Thyroid gland

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

This article was last reviewed on November 20, 2019 by Jason Wasserman, MD PhD FRCPC

Quick facts:

  • Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a pre-cancerous thyroid tumour.
  • Until 2016 this tumour was called non-invasive encapsulated follicular variant papillary thyroid carcinoma and was considered a type of thyroid cancer.
  • This diagnosis can only be made after the entire tumour has been removed and sent to a pathologist for examination.

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.

Anatomy thyroid gland

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.

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

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

Like the normal thyroid gland, NIFTP is made up of follicular cells that connect together to form follicles.

Most of the genetic material inside of a cell is found in a small round structure called the nucleus. The genetic material inside the cell is called chromatin. The nucleus is surrounded by a thin border called the nuclear membrane.

In a normal, healthy follicular cell, the nucleus is small and round, the nuclear membrane is smooth, and the chromatin fills the entire nucleus. In a NIFTP tumour cell, the nucleus is larger than normal, the membrane is not smooth, and the nucleus looks clear because the chromatin has been pushed to the side. Pathologists call these changes papillary-like nuclear features because the same changes are seen in a type of thyroid cancer called papillary thyroid carcinoma.

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

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 tumour cells did not cross the capsule into the surrounding normal thyroid gland. Invasion is a word pathologists use to describe the movement of cancer cells into normal, healthy 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.

How do pathologists make this diagnosis?

In order to make the diagnosis of NIFTP, your pathologist needs to examine the entire border between the tumour and the normal surrounding thyroid tissue under the microscope. This examination needs to be performed in order to make sure that the tumour cells do not cross the capsule or spread into the normal surrounding thyroid tissue.

The diagnosis of NIFTP cannot be made if tumour cells are seen crossing the capsule or spreading into the surrounding thyroid tissue. Pathologists use the term capsular invasion to describe tumour cells that cross the capsule into the surrounding thyroid tissue.

Because the entire border of the tumour needs to be examined under the microscope, the diagnosis of NIFTP can only be made after the entire tumour has been removed. The diagnosis cannot be made after a small sample of tissue is removed from the tumour is a procedure called a fine needle aspiration.

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 papilla is a group of cells connected together to form a piece of tssie 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 a 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 a metastasis. When this happens, it is likely that a small area of capsular invasion or other exclusion criteria (see above) were 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 (see above). The movement of tumour cells to a lymph node is called a 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 describe as negative.

Why is this important? Because NIFTP is a pre-cancerous tumour, no tumour cells should be found in any of the lymph nodes examined.

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