by Jason Wasserman MD PhD FRCPC
November 14, 2022
NUT carcinoma is an aggressive type of cancer that can arise anywhere along the midline of the body including the thorax, mediastinum, lung, nasal cavity, and paranasal sinuses. Another name for this type of cancer is NUT midline carcinoma.
NUT carcinoma is defined by the presence of a genetic alteration involving a gene called NUTM1. At present doctors do not know what causes this genetic alteration to occur.
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.
Lymphovascular invasion means that cancer cells were seen inside a blood vessel or lymphatic vessel. Blood vessels are long thin tubes that carry blood around the body. Lymphatic vessels are similar to small blood vessels except that they carry a fluid called lymph instead of blood. The lymphatic vessels connect with small immune organs called lymph nodes that are found throughout the body. Lymphovascular invasion is important because cancer cells can use blood vessels or lymphatic vessels to spread to other parts of the body such as lymph nodes or the lungs. If lymphovascular invasion is seen, it will be included in your report.
Perineural invasion is a term pathologists use to describe cancer cells attached to or inside a nerve. A similar term, intraneural invasion, is used to describe cancer cells inside a nerve. 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 important because the cancer cells can use the nerve to spread into surrounding organs and tissues. This increases the risk that the tumour will regrow after surgery. If perineural invasion is seen, it will be included in your report.
In pathology, a margin is the edge of a tissue that is cut when removing a tumour from the body. The margins described in a pathology report are very important because they tell you if the entire tumour was removed or if some of the tumour was left behind. The margin status will determine what (if any) additional treatment you may require.
Most pathology reports only describe margins after a surgical procedure called an excision or resection has been performed for the purpose of removing the entire tumour. For this reason, margins are not usually described after a procedure called a biopsy is performed for the purpose of removing only part of the tumour. Because NUT carcinoma is often removed in multiple pieces, your pathologist may not be able to determine the margin status.
Pathologists carefully examine the margins to look for tumour cells at the cut edge of the tissue. If tumour cells are seen at the cut edge of the tissue, the margin will be described as positive. If no tumour cells are seen at the cut edge of the tissue, a margin will be described as negative. Even if all of the margins are negative, some pathology reports will also provide a measurement of the closest tumour cells to the cut edge of the tissue.
A positive (or very close) margin is important because it means that tumour cells may have been left behind in your body when the tumour was surgically removed. For this reason, patients who have a positive margin may be offered another surgery to remove the rest of the tumour or radiation therapy to the area of the body with the positive margin. The decision to offer additional treatment and the type of treatment options offered will depend on a variety of factors including the type of tumour removed and the area of the body involved.
Lymph nodes are small immune organs found throughout the body. Cancer cells can spread from a tumour to lymph nodes through small vessels called lymphatics. Lymph nodes are not always removed at the same time as the tumour. However, when lymph nodes are removed, they will be examined under a microscope and the results will be described in your report.
Cancer cells typically spread first to lymph nodes close to the tumour although lymph nodes far away from the tumour can also be involved. For this reason, the first lymph nodes removed are usually close to the tumour. Lymph nodes further away from the tumour are only typically removed if they are enlarged and there is a high clinical suspicion that there may be cancer cells in the lymph node. Most reports will include the total number of lymph nodes examined, where in the body the lymph nodes were found, and the number (if any) that contain cancer cells. If cancer cells were seen in a lymph node, the size of the largest group of cancer cells (often described as “focus” or “deposit”) will also be included.
The examination of lymph nodes is important for two reasons. First, this information is used to determine the pathologic nodal stage (pN). Second, finding cancer cells in a lymph node increases the risk that cancer cells will be found in other parts of the body in the future. As a result, your doctor will use this information when deciding if additional treatment such as chemotherapy, radiation therapy, or immunotherapy is required.
Pathologists often use the term “positive” to describe a lymph node that contains cancer cells. For example, a lymph node that contains cancer cells may be called “positive for malignancy” or “positive for metastatic carcinoma”.
Pathologists often use the term “negative” to describe a lymph node that does not contain any cancer cells. For example, a lymph node that does not contain cancer cells may be called “negative for malignancy” or “negative for metastatic carcinoma”.
All lymph nodes are surrounded by a thin layer of tissue called a capsule. Extranodal extension means that cancer cells within the lymph node have broken through the capsule and have spread into the tissue outside of the lymph node. Extranodal extension is important because it increases the risk that the tumour will regrow in the same location after surgery. For some types of cancer, extranodal extension is also a reason to consider additional treatment such as chemotherapy or radiation therapy.