Content overview

What is poorly differentiated thyroid cancer?

How common is it?

What causes PDTC?

How is PDTC treated?

Genetic testing

What research is there in this field?

Further reading

What is poorly differentiated thyroid cancer?

When clinicians talk about cancer differentiation, we mean how much the cancer cell still resembles its cell of origin. In thyroid cancer therefore we are looking to see if the cancer cell still shows the characteristics of a thyroid cell. Well-differentiated cancer cells look more like normal thyroid cells and tend to grow and spread more slowly than poorly differentiated or undifferentiated cancer cells.

Differentiation is a spectrum with the most common papillary and follicular thyroid cancers remaining well differentiated (or similar to the original, healthy cell) and the rare, aggressive anaplastic thyroid cancers, being undifferentiated (where the cancer cells have little or no resemblance to the original, healthy thyroid cells). Poorly differentiated cancers sit somewhere between these two extremes.

How common is it?

Poorly differentiated thyroid cancer (PDTC) is rare and makes up about 3-5% of all thyroid cancers. There is an urgent need for more research in this area. Unfortunately, there is not currently a standard treatment approach specifically for PDTC but it is understood that this subset of thyroid cancer requires further clinical trials to improve outcomes and to identify more targeted therapeutic approaches.

What causes PDTC?

Thyroid cancer develops when the DNA in thyroid cells changes (mutates) and the cells grow without control to form a tumour. The specific reasons that trigger this change are often not clear. There is no evidence to suggest that this type of thyroid cancer is inherited so it cannot be passed on to family members.

Our understanding of the biology of thyroid cancer is improving, particularly with molecular profiling which provides us with information about the genetic changes (mutations, fusions) which have caused the development of a tumour. This knowledge is enabling us to begin to build up patterns of tumour characteristics and signatures that may be associated with disease behaviour and prognosis. Despite the World Health Organisation defining PDTC based on pathological characteristics, the point at which a differentiated thyroid cancer becomes a PDTC is not black and white, and this is an area of continued observation and learning.

How is PDTC treated?

The treatment of PDTC is initially surgery, usually a total thyroidectomy (complete removal of the thyroid). Sometimes there will be a two-phase procedure with a hemithyroidectomy (removal of half of the thyroid) followed by a completion thyroidectomy (removal of the rest of the thyroid) if the diagnosis was not certain on biopsy. Radioiodine (RAI) is usually recommended because until this is given, we cannot fully predict which tumours will respond or not. RAI can be very effective in controlling and/or getting rid of the disease so it is important to consider this after thyroid surgery.

In cases where RAI is not helpful, or is only helpful in the short term, which is unfortunately more likely in PDTC, the cancer is termed ‘iodine-refractory’ (and sometimes called 'iodine-resistant' or ‘non-iodine-avid’). At this point drug treatment with tyrosine kinase inhibitors such as Lenvatinib or Sorafenib are considered. These drugs will not cure the cancer but slow down the progression and may reduce the size of the tumour or amount of disease. These drugs are taken orally (tablets) and patients are treated in outpatient settings. The drugs may have side effects which can include high blood pressure, diarrhoea, rashes, weight loss and fatigue. Clinical trials are in progress to look at drugs that might be useful in the second line, i.e. once the cancer has escaped the control of either Lenvatinib or Sorafenib.

As part of your treatment for thyroid cancer, you will be given a medication called levothyroxine after your thyroid has been removed. This medicine replaces the hormone your thyroid used to make before it was removed. The dose you are getting may be higher than someone would normally need just to replace that thyroid hormone.

This slightly higher dose helps lower the level of another hormone in your body called TSH (Thyroid Stimulating Hormone), which is made by the pituitary gland in your brain. Lowering (or suppressing) TSH is important because it can help prevent any remaining thyroid cancer cells from growing. This dose is carefully chosen to give you the best chance of stopping the cancer from coming back or spreading.

Your thyroid hormone levels must be kept to a certain range. Your Oncology team will advise you and your GP about the ideal values.

Genetic testing

If thyroid cancer becomes iodine-refractory, it is recommended that the tumour tissue is further examined to look for genetic abnormalities. This is called molecular profiling. In rare cases a particular genetic change can be identified and there may be a drug that specifically targets this change, so it is sensible to test all tumours in this way. In most cases it will be possible to do this testing on the specimen from your original surgery which will have been preserved in case further analysis is required.

Genetic testing of most of the known variants (including BRAF V600E, RAS and RET) is now available in most large centres in the UK. The results of the test will help doctors identify reasons why the cancer occurred and whether there are any specific drugs to treat it.

What research is there in this field?

PDTC is now a focus for research. Trials are looking into the use of immunotherapy with or without kinase inhibitors but this is not yet a proven, licensed or funded treatment option. We await further data. Another approach is to try to redifferentiate the tumour, therefore enabling it to take up radioiodine again. This is also an area of research and only available through clinical trials. Unfortunately, there are no clinical trials currently open in the UK for PDTC but it is always worth asking your oncologist as trials may become available in the future.

March 2026

Further reading

Judy's story - poorly differentiated thyroid cancer

Targeted treatment for advanced thyroid cancer FAQs 

BTF Joe Plater Research Award 2021