Rhabdomyosarcoma

by Jason Wasserman MD PhD FRCPC
September 25, 2024

Rhabdomyosarcoma is a type of cancer that develops from skeletal muscle tissue, the muscle responsible for voluntary movements like walking or lifting objects. This cancer most commonly affects children, but it can also be found in adults. Rhabdomyosarcoma can occur almost anywhere in the body, but it most frequently arises in areas such as the head and neck, arms, legs, or the urinary and reproductive organs. It is considered an aggressive cancer, meaning it has the potential to grow and spread quickly if not treated.

What are the symptoms of rhabdomyosarcoma?

The symptoms of rhabdomyosarcoma depend on where the tumour is located. Common symptoms include:

• A lump or swelling that may or may not be painful
• Difficulty using a part of the body (e.g., moving an arm or leg)
• Problems with breathing or swallowing if the tumour is located in the head or neck
• Difficulty urinating or blood in the urine if the tumour is in the urinary system
• Other symptoms may arise if the tumour presses on nearby organs or structures.

What causes rhabdomyosarcoma?

The exact cause of rhabdomyosarcoma is not fully understood. In most cases, no specific risk factors are identified. However, certain genetic conditions, such as Li-Fraumeni syndrome or neurofibromatosis, increase the risk of developing rhabdomyosarcoma. In many cases, rhabdomyosarcoma develops without any known cause.

What genetic changes occur in rhabdomyosarcoma?

In some types of rhabdomyosarcoma, specific genetic changes are known to play a role in the development of the tumour. For example, alveolar rhabdomyosarcoma is often associated with a specific genetic fusion, where two genes (PAX3 or PAX7 and FOXO1) become joined together abnormally. This genetic change drives the growth of cancerous cells. Other types of rhabdomyosarcoma may have different genetic mutations, but not all cases have identifiable genetic abnormalities.

What are the types of rhabdomyosarcoma?

There are several types of rhabdomyosarcoma, each with unique features:

• Embryonal rhabdomyosarcoma: The most common type, usually found in children, often occurs in the head and neck or the urinary and reproductive organs.
• Alveolar rhabdomyosarcoma: This type is more aggressive and is often found in the arms, legs, chest, or abdomen. It is associated with specific genetic changes (PAX3-FOXO1 or PAX7-FOXO1).
• Pleomorphic rhabdomyosarcoma: This rare type typically affects adults and is characterized by various cell shapes and sizes.
• Spindle cell/sclerosing rhabdomyosarcoma: These are less common subtypes with different cellular appearances under the microscope.

How is this diagnosis made?

The diagnosis of rhabdomyosarcoma is made through a combination of clinical evaluation, imaging studies (such as MRI or CT scans), and a tumour biopsy. A biopsy involves removing a small tissue sample from the tumour, which a pathologist examines under a microscope. The pathologist looks for specific features that help distinguish rhabdomyosarcoma from other types of cancer.

What types of tests are used to confirm the diagnosis?

To confirm the diagnosis of rhabdomyosarcoma and determine its specific type, pathologists use several tests:

• Immunohistochemistry (IHC): This test looks for proteins typically found in rhabdomyosarcoma cells. Desmin, MYOD1, and myogenin are examples of proteins commonly present in these tumours. Immunohistochemistry helps confirm that the tumour is of muscle origin and can provide clues about the specific type of rhabdomyosarcoma.
• Molecular tests: These tests look for specific genetic changes in the tumour cells. For example, next-generation sequencing (NGS) can identify genetic fusions or mutations, such as the PAX3-FOXO1 fusion in alveolar rhabdomyosarcoma. These tests are important for accurately diagnosing the type of rhabdomyosarcoma and may help guide treatment options.