23rd May 2025

Thyroid cancers

Thyroid cancer can arise from either the thyrocytes or parafollicular cells of the gland. It typically manifests as a firm thyroid nodule. Thyroid cancer is more predominant in females especially of age between 30-50 years old. Its incidence varies geographically with higher rates occurring in North America and lowest incidence rates in Africa. Even though thyroid nodules are common, clinically detectable malignant nodules are rare. 

Aetiology and risk factors

• There are some genetic associations with thyroid carcinomas:
  • Medullary type is known to be associated with MEN2 (RET gene mutations) Papillary carcinoma is associated with RET/PTC rearrangements and BRAF mutations.
  • Follicular carcinoma is associated with PAX8-PPAR-γ rearrangement and RAS mutation. 
  • TP53 mutation is found in anaplastic carcinomas.
• Radiation exposure significantly increases the risk for thyroid malignancies, especially the papillary type. This has been noticed in the children that were exposed to radiation in Hiroshima and Nagasaki during World War II. There is a latency if at least 5 years post-exposure, with maximum risk at 20 years. However, low dose radiation exposure from imaging studies has not been found to have the same carcinogenic effect. Some evidence showed populations with low dietary iodine have higher risk for developing the follicular and anaplastic carcinomas.

Types and subtypes of thyroid cancers

Thyroid cancers are divided into differentiated and undifferentiated types, as summarised in table 6.

Table 6: Thyroid cancer types overview

TNM staging of thyroid cancer for papillary and follicular thyroid carcinoma

Thyroid cancer is classified according to size and extent of the tumour (T), regional LN involvement (N), and the distant metastasis (M). 

• T1 is tumour size ≤2 cm and limited to the thyroid. 
• T2 is tumour size >2cm but ≤4cm and limited to the gland. 
• T3 is tumour size >4cm limited to the thyroid or any tumour with minimal extrathyroidal invasion. 
• T4 is subdivided into T4a and T4b where tumour can be of any size and invading structures beyond thyroid capsule. 
• N0 has no regional lymph node metastasis; N1/N2 suggests lymph node involvement 
• M0 denotes no distant metastasis present; M1 denotes presence of distant metastasis. 

The eighth edition for TNM staging  for differentiated thyroid carcinoma depends on the cut-off age of 55 years old. 

• Patients of age <55 years old, cancer can be subdivided into: 
  • Stage I (with M0)
  • Stage II (with M1). 
• Patients ≥55 years old, thyroid carcinoma is subdivided to 4 stages: 
  • Stage I (T1 or T2 with N0 and M0) 
  • Stage II (T1+N1+M0 or T1+N1+M0 or T3+N0/N1+M0)
  • Stage III (T4a+N0/N1+M0)
  • Stage 4 (T4b+N0/N1+M0 or any T+ any N +M1)

Clinical picture

• The most common manifestation for thyroid cancer  is a painless palpable solitary thyroid nodule. Sometimes these nodules are discovered incidentally. Painful nodules are more suggestive of benign disease, haemorrhagic, or inflammatory changes.  
• Features of local infiltration or compression are fixed nodules; hoarseness of voice (due to recurrent laryngeal nerve infiltration); dyspnoea; dysphagia; or rare features such as Horner’s syndrome and SVC obstruction. 
• Painless cervical lymphadenopathy is more commonly seen in papillary and anaplastic thyroid cancers. 
• Features of distant metastasis are common with follicular and anaplastic thyroid cancer. Metastasis can be pulmonary, bones or brain with relevant features (e.g. pain, shortness of breath, neurological dysfunction) 
• Advanced medullary thyroid cancer shows paraneoplastic syndrome activity. Patients may present with flushing and diarrhoea due to excess calcitonin secretion from the tumour.

Investigations

As part of initial investigations, it is useful to assess the TSH, which tends to be within normal levels in thyroid cancer. Ultimate diagnosis is reached through US neck and doppler and FNAC to confirm histological features. Radioisotope scans are not routinely used for initial diagnosis of cancer. Cross-sectional imaging CT or MRI are offered in cancers of T3, T4, N1,M1 gradings or if there is suspicion of metastatic spread.

Management of thyroid cancer

Differentiated types

Management of differentiated types depends on grading of the tumour:

• If it is a very low risk tumour, active surveillance is recommended with US of the gland and neck lymph nodes (LNs) every 6-12 months. 
• For other grades or if active surveillance shows tumour size increase by ≥3mm or development of LN metastasis then thyroidectomy is recommended.
• In case of total thyroidectomy, thyroxine replacement is required. Additionally, TSH-suppressive doses of thyroid hormone therapy are used to prevent TSH cancer cells proliferation.
• In high-risk patients, following thyroidectomy, and in selected patients with intermediate-risk disease, radioactive iodine therapy is recommended.

Undifferentiated types

Management of undifferentiated types:

• Anaplastic thyroid cancer
  • This type of cancer usually presents late, hence, combining multiple therapeutic modalities is most effective and is individualised to each patient. 
  • Different combined modalities can be surgery and radiotherapy;  surgery and systemic therapy; or surgery and radiotherapy and systemic therapy. 
  • TSH suppression doses of levothyroxine if total thyroidectomy is done.
  • Radiotherapy is usually started early regardless of the surgical status, due to the aggressive nature of the cancer.
• Medullary thyroid cancer
  • 1st line management is surgical excision of the gland alongside central compartment lymph node dissection. 
  • Thyroxine hormone replacement is advised. 
  • Radiotherapy is advised for metastatic or recurrent tumours.
• Primary thyroid lymphoma
  • Management of this type depends on cell change. However, surgery alone is not sufficient for the management of this type of cancer. Hence combined chemotherapy and radiation is required.