by Jason Wasserman MD PhD FRCPC
July 22, 2024

Background:

Alveolar rhabdomyosarcoma is a type of cancer made up of immature muscle cells. Most alveolar rhabdomyosarcomas contain a genetic change involving the FOXO1 gene. Most tumours start in the arms or legs, but other common sites include the head and neck, spine, and perineum. This aggressive type of cancer frequently spreads to lymph nodes and other parts of the body.

What causes alveolar rhabdomyosarcoma?

Most alveolar rhabdomyosarcomas are caused by the fusion (combination) of the gene FOXO1 with one of the genes PAX3 or PAX7. The new fusion gene leads to the production of proteins that allow the tumour cells to grow and divide. Now, doctors do not know what causes the FOXO1-PAX3/PAX7 fusion gene to form.

What are the symptoms of alveolar rhabdomyosarcoma?

Most people do not notice any symptoms until the tumour becomes large enough to pressure surrounding organs and tissues. At that point, the symptoms depend on the location of the tumour. Tumours in the arms or legs may result in swelling and pain. Tumours in the head and neck may cause headaches, facial pain, nasal obstruction, nose bleeds, decreased sense of smell, or vision changes. Tumours near the spine may cause neurological symptoms such as weakness or pain in the legs, while tumours in the perineum may result in difficulty urinating or constipation.

How is this diagnosis made?

The first diagnosis of alveolar 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 alveolar 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.

Microscopic features of this tumour

When examined under the microscope, the tumour comprises primitive appearing small round blue cells. The tumour cells are often arranged in groups called nests, and the cells in the centre of the nest may appear separated. Pathologists sometimes describe this pattern as alveolar and the cells as discohesive. Mitotic figures (tumour cells that are dividing to create new tumour cells) are usually frequent.

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 alveolar 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 FOXO1 gene combining with either the PAX3 or PAX7 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 alveolar rhabdomyosarcoma, your report will say which test was performed and which translocation was found in the tumour.

Grade

At present, pathologists do not provide a grade for alveolar 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 alveolar 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. Tumour e 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 alveolar 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).

There are different systems used to describe the treatment effects for alveolar 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 of the tumour is still alive) is considered a good 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 from a tumour to lymph nodes through small lymphatic vessels. 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 alveolar 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 alveolar rhabdomyosarcoma in adults

Alveolar 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