Well Differentiated Liposarcoma: Understanding Your Pathology Report

Section Editor: Bibianna Purgina, MD FRCPC
September 20, 2026

Well differentiated liposarcoma is a slow-growing cancer that develops from fat cells. It is a type of sarcoma, a cancer that begins in the body’s connective tissues. Together with dedifferentiated liposarcoma, it is the most common type of liposarcoma.

Under the microscope, the tumor cells still resemble normal fat cells, although they are larger and more irregular in size and shape. Well differentiated liposarcoma does not spread to other parts of the body. The main concerns are that it can come back in the same place after surgery and that, over time, part of it can change into a faster-growing cancer.

This tumor usually affects adults between 50 and 70 years old. It most often starts deep in the thigh or elsewhere in the arms and legs. It can also start in the retroperitoneum, which is the space at the back of the abdomen, or beside the testicle.

This article explains how well differentiated liposarcoma is diagnosed and what the MDM2 result, grade, margins, and stage in your pathology report mean.

What is the difference between well differentiated liposarcoma and atypical lipomatous tumor?

These two names describe the same tumor. The cells look the same under the microscope, and both have the same genetic change. The name depends on where the tumor started because location affects how easily the tumor can be removed completely.

Atypical lipomatous tumor. This name is used for tumors in the arms, legs, and the tissue just under the skin of the trunk. In these locations, surgery can usually remove the whole tumor, and the outlook is very good. Our article on atypical lipomatous tumor describes this group.
Well differentiated liposarcoma. This name is used for tumors deep inside the body, such as the retroperitoneum, the abdomen, the chest, and the area beside the testicle. In these locations, removing the whole tumor with a rim of normal tissue is harder, so the tumor comes back more often.

Some older reports use the term atypical lipoma. That term is no longer recommended.

What causes well differentiated liposarcoma?

Well differentiated liposarcoma is caused by extra copies of a gene called MDM2. This is called amplification. Most tumors also have extra copies of a gene called CDK4. In the tumor cells, these extra copies are carried on unusual ring-shaped or oversized chromosomes.

The MDM2 protein normally keeps another protein called p53 in check, and p53 acts as a brake on cell growth. When there are too many copies of MDM2, that brake stops working, and the fat cells grow without the usual controls.

This genetic change develops in the tumor cells during a person’s lifetime. It is not inherited and cannot be passed on to children.

What are the symptoms of well differentiated liposarcoma?

The most common symptom of well differentiated liposarcoma is a painless lump that grows slowly. Because the tumor grows slowly and causes little discomfort, it is often large by the time it is found.

Tumors in the retroperitoneum may reach 20 cm or more before causing symptoms. These can include abdominal fullness, a change in bowel habits, or pressure on the kidney or other organs. Tumors in an arm or leg usually appear as a deep, firm lump that may limit movement.

How is the diagnosis made?

The diagnosis of well differentiated liposarcoma is made after a pathologist examines a sample of the tumor under the microscope. The sample may come from a core needle biopsy or from surgery that removes the whole tumor.

Under the microscope, well differentiated liposarcoma is made of fat cells that vary widely in size. Scattered among them are abnormal cells with large, dark nuclei, which contain the cell’s genetic material. Bands of fibrous tissue run through the tumor. Lipoblasts, immature fat cells with fat droplets that press into the nucleus, may be present but are not required for diagnosis.

The main challenge is separating this tumor from a lipoma, a noncancerous fatty tumor that can look very similar. A test called fluorescence in situ hybridization (FISH) looks for extra copies of the MDM2 gene. Finding extra copies confirms well-differentiated liposarcoma, and lipomas do not have this change.

Once the diagnosis is confirmed, imaging such as CT or MRI shows the full size of the tumor and its relationship to nearby organs.

Immunohistochemistry

Immunohistochemistry is a test that uses antibodies to show which proteins tumor cells make. For well differentiated liposarcoma, it supports the diagnosis but does not replace FISH testing. Your report may include some of the following:

MDM2 and CDK4. These proteins are usually positive in the abnormal cells, which fits with the extra copies of these genes. A positive result supports the diagnosis, and FISH can confirm it.
p16. This protein is often positive and is sometimes used alongside MDM2 and CDK4.
S100. This protein is positive in fat cells, both normal and abnormal, so it does not separate this tumor from a lipoma.

Not every case needs every stain. When the microscope findings are clear, the pathologist may go straight to FISH testing.

Histologic subtype

Your report may describe a subtype of well differentiated liposarcoma. These subtypes describe what the tumor looks like under the microscope, and they do not change the diagnosis:

Lipoma-like. This is the most common subtype. The tumor is made mostly of fat cells that resemble a lipoma, with scattered abnormal cells.
Sclerosing. The tumor contains large areas of dense fibrous tissue between the fat cells. This subtype is common in the retroperitoneum and the area beside the testicle.
Inflammatory. The tumor contains many immune cells, which can make it resemble an inflammatory condition. This subtype is uncommon.

Histologic grade

Pathologists grade sarcomas using the FNCLCC system. It adds together scores for how closely the tumor cells resemble normal tissue, how many cells are dividing, and how much dead tumor tissue is present.

Well differentiated liposarcoma always receives a differentiation score of 1, because the tumor cells still resemble fat. Dividing cells are few, and dead tumor tissue is usually absent. As a result, almost all of these tumors are grade 1, the lowest grade. A grade 1 tumor grows slowly and does not spread to other organs.

Tumor size

Tumor size is the greatest dimension of the well differentiated liposarcoma, measured in centimeters (cm). The final measurement comes from the tumor removed at surgery rather than from a biopsy. Size is used to determine the tumor stage (pT). Retroperitoneal tumors are often very large when found, sometimes 20 cm or more.

Tumor extension

Tumor extension describes whether the well differentiated liposarcoma has grown beyond the fat where it started. This tumor tends to spread along the thin layers of tissue that separate muscles and organs, rather than pushing them aside. That growth pattern is one reason complete removal can be difficult, especially in the retroperitoneum.

The pathologist examines the tissue removed with the tumor and reports which structures contain tumor cells. For tumors of the trunk, arms, legs, and retroperitoneum, the stage depends on size alone. For tumors in the head and neck, the orbit (the space around the eye), and internal organs, growth into nearby structures raises the stage.

Dedifferentiation

Over time, part of a well differentiated liposarcoma can change into a faster-growing cancer. This change is called dedifferentiation, and the diagnosis then becomes dedifferentiated liposarcoma. Unlike well differentiated liposarcoma, the dedifferentiated form can spread to other organs.

Reported rates vary, and about 10% to 15% of these tumors dedifferentiate. The risk is higher for tumors in the retroperitoneum and for tumors that have been present or have come back over many years. It is much lower for tumors in the arms and legs. This risk is the main reason follow-up continues for many years.

Surgical margins

A margin is the edge of tissue cut by the surgeon to remove a well differentiated liposarcoma. The pathologist examines each margin to see whether tumor cells reach it. 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.

Because this tumor blends into the surrounding fat, positive margins are common in large retroperitoneal tumors. A positive margin does not mean the tumor will certainly come back, and your team may recommend monitoring rather than more surgery.

Lymphovascular invasion

Lymphovascular invasion means that tumor cells are seen inside a small blood vessel or lymphatic channel. This finding is rare in well differentiated liposarcoma, and most reports state that it was not identified. Current reports may list it as “lymphatic and/or vascular invasion.”

Lymph nodes

Lymph nodes are small immune organs that filter fluid from the tissues. Well differentiated liposarcoma does not spread to lymph nodes, so nodes are usually not removed. If a node was removed because it looked enlarged on imaging, the report will state whether it contains tumor cells.

Biomarker and molecular testing

For well differentiated liposarcoma, MDM2 testing by FISH is a diagnostic test rather than a test that selects treatment. It confirms the diagnosis and separates this tumor from a lipoma.

MDM2 and CDK4 are also targets of drugs being studied in clinical trials, mainly for tumors that have come back or cannot be removed. If this applies to you, your oncologist can explain whether a trial is an option. You can learn more in our Biomarkers and Genetic Testing section.

Pathologic stage (pTNM)

The pathologic stage for well differentiated 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.

The tumor stage (pT) 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.

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 usual for this tumor, the report will 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?

Well differentiated liposarcoma has the most favorable outlook of all the liposarcomas. In a large population study, about 82% of people were alive five years after diagnosis and about 68% at 10 years. Because this tumor mainly affects older adults, some of these deaths were from other causes.

The outlook depends most on where the tumor started. Tumors of the arms and legs are usually removed completely and rarely cause serious problems. In published series, these tumors came back in about 1 in 10 to 4 in 10 people, often many years later.

Retroperitoneal tumors are harder to remove completely, and reported rates of the tumor coming back range from about 40% to 60%. Repeated recurrences over many years can eventually make further surgery impossible, and this, along with dedifferentiation, is the main way this cancer causes harm.

Features associated with the outcome of well differentiated liposarcoma include:

Tumor location. Tumors of the arms and legs do better than tumors in the retroperitoneum or other deep sites.
Completeness of surgery. A positive margin raises the chance that the tumor will come back in the same place.
Dedifferentiation. A tumor that has changed into dedifferentiated liposarcoma behaves differently and can spread.
Tumor size. Larger tumors are harder to remove completely.

What happens after the diagnosis?

After a team at a sarcoma-experienced center confirms well-differentiated liposarcoma, they usually plan care. The findings in your report, especially the location, the margins, and whether any dedifferentiated area was found, guide what happens next.

Surgery. Removing the tumor is the main treatment. For tumors of the arms and legs, surgery usually removes the whole tumor. For retroperitoneal tumors, surgery may include part of a nearby organ to improve the chance of clear margins.
Radiation therapy. Radiation is not routine. It may be considered when margins are positive or close. In one multicenter study of tumors of the arms and legs, radiation after surgery lowered the rate of the tumor coming back but caused more wound complications.
Chemotherapy. Chemotherapy is not used for well differentiated liposarcoma, because the tumor grows slowly and responds poorly.
Follow-up. Regular examination and imaging continue for many years. In one study, the tumor came back a median of about 8 years after surgery, which is why follow-up for 10 years or longer is recommended.

Questions to ask your doctor

Was my tumor called an atypical lipomatous tumor or a well differentiated liposarcoma, and why?
Was MDM2 testing performed, and what did it show?
Was any dedifferentiated area found in the tumor?
Where did the tumor start, and how large was it?
Were all the margins negative? How close was the closest margin?
What is my pathologic stage?
Do I need more surgery or radiation therapy?
What is the chance that this tumor comes back?
How often will I need imaging, and for how many years?
What symptoms should I watch for between appointments?