Thyroid carcinoma


Carcinoma of the thyroid gland is an uncommon cancer but is the most common malignancy of the endocrine system. 


  • soft-to-hard thyroid nodule, usually non-tender to palpatation 
  • firm cervical masses often indicate lymph node metastases
  • vocal chord paralysis implies involvement of the laryngeal nerve
  • unexplained hoarseness
  • stridor or goiter 
  • painless thyroid mass 
  • persistent pain lasting weeks 


Differentiated tumours (papillary or follicular) are highly treatable and usually curable. Poorly differentiated tumours (medullary or anaplastic) are much less common, are aggressive, metastasise early, and have a much poorer prognosis. The thyroid gland may occasionally be the site of other primary tumours, including sarcomas, lymphomas, epidermoid carcinomas and teratomas, and may be the site of metastasis from other cancers, particularly of the lung, breast, and kidney.

Papillary thyroid carcinoma (PTC)

  • This is the most common form of thyroid cancer. 70% of thyroid cancers are papillary.
  • It usually presents between 35 and 40 years of age and is three times more common in women.
  • Most often, it presents as micropapillary thyroid carcinoma (<1 cm in size) with an excellent long-term prognosis.[2]
  • It tends to spread locally in the neck, compressing the trachea and possibly involving the recurrent laryngeal nerve.
  • Metastases most often occur in lung and bone.

Follicular thyroid carcinoma (FTC)

  • This is the second most common form of thyroid cancer at about 10%.
  • It tends to occur in areas of low iodine.
  • It is three times more common in women and most often presents 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 thyroid carcinoma (MTC)[2]

  • Medullary thyroid cancer arises from the parafollicular calcitonin-producing C cells of the thyroid and accounts for between 5% and 8% of all thyroid malignancies.
  • Female preponderance is less marked.
  • Malignant transformed C cells produce and secrete large amounts of peptides, including carcinoembryonic antigen (CEA) and calcitonin and so elevated serum calcitonin is a marker of the presence of MTC or metastatic MTC after surgery.
  • Up to 75% of MTC cases occur sporadically. The hereditary form of MTC (23% of cases) shows an autosomal dominant pattern of transmission. Familial MTC arises as part of multiple endocrine neoplasia (MEN) syndrome type 2A or 2B or familial MTC (FMTC).
  • Prognostic factors that predict adverse outcome include calcitonin doubling time, advanced age at diagnosis, extent of the primary tumour, nodal disease and distant metastases.

Thyroid lymphomas

  • Thyroid lymphomas are almost always non-Hodgkin lymphomas, representing 4-10% of thyroid malignancies.
  • Mainly women aged 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 overthypothyroidism in 70-80%.
  • The prognosis depends on the stage of the disease at diagnosis.
  • The five-year survival rate ranges from 89% in early disease to 5% in disseminated disease.

Hürthle cell carcinoma[3]

  • Hürthle cell carcinoma accounts for about 3-10% of all differentiated thyroid cancers.
  • They are composed of 75-100% Hürthle cells.
  • There is a female preponderance.
  • It may present from 20-85 years of age but most often between the ages of 50-60 years.
  • It is impossible to distinguish benign from malignant tumours on fine-needle aspiration (FNA).
  • Surgical excision is the main treatment. Other treatments include postoperative radioactive iodine-131 treatment, levothyroxine (T4) and external radiotherapy.
  • Hürthle cell carcinomas behave more aggressively than other well-differentiated thyroid cancers with a higher incidence of metastasis and a lower survival rate.

Anaplastic thyroid carcinoma (ATC)[2]

  • Anaplastic thyroid carcinoma (ATC) is the most aggressive thyroid tumour and one of the most aggressive cancers in humans.
  • ATC arises from the follicular cells of the thyroid gland but does not retain any of the biological features of the original cells, such as uptake of iodine and synthesis of thyroglobulin.
  • The peak incidence is in the sixth to seventh decades (mean age at diagnosis 55-65 years) and the prevalence is very low (<2% of all thyroid tumours).
  • In most cases ATC develops from a pre-existing well-differentiated thyroid tumour, which has undergone additional mutational events.
  • The clinical diagnosis is usually easy with a large, hard mass invading the neck and causing compression (dyspnoea, cough, vocal cord paralysis, dysphagia and hoarseness). Almost 50% of the patients present with distant metastasis, mostly in the lungs but also in the bones, liver and brain.
  • The mean overall survival is often less than six months, whatever treatment is performed.


  • TFTs should be performed for any patient with a thyroid nodule. However, TFTs (most patients will be euthyroid) and thyroglobulin (Tg) measurement are of little help in the diagnosis of thyroid cancer.
  • Serum calcitonin is a reliable tool for the diagnosis of medullary thyroid cancer (5-7% of all thyroid cancers).
  • Ultrasound:
    • Thyroid ultrasound is used as a first-line diagnostic procedure for detecting and characterising nodular thyroid disease.
    • Ultrasound features associated with malignancy include hypoechogenicity, microcalcifications, absence of peripheral halo, irregular borders, solid aspect, intranodular blood flow and shape (taller than wide).
    • Ultrasound should also be used to explore the neck carefully to assess the status of lymph node chains.
  • Fine-needle aspiration cytology (FNAC):
    • This should be performed in any thyroid nodule >1 cm and in those <1 cm if there is any clinical (history of head and neck irradiation, family history of thyroid cancer, suspicious features on palpation, presence of cervical lymphadenopathy) or ultrasound suspicion of malignancy.
    • The results of FNAC are very sensitive for the differential diagnosis of benign and malignant nodules, although limitations include inadequate samples and follicular neoplasia.
  • Radionuclide imaging: distinguishing functioning toxic nodules and thyroid metastases from follicular and papillary carcinomas is best with 123 Iodine 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.
    • Gallium 67 Ga 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.


  • 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 local or metastatic spread. The exception is anaplastic cancer, with a 5-year survival of 5%.
  • Despite increasing incidence, the mortality from thyroid cancer has declined over the last 30 years. The mortality rate in the UK in 2008 was 0.4 per 100,000 population.


  • 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.[7]
  • 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.
  • Solitary thyroid nodules that are malignant, suspicious or indeterminate on FNA require operation.[7]
  • Because of the proximity of the right and left recurrent laryngeal nerves and risk of damage to the nerves, intraoperative nerve monitoring may be used during thyroid surgery, especially for reoperative surgery and operations on large thyroid glands.[8]
  • Annual lifelong follow-up is recommended.

Differentiated thyroid carcinoma (DTC)

  • The initial treatment for DTC is total or near-total thyroidectomy whenever the diagnosis is made before surgery and the nodule is >1 cm, or regardless of the size and histology (papillary or follicular) if there is metastatic, multifocal or familial DTC.
  • Less extensive surgical procedures may be acceptable in the case of unifocal DTC diagnosed at final histology after surgery performed for benign thyroid disorders, provided that the tumour is small, intrathyroidal and of favourable histology.
  • The benefit of prophylactic central node dissection in the absence of evidence of nodal disease is controversial.
  • Compartment-oriented microdissection of lymph nodes should be performed in cases of preoperatively suspected and/or intraoperatively proven lymph node metastases.
  • Surgery is usually followed by the administration of iodine-131 aimed at ablating any remnant thyroid tissue and potential microscopic residual tumour. This decreases the risk of loco-regional recurrence and allows long-term surveillance based on serum Tg measurement and diagnostic radioiodine whole body scan. Radioiodine ablation is recommended for all patients except those at very low risk (those with unifocal T1 tumours, <1 cm in size, with favourable histology, no extrathyroidal extension or lymph node metastases). Effective thyroid ablation requires adequate stimulation by thyroid-stimulating hormone (TSH). The method of choice for preparation to perform radioiodine ablation is based on the administration of recombinant human TSH (rhTSH) while the patient is on levothyroxine (LT4) therapy.