Poorly differentiated thyroid carcinoma

by Jason Wasserman MD PhD FRCPC
June 8, 2022

What is poorly differentiated thyroid carcinoma?

Poorly differentiated thyroid carcinoma is a rare and aggressive form of thyroid cancer. Poorly differentiated thyroid carcinoma often develops from a well-differentiated type of thyroid cancer such as papillary thyroid carcinoma or follicular thyroid carcinoma.

What causes poorly differentiated thyroid carcinoma?

Current research suggests that a combination of genetic and environmental factors contribute to the development of poorly differentiated thyroid carcinoma. However, to date, no single factor has been identified that makes a person more likely to develop this tumour.

What are the symptoms of poorly differentiated thyroid carcinoma?

Poorly differentiated thyroid carcinoma is a fast-growing tumour that starts in the thyroid gland. As a result, people often notice a growth in the front of the neck. As the tumour grows it can put pressure on surrounding tissues such as the esophagus or trachea. This can result in difficulty breathing or swallowing food. A lump may be felt or seen on the side of the neck if tumour cells have spread to lymph nodes in this area.

How is the diagnosis of poorly differentiated thyroid carcinoma made?

The diagnosis of poorly differentiated thyroid carcinoma is usually made after part or all of the thyroid gland has been removed in a procedure called a resection. The thyroid gland is then sent to a pathologist for examination under the microscope. The diagnosis can also be made after examination of an enlarged lymph node.

What does poorly differentiated thyroid carcinoma look like under the microscope?

When examined under the microscope, the tumour is made up of follicular thyroid cells. The pattern of growth may be described as solid, trabecular, or insular. Mitotic figures (tumour cells dividing to create new tumour cells) are usually seen and the number of mitotic figures may be described in your report. A type of cell death called necrosis may also be seen.

In some cases, poorly differentiated thyroid carcinoma arises from a well-differentiated type of thyroid cancer such as papillary thyroid carcinoma or follicular carcinoma. If a more well-differentiated tumour is seen, it will be described in your report.

Why is the size of the tumour important?

For poorly differentiated thyroid carcinoma, the size of the tumour is important because it is used to determine the pathologic tumour stage (pT). Larger tumours are also associated with a worse prognosis because the tumour cells are more likely to spread to lymph nodes or other parts of the body.

What does vascular invasion mean and why is it important?

​Vascular invasion is the movement of tumour cells into a blood vessel. Once tumour cells are inside a blood vessel, they are able to spread to other parts of the body. For this reason, vascular invasion increases the risk of developing metastatic disease. It is very common for poorly differentiated thyroid carcinoma to show vascular invasion.

What does lymphatic invasion mean and why is it important?

Lymphatic invasion is the movement of tumour cells into a lymphatic vessel (small tubes that move fluid and immune cells around the body). Once tumour cells are inside a lymphatic vessel, they are able to spread to small immune organs called lymph nodes. For this reason, lymphatic invasion increases the risk of developing lymph node metastasis.

What does extrathyroidal extension mean and why is it important?

​Extrathyroidal extension is the spread of tumour cells out of the thyroid gland and into the surrounding tissues. Tumour cells that spread far enough out of the thyroid gland may come into contact with other organs such as muscles, the esophagus, or the trachea.​

There are two types of extrathyroidal extension:

• Microscopic – The tumour cells outside of the thyroid gland were only found after the tumour was examined under the microscope.
• Macroscopic (gross) – The tumour can be seen growing into the surrounding tissues without the use of a microscope. This type of extrathyroidal extension may be seen by your surgeon at the time of surgery or by the pathologist assistant performing the gross examination of the tissue sent to pathology.

Macroscopic (gross) extrathyroidal extension is important because it increases the pathologic tumour stage (pT) and is associated with a worse prognosis. Microscopic extrathyroidal extension does not change the tumour stage.

What is a margin?

​A margin is tissue that has to be cut by the surgeon to remove the tumour and thyroid gland from your body.  A margin is considered positive when there are cancer cells at the very edge of the cut tissue. A negative margin means there were no cancer cells seen at the cut edge of the tissue.

Were lymph nodes examined?

Lymph nodes are small immune organs located throughout the body. Tumour cells can travel from the thyroid to a lymph node through lymphatic channels located in and around the tumour (see Lymphatic invasion above). The movement of tumour cells from the thyroid to a lymph node is called metastasis.

Lymph nodes from the neck are sometimes removed at the same time as the thyroid in a procedure called a neck dissection. The lymph nodes removed usually come from different areas of the neck and each area is called a level. The levels in the neck are numbered 1 through 7. Your pathology report will often describe how many lymph nodes were seen in each level sent for examination. Lymph nodes on the same side as the tumour are called ipsilateral while those on the opposite side of the tumour are called contralateral.

Your pathologist will carefully examine each lymph node for tumour cells. Lymph nodes that contain tumour cells are often called positive while those that do not contain any cancer cells are called negative. Most reports include the total number of lymph nodes examined and the number that contain tumour cells.

Tumour deposit

A group of tumour cells inside a lymph node or soft tissue outside of the thyroid gland is called a tumour deposit. If a tumour deposit is found, your pathologist will measure the deposit and the largest tumour deposit found will be described in your report.

Extranodal extension

All lymph nodes are surrounded by a thin layer of tissue called a capsule. Tumour cells that have spread to a lymph node can break through the capsule and into the tissue surrounding the lymph node. This is called extranodal extension (ENE). Extranodal extension does not change the pathologic stage but your doctors may use this information when deciding which treatment is best for you.

Pathologic stage (pTNM)

​​The pathologic stage for poorly differentiated thyroid carcinoma is based on the TNM staging system, an internationally recognized system originally created by the American Joint Committee on Cancer. This system uses information about the primary tumour (T), lymph nodes (N), and distant metastatic disease (M)  to determine the complete pathologic stage (pTNM). Your pathologist will examine the tissue submitted and give each part a number. In general, a higher number means a more advanced disease and a worse prognosis.

Tumour stage (pT) for poorly differentiated thyroid carcinoma

Poorly differentiated thyroid carcinoma is given a tumour stage between 1 and 4 based on the size of the tumour and the presence of tumour cells outside of the thyroid (see Extrathyroidal extension above).

• T1 – The tumour is less than or equal to 2 cm and the tumour cells do not extend beyond the thyroid gland.
• T2 – The tumour is greater than 2 cm but less than or equal to 4 cm and the tumour cells do not extend beyond the thyroid gland.
• T3 – The tumour is greater than 4 cm OR the tumour cells extend into the muscles outside of the thyroid gland.
• T4 – The tumour cells extend to structures or organs outside of the thyroid gland including the trachea, larynx, or esophagus.

Nodal stage (pN) for poorly differentiated thyroid carcinoma

Anaplastic thyroid carcinoma is given a nodal stage of 0 or 1 based on the presence or absence of tumour cells in a lymph node and the location of the involved lymph nodes.

• N0 – No tumour cells were found in any of the lymph nodes examined.
• N1a – Tumour cells were found in one or more lymph nodes from levels 6 or 7.
• N1b – Tumour cells were found in one or more lymph nodes from levels 1 through 5.
• NX – No lymph nodes were sent to pathology for examination.

Metastatic stage (pM) for poorly differentiated thyroid carcinoma

Anaplastic thyroid carcinoma is given a metastatic stage of 0 or 1 based on the presence of tumour cells at a distant site in the body (for example the lungs). The metastatic stage can only be determined if tissue from a distant site is sent for pathological examination. Because this tissue is rarely sent, the metastatic stage cannot be determined and is listed as MX.