Thyroid Carcinoma

Thyroid tumours represent 1.5% of all cancers in adults, 3% of childhood malignancies but 92% of endocrine malignancies.

• 70% of thyroid cancers are papillary and 3 to 10% are medullary or C-cell carcinoma. They originate from the cells that produce calcitonin and hence the calcitonin level may be raised. 8 to 16% are anaplastic and usually in the age range 60 to 80 years.
• All the various types of thyroid cancers are 3 to 4 times as common in women as men, but with solitary thyroid nodules the risk of malignancy is greater in men.¹
• The risk of malignancy rises with age.

Risk factors

• Lumps are more common in areas of low iodine consumption and the incidence of malignancy rises from 5% to as high as 40%. Malignancy is more common where benign thyroid disease has existed.
• Thyroid cancers are more common after exposure to radiation, with a peak 5 to 30 years later.²
  7% of survivors of the atomic bombs at Hiroshima and Nagasaki developed thyroid cancer. After the Chernobyl disaster there was a rapid and dramatic increase in papillary carcinoma of thyroid in children in affected countries.³
• 10 to 20% of malignancy has a familial component e.g. multiple endocrine neoplasia (MEN). This is an autosomal dominant as is familial C-cell carcinoma without MEN.⁴

There are a number of histological types that behave differently.

Papillary thyroid carcinoma (PTC)

• This is the commonest form of thyroid cancer.
• It usually presents between 35 and 40 years of age and is 3 times more common in women.
• It tends to spread locally in the neck, compressing the trachea and possibly involving the recurrent laryngeal nerve.
• It can metastasise to lung and bone.

Follicular thyroid carcinoma (FTC)

• This is the second commonest form of thyroid cancer at about 10%.
• It tends to occur in areas of low iodine.
• It is 3 times as common in women and tends to strike between 30 and 60 years of age.
• It may infiltrate the neck as does papillary carcinoma but it has a greater propensity to metastasise to lung and bones.

Medullary cell carcinoma

• This is about 5% of thyroid cancers.
• About 25% of patients give a family history.
• Female prepronderance is less marked.
• Prophylactic thyroidectomy is advocated for those at risk.

The familial form is discussed in the article Multiple Endocrine Neoplasia Type 2 (MEN2).

Thyroid lymphomas

• Thyroid lymphomas are almost always non-Hodgkin lymphomas, representing 4 to 10% of thyroid malignancies.
• Mainly women over 50 are affected and they often have Hashimoto's thyroiditis.
• Patients usually present with a rapidly growing mass in the neck, which may cause symptoms of obstruction such as dyspnoea and dysphagia.
• Thyroid lymphoma arises in a pre-existing chronic thyroiditis with subclinical or overt hypothyroidism in 70 to 80%.
• The prognosis depends on the stage of the disease at diagnosis.
• The 5-year survival rate ranges from 89% in early disease to 5% in disseminated disease.

Hurthle cell carcinoma

• About 2 to 5% of thyroid cancers are Hurthle cell carcinoma.⁶
• There is a female preponderance - mainly in their 40s.
• They are composed of 75 to 100% Hurthle cells.
• It is impossible to distinguish benign from malignant tumours on fine needle aspiration (FNA).
• They do not take up iodine nor respond to TSH.
• 5-year survival rate is around 50%.

Anaplastic carcinoma

• This represents less than 2% of thyroid cancers.
• Women are affected more often than men.
• It is found aged 50 to 60.
• Half have metastases at presentation and prognosis is poor.

Perform thyroid function tests, (most will be euthyroid).
Plasma calcitonin level is also measured when medullary thyroid cancer is suspected.

Ultrasound

• Ultrasound is useful to detect and characterise most thyroid nodules.
• It can show cystic lesions 2 mm wide and solid lesions 3 mm wide.

Fine needle aspiration

• FNA gives tissue for cytology.
• It is performed under ultrasound guidance for maximum efficacy but for palpable nodules it can be performed with palpation alone.
• It is safe, inexpensive and provides direct information.
• FNA is best for uninodular lesions.⁷
• Sensitivity is near 80% with specificity approaching 100%. False-negative and false-positive results occur in less than 6%.
• FNA is the first, and in the vast majority of cases after ultrasound, the only test required for the evaluation of a solitary thyroid nodule.^8,9
• Follicular carcinoma and Hurthle cell carcinoma cannot be diagnosed by FNA. They represent 12% of all thyroid cancers, so these patients with suspicious biopsy need removal of the thyroid lobe with the nodule for histology. Suspicious cytology is reported in 10% of FNAs - these are neither clearly benign nor malignant.
• 25% are malignant, usually follicular or Hurthle cell cancers.
• Suspicious aspiration requires surgery.

Radionuclide imaging

Distinguishing functioning toxic nodules and thyroid metastases from follicular and papillary carcinomas is best with ¹²³Iodine uptake studies:

• Normal iodine uptake is seen in "warm" nodules.
• Lesions that take up excessive amounts of iodine are called "hot" and those that do not take it up are called "cold".

4% of hot nodules contain tumour, compared with 16% of cold nodules. This makes radionuclide imaging unreliable to exclude or confirm cancer. Low ¹²³Iodine uptake in a single palpable nodule gives a risk of malignancy of 10-25%, falling to 1-3% if multiple nodules are demonstrated on the scan.

About half of papillary carcinomas and a smaller number of follicular carcinomas take up enough iodine in metastases to be detected.

⁶⁷Ga is used in the diagnosis of thyroid lymphoma.

CT and MRI scan

CT scans and MRI scans are valuable to detect local and mediastinal spread and regional lymph nodes.

Referral

• Patients who have suspicious features (red flags - as above) should be referred urgently to a secondary care physician with expertise in the diagnosis and management of thyroid cancer, and seen within two weeks.¹⁰
• Any patient with a thyroid lump and associated stridor should be referred for same day review by a secondary care specialist, as this may be due to recurrent laryngeal nerve involvement secondary to a thyroid carcinoma.

Pharmacological

• After surgical excision of a cancer radio-iodine is given 4 to 6 weeks later to ablate any residual tissue. Thyroxine replacement must continue for life. 15 to 20% of cancers respond to TSH, so it should be kept suppressed.
• After thyroid cancer it is common to use tri-iodothyronine (T3) rather than thyroxine(T4). The reason for this is that it has a rather shorter biological life and so it may be stopped for a shorter time to let endogenous TSH rise before doing a ¹³¹I scan for recurrence or metastases.

Surgical

Solitary thyroid nodules that are malignant, suspicious or indeterminate on FNA require operation:¹⁰

• Patients with a papillary thyroid cancer more than 1 cm in diameter or with high-risk follicular thyroid cancer should undergo near-total or total thyroidectomy.
• Patients with low-risk FTC or PTC less than or equal to 1 cm in diameter may be treated with thyroid lobectomy alone.

Radiotherapy

External beam radiotherapy is only occasionally used, for patients with advanced and presumed residual disease in the neck which is not amenable to further surgery.

External beam radiotherapy also has a role as a palliative measure in patients with advanced local or distant disease.

All patients with FTC or PTC should have serum thyroglobulin levels checked 6 weeks post-operatively.
The majority of patients with a tumour more than 1 cm in diameter, who have undergone a near-total/total thyroidectomy, should have ¹³¹Iodine ablation. A post-ablation scan (3–10 days after) should be performed.
Annual life-long follow-up is recommended.

Surgery can cause recurrent laryngeal nerve palsy. The primary disease can cause nerve damage in both benign and malignant conditions.

This depends upon type and stage but most thyroid cancer has a good prognosis with 90% survival at 10 years, higher in young people without spread.

The exception is anaplastic cancer, with a life expectancy of 6 to 12 months and a 5 years' survival of 5%.