Pleomorphic rhabdomyosarcoma

By Jason Wasserman MD PhD FRCPC
September 25, 2024

Pleomorphic rhabdomyosarcoma is a rare type of cancer that starts in the skeletal muscle tissue, the muscle responsible for voluntary movements like walking or lifting objects. This cancer is called “pleomorphic” because the tumour cells can take on many different shapes and sizes. It is most commonly found in adults, especially in the arms, legs, and sometimes the abdomen or chest. Pleomorphic rhabdomyosarcoma is an aggressive cancer, meaning it can grow quickly and spread to other parts of the body if not treated.

What are the symptoms of pleomorphic rhabdomyosarcoma?

The symptoms of pleomorphic rhabdomyosarcoma depend on where the tumour is located, but common symptoms include:

• A rapidly growing lump or mass, often in the arms or legs
• Pain or tenderness in the area of the tumour
• Swelling in the affected area
• Difficulty moving the part of the body where the tumour is located
• If the tumour grows large enough, it may press on nearby organs or structures, causing additional symptoms, such as difficulty breathing if the tumour is in the chest.

What causes pleomorphic rhabdomyosarcoma?

The exact cause of pleomorphic rhabdomyosarcoma is not well understood. In most cases, there is no apparent risk factor or cause. However, certain genetic conditions and previous exposure to radiation therapy (for example, treatment for another cancer) may increase the risk of developing this type of cancer. In many cases, pleomorphic rhabdomyosarcoma occurs without any known cause.

How is this diagnosis made?

The first diagnosis of pleomorphic rhabdomyosarcoma is usually made after a small tumour sample is removed in a biopsy procedure. The biopsy tissue is then sent to a pathologist, who examines it under a microscope. After a pathologist makes a diagnosis of pleomorphic 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 are the microscopic features of pleomorphic rhabdomyosarcoma?

Under a microscope, pleomorphic rhabdomyosarcoma is composed of sheets of large, abnormal cells. These cells often appear atypical, with many of them being multinucleated (having more than one nucleus). The shape of the cells can vary widely, ranging from polygonal (many-sided) to spindled (long and thin) or rhabdoid (resembling immature muscle cells). The cytoplasm, or the material inside the cell, typically has an eosinophilic (pinkish) colour, which is a common feature of muscle cells. These characteristics help pathologists identify pleomorphic rhabdomyosarcoma and differentiate it from other types of cancer.

Immunohistochemistry

Immunohistochemistry (IHC) is a special test that pathologists use to help confirm the diagnosis of pleomorphic rhabdomyosarcoma. This test uses specific antibodies to detect proteins in the tumour cells. In pleomorphic rhabdomyosarcoma, the following results are typically seen:

• Strong desmin expression: Desmin is a protein found in muscle cells, and tumours of this type usually show a strong positive result for this protein.
• MYOD1 and myogenin: MYOD1 and myogenin are two other proteins associated with muscle development. Tumours often show some limited expression of these proteins, helping to confirm that the tumour started in muscle tissue.

Grade

At present, pathologists do not provide a grade for pleomorphic rhabdomyosarcoma.

Tumour size

Tumour size is important because tumours less than 5 cm are less likely to spread to other body parts and are associated with a better prognosis. Tumour size is also used to determine the pathologic tumour stage (pT).

Tumour extension

Most pleomorphic rhabdomyosarcomas start inside a muscle, but the tumour can grow into other organs or tissues outside 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. Tumour extension into surrounding organs or tissues increases the pathologic tumour stage (pT).

Perineural invasion

Perineural invasion means that tumour cells were seen attached to a nerve. Nerves are found all over the body and are responsible for sending information (such as temperature, pressure, and pain) between the body and the brain. Perineural invasion is important because tumour cells that have become attached to a nerve can spread into surrounding tissues by growing along the nerve. This increases the risk that the tumour will regrow after treatment.

Lymphovascular invasion

Lymphovascular invasion means that tumour 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. Lymphovascular invasion is important because it increases the risk that the tumour will metastasize or spread to other body parts, such as lymph nodes or the lungs.

Margins

In pathology, a margin is the edge of tissue removed during tumour surgery. The margin status in a pathology report is important as it indicates whether the entire tumour was removed or if some was left behind. This information helps determine the need for further treatment.

Pathologists typically assess margins following a surgical procedure, like an excision or resection, that removes the entire tumour. Margins aren’t usually evaluated after a biopsy, which removes only part of the tumour. The number of margins reported and their size—how much normal tissue is between the tumour and the cut edge—vary based on the tissue type and tumour location.

Pathologists examine margins to check if tumour cells are present at the tissue’s cut edge. A positive margin, where tumour cells are found, suggests that some cancer may remain in the body. In contrast, a negative margin, with no tumour cells at the edge, suggests the tumour was fully removed. Some reports also measure the distance between the nearest tumour cells and the margin, even if all margins are negative.

Treatment effect

If you have been diagnosed with pleomorphic rhabdomyosarcoma on a biopsy, you may be offered chemotherapy and/or radiation therapy before the operation to remove the 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).

Different systems are used to describe the effects of treatment for pleomorphic rhabdomyosarcoma. Most commonly, your pathologist will describe the percentage of dead tumour. Pathologists use the word necrosis to describe dead (non-viable) tumours. A tumour showing 90% or more therapy response (meaning 90% of the tumour is dead and 10% or less alive) is considered an excellent response to therapy and is associated with a better prognosis.

Lymph nodes

Lymph nodes are small immune organs found throughout the body. Cancer cells can spread through small lymphatic vessels from a tumour to lymph nodes. For this reason, lymph nodes are commonly removed and examined under a microscope to look for cancer cells. The movement of cancer cells from the tumour to another part of the body, such as a lymph node, is called a metastasis.

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.

If any lymph nodes were removed from your body, they will be examined under the microscope by a pathologist, and the results of this examination will be described in your report. The examination of lymph nodes is important for two reasons. First, this information determines 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.

Some helpful definitions:

• Positive: Positive means that cancer cells were found in the lymph node being examined.
• Negative: Negative means that no cancer cells were found in the lymph node being examined.
• Deposit: The term deposit describes a group of cancer cells inside a lymph node. Some reports include the size of the largest deposit. A similar term is “focus”.
• Extranodal extension: Extranodal extension means that the tumour cells have broken through the capsule on the outside of the lymph node and have spread into the surrounding tissue.

Pathologic stage (pTNM)

​Tumours in adults are given a pathologic stage based on the TNM staging system, an internationally recognized system 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 a more advanced disease and a worse prognosis. Tumours that start in the head and neck are not staged using this system.

Tumours in children are given a pathologic stage based on a modified TNM staging system (the Intergroup Rhabdomyosarcoma Study Group grouping system). This system uses information about the location of the tumour and the type of surgery performed to determine the final pathologic stage.  All of this information is then combined to determine the risk of cancer coming back in the future.

Tumour stage (pT) for pleomorphic rhabdomyosarcoma in adults

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 chest 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.

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 surrounding the organ from which it 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.

Nodal stage (pN) for pleomorphic rhabdomyosarcoma in adults

Pleomorphic 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.

About this article

Doctors wrote this article to help you read and understand your pathology report. Contact us with any questions about this article or your pathology report. Read this article for a more general introduction to the parts of a typical pathology report.

Other helpful resources

Atlas of Pathology