NUT carcinoma

by Jason Wasserman MD PhD FRCPC
April 6, 2022

What is NUT carcinoma?

NUT carcinoma is an aggressive type of cancer defined by the presence of a genetic alteration involving a gene called NUTM1. This tumour can arise anywhere along the midline of the body including the thorax, mediastinum, lung, nasal cavity, and paranasal sinuses.

What causes NUT carcinoma?

At present doctors do not know what causes NUT carcinoma.

How do pathologists make this diagnosis?

The diagnosis of NUT is usually made after a small sample of tissue is removed in a procedure called a biopsy. The diagnosis can also be made after the entire tumour is removed in a procedure called a resection. The tissue is then sent to a pathologist who examines it under a microscope.

What does NUT carcinoma look like under the microscope?

When examined under the microscope, the tumour is made up of cells with large, round, open nuclei. The genetic material inside of the nucleus may be described as vesicular and large clumps of genetic material called nucleoli are often seen. Pathologists often describe the tumour cells as monotonous because all of the cells look very similar to each other. Dividing tumour cells called mitotic figures and a type of cell death called necrosis are typically seen. Some of the tumour cells may produce a protein called keratin that is normally found in specialized squamous cells. Pathologists describe this as keratinization and in NUT carcinoma this process tends to be “abrupt” or without any transition from the non-keratinizing tumour cells.

NUT carcinoma

What other tests may be performed to confirm the diagnosis of NUT carcinoma?

The diagnosis of NUT requires confirmation of a genetic alteration involving the NUTM1 gene. The alteration results in the NUTM1 gene combining with another gene (typically BRD4 or BRD3) to form a new gene called a fusion gene. Tests that can be used to identify this genetic alteration include fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), or polymerase chain reaction (RT-PCR).

Your pathologists may perform another test called immunohistochemistry to confirm the diagnosis. When performed, the tumour cells in NUT carcinoma are usually positive for p40, p63, and cytokeratins. When performed, the tumour cells are always positive for NUT protein.

What does perineural invasion mean?

Nerves are like long wires made up of groups of cells called neurons. Nerves transmit information (such as temperature, pressure, and pain) between your brain and your body. Perineural invasion is a term pathologists use to describe cancer cells attached to a nerve.

Perineural invasion is important because cancer cells that have attached to a nerve can use the nerve to travel into tissue outside of the original tumour. For this reason, perineural invasion is associated with a higher risk that the tumour will come back in the same area of the body (local recurrence) after treatment.

perineural invasion

What does lymphovascular invasion mean?

Blood moves around the body through long thin tubes called blood vessels. Another type of fluid called lymph contains waste and immune cells that move around the body through lymphatic channels. Cancer cells can use blood vessels and lymphatics to travel away from the tumour to other parts of the body. The movement of cancer cells from the tumour to another part of the body is called metastasis.

Before cancer cells can metastasize, they need to enter a blood vessel or lymphatic. This is called lymphovascular invasion. Seeing lymphovascular invasion increases the risk that cancer cells will be found in a lymph node or a distant part of the body such as the lungs. Lymphovascular invasion is very common in NUT carcinoma.

lymphovascular invasion

What is a margin?

A margin is any tissue that was cut by the surgeon in order to remove the tumour from your body. Whenever possible, surgeons will try to cut tissue outside of the tumour to reduce the risk that any cancer cells will be left behind after the tumour is removed.

The number and types of margins described in your report will depend on the location in the body where the tumour was found. For example, a tumour located in the lung or mediastinum may be removed with a margin of normal lung tissue around it. In contrast, a tumour located at the base of the skull may be removed with a margin of normal bone around it.

A negative margin means there were no cancer cells at the very edge of the cut tissue. A margin is considered positive when there are cancer cells at the very edge of the cut tissue. A positive margin is associated with a higher risk that the tumour will grow back (recur) in the same site after treatment.

Because these tumours are often removed in multiple pieces, your pathologist may not be able to reliably assess the margins of the tumour. For that reason, some pathology reports for NUT carcinoma do not have information about margins.


What are lymph nodes?

Lymph nodes are small immune organs located throughout the body. Cancer cells can travel from the tumour to a lymph node through lymphatic channels located in and around the tumour (see Lymphovascular invasion above). The movement of cancer cells from the tumour to a lymph node is called metastasis.

For tumours that start in the head and neck, lymph nodes from the neck are sometimes removed at the same time as the main tumour 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 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.

Your pathologist will carefully examine each lymph node for cancer cells. Lymph nodes that contain cancer 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. The number of lymph nodes that contain cancer cells and their location in the body is important because it is used to determine the nodal stage.

Lymph node

What is a 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. Larger tumour deposits are associated with a worse prognosis.

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