by Jason Wasserman MD PhD FRCPC
July 29, 2024

Background:

Hurthle cell carcinoma, also known as oncocytic carcinoma, is a rare and distinct type of thyroid cancer characterized by the presence of Hurthle cells. These cells are large, with abundant granular eosinophilic cytoplasm due to the high number of mitochondria and a prominent nucleolus.

What are the symptoms of Hurthle cell carcinoma?

Symptoms of Hurthle cell carcinoma may include:

• A lump or swelling in your neck that you can see or feel.
• Voice changes, like hoarseness.
• Trouble with swallowing or breathing.

What causes Hurthle cell carcinoma?

What causes Hurthle cell carcinoma isn’t fully understood. However, it seems to involve a combination of both genetic changes and environmental risk factors, such as exposure to ionizing radiation and dietary influences. This type of cancer is also much more common in older adults.

How is this diagnosis made?

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. A pathologist then examines this tissue under a microscope. The FNA biopsy provides a preliminary diagnosis that helps guide further management.

Microscopic features of Hurthle cell carcinoma

When examined under the microscope, Hurthle cell carcinoma comprises large pink cells called 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 to form small round structures called follicles, or they may be in large groups that pathologists describe as a ‘solid pattern’.

Capsular invasion

Most Hurthle cell carcinomas are surrounded by a layer of fibrous tissue called a tumour capsule. Capsular invasion refers to the penetration of this fibrous capsule by tumour cells. This invasion is a critical feature distinguishing Hurthle cell carcinoma from benign Hurthle cell adenoma.

Subtypes of Hurthle cell carcinoma

After microscopic examination, Hurthle cell carcinoma can be categorized into different subtypes:

1. Minimally invasive Hurthle cell carcinoma.
2. Widely invasive Hurthle cell carcinoma.
3. Encapsulated angioinvasive Hurthle cell carcinoma.

These subtypes are described in greater detail in the sections below.

Minimally invasive Hurthle cell carcinoma

In minimally invasive Hurthle cell carcinoma, the tumour is surrounded by a fibrous tumour capsule. However, microscopic examination shows tumour cells breaking through the capsule and spreading into the surrounding thyroid gland tissue. This subtype is usually associated with a better prognosis and a lower risk of metastasis compared to encapsulated angioinvasive and widely invasive Hurthle cell carcinoma.

Widely invasive Hurthle cell carcinoma

Widely invasive Hurthle cell carcinoma exhibits extensive invasion into the surrounding thyroid tissue and may or may not show vascular invasion. This subtype is more aggressive and has a higher risk of distant metastasis and recurrence compared to minimally invasive Hurthle cell carcinoma.

Encapsulated angioinvasive Hurthle thyroid carcinoma

Encapsulated angioinvasive Hurthle cell carcinoma is characterized by a well-defined capsule and vascular invasion without significant capsular invasion. In terms of aggressiveness and prognosis, this subtype falls between minimally invasive and widely invasive Hurthle cell carcinoma.

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 it as being 4.0 cm. Tumour size is important for Hurthle cell carcinoma because it determines the pathologic tumour stage (pT) and because larger tumours are more likely to spread to other body parts, such as lymph nodes.

Extrathyroidal extension

Extrathyroidal extension (ETE) refers to the spread of cancer cells beyond the thyroid gland into surrounding tissues. It is an important prognostic factor in thyroid cancer, as it can significantly influence both the staging and management of the disease.

Extrathyroidal extension is classified into two types based on the extent of the spread:

• Microscopic extrathyroidal extension: This form of extension is only visible under a microscope and indicates that the cancer has spread just beyond the thyroid capsule but cannot be seen with the naked eye. It may involve minimal infiltration into surrounding soft tissues.
• Macroscopic (or gross) extrathyroidal extension: This type is visible to the naked eye or detectable during surgery. It involves more obvious and extensive invasion into neighbouring structures such as muscles, trachea, esophagus, or major blood vessels.

Extrathyroidal extension is important for the following reasons:

• Prognosis: Macroscopic (gross) extrathyroidal extension is associated with a worse prognosis. It suggests a more aggressive cancer that is more likely to recur and metastasize.
• Staging: Extrathyroidal extension impacts the staging of thyroid cancer. For instance, in the TNM (Tumor, Node, Metastasis) classification system used for thyroid cancer, macroscopic extrathyroidal extension results in a higher pathologic tumour stage (pT).
• Treatment and follow-up: The presence of macroscopic (gross) extrathyroidal extension might lead to more aggressive treatment strategies and closer follow-up to reduce the risk of recurrence.

Vascular invasion (angioinvasion)

Vascular invasion, or angioinvasion, in the context of Hurthle cell carcinoma, means that the cancer cells have spread into the blood vessels in or around the tumour. This is an important sign because it can indicate that the cancer might spread to other body parts, such as the lungs or bones.

Pathologists use two terms to describe how much vascular invasion (angioinvasion) is present:

• Focal vascular invasion (angioinvasion): This means cancer cells are found in less than 4 blood vessels.
• Extensive vascular invasion (angioinvasion): This means cancer cells are found in 4 or more blood vessels.

Extensive vascular invasion (4 or more blood vessels) usually means a higher risk of the cancer spreading, which can lead to a worse prognosis. If there is extensive angioinvasion, doctors often recommend more aggressive treatments to try to control the cancer better. This could include additional surgery, radioactive iodine therapy, or more frequent follow-up visits to monitor for any signs of cancer spreading.

Lymphatic invasion

Lymphatic invasion in the context of Hurthle cell carcinoma of the thyroid gland refers to the infiltration and spread of cancer cells into the lymphatic system. Cancer cells that enter the lymphatic system can travel to lymph nodes. It is relatively uncommon to find lymphatic invasion with Hurthle cell carcinoma, and unlike vascular invasion, the presence of lymphatic invasion is not necessarily associated with a more aggressive disease or a worse prognosis.

Margins

​In pathology, a margin is the edge of tissue removed during tumour surgery. The margin status in a pathology report is important as it indicates whether the entire tumour was removed or if some was left behind. This information helps determine the need for further treatment.

Pathologists examine margins to check if tumour cells are present at the tissue’s cut edge. A positive margin, where tumour cells are found, suggests that some tumour cells may remain in the body. In contrast, a negative margin, with no tumour cells at the edge, suggests the tumour was fully removed. Some reports also measure the distance between the nearest tumour cells and the margin, even if all margins are negative.

Lymph nodes

Lymph nodes are small immune organs found throughout the body. Cancer cells can spread from a 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 cancer cells from the tumour to another part of the body, such as a lymph node, is called metastasis.

Cancer 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. Lymph nodes on the same side as the tumour are called ipsilateral, while those on the opposite side of the tumour are called contralateral.

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 cancer cells were found in the lymph node. “Negative” means that no cancer cells were found. If cancer cells are found in a lymph node, the size of the largest group of cancer 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 determines the pathologic nodal stage (pN). Second, finding cancer 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 Hurthle cell 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)

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.

• 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)

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 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.

About this article

This article was written by doctors to help you read and understand your pathology report. Contact us with 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