSH less than 0.1 mU/L for high-risk; 0.1-0.5 for low-risk).
- Rationale: TSH promotes thyroid cell growth. Suppression reduces recurrence.
- Side Effects: Subclinical hyperthyroidism → AF, Osteoporosis risk (especially in elderly women).
Surveillance (Post-Treatment)
- Thyroglobulin (Tg): Should be undetectable after total thyroidectomy + RAI. Rising Tg = Recurrence. Measure with TSH stimulation.
- Anti-Tg Antibodies: Can interfere with Tg assay. If present, Tg unreliable; follow antibody trend.
- Ultrasound Neck: Regular surveillance for local recurrence/nodes.
8. Specific Cancer Types
Papillary Thyroid Cancer (PTC)
- Most Common (70-80%). Excellent prognosis.
- Peak Age: 30-50 years. Female predominance.
- Histology: "Orphan Annie" nuclei, Psammoma bodies (concentric calcifications).
- Spread: Lymphatic (Cervical lymph nodes common, often multifocal).
- Treatment: Surgery + RAI + TSH Suppression.
- Prognosis: >95% 10-year survival.
Follicular Thyroid Cancer (FTC)
- 10-15%. Older than PTC (40-60 yrs).
- Histology: Capsular and/or Vascular Invasion (defines malignancy). Cannot diagnose on FNA.
- Spread: Haematogenous (Bone, Lung). Lymph nodes less common.
- Treatment: Total Thyroidectomy + RAI.
- Prognosis: 80-90% 10-year survival.
Medullary Thyroid Cancer (MTC)
- 5%. Arises from Parafollicular C-Cells (secrete Calcitonin).
- 25% Hereditary: MEN2A, MEN2B, Familial MTC.
- MEN2A: MTC + Phaeochromocytoma + Primary Hyperparathyroidism.
- MEN2B: MTC + Phaeochromocytoma + Marfanoid Habitus + Mucosal Neuromas.
- Key Action: Screen ALL MTC patients for RET mutation. If RET +ve: Screen for Pheo (before surgery!), Family screening, Prophylactic thyroidectomy for gene carriers.
- Treatment: Total Thyroidectomy + Central Neck Dissection. No RAI (doesn't take up iodine). Tyrosine Kinase Inhibitors (Vandetanib, Cabozantinib) for metastatic.
- Markers: Calcitonin, CEA (for follow-up).
Anaplastic Thyroid Cancer (ATC)
- 1-2%. Elderly (>65 yrs).
- Aggressive: Rapidly growing, locally invasive, compressive (Stridor, Dysphagia).
- Histology: Undifferentiated. May arise from pre-existing DTC.
- Prognosis: Very poor (less than 10% 1-year survival). Median survival 3-6 months.
- Treatment: Often palliative. External beam radiotherapy. Chemotherapy (Doxorubicin). BRAF/MEK inhibitors (Dabrafenib/Trametinib) if BRAF mutated. Tracheostomy for airway.
9. Complications
Of Disease
- Local Invasion: Trachea (Stridor), Oesophagus (Dysphagia), Recurrent Laryngeal Nerve (Hoarseness).
- Metastases: Lymph nodes (PTC), Bone/Lung (FTC).
Of Treatment
| Surgery | RAI | TSH Suppression |
|---|---|---|
| Hypocalcaemia (Parathyroid damage) | Salivary gland dysfunction (Sialadenitis) | AF, Osteoporosis |
| Recurrent Laryngeal Nerve injury (Hoarseness, Bilateral = Stridor) | Bone marrow suppression (rare) | Subclinical hyperthyroid symptoms |
| Bleeding/Haematoma | Secondary malignancy (rare, high cumulative dose) | |
| Hypothyroidism (Requires lifelong Levothyroxine) |
10. Prognosis and Outcomes
| Type | 10-Year Survival |
|---|---|
| Papillary | >95% |
| Follicular | 80-90% |
| Medullary | 70-80% |
| Anaplastic | less than 10% (1-year) |
- Risk Stratification (ATA Guidelines): Low, Intermediate, High risk based on tumour size, extension, nodal status, completeness of resection, molecular features → guides intensity of treatment and surveillance.
11. Evidence and Guidelines
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| DTC Management | ATA (2015) | Risk stratification. RAI for intermediate/high risk. TSH suppression. Tg surveillance. |
| BTA Thyroid Nodule Guidelines | BTA | USS + FNA algorithm. Thy scoring. |
| MTC Guidelines | ATA | RET screening. Screen for Pheo. Prophylactic thyroidectomy. |
12. Patient and Layperson Explanation
What is Thyroid Cancer?
Thyroid cancer is a cancer of the thyroid gland (the butterfly-shaped gland in your neck that makes hormones). The good news is that most thyroid cancers are very treatable and have an excellent outlook.
How is it treated?
Usually with surgery to remove the thyroid gland (thyroidectomy). Afterwards, you may have radioactive iodine treatment to destroy any remaining thyroid cells. You will then take a thyroid hormone tablet (Levothyroxine) for life, which replaces your thyroid and also helps prevent cancer coming back.
What is the outlook?
For the most common types (Papillary and Follicular), the outlook is excellent – over 95% of patients are cured. Medullary thyroid cancer has a good prognosis if caught early, but requires special genetic testing. Anaplastic thyroid cancer is rare but aggressive.
Will I need lifelong follow-up?
Yes. We monitor for recurrence with blood tests (Thyroglobulin) and neck ultrasounds.
13. References
Primary Sources
- Haugen BR, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1-133. PMID: 26462967.
- British Thyroid Association. Guidelines for the Management of Thyroid Cancer. 2014.
14. Examination Focus
Common Exam Questions
- Most Common Type: "Most common type of thyroid cancer?"
- Answer: Papillary Thyroid Cancer (70-80%).
- Histology: "Describe the histology of Papillary Thyroid Cancer."
- Answer: "Orphan Annie" nuclei (ground glass, nuclear grooves, inclusions). Psammoma bodies.
- MTC Association: "What syndrome is associated with Medullary Thyroid Cancer?"
- Answer: MEN2 (Multiple Endocrine Neoplasia Type 2). Also test for RET mutation.
- Follow-Up Marker: "Post-thyroidectomy tumour marker for DTC?"
- Answer: Thyroglobulin (should be undetectable). Rising Tg = Recurrence.
Viva Points
- Follicular vs Adenoma: Explain why FNA cannot differentiate (need capsular/vascular invasion on histology).
- MEN2 Workup: Before thyroidectomy for MTC, must exclude Phaeochromocytoma (or patient dies on the table).
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.