Myxofibrosarcoma

by Jason Wasserman MD PhD FRCPC and Bibianna Purgina MD FRCPC
December 30, 2022

What is myxofibrosarcoma?

Myxofibrosarcoma is a type of cancer that starts in connective tissue. It is one of the most common types of sarcomas to affect older adults.

What type of cancer is myxofibrosarcoma?

Myxofibrosarcoma is a type of sarcoma. Sarcomas are malignant (cancerous) tumours that start in connective tissue, muscle, or bone.

What are the symptoms of myxofibrosarcoma?

This tumour typically presents as a slow-growing and painless mass. Larger tumours may cause pain as a result of pressure on surrounding tissues.

What causes myxofibrosarcoma?

At this time, there are no known risk factors for myxofibrosarcoma.

Where is myxofibrosarcoma typically found?

The arms and legs are the most common sites for myxofibrosarcoma. Most tumours develop in the soft tissue below the skin (the dermis and subcutaneous tissue) with a smaller number developing in the muscle.

Can myxofibrosarcoma spread to other parts of the body?

Yes. Myxofibrosarcoma can metastasize (spread) to other parts of the body, with common sites being the lungs and bones. High grade tumours (see FNCLCC grade below) are much more likely to spread compared to low grade tumours.

How do pathologists make this diagnosis?

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

What does myxofibrosarcoma look like under the microscope?

When examined under the microscope, myxofibrosarcoma is made up of spindle cells surrounded by light blue connective tissue. Pathologists describe this type of connective tissue as ‘myxoid’. The appearance of the tumour cells depends on the grade of the tumour. Low grade tumours tend to be made up of long thin cells while high grade tumours are made up of large, highly abnormal-looking cells that vary greatly in shape and size. Pathologists use terms such as atypical and pleomorphic to describe these cells. Mitotic figures (tumour cells dividing to create new tumour cells) are usually seen and atypical mitotic figures may also be found. It is common for myxofibrosarcoma to contain long thin blood vessels which pathologists often describe as curvilinear.

What is the FNCLCC grade and why is it important for myxofibrosarcoma?

Pathologists divide myxofibrosarcoma into three grades based on a system created by the French Federation of Cancer Centers Sarcoma Group (FNCLCC). This system uses three microscopic features to determine the tumour grade: differentiation, mitotic count, and necrosis. These features are explained in more detail below. The grade can only be determined after a sample of the tumour has been examined under the microscope.

Points (from 0 to 3) are assigned for each of the microscopic features (0 to 3) and the total number of points determines the final grade of the tumour. According to this system, myxofibrosarcoma may be either low or high-grade tumours. The tumour grade is important because high-grade tumours (grades 2 and 3) are more likely to regrow after surgery and metastasize (spread) to other parts of the body.

Points associated with each grade:

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

Microscopic features used to determine the grade:

1. Tumour differentiation – Tumour differentiation describes how closely the tumour cells look like normal, healthy cells. Tumours that look very similar to normal healthy cells are given 1 point while those that look very different from normal fat cells are given 2 or 3 points. All myxofibrosarcomas are given 2 points for tumour differentiation.
2. 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 figures 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.
3. 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 makes up less than 50% of the tumour or 2 points if necrosis makes up more than 50% of the tumour.

Why is the size of the tumour important for myxofibrosarcoma?

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. Tumour size is also used to determine the pathologic tumour stage (pT).

What does tumour extension mean for myxofibrosarcoma?

Myxofibrosarcoma typically starts in the connective tissue below the skin or muscle. However, as the tumour gets bigger, it can grow into surrounding organs and tissues. This is called tumour extension. Your pathologist will carefully examine any surrounding tissues or organs submitted for tumour cells and the result of this examination will be described in your report.

What does treatment effect mean for myxofibrosarcoma?

If you received chemotherapy and/or radiation therapy before the operation to remove the 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 non-viable (dead tumour cells). For example, a treatment effect of 90% means that 90% of the tumour is made up of non-viable tumour cells.

What is lymphovascular invasion and why is it important?

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.

What is perineural invasion and why is it important?

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.

What is a margin?

A margin is any tissue that was cut by the surgeon to remove the tumour from your body.  Depending on the type of surgery you have had, the margins can include bones, muscles, blood vessels, and nerves that were cut to remove the tumour from your body. All margins will be very closely examined under the microscope by your pathologist to determine the margin status. Specifically, a margin is called negative when there are no cancer cells at the edge of the cut tissue. A margin is called positive when there are cancer cells at the edge of the cut tissue. A positive margin is associated with a higher risk that the tumour will recur (regrow) in the same site after treatment.

Were lymph nodes examined and did any contain cancer cells?

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. The movement of cancer cells from the tumour to a lymph node is called metastasis.

Many cancers can spread to the lymph nodes, but myxofibrosarcoma does this very rarely. If lymph nodes were part of the surgery to remove your tumour, your pathologist will examine them under the microscope and report whether cancer cells were found in any of the lymph nodes.

What is the pathologic stage for myxofibrosarcoma?

​The pathologic stage for myxofibrosarcoma 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 a more advanced disease and a worse prognosis.

Tumour stage (pT) for myxofibrosarcoma

The tumour stage for myxofibrosarcoma 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 it 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 a 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 myxofibrosarcoma

Myxofibrosarcoma is given a 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 myxofibrosarcoma

Myxofibrosarcoma 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.