Thyroid carcinoma is a malignant tumour arising from the thyroid gland, an endocrine organ located in the anterior neck responsible for production of thyroid hormones. It is the most common endocrine malignancy and represents a heterogeneous group of cancers with different biological behaviours, treatment responses, and prognoses.

Thyroid carcinomas are broadly classified according to their cell of origin and histological characteristics into:

• Differentiated thyroid carcinoma (DTC) arising from follicular thyroid cells:

  • Papillary thyroid carcinoma (PTC) – the commonest subtype worldwide.

  • Follicular thyroid carcinoma (FTC).

  • Hurthle cell carcinoma.

  • Variants of papillary carcinoma including follicular variant, tall cell, columnar cell, solid and clear cell variants.

• Medullary thyroid carcinoma (MTC) arising from parafollicular C cells, which produce calcitonin.

• Anaplastic thyroid carcinoma (ATC) arising from follicular cells and characterized by highly aggressive behaviour and poor prognosis.

In Tanzania, thyroid cancer is among the common endocrine malignancies managed at specialized oncology centres. At the Ocean Road Cancer Institute, thyroid cancer accounts for approximately 0.8–1% of all malignancies seen annually. The majority of cases are differentiated thyroid cancers, with follicular carcinoma being commonly reported, followed by papillary carcinoma.

Management depends on histological subtype, tumour stage, presence of metastasis, molecular characteristics, and resectability. Surgery remains the mainstay of treatment, with radioactive iodine therapy, thyroid hormone suppression therapy, radiotherapy, and systemic therapy used according to disease characteristics.

Epidemiology

Thyroid carcinoma occurs worldwide and represents the most common malignancy of the endocrine system.

• It accounts for approximately 1–3% of all human cancers.

• It occurs more commonly in females than males.

• The female-to-male ratio is approximately 3:1.

• Incidence increases with age, although papillary thyroid carcinoma can occur in younger adults.

• Differentiated thyroid carcinoma accounts for approximately 90% of thyroid malignancies.

In Tanzania, thyroid carcinoma contributes approximately 0.8–1% of annual cancer cases managed at Ocean Road Cancer Institute. Differentiated thyroid cancer represents the majority of cases.

Risk factors

Risk factors associated with development of thyroid carcinoma include:

1. Ionizing radiation exposure

• Previous therapeutic radiation to the head, neck, or chest during childhood.

• Environmental radiation exposure.

• Radiation accidents.

2. Female sex

• Thyroid carcinoma is significantly more common among females.

3. Family history and genetic predisposition

• First-degree relative with thyroid carcinoma.

• Familial thyroid cancer syndromes including:

  • Multiple endocrine neoplasia type 2 (MEN 2).

  • Familial medullary thyroid carcinoma.

  • Familial adenomatous polyposis.

  • Cowden syndrome.

4. Thyroid disorders

• Long-standing multinodular goitre.

• Chronic autoimmune thyroiditis (Hashimoto thyroiditis), particularly associated with papillary thyroid carcinoma.

5. Iodine-related factors

• Iodine deficiency is associated with increased risk of follicular thyroid carcinoma.

• Excess iodine exposure may increase risk of papillary thyroid carcinoma in susceptible individuals.

6. Increasing age

• Older age is associated with more aggressive disease and poorer prognosis.

Pathophysiology

Thyroid carcinoma develops through genetic and molecular alterations that promote uncontrolled proliferation, invasion, and metastatic potential of thyroid cells.

Differentiated thyroid carcinoma

Papillary and follicular thyroid cancers arise from follicular thyroid epithelial cells.

Papillary thyroid carcinoma

• Characterized by mutations involving pathways regulating cell growth, including:

  • BRAF mutations.

  • RET/PTC rearrangements.

• Usually spreads through lymphatic channels to cervical lymph nodes.

• Generally has slow progression and excellent response to treatment.

Follicular thyroid carcinoma

• Associated with mutations affecting the RAS pathway and PI3K/AKT pathway.

• Spreads mainly through blood vessels.

• Common metastatic sites include:

  • Lungs.

  • Bones.

Medullary thyroid carcinoma

• Originates from parafollicular C cells.

• Produces calcitonin, which serves as a tumour marker.

• Approximately 25% of cases are hereditary and associated with RET gene mutations.

Anaplastic thyroid carcinoma

• Represents transformation from differentiated thyroid carcinoma.

• Characterized by:

  • Rapid cellular proliferation.

  • Extensive local invasion.

  • Resistance to conventional therapy.

• Frequently presents with advanced local disease.

Clinical presentation

Thyroid carcinoma may present as an asymptomatic thyroid nodule discovered incidentally or as an enlarging neck mass with compressive symptoms.

Clinical manifestations depend on:

• Tumour size.

• Histological subtype.

• Local invasion.

• Presence of metastatic disease.

Symptoms

Patients may present with:

Local symptoms

• Anterior neck swelling or thyroid mass.

• Progressive enlargement of neck mass.

• Neck discomfort or pain.

• Difficulty swallowing (dysphagia).

• Difficulty breathing due to airway compression.

• Hoarseness of voice.

• Sensation of neck pressure.

Symptoms due to local invasion

• Stridor.

• Persistent cough.

• Vocal changes due to recurrent laryngeal nerve involvement.

Symptoms due to metastatic disease

• Unintentional weight loss.

• Shortness of breath due to pulmonary metastases.

• Bone pain.

• Pathological fractures due to skeletal metastases.

Medullary thyroid carcinoma-associated symptoms

Due to calcitonin secretion:

• Chronic diarrhoea.

• Flushing (less common).

Clinical signs

Clinical findings include:

Thyroid gland findings

• Solitary thyroid nodule.

• Firm or hard thyroid mass.

• Irregular thyroid swelling.

• Fixed thyroid lesion.

• Rapidly enlarging neck mass.

Signs of local invasion

• Cervical lymphadenopathy.

• Hoarseness due to vocal cord paralysis.

• Stridor.

• Reduced vocal cord mobility on laryngoscopy.

• Tracheal deviation or compression.

Signs of metastatic disease

• Enlarged cervical lymph nodes.

• Respiratory signs due to lung metastases.

• Bone tenderness or pathological fractures.

Differential diagnosis

Differential diagnoses of thyroid carcinoma include:

• Benign thyroid nodule.

• Multinodular goitre.

• Thyroid adenoma.

• Thyroid cyst.

• Hashimoto thyroiditis.

• Thyroid abscess.

• Thyroid lymphoma.

• Metastatic lymph node disease.

• Parathyroid tumour.

Diagnostic criteria

Diagnosis of thyroid carcinoma is based on clinical suspicion supported by imaging and cytological/histological confirmation.

Features suggestive of thyroid carcinoma include:

• Thyroid mass or anterior neck swelling.

• Rapidly enlarging thyroid lesion.

• Hard or fixed thyroid nodule.

• Cervical lymphadenopathy.

• Hoarseness of voice or recurrent laryngeal nerve palsy.

• Dysphagia or airway obstruction symptoms.

• Evidence of metastatic disease:

  • Weight loss.

  • Bone pain.

  • Respiratory symptoms.

  • Pathological fractures.

Definitive diagnosis requires:

• Fine needle aspiration cytology (FNAC) showing malignant features.

• Histopathological confirmation following surgery.

Investigations

Laboratory investigations

Thyroid function tests

• Thyroid stimulating hormone (TSH).

• Free T4.

• T3.

Most thyroid cancers are euthyroid; thyroid function tests are mainly used to assess gland function.

Tumour markers

Serum thyroglobulin

• Used for follow-up of differentiated thyroid carcinoma after thyroidectomy and radioactive iodine ablation.

• Helps detect recurrence or persistent disease.

Serum calcitonin

• Used in diagnosis and follow-up of medullary thyroid carcinoma.

Baseline investigations

• Full blood count (FBC).

• Liver function tests (LFTs).

• Urea and creatinine.

Imaging investigations

Thyroid ultrasound

• First-line imaging investigation.

• Assesses:

  • Thyroid nodules.

  • Suspicious features.

  • Cervical lymph nodes.

Thyroid scan

• Helps classify thyroid nodules as:

  • Hot nodules.

  • Cold nodules.

CT scan of neck

Indications:

• Suspected local invasion.

• Assessment of airway involvement.

• Surgical planning.

Chest X-ray

• Assessment for pulmonary metastases.

Isotope bone scan

• Assessment of skeletal metastases.

Tissue diagnosis

Fine needle aspiration cytology (FNAC)

• Recommended for suspicious thyroid nodules.

• Provides cytological classification using Bethesda system.

Histopathology

• Required after thyroidectomy to determine:

  • Histological subtype.

  • Tumour size.

  • Invasion.

  • Margins.

  • Lymph node involvement.

Staging

Thyroid carcinoma is staged using the TNM staging system:

• T (Tumour): size and local invasion.

• N (Nodes): cervical lymph node involvement.

• M (Metastasis): distant metastatic disease.

Staging guides treatment decisions and prognosis.

Management

Management should be individualized according to:

• Histological subtype.

• TNM stage.

• Patient age.

• Tumour risk category.

• Presence of metastasis.

Initial management includes:

1. Clinical assessment and staging.

2. Confirmation of diagnosis.

3. Multidisciplinary treatment planning.

Non-pharmacological treatment

Patient education and counselling

Patients should receive counselling regarding:

• Disease nature and treatment options.

• Need for lifelong follow-up.

• Importance of thyroid hormone monitoring.

• Symptoms suggesting recurrence.

Surgery

Surgery is the primary treatment modality.

Surgical options include:

Lobectomy

Indicated for:

• Selected low-risk differentiated thyroid cancers confined to one thyroid lobe.

Total or near-total thyroidectomy

Indicated for:

• Multifocal disease.

• Large tumours.

• High-risk differentiated thyroid carcinoma.

• Patients requiring radioactive iodine therapy.

Pharmacological treatment

Radioactive iodine therapy

Radioactive iodine I-131 (sodium iodide or potassium iodide)

Indication:

• Ablation therapy after surgery in differentiated thyroid carcinoma.

Purpose:

• Destroy remaining thyroid tissue.

• Treat microscopic residual disease.

• Treat iodine-avid metastatic disease.

Thyroid-stimulating hormone suppression therapy

Levothyroxine

Drug: LevothyroxineDose: Individualized according to TSH targetRoute: OralFrequency: Once dailyDuration: Lifelong in patients after total thyroidectomy

Target:

• Maintain TSH suppression, commonly:

  • TSH <0.1 mU/L in high-risk disease.

Treatment of recurrence or metastatic disease

Surgical management

Local recurrence should be treated with:

• Surgical resection where feasible.

Radioactive iodine therapy

Indicated for:

• Persistent disease.

• Recurrence.

• Distant metastases that demonstrate iodine uptake.

Palliative chemotherapy

Indicated for:

• Visceral metastatic disease.

• Progressive disease not responding to radioactive iodine therapy.

Recommended regimen:

Paclitaxel + Doxorubicin

• Paclitaxel – 175 mg/m² – intravenous infusion over 3 hours – once on day 1

  
  

  AND

• Doxorubicin – 60 mg/m² – intravenous bolus – once on day 1

Frequency: Every 3 weeksDuration: Up to 6 cycles

Radiotherapy

Differentiated thyroid carcinoma

Indications:

• Adjuvant treatment after surgery with:

  • Microscopic or macroscopic residual disease.

• Unresectable recurrence.

• Recurrence not taking up radioactive iodine.

• Palliation of bone and brain metastases.

Palliative regimen:

• External beam radiotherapy – 30 Gy in 10 fractions

Anaplastic thyroid carcinoma

Radiotherapy is indicated because of aggressive local behaviour.

Recommended dose:

• External beam radiotherapy – 50–60 Gy in 20–30 fractions

Management according to underlying cause

Differentiated thyroid carcinoma

Management:

1. Total/near-total thyroidectomy where indicated.

2. Radioactive iodine I-131 ablation.

3. Lifelong levothyroxine suppression therapy.

4. Surveillance using:

   • Thyroglobulin levels.

   • Neck ultrasound.

   • Imaging when indicated.

Medullary thyroid carcinoma

Management:

• Primary treatment is surgical.

Recommended approach:

• Total thyroidectomy with appropriate cervical lymph node dissection.

Additional management:

• Radiotherapy may be considered for:

  • Residual disease.

  • Unresectable disease.

  • Local recurrence.

Monitoring:

• Serum calcitonin.

• Carcinoembryonic antigen (CEA).

Anaplastic thyroid carcinoma

Anaplastic thyroid carcinoma is an aggressive malignancy.

Resectable disease

Management:

1. Total thyroidectomy where feasible.

2. Adjuvant radiotherapy.

3. Combination chemotherapy where indicated.

Unresectable disease

Management:

• Palliative radiotherapy.

• Combination chemotherapy.

Chemotherapy regimen:

• Paclitaxel – 175 mg/m² – intravenous infusion over 3 hours – day 1

  
  

  AND

• Doxorubicin – 60 mg/m² – intravenous bolus – day 1

Every 3 weeks up to 6 cycles.

Referral

All patients with suspected or confirmed thyroid carcinoma should be referred to a specialized multidisciplinary cancer centre.

Urgent referral indications

• Airway obstruction or stridor.

• Rapidly enlarging neck mass.

• Vocal cord paralysis.

• Suspected anaplastic carcinoma.

• Evidence of distant metastases.

Referral should involve:

• Endocrinology.

• Head and neck surgery.

• Oncology.

• Nuclear medicine.

• Radiotherapy specialists.

Complications

Complications may result from the disease or treatment.

Disease-related complications

• Airway obstruction.

• Recurrent laryngeal nerve palsy.

• Dysphagia.

• Local invasion.

• Cervical lymph node metastases.

• Lung metastases.

• Bone metastases.

• Pathological fractures.

Treatment-related complications

Surgery

• Hypocalcaemia due to parathyroid injury.

• Recurrent laryngeal nerve injury.

• Bleeding.

• Neck haematoma.

Radioactive iodine therapy

• Salivary gland dysfunction.

• Dry mouth.

• Taste disturbances.

Hormonal therapy

• Symptoms of excessive thyroid hormone suppression:

  • Palpitations.

  • Osteoporosis risk.

  • Cardiac arrhythmias.

Prognosis

Prognosis depends on:

• Histological subtype.

• Tumour stage.

• Age at diagnosis.

• Presence of metastasis.

• Response to treatment.

Differentiated thyroid carcinoma

• Generally has excellent prognosis.

• Most patients achieve long-term survival after appropriate treatment.

Medullary thyroid carcinoma

• Prognosis depends on:

  • Stage at diagnosis.

  • Calcitonin level.

  • Presence of metastases.

Anaplastic thyroid carcinoma

• Has poor prognosis due to rapid progression and aggressive invasion.

Prevention

Strategies include:

• Avoid unnecessary radiation exposure, especially in children.

• Early assessment of thyroid nodules.

• Regular follow-up for individuals with:

  • Family history of thyroid cancer.

  • Genetic syndromes.

  • Previous neck irradiation.

• Adequate iodine nutrition through appropriate dietary intake.

• Health education regarding early presentation of neck masses.