Follicular carcinoma of the thyroid gland

What is follicular carcinoma?

Follicular carcinoma is a type of thyroid cancer. The tumour starts from the follicular cells normally found in the thyroid gland and is the second most common thyroid cancer in adults. Follicular carcinoma is more likely to develop in older adults and it is rarely seen in children.

Patients with follicular 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. Most tumours are separated from the normal surrounding thyroid gland by a thin tissue barrier called a tumour capsule. Over time, some of the tumour capsule may disappear and large tumours may not have any capsule at all.

The thyroid gland

The thyroid is a U-shaped gland located in the front of the neck. The normal thyroid gland is divided into right and left lobes that are connected in the middle by the isthmus. Some people also have another small lobe above the isthmus called the pyramidal lobe.

The thyroid gland makes thyroid hormone. Most of the cells in the thyroid gland are called follicular cells. The follicular cells connect together to form small round structures called follicles. Thyroid hormone is stored in a material called colloid which fills the centre of follicles.

How do pathologists make this diagnosis?

The diagnosis of follicular carcinoma is made after the entire tumour is removed and sent to a pathologist for examination. When viewed under the microscope, the cells in a follicular carcinoma can look very similar to the cells in a non-cancerous type of thyroid tumour called a called follicular adenoma. The only difference between follicular carcinoma and a follicular adenoma is that the tumour cells in a follicular carcinoma have broken through a thin tissue barrier called the tumour capsule and have spread into the surrounding normal thyroid gland. Pathologists describe this as tumour capsule invasion. In contrast, all of the abnormal cells in a follicular adenoma are separated from the normal thyroid gland by the tumour capsule.

Because the entire tumour capsule needs to be examined, the diagnosis of follicular carcinoma can only be made after the tumour has been removed and sent to a pathologist for examination under the microscope.

Fine needle aspiration (FNA)

A fine-needle aspiration (FNA) is a procedure that removes a small amount of thyroid tissue. This tissue is then examined by a pathologist under the microscope. When examined under the microscope, the tumour cells in a follicular carcinoma will look very similar to normal, healthy follicular cells. The follicles in the tumour, however, may be smaller than normal follicles and they may contain less colloid. The fine needle aspiration pathology report will describe the tumour as a follicular neoplasm, a category that includes both follicular carcinoma and follicular adenoma.

Tumour size

This is the size of the tumour measured in centimetres (cm). 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. Tumour size plays an important role in determining the pathologic tumour stage for follicular carcinoma (see Pathologic stage below).

Tumour capsule invasion

Most follicular carcinomas are at least partially separated from the normal, healthy thyroid gland by a thin layer of tissue called a tumour capsule. In order to make the diagnosis of follicular carcinoma, your pathologist must see the tumour cells spreading past the capsule into the surrounding normal thyroid gland. This is called tumour capsule invasion.

Follicular carcinoma can show two patterns of invasion:

• Minimally invasive – This means that the tumour is surrounded by a 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.
• Widely invasive – This means that the tumour is not surrounded by a capsule or that 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.

Widely invasive tumours are more likely to spread to other parts of the body such as the lungs or bone. The spread of tumour cells to another body site is called metastasis.

Vascular invasion (angioinvasion)

​Blood vessels carry blood around the body. Tumour cells that enter a blood vessel are able to spread to distant parts of the body such as the lungs and bones. The movement of tumour cells to another part of the body is called metastasis.

Tumour cells seen inside of a blood vessel is called vascular invasion (angioinvasion). If vascular invasion is seen, your pathologist will count the number of vessels that contain tumour cells.

Your report will describe vascular invasion as negative if no cancer cells are seen inside of a blood vessel, positive and focal if there are less than 4 blood vessels with cancer cells, and positive and diffuse if there are 4 or more blood vessels with cancer cells.

Follicular carcinoma is more likely to show vascular invasion than other types of thyroid cancer.

Lymphatic invasion

​Lymphatics are small thin vessels that provide a way for fluids and cells to leave a tissue. Lymphatics are found all over the body. Tumour cells that enter a lymphatic vessel are able to spread to other parts of the body, in particular lymph nodes.

Tumour cells seen inside a lymphatic vessel is called lymphatic invasion. Your pathologist will carefully examine your tissue for lymphatic invasion. If lymphatic invasion is seen, it will be called positive. If no lymphatic invasion is seen, it will be called negative. Follicular carcinoma is less likely to spread to lymph nodes than other types of thyroid carcinoma.

Extra thyroidal extension

​Extra thyroidal 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 extra thyroidal 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) extra thyroidal extension increases the tumour stage (see Pathologic stage below) and is associated with a worse prognosis. In contrast, microscopic extra thyroidal 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 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.

Lymph nodes

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. Follicular carcinoma is less likely than other types of thyroid cancer to spread to lymph nodes.

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.

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.

Extranodal extension (ENE)

All lymph nodes are surrounded by a thin layer of tissue called 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 follicular 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 follicular carcinoma

Follicular 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 follicular carcinoma

Follicular 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 follicular 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.

by Jason Wasserman, MD PhD FRCPC (updated August 31, 2021)