Hurthle cell carcinoma

by Jason Wasserman MD PhD FRCPC
December 20, 2022

What is Hurthle cell carcinoma?

Hurthle cell carcinoma is a type of thyroid cancer. It is made up of large pink cells called Hurthle cells. This type of cancer is more likely to develop in older adults and it is rarely seen in children. Patients with Hurthle cell carcinoma may notice a growth or lump in the front of their neck. An ultrasound performed may show one or more nodules in the thyroid gland.

How do pathologists make this diagnosis?

The diagnosis of Hurthle cell carcinoma can only be made after the entire tumour is removed and sent to a pathologist for examination under the microscope. However, most patients undergo a minor surgical procedure called a fine-needle aspiration (FNAB) before the tumour is removed completely. This procedure uses a very thin needle to remove a small amount of tissue from the abnormal area of the thyroid gland. This tissue is then examined by a pathologist under a microscope. The FNA biopsy provides a preliminary diagnosis that helps guide further management.

What does Hurthle cell carcinoma look like under the microscope?

When examined under the microscope the tumour is made up of large pink cells that pathologists call Hurthle cells. This name is technically a misnomer as these were not the original “Hurthle cells” described by Karl Hurthle. The cells we today call Hurthle cells appear pink because the cytoplasm (body of the cell) is full of a cellular part called mitochondria. Hurthle cells also have a large round nucleus (the part of the cell that holds the genetic material) and a prominent central nucleolus (a clump of genetic material in the middle of the nucleus). The Hurthle cells can connect together to form small round structures called follicles or they may be in large groups that pathologists describe as a ‘solid pattern’.

Some tumours are surrounded by a thin band of fibrous tissue called a tumour capsule. The tumour capsule separates the tumours from the surrounding normal thyroid gland. Examination of the tumour capsule is very important because it helps distinguish Hurthle cell carcinoma from a very similar-looking but non-cancerous tumour called Hurthle cell adenoma. In Hurthle cell adenoma, all of the tumour cells are inside the tumour capsule. In contrast, in Hurthle cell carcinoma, tumour cells can be seen crossing the capsule into the surrounding normal thyroid gland tissue. This is called tumour capsule invasion.

Types of invasion

Pathologists use the term invasion to describe the spread of tumour cells into surrounding healthy tissue. The tumour cells in Hurthle cell carcinoma can show three different patterns of invasion: minimally invasive, encapsulated angioinvasive, and widely invasive. The pattern of invasion is very important because encapsulated angioinvasive and widely invasive tumours are much more likely to spread to other parts of the body.

Minimally invasive

Hurthle cell carcinoma is called minimally invasive when the tumour is surrounded by a tumour capsule but tumour cells were found spreading past the capsule into the normal thyroid gland. The tumour cells that have spread past the capsule are usually only found after the tissue has been examined under the microscope.

Encapsulated angioinvasive

Hurthle cell carcinoma is called encapsulated angioinvasive when tumour cells have broken through the tumour capsule and have spread into a blood vessel. This process is called angioinvasion. The rest of the tumour is usually still separated from the normal thyroid gland by a tumour capsule.

Widely invasive

Hurthle cell carcinoma is called widely invasive when the tumour is not surrounded by a tumour capsule or when only a small area of the capsule still remains. The cells in a widely invasive tumour have spread much further into the normal thyroid than the cells in a minimally invasive tumour. In some cases, the spread of tumour cells into the normal thyroid gland can be seen without a microscope during the gross examination.

Why is the tumour size important?

After the entire tumour is removed, it will be measured and the size of the tumour will be included in your pathology report. The size of the tumour is important because it is used to determine the pathologic tumour stage (pT) and because larger tumours are more likely to spread to 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.

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 movement of tumour cells out of the thyroid gland and into the surrounding tissues. Tumour cells that move far enough out of the thyroid gland may come into contact with additional structures 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 increases the tumour stage (see Pathologic stage below) and is associated with a worse prognosis. Microscopic extrathyroidal extension does not change the tumour stage.

Margins

​A margin is 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?

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, if any, that contain cancer cells.

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 capsule. Extranodal extension (ENE) means that tumour cells have broken through the capsule and spread into the tissue that surrounds the lymph node.

Pathologic stage (pTNM)

​​The pathologic stage for Hurthle cell 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 Hurthle cell carcinoma

Hurthle cell 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 Hurthle cell carcinoma

Hurthle cell 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 node from levels 6 or 7.
• N1b – Tumour cells were found in one or more lymph node from levels 1 through 5.
• NX – No lymph nodes were sent to pathology for examination.

Metastatic stage (pM) for Hurthle cell carcinoma

Follicular 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.