Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)

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What is non-invasive follicular thyroid neoplasm with papillary-like nuclear features?

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a pre-cancerous and non-invasive type of thyroid tumour. It is called pre-cancerous because if not removed, it can over time turn into a type of cancer called papillary thyroid carcinoma.

Until 2016, NIFTP was called non-invasive encapsulated follicular variant papillary thyroid carcinoma (EFVPTC). At that time, it was also considered a type of thyroid cancer. The tumour was described as non-invasive because the entire tumour was surrounded by a capsule and the tumour cells were not seen spreading into or invading the normal thyroid tissue. The name and classification were changed after several large, scientific studies found that patients diagnosed with non-invasive EFVPTC could be cured with surgery alone.

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 NIFPT can only be made after the entire tumour is removed and sent for examination under the microscope by a pathologist. This examination needs to be performed in order to make sure that the tumour cells do not cross the tumour capsule or spread into the normal surrounding thyroid tissue. The diagnosis cannot be made after a small tissue sample is removed from the thyroid gland in a procedure called fine-needle aspiration.

When examined under the microscope, the tumour cells in NIFTP are often separated from the surrounding normal thyroid gland by a thin tissue barrier called a tumour capsule. If no capsule is seen, the tumour cells should still be separated from the normal thyroid gland by a small space.

Like the normal thyroid gland, NIFTP is made up of follicular cells that connect together to form follicles. The follicular cells show changes that pathologists describe as “papillary-like nuclear features” because they look similar to the cells in a type of cancer called papillary thyroid carcinoma.

In these cells, the part of the cell that holds the genetic material, the nucleus, is larger and the genetic material or chromatin is pushed to the edge of the nucleus. Pathologists describe this change as chromatin clearing. The outer border or membrane of the nucleus is often irregular in shape and lines or grooves can be seen running down the middle of the cells. Finally, unlike normal, healthy follicular cells, the cells are crowded which causes the nuclei to overlap.

Exclusion criteria

Your pathologist also needs to examine the tumour to make sure it does not have other features that are seen in cancers of the thyroid gland but not seen in NIFTP. Pathologists call these features exclusion criteria and they include:

• Papilla – A papillae (papillae means one, multiple are called papilla) is a group of cells connected together to form a piece of tissue that looks like a finger sticking out into the air. The centre of the finger is usually made up of small blood vessels and connective tissue. Papilla are very commonly seen in a type of cancer called papillary thyroid carcinoma and are not seen in NIFTP.
• Psammoma bodies – A psammoma body is a small round structure made up of dead cells and calcium. It looks dark purple when examined under the microscope. Psammoma bodies are very commonly seen in a type of cancer called papillary thyroid carcinoma and are not seen in NIFTP.
• Vascular invasion – Vascular invasion means that some of the tumour cells have entered a blood vessel. Once inside a blood vessel, the tumour cells are able to spread to other parts of the body. Because vascular invasion is a way for tumour cells to spread outside of the tumour, it should not be seen in NIFTP.
• Lymphatic invasion – Lymphatic invasion means that some of the tumour cells have entered a small channel called a lymphatic vessel. Lymphatics are connected to small organs called lymph nodes. Once inside a lymphatic channel, the tumour cells are able to spread to nearby lymph nodes. Because lymphatic invasion is a way for tumour cells to spread outside of the tumour, it should not be seen in NIFTP.

Treatment and prognosis

Once removed completely, the cells in an NIFTP should not be able to spread to other parts of the body. Patients with NIFTP alone also do not require additional surgery or treatment with radioactive iodine.

However, for a small number of patients initially diagnosed with NIFTP, tumour cells will be found later in a lymph node or other part of the body. Tumour cells that spread to a lymph node or other part of the body are called metastasis. When this happens, it is likely that a small area of tumour capsule invasion or other exclusion criteria (see above) was not seen when the tumour was examined. In this situation, the original diagnosis may need to be changed.

Lymph nodes

Lymph nodes are small immune organs located throughout the body. Tumour cells can spread to a lymph node through lymphatic channels located in and around the tumour. The movement of tumour cells to a lymph node is called metastasis.

Lymph nodes may be removed at the same time as your thyroid gland. Your pathologist will examine each lymph node carefully for tumour cells. Lymph nodes that show tumour cells are described as positive while those that do not show any tumour called are described as negative. Because NIFTP is a pre-cancerous and non-invasive tumour, no tumour cells should be found in any of the lymph nodes examined.

by Jason Wasserman, MD PhD FRCPC (updated September 20, 2021)