Infiltrative follicular variant papillary thyroid carcinoma

by Jason Wasserman MD PhD FRCPC
January 23, 2023

What is infiltrative follicular variant papillary thyroid carcinoma?

Infiltrative follicular variant papillary thyroid carcinoma (FVPTC) is a type of thyroid cancer. This type of cancer is more common in adults although it can be seen in children. It is called ‘infiltrative’ because when examined under the microscope, the tumour cells are seen spreading (infiltrating) widely throughout the surrounding normal (non-cancerous) thyroid gland tissue.

What causes infiltrative follicular variant papillary thyroid carcinoma?

For most people who develop infiltrative FVPTC, the cause is unknown. However, the risk of developing infiltrative FVPTC is higher for people with specific genetic tumour syndromes including PTEN hamartoma syndrome, DICER1 syndrome, and Carney complex.

What are the symptoms of infiltrative follicular variant papillary thyroid carcinoma?

The most common presentation of infiltrative FVPTC is a painless lump in the front of the neck. Larger tumours can cause difficulty swallowing or breathing, especially when lying down.

Can infiltrative follicular variant papillary thyroid carcinoma spread?

Yes. The tumour cells in infiltrative FVPTC can metastasize (spread) to other body parts, including the lungs and bones.

Why is the size of the tumour important for infiltrative follicular variant papillary 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 infiltrative FVPTC because it is used to determine the pathologic stage (pT) and because larger tumours are more likely to metastasize (spread) to other parts of the body.

What is angioinvasion?

Angioinvasion means that tumour cells were seen inside a blood vessel. Vascular invasion is another term that pathologists use to describe tumour cells inside a blood vessel. Angioinvasion is important because it increases the risk that tumour cells will metastasize (spread) to another part of the body such as the lungs or bones.

What does extrathyroidal extension mean?

​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’s 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. In contrast, microscopic extrathyroidal extension does not change the tumour stage.

What is lymphatic invasion?

​Lymphatic invasion means that tumour cells were seen inside a lymphatic vessel. Lymphatic vessels are small hollow tubes that allow the flow of a fluid called lymph from tissues to immune organs called lymph nodes. Lymphatic invasion is important because tumour cells can use lymphatic vessels to spread to other parts of the body such as lymph nodes or the lungs. If lymphatic invasion is seen, it will be called positive. If no lymphatic invasion is seen, it will be called negative.

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. Pathologists examine all margins to see if there are any tumour cells at the cut edge of the tissue. 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.

Were lymph nodes examined and did any contain tumour cells?

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. Compared to other types of papillary thyroid carcinoma, the tumour cells from infiltrative FVPTC are less likely to spread to lymph nodes.​

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 tumour cells are called negative. Most reports include the total number of lymph nodes examined and the number, if any, that contain tumour 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 tumour cells inside 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. Tumour 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 for infiltrative follicular variant papillary thyroid carcinoma?

​​The pathologic stage for infiltrative FVPTC 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 infiltrative follicular variant papillary thyroid carcinoma

Infiltrative FVPTC 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 gland.

• 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 tumour cells extend into the muscles outside of the thyroid gland.
• T4 – The tumour cells were found in structures or organs outside of the thyroid gland including the trachea, larynx, or esophagus.

Nodal stage (pN) for infiltrative follicular variant papillary thyroid carcinoma

Infiltrative FVPTC 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 infiltrative follicular variant papillary thyroid carcinoma

Infiltrative FVPTC 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.