Rhabdomyosarcoma: Understanding Your Pathology Report

Section Editor: Bibianna Purgina MD FRCPC
September 3, 2026

Rhabdomyosarcoma is a type of cancer that develops from cells that would normally become skeletal muscle, the muscle that moves the arms, legs, and other parts of the body. It is the most common soft tissue sarcoma in children, although it can also occur in adults. It can start almost anywhere, including places where there is no skeletal muscle at all, such as the bladder, the prostate, and the bile ducts. The cells it grows from are present throughout the developing body.

Most people with rhabdomyosarcoma are children, so this article is written for adults with the diagnosis and for parents reading a report about their child. It explains what appears on a rhabdomyosarcoma pathology report, what each finding describes, and how those findings are used to plan treatment.

What causes rhabdomyosarcoma?

Rhabdomyosarcoma develops when cells that would normally form skeletal muscle acquire genetic changes that keep them dividing instead of maturing. In most people, no cause is ever identified. These changes usually happen by chance during normal cell division during growth and development, and they are not linked to diet, injury, activity, or anything in the environment.

A small proportion of cases occur in people with an inherited condition that raises the risk of cancer. Estimates vary, but roughly 1 in 10 children with rhabdomyosarcoma carry such a condition. The most common are Li-Fraumeni syndrome, neurofibromatosis type 1, DICER1 syndrome, Costello syndrome, Noonan syndrome, and Beckwith-Wiedemann syndrome. Features that prompt an assessment include a young age at diagnosis, more than one cancer in the same person, or a pattern of cancer in close relatives.

What are the symptoms of rhabdomyosarcoma?

The symptoms of rhabdomyosarcoma depend almost entirely on where the tumor starts. Many tumors first appear as a lump that does not hurt, which is one reason the diagnosis is sometimes made later than expected.

Around the eye. A bulging eye, a drooping eyelid, swelling, or double vision.
Nose, sinuses, or middle ear. Persistent congestion, discharge, nosebleeds, or earache that does not clear.
Bladder or prostate. Difficulty passing urine, a weak stream, or blood in the urine.
Vagina. Bleeding or tissue with a grape-like appearance at the opening.
Testicle or scrotum. Painless swelling on one side.
Arm, leg, or trunk. A firm lump under the skin or deep within the muscle, sometimes growing quickly.

Tumors in any of these locations can also press on nearby structures and cause pain, weakness, or difficulty moving the affected part of the body.

What are the types of rhabdomyosarcoma?

Pathologists divide rhabdomyosarcoma into four main types based on how the tumor cells look under the microscope and what genetic changes they carry. The type is usually stated in the diagnosis line of the pathology report, and it influences how the tumor is expected to behave.

Embryonal rhabdomyosarcoma. The most common type, making up roughly 60 to 70 percent of cases. It is seen mainly in children under 10 and starts most often in the head and neck or the urinary and reproductive organs. A pattern called botryoid, meaning grape-like, occurs when the tumor grows into a hollow space such as the bladder or vagina. Some reports also describe anaplasia, meaning unusually large and irregular tumor cells.
Alveolar rhabdomyosarcoma. Roughly 20 to 25 percent of cases. It is more common in older children and adolescents and starts most often in an arm, leg, or the trunk. Most, though not all, carry a fusion gene involving FOXO1.
Spindle cell and sclerosing rhabdomyosarcoma. An uncommon group made of long, thin cells, often set in dense tissue. It covers several distinct situations, including a form in infants that behaves favorably and a form carrying a MYOD1 mutation that does not.
Pleomorphic rhabdomyosarcoma. Rare, seen almost only in adults, and made of cells that vary widely in size and shape. It usually starts deep within the muscles of an arm or leg.

Rhabdomyosarcoma is treated as a high-grade cancer, whatever the type, so most reports do not include a grade. A report without a grade is not incomplete.

How is the diagnosis made?

A pathologist diagnoses rhabdomyosarcoma by examining tumor tissue under a microscope. Imaging can show a mass, but it cannot make the diagnosis on its own. The tissue is obtained by biopsy, either with a needle passed into the mass or by removing a small piece through a small incision. In some locations, the surgeon removes the entire tumor at the first operation, and the pathologist then examines the whole specimen.

Under the microscope, rhabdomyosarcoma is made of small cells with round or oval nuclei and very little cytoplasm around them. Scattered among these are larger cells with bright pink cytoplasm called rhabdomyoblasts, which are the cells attempting to become muscle. Some show fine internal lines known as cross-striations. Because several other childhood tumors look similar, reports sometimes use the phrase small round blue cell tumor, which is a description rather than a diagnosis.

Immunohistochemistry confirms that the tumor is made of developing skeletal muscle. This test uses antibodies to detect specific proteins inside the tumor cells, and each result is reported as positive or negative. Rhabdomyosarcoma is typically positive for desmin and positive for myogenin and MyoD1, two proteins found only in cells developing into skeletal muscle. Strong and widespread myogenin staining points toward the alveolar type.

Once the diagnosis is confirmed, imaging determines how far the tumor has spread. This usually includes MRI or CT of the original site, a chest CT, and a PET scan. A bone marrow biopsy is part of standard staging, and tumors near the lining of the brain and spinal cord also require examination of the spinal fluid.

Molecular testing and FOXO1 fusion status

Molecular testing looks for changes in the genes inside rhabdomyosarcoma cells rather than their appearance. The most important of these is whether the tumor carries a fusion gene involving FOXO1. This is now the single most informative test on the report after the extent of disease, and every rhabdomyosarcoma is tested for it.

A fusion gene forms when two separate genes join together and produce a protein that drives the tumor. In rhabdomyosarcoma, the FOXO1 gene joins either PAX3 or PAX7. Laboratories detect this using fluorescence in situ hybridization or sequencing, often as part of a larger panel described as next-generation sequencing.

Fusion-positive. The tumor carries PAX3::FOXO1 or PAX7::FOXO1. These tumors behave less favorably and are treated more intensively.
Fusion-negative. No FOXO1 fusion is present. These tumors behave more favorably, including tumors that look alveolar under the microscope but carry no fusion.
MYOD1 mutation. Reported in some spindle cell and sclerosing tumors. It identifies a group that behaves less favorably despite a reassuring appearance.

Fusion status matters because it has replaced the microscopic type in deciding how intensively localized rhabdomyosarcoma is treated. A tumor called alveolar under the microscope but found to be fusion-negative behaves much like an embryonal tumor. If the report gives a microscopic type but no fusion result, the test may still be pending, and it is reasonable to ask when it is expected.

Surgical margins

Margins are the edges of tissue the surgeon cuts to remove a rhabdomyosarcoma. The pathologist inks these edges and examines them under the microscope. A negative margin means no tumor cells were seen at the inked edge. A positive margin means tumor cells reach the edge, and some tumor may have been left behind.

Margins are only reported when the tumor was removed rather than sampled. For many rhabdomyosarcomas, complete removal at the first operation is not possible without damaging an eye, a limb, or an organ that is worth preserving. In those situations, a biopsy alone is the correct first step, and chemotherapy and radiation are used to control the tumor. A report that describes a biopsy and gives no margins does not mean you missed an opportunity.

Lymph nodes

Lymph nodes are small immune organs found throughout the body, and rhabdomyosarcoma can spread to the nodes near where it started. When doctors remove nodes, the pathology report lists how many were examined and how many contained tumor cells.

Node sampling matters most for tumors of the arms and legs, and for tumors beside the testicle in boys aged 10 and older. In these situations, doctors check nodes even when imaging looks normal. A sentinel lymph node biopsy is sometimes used, which removes only the first node or nodes the tumor would reach. Tumor found in a lymph node raises both the stage and the risk group.

Stage, clinical group, and risk group

Three separate systems describe Rhabdomyosarcoma, and all three may appear in the record. This is different from most adult cancers, which use a single staging system, and it is a common source of confusion for families.

Stage, from 1 to 4. It is based on where the tumor started, its size, whether lymph nodes are involved, and whether it has spread to distant sites. Sites are divided into favorable and unfavorable. Favorable sites include the area around the eye, the head and neck away from the lining of the brain, and the biliary tract. They also include the urinary and reproductive organs, except the bladder and prostate.
Clinical group, from I to IV. Based on how much tumor was removed at the first operation. Group I means the tumor was completely removed. Group II means small amounts remained or a lymph node was involved. Group III means visible tumor remained, which includes tumors that were only biopsied. Group IV means the tumor had already spread to distant sites.
Risk group: low, intermediate, or high. This combines stage, clinical group, FOXO1 fusion status, and age and site. This number determines how intensive treatment will be.

The pathology report provides several of these ingredients but usually does not state the risk group itself. The treating team assigns that once the imaging, surgery, and molecular results are available.

What is the prognosis?

The outlook for rhabdomyosarcoma depends far more on disease extent, FOXO1 fusion status, and site than on any single number. Overall, about 70 percent of children diagnosed with rhabdomyosarcoma are alive five years later, and that figure covers a very wide range of individual situations.

Large cooperative group studies give a clearer picture. Among children whose tumor had not spread at diagnosis, roughly 84 percent were alive at five years, compared with roughly 42 percent of those whose tumor had already spread. Fusion status further divides each group. For localized tumors, five-year survival was roughly 88 percent when no FOXO1 fusion was present and roughly 65 percent when one was. For tumors that had already spread, the corresponding figures were roughly 58 percent and 19 percent.

Features associated with a less favorable outcome include the following.

Spread to distant sites at diagnosis. The strongest single factor, and the reason staging investigations are done before treatment starts.
A FOXO1 fusion. The most important factor after disease extent.
An unfavorable primary site. Including the bladder and prostate, the arms and legs, the trunk, and sites next to the lining of the brain.
Larger tumor size. Tumors greater than 5 centimeters do less well than smaller ones.
Lymph node involvement. Tumor found in nearby nodes.
Age. Children under 1 and those over 10 do less well than those in between, and adults do less well than children.
Tumor remaining after surgery. A higher clinical group, particularly when radiation cannot be given at a full dose.

These figures come from groups of patients treated over many years and cannot predict what will happen to one person. Children with localized rhabdomyosarcoma at a favorable site, with no fusion gene, are cured most of the time. The treating team can give figures that match the specific stage, group, fusion status, and site.

What happens after the diagnosis?

After a rhabdomyosarcoma diagnosis, a team usually plans care, including an oncologist, surgeon, radiation oncologist, and pathologist. The findings on the pathology report, in particular the type, the FOXO1 fusion status, and the margins, are combined with imaging and surgical findings to assign the risk group. The risk group then determines the treatment plan.

Chemotherapy is given to everyone with rhabdomyosarcoma, including those whose tumor was completely removed, because tumor cells can be present elsewhere in the body without being visible on scans. Local control of the original tumor is achieved with surgery, radiation, or both, and the choice depends on the site and on how much tumor remains. Most children are treated on a protocol developed by a cooperative research group, which is standard care in pediatric oncology rather than an experimental option.

A referral for genetic assessment may be offered, particularly for a young child or when family history suggests an inherited condition. After treatment ends, long-term follow-up continues for many years. It watches for the cancer returning and monitors the late effects of chemotherapy and radiation on growth, fertility, and organ function.

Questions to ask your doctor

What type of rhabdomyosarcoma is described on the report?
Has the tumor been tested for a FOXO1 fusion gene, and what was the result?
If the fusion test is still pending, when is the result expected?
Is the primary site considered favorable or unfavorable?
What stage and clinical group have been assigned, and what do they mean?
Which risk group does this fall into, and what determined it?
Was the whole tumor removed, and were the margins negative?
If only a biopsy was done, is further surgery planned, or will radiation be used instead?
Were any lymph nodes examined, and did any contain tumor?
Have the staging investigations, including the bone marrow biopsy, been completed?
Has a pathologist who specializes in children’s tumors reviewed the slides?
Will treatment be given on a cooperative group protocol or clinical trial?
Should genetic testing for an inherited condition be considered?
What are the expected outcomes for this specific risk group, and what long-term follow-up will be needed?