Pleomorphic liposarcoma is a rare cancer that develops from fat cells. It is a type of sarcoma, a cancer that begins in the body’s connective tissues. It is the least common type of liposarcoma, making up roughly 5% to 10% of these tumors.
The word “pleomorphic” means the tumor cells vary widely in size and shape. Unlike well differentiated liposarcoma, the cells in this tumor no longer look like normal fat. The only clue that the tumor came from fat may be scattered cells called lipoblasts, which are immature fat cells with bubbles of fat inside them.
Pleomorphic liposarcoma usually affects adults over 50, with a median age at diagnosis of about 63. It most often starts deep in the thigh or elsewhere in the arms and legs. It can also start in the trunk wall, inside the abdomen, or in the retroperitoneum, which is the space at the back of the abdomen.
This article explains how pleomorphic liposarcoma is diagnosed and what the grade, size, margins, and stage in your pathology report mean.
Pleomorphic liposarcoma develops when fat cells accumulate changes in their genes and chromosomes that allow them to grow out of control. The changes differ from one tumor to another, and no single change defines it.
Pleomorphic liposarcoma does not have extra copies of the MDM2 gene. That change, called MDM2 amplification, defines well differentiated liposarcoma and dedifferentiated liposarcoma. Testing for it is one of the main ways doctors tell these tumors apart.
For most people, no cause is found. Pleomorphic liposarcoma is not inherited and cannot be passed on to children.
The most common symptom of pleomorphic liposarcoma is a lump that grows over weeks to months. The lump may be painful, particularly as it presses on nearby nerves or muscles. Tumors in a limb can limit movement, while tumors deep in the abdomen may not cause symptoms until they are large.
The diagnosis of pleomorphic liposarcoma 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 liposarcoma consists of large, highly abnormal cells that vary widely in size and shape. Scattered among them are pleomorphic lipoblasts, the abnormal fat cells that give this tumor its name. Many cells are dividing, and areas of dead tumor tissue, called necrosis, are common.
Parts of the tumor may look like other high-grade sarcomas. Some tumors contain areas resembling myxofibrosarcoma, and others contain round, epithelial-like cells. Finding lipoblasts is what separates pleomorphic liposarcoma from undifferentiated pleomorphic sarcoma.
A test called FISH is usually performed to look for extra copies of the MDM2 gene. In pleomorphic liposarcoma, no extra copies are found. This result helps rule out well differentiated and dedifferentiated liposarcoma, which are treated differently.
Once pleomorphic liposarcoma is confirmed, imaging tests look for spread. A CT scan of the chest is usually done, because the lungs and the lining around them are the most common sites of spread.
Immunohistochemistry is a test that uses antibodies to show which proteins tumor cells make. No single stain confirms pleomorphic liposarcoma. The results are used mainly to rule out other cancers that look similar. Your report may include some of the following:
Not every case of pleomorphic liposarcoma needs every stain. The pathologist chooses tests based on how the tumor looks and where it started.
Histologic grade describes how abnormal the cells of a pleomorphic liposarcoma look and how quickly they appear to be growing. Pathologists grade it using the FNCLCC system, which adds together scores for three features:
The total score gives the final grade:
Because pleomorphic liposarcoma always starts with a differentiation score of 3, it is always grade 2 or grade 3. Both grades are considered high grade. In one series of 63 tumors, about 7 in 10 were grade 3.
Tumor size is the greatest dimension of the pleomorphic liposarcoma, 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). Larger tumors are associated with a less favorable outcome, and many of these tumors are already 10 cm or larger when they are found.
Tumor depth describes whether the pleomorphic liposarcoma sits in the tissue just under the skin or deep to the fascia, the thin layer of tissue covering the muscles. Most of these tumors are deep. Tumors limited to the skin and the fat just beneath it rarely spread to other organs.
Tumor extension describes whether the tumor has grown into nearby structures such as muscle, bone, nerves, blood vessels, 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.
Some people with pleomorphic liposarcoma receive radiation therapy, chemotherapy, 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, including pleomorphic liposarcoma, 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 means that cells from the pleomorphic liposarcoma 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.”
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 liposarcoma. 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.
A margin is the edge of tissue cut by the surgeon to remove a pleomorphic liposarcoma. The pathologist examines each margin to see whether tumor cells reach it. Incomplete removal is one of the strongest predictors of a less favorable outcome for this tumor.
Lymph nodes are small immune organs that filter fluid from the tissues. Pleomorphic liposarcoma rarely spreads to lymph nodes. It much more often spreads through the bloodstream to the lungs. 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.
For pleomorphic liposarcoma, no biomarker test currently selects a targeted drug. Molecular testing for this tumor, mainly FISH for MDM2, is used to confirm the diagnosis rather than choose treatment.
When the cancer 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. You can learn more in our Biomarkers and Genetic Testing section.
The pathologic stage for pleomorphic liposarcoma 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) depends on where the tumor started in the body.
Trunk and extremities (chest, back, abdominal wall, arms, and legs):
Retroperitoneum (the space at the back of the abdomen):
Head and neck:
Abdominal and thoracic visceral organs (internal organs such as the stomach, intestines, and lungs):
Orbit (the space around the eye):
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:
If no lymph nodes were removed, which is common for pleomorphic liposarcoma, 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.
Pleomorphic liposarcoma has a less favorable outlook than the other types of liposarcoma. In a large population study, about 54% of people were alive five years after diagnosis, and about 40% were alive at 10 years. When only deaths from this cancer were counted, about 60% were alive at five years.
The tumor comes back in the same place in roughly 1 in 3 people, and a similar or larger proportion develop spread to other organs. Spread is most often to the lungs and the lining around them.
Features associated with the outcome of pleomorphic liposarcoma include:
After a pleomorphic liposarcoma diagnosis is confirmed, a team at a center experienced in treating sarcoma usually plans 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.
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.