by Jason Wasserman MD PhD FRCPC
April 6, 2022
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.
At present doctors do not know what causes NUT carcinoma.
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.
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.
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.
Nerves are like long wires made up of groups of cells called neurons. Nerves are found all over the body and they are responsible for sending information (such as temperature, pressure, and pain) between your body and your brain. Perineural invasion is a term pathologists use to describe tumour cells attached to a nerve. Perineural invasion is important because the tumour cells can use the nerve to spread into surrounding tissues. This increases the risk that the tumour will re-grow after treatment.
Blood moves around the body through long thin tubes called blood vessels. Another type of fluid called lymph which contains waste and immune cells moves around the body through specialized vessels called lymphatics. The term lymphovascular invasion is used to describe tumour cells that are found inside a blood or lymphatic vessel. Lymphovascular invasion is important because these cells are able to metastasize (spread) to other parts of the body such as lymph nodes or the lungs. Lymphovascular invasion is very common in NUT carcinoma.
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 types of margins described in your report will depend on where the tumour started and the type of surgery performed. Margins are usually only described in your report after the entire tumour has been removed.
A negative margin means that no tumour cells were seen at any of the cut edges of tissue. A margin is called positive when there are tumour cells at the very edge of the cut tissue. A positive margin is associated with a higher risk that the tumour will recur in the same site after treatment.
Because NUT carcinoma is often removed in multiple pieces, your pathologist may not be able to reliably assess the margins of the tumour. For that reason, most pathology reports for NUT carcinoma do not have information about margins.
Lymph nodes are small immune organs located throughout the body. Tumour 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 tumour cells from the tumour to a lymph node is called metastasis.
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.
A group of tumour 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. The size of the largest tumour deposit is also used to determine the nodal stage (see Pathologic stage below).