Pleomorphic Rhabdomyosarcoma: Understanding Your Pathology Report

Section Editor: Bibianna Purgina, MD FRCPC
September 17, 2026

Pleomorphic rhabdomyosarcoma is a rare cancer that develops from cells that show features of skeletal muscle. Skeletal muscle is the muscle that moves the arms, legs, and other parts of the body. It is a type of sarcoma, a cancer that begins in the body’s connective tissues. It is one of four main types of rhabdomyosarcoma, along with embryonal, alveolar, and spindle cell/sclerosing rhabdomyosarcoma.

The word “pleomorphic” means the tumor cells vary widely in size and shape. This feature separates pleomorphic rhabdomyosarcoma from the other types under the microscope.

Pleomorphic rhabdomyosarcoma is almost entirely a disease of adults, and it is the most common type of rhabdomyosarcoma in adults. In the largest reported series, the median age at diagnosis was 63 years. It usually starts deep in the thigh muscles or another part of the leg. It can also start in the arms or the trunk, and it rarely starts in the head and neck.

This article explains how doctors diagnose pleomorphic rhabdomyosarcoma and what the size, margins, lymph nodes, and stage in your pathology report mean.

What causes pleomorphic rhabdomyosarcoma?

Pleomorphic rhabdomyosarcoma develops when cells in the soft tissue accumulate many changes in their genes and chromosomes that allow them to grow without control. Unlike the other types of rhabdomyosarcoma in children, it does not have a single defining genetic change such as a gene fusion. Instead, the tumor cells usually have many changes, often including loss of genes that normally act as brakes on cell growth.

For most people, doctors find no cause. A small number of cases develop in an area of the body treated with radiation therapy years earlier. These genetic changes develop in the tumor cells during a person’s lifetime and are not inherited.

What are the symptoms of pleomorphic rhabdomyosarcoma?

The most common symptom of pleomorphic rhabdomyosarcoma is a lump that grows over weeks to months, usually deep in the thigh or another part of a limb. The lump may be painful, especially as it enlarges. Other symptoms depend on the location and can include swelling, difficulty moving the affected limb, or pressure on nearby structures.

How is the diagnosis made?

The diagnosis of pleomorphic rhabdomyosarcoma is made after a pathologist examines a sample of the tumor under the microscope. The sample is usually obtained by a core needle biopsy, which removes small pieces of the tumor with a needle. The diagnosis is often confirmed after the entire tumor is removed.

Under the microscope, pleomorphic rhabdomyosarcoma consists of sheets of large, highly abnormal cells that vary widely in size and shape. Some cells contain more than one nucleus, the part of the cell that holds the genetic material. Many cells have deep pink cytoplasm, which is the body of the cell, and this appearance suggests muscle. Confirming the diagnosis requires showing that the tumor cells are developing skeletal muscle cells, which is done with immunohistochemistry.

Because many other cancers are made of large, abnormal cells, the pathologist also rules out other diagnoses. These include undifferentiated pleomorphic sarcoma, dedifferentiated liposarcoma with muscle-like areas, and a nerve sheath tumor with muscle-like areas. A test for extra copies of the MDM2 gene is often used because MDM2 amplification points to dedifferentiated liposarcoma instead.

Once pleomorphic rhabdomyosarcoma is confirmed, imaging tests look for spread. A chest CT scan is usually done because the lungs are the most common site of spread. The next section describes the immunohistochemistry tests used to confirm the diagnosis.

Immunohistochemistry

Immunohistochemistry uses antibodies to show which proteins tumor cells make. For pleomorphic rhabdomyosarcoma, it is required for diagnosis because the microscopic appearance alone is not enough. Your report may include some of the following:

Desmin. This muscle protein is usually positive in many of the tumor cells.
MyoD1 and myogenin. These proteins are found only in developing skeletal muscle cells. In pleomorphic rhabdomyosarcoma, they are often positive in only some of the tumor cells. Staining must be nuclear to count as a positive result.
MDM2 and CDK4. These proteins are usually negative. A positive result suggests dedifferentiated liposarcoma and is usually confirmed with a test called FISH.
S100 and SOX10. These proteins are negative. A positive result would suggest melanoma or a nerve sheath tumor instead.

Not every case of pleomorphic rhabdomyosarcoma needs every stain. The pathologist chooses tests based on how the tumor looks and where it started.

Histologic grade

Pathologists do not assign an FNCLCC grade to pleomorphic rhabdomyosarcoma. All types of rhabdomyosarcoma are treated as high-grade cancers, so your report will usually not include a grade. A report without a grade is not incomplete.

Tumor size

Tumor size is the greatest dimension of the pleomorphic rhabdomyosarcoma, measured in centimeters (cm). The final measurement comes from the tumor removed at surgery rather than from a biopsy. For most body sites, size is used to determine the tumor stage (pT). Tumors 5 cm or smaller are less likely to spread than larger tumors.

Tumor extension

Tumor extension describes whether pleomorphic rhabdomyosarcoma has grown beyond the muscle where it started into nearby structures such as bone, blood vessels, nerves, or organs. The pathologist examines the tissue removed with the tumor and reports which structures contain tumor cells.

For tumors in the head and neck, the orbit (the space around the eye), and internal organs, growth into nearby structures raises the tumor stage. For tumors of the trunk, arms, legs, and retroperitoneum (the space behind the abdomen), stage depends on size alone. Extension into nearby structures still affects how doctors plan surgery and radiation.

Treatment effect

Some people with pleomorphic rhabdomyosarcoma receive chemotherapy, radiation therapy, or both before surgery. This is called neoadjuvant or pre-operative treatment. When this happens, the pathologist estimates what percentage of the removed tumor is non-viable (dead) and what percentage is still viable (alive).

A tumor that is 90% or more non-viable is often considered a strong response to pre-operative treatment. For soft tissue sarcomas in adults, including pleomorphic rhabdomyosarcoma, experts have not agreed on a single cut-off that predicts outcome. Your doctors interpret the percentage alongside the other findings in your report and your imaging.

Lymphovascular invasion

Lymphovascular invasion means that cells from the pleomorphic rhabdomyosarcoma are seen inside a small blood vessel or lymphatic channel. These vessels give cancer cells a route to other parts of the body. Current reports may list this finding as “lymphatic and/or vascular invasion.”

Present. Tumor cells were seen inside a vessel. This finding is associated with a higher risk of tumor spread.
Not identified. No tumor cells were seen inside vessels in the tissue examined.

Perineural invasion

Perineural invasion means tumor cells are growing around or along a nerve. It is not a standard item in soft tissue sarcoma reports, but a pathologist may mention it when it is seen in pleomorphic rhabdomyosarcoma. When present, it suggests the tumor may extend beyond its visible edge and may raise the risk of the tumor coming back in the same place.

Surgical margins

A margin is the edge of tissue cut by the surgeon to remove a pleomorphic rhabdomyosarcoma. The pathologist examines each margin to see whether tumor cells reach it. Complete removal with negative margins has been linked to longer survival in adults with rhabdomyosarcoma.

Negative margin. No tumor cells are seen at the cut edge. The report usually names the closest margin and gives its distance from the tumor.
Close margin. Tumor cells are near the cut edge but do not reach it. Reports often list every margin that is less than 0.5 cm from the tumor.
Positive margin. Tumor cells are present at the cut edge. This means some tumor may remain in the body and raises the risk of the tumor coming back. Further surgery or radiation therapy may be considered.

Lymph nodes

Lymph nodes are small immune organs that filter fluid from the tissues. Pleomorphic rhabdomyosarcoma spreads mainly through the bloodstream to the lungs rather than to lymph nodes. For this reason, lymph nodes are usually removed only if they look enlarged or suspicious on imaging.

If lymph nodes are examined, the report states how many were examined and how many contain tumor cells. Tumor cells in a lymph node change the nodal stage to pN1 and are associated with a less favorable outcome.

Biomarker and molecular testing

For pleomorphic rhabdomyosarcoma, no biomarker test currently selects a targeted drug. Molecular tests are used mainly to rule out other diagnoses, especially dedifferentiated liposarcoma. Treatment is chosen based on the size and location of the tumor and on whether the cancer has spread.

When the cancer comes back or spreads, the tumor may be tested with a broad next-generation sequencing (NGS) panel. This test looks for changes that could make a person eligible for a clinical trial. A result that finds no targetable change is common and does not change the diagnosis. You can learn more in our Biomarkers and Genetic Testing section.

Pathologic stage (pTNM)

The pathologic stage for pleomorphic rhabdomyosarcoma is assigned using the TNM system from the American Joint Committee on Cancer (AJCC), 8th edition. Because this cancer occurs almost entirely in adults, it is staged in the same way as other soft tissue sarcomas in adults. The stage, clinical group, and risk group systems used for rhabdomyosarcoma in children do not usually apply.

The tumor stage (pT) is based on the tissue removed at surgery, and the nodal stage (pN) describes the lymph nodes. The metastasis stage (M) is usually determined by imaging and is often not included in the pathology report. If you received treatment before surgery, the stage may begin with the letter “y,” as in ypT2. A stage beginning with “r” describes a tumor that has come back after treatment.

Trunk and extremities (chest, back, abdominal wall, arms, and legs):

pT1. The tumor is 5 cm or smaller.
pT2. The tumor is larger than 5 cm but not larger than 10 cm.
pT3. The tumor is larger than 10 cm but not larger than 15 cm.
pT4. The tumor is larger than 15 cm.

Retroperitoneum (the space at the back of the abdomen):

pT1. The tumor is 5 cm or smaller.
pT2. The tumor is larger than 5 cm but not larger than 10 cm.
pT3. The tumor is larger than 10 cm but not larger than 15 cm.
pT4. The tumor is larger than 15 cm.

Head and neck:

pT1. The tumor is 2 cm or smaller.
pT2. The tumor is larger than 2 cm but not larger than 4 cm.
pT3. The tumor is larger than 4 cm.
pT4a. The tumor has grown into the eye socket, the bones of the face, or the base of the skull and its lining. It may instead involve the organs in the center of the neck or the chewing muscles called the pterygoid muscles.
pT4b. The tumor has grown into the brain, surrounds the carotid artery, or has grown into the muscles in front of the spine. A tumor that has spread along a nerve into the brain or spinal cord is also pT4b.

Abdominal and thoracic visceral organs (internal organs such as the stomach, intestines, and lungs):

pT1. The tumor is confined to the organ where it started.
pT2a. The tumor has grown into the organ’s thin outer lining.
pT2b. The tumor has grown beyond the outer lining into the surrounding tissue.
pT3. The tumor has grown into another organ or a nearby structure such as the diaphragm or abdominal wall.
pT4a. Tumor is found in 2 separate sites.
pT4b. Tumor is found in 3 to 5 separate sites.
pT4c. Tumor is found in more than 5 separate sites.

A stage of pT0 means no tumor was found in the tissue removed, which can happen after treatment before surgery. If the tumor cannot be assessed, for example because it was removed in many pieces, the report may say that pT was not assigned.

The nodal stage (pN) describes whether tumor cells were found in the lymph nodes:

pN0. No tumor cells were found in the lymph nodes examined.
pN1. Tumor cells were found in at least one nearby lymph node.

If no lymph nodes were removed, which is common for pleomorphic rhabdomyosarcoma, the report will usually say that pN was not assigned. Older reports may show pNX, but current reporting standards no longer use this term for soft tissue sarcomas.

What is the prognosis?

Pleomorphic rhabdomyosarcoma has a less favorable outlook than the types of rhabdomyosarcoma seen in children. The most important factor is whether the cancer has already spread when it is found. In the largest registry study, people whose cancer had spread at diagnosis had a much higher risk of dying of the disease. Median survival for this group was about 9 months.

Reported survival varies widely between studies, partly because the people included differ in age and in how much treatment they received. In a European series with a median age of 71, median survival was about 13 months for people whose cancer had not spread. In other series, in which most people had surgery, about 1 in 2 people were alive five years after diagnosis. Across all types of rhabdomyosarcoma in adults, five-year survival has been reported at about 27%.

Features associated with the outcome of pleomorphic rhabdomyosarcoma include:

Spread at diagnosis. This is the strongest predictor of a less favorable outcome.
Complete removal of the tumor. Surgery that removes all of the tumor with negative margins is associated with longer survival.
Radiation therapy after surgery. This has been associated with longer survival in adults with rhabdomyosarcoma.
Tumor size. Larger tumors are more likely to spread.
Age. Older adults tend to have a less favorable outcome.

What happens after the diagnosis?

After a team at a sarcoma-experienced center confirms pleomorphic rhabdomyosarcoma, they usually plan care. The team often includes surgeons, radiation oncologists, and medical oncologists. The findings in your report, including the size, margins, and stage, help the team decide which options to consider.

Surgery. Complete removal of the tumor with negative margins is the main treatment when the cancer has not spread.
Radiation therapy. Radiation may be given before or after surgery to lower the risk of the tumor coming back in the same place.
Chemotherapy. Chemotherapy is often recommended, and the best regimen is still debated. Some centers use combinations developed for children with rhabdomyosarcoma, while others use regimens developed for adult soft tissue sarcomas. Pooled studies of adults found that combinations including cyclophosphamide, an anthracycline such as doxorubicin, or ifosfamide were associated with better outcomes.
Clinical trials. Because treatment is not standardized for this rare cancer, your oncologist may discuss clinical trials.

After treatment, follow-up usually includes regular imaging of the chest and of the area where the tumor started. Visits are most frequent in the first few years, when the risk of the cancer coming back or spreading is highest.

Questions to ask your doctor

How was the diagnosis of pleomorphic rhabdomyosarcoma confirmed?
Which other diagnoses were ruled out, and was my tumor tested for MDM2?
How large was the tumor, and did it grow into nearby structures?
Were all the margins negative? How close was the closest margin?
What is my pathologic stage, and has the cancer spread to my lungs or elsewhere?
If I had treatment before surgery, what percentage of the tumor was non-viable?
Will radiation therapy be given before or after my surgery?
Which chemotherapy regimen do you recommend, and why?
Is there a clinical trial I could join?
How often will I need imaging, and for how long?