Anaplastic thyroid carcinoma

by Jason Wasserman MD PhD FRCPC
March 26, 2024

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, resulting 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.

Your pathology report for anaplastic thyroid carcinoma

The information found in your pathology report for anaplastic thyroid carcinoma will depend on the type of procedure performed. For example, the information in a report after a biopsy is usually limited to the diagnosis. However, some reports may also describe the results of additional tests such as immunohistochemistry (IHC). After the entire tumour has been removed, your pathology report will include additional information such as the tumour size, extent of invasion, presence or absence of lymphovascular invasion, and the assessment of margins. The results of any lymph nodes examined should also be included in this final report. These topics are described in more detail in the sections below.

Microscopic features of anaplastic thyroid carcinoma

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.

Immunohistochemistry

Pathologists often perform a test called immunohistochemistry before diagnosing 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.

Tumour size

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 tumour size is important for anaplastic thyroid carcinoma because it determines the pathologic tumour stage (pT) and because larger tumours are more likely to spread to other parts of the body, such as lymph nodes.

Vascular invasion (angioinvasion)

​Vascular invasion (also known as angioinvasion) is the spread of tumour cells into a blood vessel. Once tumour cells are inside a blood vessel, they can 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.

Lymphatic invasion

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

Extrathyroidal extension

​Extrathyroidal extension is the spread of tumour cells from the thyroid gland and into the surrounding tissues. Tumour cells that spread far enough out of the thyroid gland may contact 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. Your surgeon may see this type of extrathyroidal extension at the time of surgery or by the pathologist’s 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.

Margins

​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 tumour cells at the very edge of the cut tissue. A negative margin means there were no tumour cells seen at the cut edge of the tissue.

Lymph nodes

Lymph nodes are small immune organs found throughout the body. Tumour cells can spread from the primary tumour to lymph nodes through small lymphatic vessels. For this reason, lymph nodes are commonly removed and examined under a microscope to look for cancer cells. The movement of tumour cells from the tumour to another part of the body such as a lymph node is called a metastasis.

Tumour cells typically spread first to lymph nodes close to the tumour although lymph nodes far away from the tumour can also be involved. For this reason, the first lymph nodes removed are usually close to the tumour. Lymph nodes further away from the tumour are only typically removed if they are enlarged and there is a high clinical suspicion that there may be cancer cells in the lymph node.

A neck dissection is a surgical procedure performed to remove lymph nodes from the neck. The lymph nodes removed usually come from different neck areas, and each area is called a level. The levels in the neck include 1, 2, 3, 4, and 5. Your pathology report will often describe how many lymph nodes were seen in each level sent for examination.

If any lymph nodes are removed from your body, they will be examined under the microscope by a pathologist, and the examination results will be described in your report. “Positive” means that tumour cells were found in the lymph node. “Negative” means that no tumour cells were found. If tumour cells are found in a lymph node, the size of the largest group of tumour cells (often described as “focus” or “deposit”) may also be included in your report. Extranodal extension means that the tumour cells have broken through the capsule on the outside of the lymph node and have spread into the surrounding tissue.

The examination of lymph nodes is important for two reasons. First, this information is used to determine the pathologic nodal stage (pN). Second, finding tumour cells in a lymph node increases the risk that cancer cells will be found in other parts of the body in the future. As a result, your doctor will use this information when deciding if additional treatment such as radioactive iodine, chemotherapy, radiation therapy, or immunotherapy is required.

Pathologic stage (pTNM)

​​The pathologic stage for anaplastic thyroid carcinoma is based on the TNM staging system, an internationally recognized system 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)

Anaplastic thyroid carcinoma is given a tumour stage between 1 and 4 based on its size 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 the thyroid gland, including the trachea, larynx, or esophagus.

Nodal stage (pN)

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.

About this article

Doctors wrote this article to help you read and understand your pathology report. Contact us if you have any questions about this article or your pathology report. Read this article for a more general introduction to the parts of a typical pathology report.

Other helpful resources

American Thyroid Association (ATA)

American Cancer Society

Learn more pathology

Atlas of Pathology