Thyroid Cancer
Commonest endocrine malignancy. Papillary carcinoma is the most frequent type (~80%) with excellent prognosis. Diagnosed by FNA cytology and treated with thyroidectomy ± radioiodine ablation ± TSH suppression. 10-year survival >95% for differentiated thyroid cancer.
Key Facts
Commonest endocrine malignancy: ~3,500 new cases/year in UK; F:M 3:1; incidence increasing (improved detection) Types: papillary (~80%) — excellent prognosis; follicular (~10%) — haematogenous spread to bone/lung; medullary (~5%) — from parafollicular C cells, calcitonin, MEN2; anaplastic (~2%) — elderly, rapidly fatal Papillary: commonest; lymph node metastasis common but good prognosis; psammoma bodies on histology; BRAF V600E mutation Treatment: total thyroidectomy → radioactive iodine (¹³¹I) ablation (differentiated types) → TSH suppression with levothyroxine → thyroglobulin monitoring (tumour marker) Medullary thyroid cancer (MTC): from C cells; calcitonin is the tumour marker; 25% familial (MEN2A/2B) — RET proto-oncogene; screen family members Prognosis: papillary 10-year survival >95%; follicular ~90%; medullary ~75%; anaplastic ~5% (median survival 6 months)
Overview
Key Facts
Differentiated thyroid cancer (papillary and follicular) has an excellent prognosis with appropriate treatment. Medullary thyroid cancer requires specific management and genetic screening for MEN2. Anaplastic thyroid cancer is one of the most aggressive human malignancies.
Epidemiology
~3,500/year in UK. F:M 3:1. Peak age 30-50 (papillary), 40-60 (follicular), >60 (anaplastic). Incidence increasing (~5%/year — largely due to incidental detection by imaging).
Aetiology
Papillary: radiation exposure (childhood neck irradiation, nuclear accidents), iodine sufficiency. Follicular: iodine deficiency. Medullary: sporadic (75%) or familial MEN2 (25%). Anaplastic: may arise from de-differentiation of long-standing papillary/follicular cancer.
Pathophysiology
Papillary: BRAF V600E (~45%), RET/PTC rearrangements; papillary architecture, psammoma bodies; lymphatic spread → cervical lymph nodes. Follicular: RAS mutations, PAX8-PPARγ; haematogenous spread → bone, lung. Medullary: parafollicular C cells; calcitonin secretion; RET mutations in MEN2. Anaplastic: TP53, TERT mutations; undifferentiated; rapidly invasive.
Clinical Presentation
Differentiated (Papillary/Follicular)
- Thyroid nodule (often asymptomatic; found incidentally or on examination)
- Cervical lymphadenopathy (especially papillary)
- Hoarseness (RLN involvement — advanced)
- Dysphagia, dyspnoea (compression — late)
- Bone pain, pathological fracture (follicular — distant metastasis)
Medullary
- Thyroid nodule
- Diarrhoea (calcitonin effect — ~30%)
- Flushing
- Family history of MEN2 (phaeochromocytoma, hyperparathyroidism)
Anaplastic
- Rapidly enlarging hard thyroid mass in elderly
- Compressive symptoms: stridor, dysphagia, hoarseness
- Widely invasive at presentation
Red Flags
- Rapidly growing thyroid mass → anaplastic or lymphoma
- Hoarseness → RLN invasion
- Family history of MEN2 or thyroid cancer → genetic screening
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| Benign thyroid nodule | Soft, mobile, Thy2 FNA | USS, FNA |
| Thyroid lymphoma | Rapid growth, Hashimoto background, elderly | Core biopsy |
| Metastasis to thyroid | Rare; known primary elsewhere | Biopsy |
| Parathyroid adenoma | Posterior to thyroid, hypercalcaemia | Calcium, PTH, sestamibi |
Diagnosis / Investigation
Pre-Operative
- FNA cytology: Thy4/5 confirms suspected/confirmed malignancy
- USS neck: assess nodule and cervical lymph nodes
- Calcitonin: if medullary thyroid cancer suspected
- CEA: elevated in MTC
- Genetic testing: RET proto-oncogene if MTC (MEN2 screening)
Post-Operative
- Thyroglobulin (Tg): tumour marker for differentiated thyroid cancer (should be undetectable after total thyroidectomy + RAI)
- Anti-Tg antibodies: may interfere with Tg assay
- Whole-body radioiodine scan: post-ablation; identifies residual/metastatic disease
- Neck USS: surveillance for recurrence
- Calcitonin: monitoring for MTC recurrence
Management
Differentiated (Papillary/Follicular)
- Total thyroidectomy ± central compartment lymph node dissection
- Radioactive iodine (¹³¹I) ablation: destroy residual thyroid tissue and micrometastases; given 4-6 weeks post-surgery
- TSH suppression: levothyroxine at doses to suppress TSH (0.1-0.5 mU/L for high-risk; 0.5-2.0 for low-risk) — TSH stimulates differentiated thyroid cancer growth
- Thyroglobulin monitoring: every 6-12 months; rising Tg suggests recurrence
- Neck USS surveillance: annually for 5-10 years
Medullary
- Total thyroidectomy + central and bilateral lateral lymph node dissection
- NO role for radioiodine (C cells do not take up iodine)
- Calcitonin and CEA monitoring
- RET genetic testing: if positive → screen family for MEN2
- Phaeochromocytoma screening: MUST exclude before thyroid surgery in MEN2
- Targeted therapy (vandetanib, cabozantinib) for advanced disease
Anaplastic
- Very poor prognosis; often unresectable at diagnosis
- Palliative: external beam radiotherapy ± chemotherapy (doxorubicin)
- Tracheostomy may be needed for airway compromise
- Targeted therapy (dabrafenib + trametinib if BRAF V600E positive)
Referral Criteria
- Thyroid cancer MDT: all suspected/confirmed thyroid cancer
- Endocrine surgery: thyroidectomy
- Clinical genetics: MTC (RET testing, MEN2 screening)
- Nuclear medicine: radioiodine ablation
Prognosis
Papillary: 10-year survival >95%; excellent even with lymph node metastasis. Follicular: 10-year survival ~90%; worse if distant metastasis. Medullary: 10-year survival ~75%; worse if MEN2B variant. Anaplastic: median survival ~6 months; one of the most lethal cancers. Recurrence of differentiated thyroid cancer: ~10-30% at 10 years; most recurrences are treatable. Thyroglobulin is an excellent tumour marker for monitoring.
Other Relevant Information
Thyroid Cancer Types Comparison
| Type | Frequency | Origin | Spread | Prognosis |
|---|---|---|---|---|
| Papillary | ~80% | Follicular cells | Lymphatic | Excellent (>95% 10-yr) |
| Follicular | ~10% | Follicular cells | Haematogenous (bone, lung) | Good (~90% 10-yr) |
| Medullary | ~5% | Parafollicular C cells | Lymphatic + haematogenous | Moderate (~75% 10-yr) |
| Anaplastic | ~2% | De-differentiated | Local invasion + distant | Very poor (~5% 10-yr) |
MEN2 Syndromes
| Feature | MEN2A | MEN2B |
|---|---|---|
| Medullary thyroid cancer | Yes (>95%) | Yes (>95%) |
| Phaeochromocytoma | ~50% | ~50% |
| Hyperparathyroidism | ~20-30% | Rare |
| Mucosal neuromas | No | Yes |
| Marfanoid habitus | No | Yes |
| RET mutation | Yes | Yes |