Malignant peripheral nerve sheath tumour (MPNST)

by Bibianna Purgina MD FRCPC
June 7, 2023

What is a malignant peripheral nerve sheath tumour?

A malignant peripheral nerve sheath tumour (MPNST) is a cancer that develops from a nerve and a type of sarcoma. Most malignant peripheral nerve sheath tumours occur in adults.  Common locations include the neck, arm, leg and buttock.

What is a nerve?

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. Nerves are found throughout your body. Some nerves are very small (like those just under the surface of the skin) while others are very large (like those that go to muscles).

Syndromes associated with malignant peripheral nerve sheath tumour

People with the genetic syndrome neurofibromatosis type 1 (NF1) are at higher risk for developing an MPNST and about half of all tumours develop in people with this syndrome. In some cases, the malignant peripheral nerve sheath tumour develops from an existing non-cancerous tumour called a neurofibroma.

How do pathologists make this diagnosis?

The diagnosis may be made after a small sample of tissue is removed in a procedure called a biopsy or after the tumour has been removed completely. Most pathologists will perform additional tests such as immunohistochemistry to confirm the diagnosis. When immunohistochemistry is performed, some of the tumour cells will be positive or reactive for a protein called S100.

Because this tumour can look very similar to other types of tumours that develop from nerves, it may not always be possible for your pathologist to make a final diagnosis after a biopsy is performed. In this situation, the entire tumour will need to be removed before a final diagnosis is made.

Molecular tests

Your pathologists may perform molecular tests such as fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS) on a sample of the tumour in order to rule out other types of tumours that can look very similar to an MPNST under the microscope. Because MPNSTs do not have any known genetic changes, a negative result supports the diagnosis of MPNST.

Histologic grade

Pathologists use the term grade to describe how different the cancer cells look and behave compared to normal nerve cells. Usually, tumours that look high grade under the microscope have a worse prognosis than tumours that look low grade under the microscope. However, some types of sarcoma are not graded because research has shown that grade does not accurately predict how the tumour will behave.

Currently, there is debate whether MPNSTs should be graded and many pathologists do not provide a tumour grade in the pathology report. If your report includes a grade it will be based on the French Federation of Cancer Centers Sarcoma Group (FNCLCC) grading system. According to this system, your pathologist will look for three microscopic features when examining the tumour sample (see below). Points are given for each feature (from 0 to 3) and the total number of points determines the final grade of the tumour.

• Tumour differentiation – Tumour differentiation describes how closely the cancer cells look like normal nerve cells. Tumours that look very similar to normal nerve cells are given 1 point while those that look very different from normal nerve cells are given 2 or 3 points. All MPNSTs receive a score of either 2 or 3 points for this category.
• Mitotic count – A cell that is in the process of dividing to create two new cells is called a mitotic figure. Tumours that are growing fast tend to have more mitotic figures than tumours that are growing slowly. Your pathologist will determine the mitotic count by counting the number of mitotic figures in ten areas of the tumour while looking through the microscope. Tumours with no mitotic figure or very few mitotic figures are given 1 point while those with 10 to 20 mitotic figures are given 2 points and those with more than 20 mitotic figures are given 3 points.
• Necrosis – Necrosis is a type of cell death. Tumours that are growing fast tend to have more necrosis than tumours that are growing slowly. If your pathologist sees no necrosis, the tumour will be given 0 points. The tumour will be given 1 point if necrosis is seen but it makes up less than 50% of the tumour or 2 points if necrosis makes more than 50% of the tumour.

The final grade is based on the total number of points given to the tumour. Low-grade sarcomas are grade 1.  High-grade sarcomas have a grade of either 2 or 3.

• Grade 1 – 2 or 3 points.
• Grade 2 – 4 or 5 points.
• Grade 3 – 6 to 8 points.

Tumour size

The tumour is measured in three dimensions but only the largest dimension is typically included in your report. For example, if the tumour measures 5.0 cm by 3.2 cm by 1.1 cm, the report may describe the tumour size as 5.0 cm in the greatest dimension. Tumour size is important because tumours less than 5 cm are less likely to spread to other parts of the body and are associated with a better prognosis.

Triton tumour

Some malignant peripheral nerve sheath tumours can have areas that start to look like the cells normally found in skeletal muscle tissue. Malignant peripheral nerve sheath tumours with skeletal muscle are sometimes called malignant Triton tumours and are more common in patients with neurofibromatosis type 1 (NF1).

Tumour extension​

Malignant peripheral nerve sheath tumours can grow into or around organs and bone.  Your pathologist will examine samples of the surrounding organs and tissues under the microscope to look for cancer cells. Any surrounding organs or tissue that contains cancer cells will be described in your report.

Treatment effect​

If you received chemotherapy and/or radiation therapy before the operation to remove your tumour, your pathologist will examine all the tissue sent to pathology to see how much of the tumour is still alive (viable). Most commonly, your pathologist will describe the percentage of tumour that is dead.

Perineural invasion

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.

Lymphovascular invasion

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 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. Lymphovascular invasion is important because it increases the risk that cancer cells will be found in a lymph node or a distant part of the body such as the lungs.

Margins

A margin is any tissue that was cut by the surgeon in order to remove the tumour from your body. The types of margins described in your report will depend on the organ involved and the type of surgery performed. Margins will only be described in your report after the entire tumour has been removed.

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. A negative margin means that no tumour cells were seen at any of the cut edges of tissue.

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.

Many cancers can spread to the lymph nodes, but malignant peripheral nerve sheath tumour does this very rarely. If lymph nodes were part of the surgery to remove your tumour, your pathologist will assess them under the microscope and report whether they are involved by tumour.

Pathologic stage

​The pathologic stage for malignant peripheral nerve sheath tumour is based on the TNM staging system, an internationally recognized system originally created by the American Joint Committee on Cancer. This system uses information about the primary tumour (T), lymph nodes (N), and distant metastatic disease (M)  to determine the complete pathologic stage (pTNM). Your pathologist will examine the tissue submitted and give each part a number. In general, a higher number means more advanced disease and a worse prognosis.

Tumour stage (pT) for malignant peripheral nerve sheath tumour

The tumour stage for malignant peripheral nerve sheath tumour varies based on the body part involved. For example, a 5-centimetre tumour that starts in the head will be given a different tumour stage than a tumour that starts deep in the back of the abdomen (the retroperitoneum). However, in most body sites, the tumour stage includes the tumour size and whether the tumour has grown into surrounding body parts.

Tumour stage for tumours starting in the head and neck

• T1 – The tumour is no greater than 2 centimetres in size.
• T2 – The tumour is between 2 and 4 centimetres in size.
• T3 – The tumour is greater than 4 centimetres in size.
• T4 – The tumour has grown into surrounding tissues such as the bones of the face or skull, the eye, the larger blood vessels in the neck, or the brain.

Tumour stage for tumours starting on the outside of the chest, back, or stomach and the arms or legs (trunk and extremities)

• T1 – The tumour is no greater than 5 centimetres in size.
• T2 – The tumour is between 5 and 10 centimetres in size.
• T3 – The tumour is between 10 and 15 centimetres in size.
• T4 – The tumour is greater than 15 centimetres in size.

Tumour stage for tumours starting in the abdomen and organs inside the chest (thoracic visceral organs)

• T1 – The tumour is only seen in one organ.
• T2 – The tumour has grown into the connective tissue that surrounds the organ from which is started.
• T3 – The tumour has grown into at least one other organ.
• T4 – Multiple tumours are found.

Tumour stage for tumours starting in the space at the very back of the abdominal cavity (retroperitoneum)

• T1 – The tumour is no greater than 5 centimetres in size.
• T2 – The tumour is between 5 and 10 centimetres in size.
• T3 – The tumour is between 10 and 15 centimetres in size.
• T4 – The tumour is greater than 15 centimetres in size.

Tumour stage for tumours starting in the space around the eye (orbit)

• T1 – The tumour is no greater than 2 centimetres in size.
• T2 – The tumour is greater than 2 centimetres in size but has not grown into the bones surrounding the eye.
• T3 – The tumour has grown into the bones surrounding the eye or other bones of the skull.
• T4 – The tumour has grown into the eye (the globe) or the surrounding tissues such as the eyelids, sinuses, or brain.

If after microscopic examination, no tumour is seen in the resection specimen sent to pathology for examination, it is given the tumour stage pT0 which means there is no evidence of primary tumour.

If your pathologist cannot reliably evaluate the tumour size or the extent of growth, it is given the tumour stage pTX (primary tumour cannot be assessed).  This may happen if the tumour is received as multiple small fragments.

Nodal stage (pN) for malignant peripheral nerve sheath tumour

Malignant peripheral nerve sheath tumour is given an nodal stage between 0 and 1 based on the presence or absence of cancer cells in one or more lymph nodes. If no cancer cells are seen in any lymph nodes, the nodal stage is N0. If no lymph nodes are sent for pathological examination, the nodal stage cannot be determined, and the nodal stage is listed as NX.  If cancer cells are found in any lymph nodes, then the nodal stage is listed as N1.

Metastasis stage (pM) for malignant peripheral nerve sheath tumour

Malignant peripheral nerve sheath tumour is given a metastatic stage of 0 or 1 based on the presence of cancer cells at a distant site in the body (for example the lungs). The metastatic stage can only be assigned if tissue from a distant site is submitted for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as MX.

The metastatic stage can only be given if tissue from a distant site is sent for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined, and it is typically not included in your report.