d) Undifferentiated Carcinoma

Undifferentiated carcinoma is an uncommon form of thyroid malignancy with a terrible prognosis.


Undifferentiated or anaplastic carcinoma occurs more commonly in the elderly. Women develop more cases than men (1.5:1). It makes up less than 5% of all thyroid malignancies but is the most common cause of death from thyroid cancer.


Undifferentiated carcinoma is thought to arise from a less aggressive malignancy, either follicular/papillary or poorly differentiated carcinoma. Other causative factors are not known.

Natural History and Clinical Features

Undifferentiated carcinoma is one of the most aggressive and treatment resistant cancers in humans. Distant metastases are present in 40% of patients at diagnosis and nearly always develop within 6 months of diagnosis. Hoarse voice, dysphagia and vocal cord paralysis are the most common presenting symptoms in addition to a rapidly growing anterior neck mass. There is involvement of the trachea and oesophagus in about 50% of cases. The most common site for distant metastases are the lungs (50%) followed by bones (15%).
Although nodal metastases are common the local invasion caused by the tumour is usually more dramatic.

Tumour Features


The tumour is light in colour and contains obvious areas of necrosis and haemorrhage. The thyroid is usually replaced and there is extension into the surrounding organs.


The tumour usually contains three populations of cells:

  • Spindle cells
  • Pleomorphic giant cells
  • Epithelioid cells

There are usually a large number of mitoses and extensive lymphovascular invasion.


Undifferentiated thyroid carcinoma is usually positive for cytokeratins but almost always negative on immunohistochemistry for thyroglobulin and TTF1. TP53 is almost always positive. Immunohistochemistry is important in distinguishing undifferentiated carcinoma from other malignancies of the thyroid.


The most commonly associated genetic change with undifferentiated thyroid carcinoma is TP53 mutation. Other mutations involve cyclin D1, inactivation of PTEN and p16, and b-catenin mutations.

Staging and Outcomes

Undifferentiated thyroid carcinoma is staged differently to other thyroid cancers. It is always stage IV, depending on the amount of local invasion (IVA/IVB) or metastatic spread (IVC). Five year survival is, at best, 14% and most series quote survival rates approaching 0%.