Anaplastic thyroid carcinoma

by Jason Wasserman MD PhD FRCPC
March 6, 2023

What is anaplastic thyroid carcinoma?

Anaplastic thyroid carcinoma is an uncommon and very aggressive type of thyroid gland cancer. While the tumour starts from cells normally found in the thyroid gland, it is often described as undifferentiated because the cells in the tumour look nothing like normal thyroid cells when examined under the microscope.

What are the symptoms of anaplastic thyroid carcinoma?

Anaplastic 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.

What causes anaplastic thyroid carcinoma?

At present, we do not know what causes a person to develop anaplastic thyroid carcinoma.

How do pathologists make the diagnosis of anaplastic thyroid carcinoma?

The diagnosis is usually made after a small piece of the tumour is removed in a procedure called a biopsy. If the tumour cells have spread to lymph nodes, the diagnosis can also be made after examining a biopsy from one of the involved lymph nodes. The tissue is then sent to a pathologist who examines it under the microscope.

What does anaplastic thyroid carcinoma look like under the microscope?

When examined under the microscope, anaplastic thyroid carcinoma is typically made up of very large and abnormal-looking cells. The cells may be described as epithelioid if they are round and stick together or spindled if they are longer than they are wide and spread apart. In addition, the tumour cells are often described as undifferentiated because they look nothing like the cells normally found in the thyroid gland. Areas of necrosis (cell death) and a large number of mitotic figures (tumour cells dividing to create new tumour cells) are commonly seen.

In some cases, anaplastic thyroid carcinoma arises from a more 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.

What other tests do pathologists perform to confirm the diagnosis?

Pathologists often perform a test called immunohistochemistry before making the diagnosis of anaplastic thyroid carcinoma. The tumour cells in anaplastic thyroid carcinoma frequently stop making proteins normally found in thyroid cells. For this reason, the tumour cells may be positive or negative for common thyroid markers including thyroglobulin, TTF-1, and PAX-8. The tumour cells in anaplastic thyroid carcinoma often over-express the protein p53.

Why is the size of the tumour important for anaplastic thyroid carcinoma?

After the tumour is removed completely it will be measured. The tumour is usually measured in three dimensions but only the largest dimension is described in your report. For example, if the tumour measures 4.0 cm by 2.0 cm by 1.5 cm, your report will describe the tumour as being 4.0 cm. The size of the tumour is important for anaplastic thyroid carcinoma because it is used to determine the pathologic stage and because larger tumours are more likely to spread to other parts of the body such as lymph nodes.

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 anaplastic 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?

​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 tumour stage (see Pathologic stage below) and is associated with a worse prognosis. Microscopic extrathyroidal extension does not change the tumour stage.

What is a margin?

​A margin is the tissue that has to be cut by the surgeon to remove the 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 and did any contain cancer cells?

Lymph nodes are small immune organs located throughout the body. Cancer 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 cancer cells from the thyroid to a lymph node is called metastasis.

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

What is a neck dissection?

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.

What is a tumour deposit?

A group of cancer cells inside of a lymph node 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.

What does extranodal extension (ENE) mean?

All lymph nodes are surrounded by a thin layer of tissue called a capsule. Cancer 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.

What is the pathologic stage (pTNM) for anaplastic thyroid carcinoma?

​​The pathologic stage for anaplastic 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 more advanced disease and a worse prognosis.

Tumour stage (pT) for anaplastic thyroid carcinoma

Anaplastic 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 cancer 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 cancer cells do not extend beyond the thyroid gland.
• T3 – The tumour is greater than 4 cm OR the cancer cells extend into the muscles outside of the thyroid gland.
• T4 – The cancer cells extend to structures or organs outside of the thyroid gland including the trachea, larynx, or esophagus.

Nodal stage (pN) for anaplastic 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 cancer cells were found in any of the lymph nodes examined.
• N1a – Cancer cells were found in one or more lymph nodes from levels 6 or 7.
• N1b – Cancer 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 anaplastic 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.