Rhabdomyosarcoma

by Jason Wasserman MD PhD FRCPC
May 4, 2022

What is rhabdomyosarcoma?​

Rhabdomyosarcoma is a type of cancer made up of immature muscle cells. It is part of a group of cancers called sarcomas. Rhabdomyosarcoma can start anywhere in the body where skeletal muscle cells are normally found. The most common locations for rhabdomyosarcoma include the head and neck, arms and legs, bladder, trunk (chest and abdomen), and the around the eye. Most rhabdomyosarcomas occur in children although they can also occur in adults.

What are the types of rhabdomyosarcoma?

Pathologists divide rhabdomyosarcoma into four types based on how the cells look when examined under the microscope and the molecular changes inside the tumour cells.

The four types of rhabdomyosarcoma are:

• Embryonal – This is the most common type of rhabdomyosarcoma and it typically occurs in children or young adults.
• Alveolar – This is the second most common type of rhabdomyosarcoma. Like the embryonal type, it typically occurs in children although it can also occur in older adults.
• Pleomorphic– This type of rhabdomyosarcoma typically occurs in older adults. Most tumours start in the arms or legs, but they can also start in the abdomen or pelvis.
• Spindle cell/sclerosing – This type of rhabdomyosarcoma can occur in children and adults. In children, it is more common in boys and the tumour typically starts in the tissue near the testicles or in the head and neck region.

How do pathologists make the diagnosis of rhabdomyosarcoma?

The first diagnosis of rhabdomyosarcoma 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. Additional tests such as immunohistochemistry and fluorescence in situ hybridization (FISH) may also be performed to confirm the diagnosis.

After a pathologist makes a diagnosis of rhabdomyosarcoma, patients are often treated first with chemotherapy and/or radiation therapy followed by surgery. The tumour is then removed completely as a resection specimen and sent to pathology for examination.

What other tests may be performed to confirm the diagnosis?

Immunohistochemistry

Immunohistochemistry is a special test that allows pathologists to look for specific types of proteins inside cells. Pathologists use the results of this test to determine the cell’s function and where in the body the cell came from. When immunohistochemistry is performed on rhabdomyosarcoma, the tumour cells are typically positive for muscle markers such as desmin, myogenin, and MyoD1.

Molecular tests

Alveolar rhabdomyosarcoma often contains a genetic change called a translocation. This genetic change results in the PAX3 or PAX7 gene combining the FOXOA1, NCOA1, or AFX gene. Pathologists test for these translocations by performing either fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS) on a piece of the tissue from the tumour. If you were diagnosed with the alveolar rhabdomyosarcoma, your report will say which test was performed and which translocation was found in the tumour.

Because the other types of rhabdomyosarcoma (embryonal, pleomorphic, and spindle/sclerosing) do not usually have translocations, no additional molecular tests may have been performed if you were diagnosed with one of these types of tumours.

How do pathologists determine the grade for rhabdomyosarcoma?

Pathologists divide pleomorphic rhabdomyosarcoma and spindle cell/sclerosing rhabdomyosarcoma into three grade 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. Embryonal and alveolar rhabdomyosarcomas are not given a grade.

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, pleomorphic rhabdomyosarcoma and spindle cell/sclerosing rhabdomyosarcoma may be either low or high-grade tumours. High-grade tumours (grades 2 and 3) are associated with a worse prognosis.

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. Tumour cells that look very similar to normal cells are given 1 point while those that look nothing like normal cells are given 3 points.
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 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.
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 it makes up less than 50% of the tumour or 2 points if necrosis makes more than 50% of the tumour.

Why is the size of the tumour important for rhabdomyosarcoma?

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 (see Pathologic stage below).

What does tumour extension mean?

Most rhabdomyosarcomas start inside of a muscle, but the tumour can grow into other organs or tissues outside of the muscle. This is called tumour extension. Your pathologist will examine samples of the surrounding organs and tissues under the microscope to look for tumour cells. Any surrounding organs or tissue that contain tumour cells will be described in your report.

What does perineural invasion mean?

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 tumour cells that have become attached to a nerve can grow along the nerve and into surrounding tissues. This increases the risk that the tumour will re-grow after treatment.

What does lymphovascular invasion mean?

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. The term lymphovascular invasion is used to describe tumour cells that are found inside a blood vessel or lymphatic channel. Lymphovascular invasion is important because once the tumour cells are inside a blood vessel or lymphatic channel they are able to metastasize (spread) to other parts of the body such as lymph nodes or the lungs.

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. Margins will only be 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.

What does treatment effect mean?

If you have been diagnosed with rhabdomyosarcoma on a biopsy, you may be offered chemotherapy and/or radiation therapy before the operation to remove your tumour. If you have received either of these treatments before your surgery, your pathologist will examine all the tissue sent to pathology to see how much of the tumour is still alive (viable).

There are different systems used to describe the treatment effects for rhabdomyosarcoma. Most commonly, your pathologist will describe the percentage of tumour that is dead. Pathologists use the word necrosis to describe dead (non-viable) tumour.

A tumour showing 90% or more therapy response (meaning 90% of the tumour is dead and 10% or less of the tumour is still alive) is considered a good response to therapy and is associated with a better prognosis.

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 lymph node metastasis.

Many cancers can spread to the lymph nodes, but rhabdomyosarcoma 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.

How do pathologists determine the pathologic stage (pTNM) for rhabdomyosarcoma?

​The pathologic stage for rhabdomyosarcoma is based on the TNM staging system, an internationally recognized system originally created by the American Joint Committee on Cancer. The TNM 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.

Additional information including the location of the tumour and the surgery performed is used for children diagnosed with embryonal, alveolar, or spindle cell/sclerosing rhabdomyosarcoma. All of this information is then combined to determine the risk of cancer coming back in the future.

Tumour stage (pT) for rhabdomyosarcoma

The method for determining the tumour stage depends on the area of the body involved. For example, a 5-centimetre tumour that starts in the neck 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.

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.

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.

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.

Retroperitoneum (the space at the very back of the abdominal cavity)

• 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.

Tissue 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.

Nodal stage (pN) for rhabdomyosarcoma

Rhabdomyosarcoma is given a nodal stage of 0 or 1 based on the presence of tumour cells in a lymph node. If no tumour cells are seen in any of the lymph nodes examined, the nodal stage is N0. If tumour cells are seen in any of the lymph nodes examined, the nodal stage becomes N1.

Metastatic stage (pM) for rhabdomyosarcoma

Rhabdomyosarcoma is given a metastatic stage of 0 or 1 based on the presence of tumour cells at a distant site in the body (for example the lungs). The metastatic stage can only be determined 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.