Undifferentiated Pleomorphic Sarcoma: Understanding Your Pathology Report

Section Editor: Bibianna Purgina, MD FRCPC
September 16, 2026

Undifferentiated pleomorphic sarcoma (UPS) is a cancer that develops in the body’s soft tissues, most often deep in the muscles of the arms or legs. It is a type of sarcoma, a cancer that begins in the body’s connective tissues. UPS is one of the more common types of soft tissue sarcoma in older adults.

The name describes how the tumor cells look under the microscope. “Undifferentiated” means the cells do not look like any particular normal tissue, such as muscle, fat, or nerve. “Pleomorphic” means the cells vary greatly in size and shape. Older reports may call this tumor malignant fibrous histiocytoma, a term no longer used.

Undifferentiated pleomorphic sarcoma most often affects adults over 50. It usually starts in the thigh or other parts of the arms and legs. It can also start in the trunk, the head and neck, or the retroperitoneum (the space at the back of the abdomen).

This article explains how undifferentiated pleomorphic sarcoma is diagnosed and what the grade, size, margins, and stage in your UPS pathology report mean.

What causes undifferentiated pleomorphic sarcoma?

Undifferentiated pleomorphic sarcoma develops when connective tissue cells accumulate many changes in their genes and chromosomes that allow them to grow without control. Unlike some sarcomas, UPS does not have a single defining genetic change such as a gene fusion. The tumor cells usually have many different changes, and these vary from one person to another.

For most people, doctors find no cause. Some cases of UPS develop in an area of the body treated with radiation therapy years earlier. UPS is one of the most common sarcomas to develop in this way.

What are the symptoms of undifferentiated pleomorphic sarcoma?

The most common symptom of undifferentiated pleomorphic sarcoma is a lump that grows over weeks to months. The lump is often painless at first, but it can become painful as it grows or presses on nearby nerves and muscles. Tumors in the retroperitoneum may not cause symptoms until they are large.

How is the diagnosis made?

The diagnosis of undifferentiated pleomorphic sarcoma 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.

Under the microscope, UPS consists of large, highly abnormal cells that vary greatly in size and shape. Many of the cells are dividing, and some areas may contain dead tumor tissue called necrosis. The cells do not show features of any specific normal tissue type.

UPS is a diagnosis of exclusion. This means the pathologist makes the diagnosis only after ruling out other cancers that can look the same under the microscope. These include other sarcomas, melanoma, and carcinomas that have lost their usual features. For this reason, the biopsy report may describe a “high-grade pleomorphic sarcoma” and list possible diagnoses, with a final diagnosis made after surgery.

Molecular tests may also help rule out other diagnoses. The most important test is for extra copies of the MDM2 gene, often done by FISH. MDM2 amplification points to a type of fat cancer called dedifferentiated liposarcoma rather than UPS. This test is especially important for retroperitoneal tumors.

Once undifferentiated pleomorphic sarcoma 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 rule out other diagnoses.

Immunohistochemistry

Immunohistochemistry uses antibodies to show which proteins tumor cells make. For undifferentiated pleomorphic sarcoma, the results are expected to be mostly negative. Each negative stain helps rule out a different cancer that can look similar. Your report may include some of the following:

SMA. SMA may be positive in some of the tumor cells. This result is common in UPS and does not by itself mean the tumor is a muscle tumor.
Desmin and h-caldesmon. These muscle proteins are negative in UPS. A strongly positive result would suggest leiomyosarcoma, a smooth muscle cancer.
S100 and SOX10. These proteins are negative in UPS. A positive result would suggest melanoma, which can look very similar.
Keratins and p40. These proteins are negative in UPS. A positive result would suggest a carcinoma, a cancer that starts from epithelial cells.
ERG and CD31. These blood vessel proteins are negative in UPS. A positive result would suggest angiosarcoma.
MDM2 and CDK4. These proteins are usually negative in UPS. A positive result would suggest dedifferentiated liposarcoma and is usually confirmed with FISH.
p53 and p16. These proteins are often abnormal in UPS. The results support a cancer but do not point to a specific type.

Not every case of undifferentiated pleomorphic sarcoma needs every stain. The pathologist chooses tests based on how the tumor looks, where it started, and your medical history.

Histologic grade

Histologic grade describes how abnormal the cells of an undifferentiated pleomorphic sarcoma look and how quickly they appear to be growing. Pathologists grade UPS using the FNCLCC system, which adds together scores for three features:

Differentiation. This describes how closely the tumor cells resemble normal tissue. UPS always receives the highest score of 3, because its cells do not resemble any normal tissue.
Mitotic count. This is the number of dividing cells in 10 high-power fields, which are areas seen through the microscope at high magnification. Fewer than 10 dividing cells scores 1, 10 to 19 scores 2, and 20 or more scores 3.
Necrosis. This is the amount of dead tumor tissue. No necrosis scores 0, less than 50% scores 1, and 50% or more scores 2.

The total score gives the final grade:

Grade 1. Total score of 2 or 3.
Grade 2. Total score of 4 or 5.
Grade 3. Total score of 6 to 8.

Because undifferentiated pleomorphic sarcoma always starts with a differentiation score of 3, it is always grade 2 or grade 3. Both grades are considered high grade. Grade 3 tumors are more likely to come back after treatment and to spread to other parts of the body.

Tumor size

Tumor size is the greatest dimension of the undifferentiated pleomorphic sarcoma, 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).

UPS tumors 5 cm or smaller are associated with a more favorable outcome than larger tumors. Tumors larger than 15 cm are associated with the least favorable outcome.

Tumor extension

Tumor extension describes whether undifferentiated pleomorphic sarcoma has grown beyond the tissue 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 stage depends on size alone. Extension into nearby structures still affects how surgeons and radiation oncologists plan treatment.

Treatment effect

Many people with undifferentiated pleomorphic sarcoma receive radiation therapy before surgery, and some also receive chemotherapy or immunotherapy. 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, including UPS, experts have not agreed on a single cut-off that predicts outcome. Your doctors interpret the percentage together with the other findings in your report.

Treatment changes how tumor cells look under the microscope. For this reason, the grade is usually taken from the biopsy done before treatment. If no treatment was given before surgery, the report may say there was no known presurgical therapy.

Lymphovascular invasion

Lymphovascular invasion means that cells from the undifferentiated pleomorphic sarcoma 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 undifferentiated pleomorphic sarcoma. 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 an undifferentiated pleomorphic sarcoma. The pathologist examines each margin to see whether tumor cells reach it. For soft tissue sarcomas, margin status is the most important predictor of whether the tumor will come back in the same place.

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. Spread of undifferentiated pleomorphic sarcoma to lymph nodes is uncommon. 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 testing

Biomarker testing looks for tumor features that guide treatment, predict outcome, or point to an inherited condition. For undifferentiated pleomorphic sarcoma, no single biomarker test currently selects a targeted drug. Immunotherapy has shown benefit for some people with UPS, but it is not chosen based on a PD-L1 result or another biomarker test.

When UPS returns 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. Rarely, it finds a feature that qualifies for a drug approved across many cancer types. A result that finds no targetable change is common for UPS and does not change the diagnosis.

You can learn more about tumor testing in our Biomarkers and Genetic Testing section.

Pathologic stage (pTNM)

The pathologic stage for undifferentiated pleomorphic sarcoma is assigned using the TNM system from the American Joint Committee on Cancer (AJCC), 8th edition. 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.

The tumor stage (pT) for UPS depends on where the tumor started in the body.

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.

Orbit (the space around the eye):

pT1. The tumor is 2 cm or smaller.
pT2. The tumor is larger than 2 cm and has not grown into the bony walls of the orbit or the eye.
pT3. The tumor, of any size, has grown into the bony walls of the orbit.
pT4. The tumor has grown into the eye or nearby structures such as the eyelid, sinuses, or brain.

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) for UPS 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 UPS, 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?

The outlook for a person with undifferentiated pleomorphic sarcoma depends mainly on whether the cancer has spread and whether it can be completely removed. The size and grade of the tumor also matter. Across published studies, about 50% to 70% of people are alive five years after diagnosis. Because many people with UPS are older adults, these figures include deaths from other causes.

About 3 in 10 people with UPS of the arms or legs develop spread to other organs, most often the lungs. When spread happens, it usually appears within the first two years after treatment. The tumor comes back in the same place in roughly 1 in 4 people, and people whose tumor comes back locally have a higher risk of later spread.

Features associated with the outcome of undifferentiated pleomorphic sarcoma include:

Spread at diagnosis. Cancer that has already spread at diagnosis is the strongest predictor of a less favorable outcome.
Tumor size. Larger tumors, especially those larger than 15 cm, are associated with a less favorable outcome.
Histologic grade. Grade 3 tumors are associated with a less favorable outcome than grade 2 tumors.
Tumor location. Tumors of the arms, legs, and trunk tend to have a more favorable outcome than tumors of the head and neck or retroperitoneum.
Previous radiation. UPS that develops after radiation therapy has been associated with a higher risk of coming back and a less favorable outcome.
Surgical margins. A positive margin raises the risk of the tumor coming back in the same place.

What happens after the diagnosis?

After a team at a sarcoma-experienced center confirms undifferentiated pleomorphic sarcoma, they usually plan care. The team often includes surgeons, radiation oncologists, and medical oncologists. The findings in your report, including the grade, 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 for UPS that has not spread.
Radiation therapy. Radiation is often given before surgery, or sometimes after, to lower the risk of the tumor coming back in the same place.
Immunotherapy. In a randomized trial called SU2C-SARC032, adding pembrolizumab to radiation and surgery improved outcomes for people with large, high-grade UPS of the arms or legs. At two years, 67% of people who received pembrolizumab were disease-free, compared with 52% of those who did not. Pembrolizumab may also be used when UPS has spread.
Chemotherapy. Chemotherapy may be considered for some large, high-grade tumors or when the cancer has spread.
Clinical trials. Your oncologist may discuss clinical trials, especially if the tumor has come back or spread.

Access to these treatments differs between countries, and your care team can explain what applies where you live. 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 tumor coming back or spreading is highest.

Questions to ask your doctor

Which other diagnoses were ruled out before my tumor was called undifferentiated pleomorphic sarcoma?
Was my tumor tested for MDM2 amplification?
Is my tumor grade 2 or grade 3?
How large was the tumor, and did it grow into nearby structures?
Were all the margins negative? How close was the closest margin?
If I had treatment before surgery, what percentage of the tumor was non-viable?
What is my pathologic stage, and has the cancer spread to my lungs or elsewhere?
Will radiation therapy be given before or after my surgery?
Is immunotherapy with pembrolizumab an option for me?
Is there a clinical trial I could join?
How often will I need imaging, and for how long?