Well Differentiated Liposarcoma: Understanding Your Pathology Report

Well differentiated liposarcoma is a type of sarcoma, which is a cancer that starts in connective tissues such as fat, muscle, or bone. In this tumor, the cancer cells come from fat cells (adipocytes). Under the microscope, the cells still resemble fat cells, but they appear more abnormal in size and shape than normal fat cells.

Well differentiated liposarcoma usually grows slowly and is less likely to spread (metastasize) to distant parts of the body than many other sarcomas. However, it can grow very large and can come back (recur), especially in areas where it is difficult to remove completely, such as the retroperitoneum, the space behind the abdominal organs.

This tumor most often arises in:

• Deep soft tissues of the arms or legs (extremities).

• Deep soft tissues of the trunk.

• The abdomen or retroperitoneum.

What are the symptoms?

Symptoms depend on the tumor’s location and size. Many well differentiated liposarcomas grow slowly and may not cause symptoms at first. As they grow larger, common symptoms include:

• A painless lump. Often, the first sign is a lump or mass under the skin or deep in the body that slowly increases in size.

• Swelling around the area of the tumor.

• Pressure or discomfort if the tumor pushes on nearby organs, nerves, or muscles.

• Pain or aching, especially when the mass is large or involves nerves.

• Difficulty moving the affected arm or leg if the tumor is in a limb.

Deep tumors in the abdomen or retroperitoneum may cause abdominal fullness, changes in bowel habits, or weight loss once they become very large.

What causes well differentiated liposarcoma?

Well differentiated liposarcoma is caused by genetic changes in fat cells that make them grow and divide more than they should. The most common genetic change is amplification of the MDM2 gene, which means there are many extra copies of the gene in tumor cells. MDM2 controls a protein that normally helps regulate cell growth. When MDM2 is amplified, this control is lost, allowing cells to grow uncontrolled.

This tumor is usually not inherited. In other words, it does not typically run in families and is not caused by a mutation passed down from parents.

How is this diagnosis made?

Imaging

Most patients first undergo imaging studies such as ultrasound, CT scan, or MRI when a mass is found on physical exam or is detected incidentally. Well differentiated liposarcoma often appears as a large fatty mass with thickened internal septa (strands) or nodules that look more solid than normal fat.

Imaging can strongly suggest a liposarcoma, particularly when the tumor is deep and large, but a tissue sample is required to make a definite diagnosis and to determine the subtype.

Biopsy

The diagnosis is confirmed after a biopsy or surgical removal of the tumor. A biopsy may be performed using a core needle, which removes small cylinders of tissue, or, less commonly, through an open surgical biopsy. When possible, surgery is performed to remove the entire tumor (excision or resection).

A pathologist examines the tissue under a microscope to determine if the tumor is a well differentiated liposarcoma and to distinguish it from a benign (non-cancerous) fatty tumor called a lipoma.

Microscopic features

Under the microscope, well differentiated liposarcoma is made up of abnormal fat cells that still resemble normal fat but have important differences. The tumor often shows:

• Enlarged fat cells with irregular shapes.

• Atypical stromal cells, which are non-fatty cells in the background tissue with enlarged, irregular nuclei (the “control center” of the cell).

• Lipoblasts are immature fat cells with more prominent, sometimes indented nuclei and small vacuoles (fat droplets) that indent the nucleus. Lipoblasts are a key feature that supports the diagnosis.

• Areas of fibrosis, meaning thickening and scarring of connective tissue within the tumor.

These features help distinguish well differentiated liposarcoma from a lipoma, which is made of mature fat cells that do not show atypia (abnormalities) or lipoblasts.

FISH for MDM2

Because well differentiated liposarcoma can look similar to a benign lipoma under the microscope, pathologists often use a special test called FISH (fluorescence in situ hybridization) to confirm the diagnosis.

FISH uses fluorescent probes that attach to specific genes in the tumor cells. For well differentiated liposarcoma, FISH is used to look for amplification of the MDM2 gene. If MDM2 is amplified, many bright signals appear in each tumor cell, confirming that there are extra copies of this gene. This result strongly supports a diagnosis of well differentiated liposarcoma and helps distinguish it from other tumors that do not have this genetic change.

FNCLCC grade

The French Federation of Cancer Centres Sarcoma Grading System (FNCLCC) is used to grade sarcomas based on their microscopic appearance. The grade helps predict how fast the tumor may grow and how likely it is to spread.

The FNCLCC grade is based on three features:

1. Differentiation – how closely the tumor cells resemble normal tissue of the same type.

2. Mitotic activity – how many cells are actively dividing.

3. Necrosis – how much of the tumor is made up of dead cells.

Each feature is given a score, and the scores are added to provide a final grade:

• Grade 1 (low grade).

• Grade 2 (intermediate grade).

• Grade 3 (high grade).

All well differentiated liposarcomas are given a differentiation score of 1, because the tumor cells still resemble fat cells. Mitotic activity is usually low, and necrosis is generally absent or minimal in this type of tumor. As a result, well differentiated liposarcomas are almost always classified as FNCLCC grade 1, indicating a low-grade tumor with slower growth and a lower risk of distant spread, although local recurrence can still occur.

Tumor size

Tumor size is an important part of your pathology report for well differentiated liposarcoma. Larger tumors are more difficult to remove completely and may be more likely to recur.

The size of the tumor is important because:

• Tumors smaller than 5 cm are less likely to spread and are associated with a better prognosis.

• Tumor size is also used to determine the pathologic tumor stage (pT), which is part of the TNM staging system and varies depending on where in the body the tumor started.

Tumor extension

Tumor extension describes how far the tumor has grown beyond its original location. Well differentiated liposarcomas often start in areas where there is normal fat. Over time, they can:

• Grow into adjacent muscles.

• It extends into nearby organs or other soft tissues.

Your pathologist will carefully examine the tissue around the tumor to see whether tumor cells are present in nearby structures. If the tumor has grown into surrounding organs or tissues, this will be noted in your report and will increase the pT stage.

Perineural invasion

Perineural invasion (PNI) means tumor cells grow along or around a nerve. Nerves carry information such as pain, temperature, and movement signals between the body and brain.

Perineural invasion is important because the tumor can spread along the nerve’s path into deeper tissues. Its presence increases the risk that the tumor may recur in the same area after treatment.

Lymphovascular invasion

Lymphovascular invasion (LVI) means tumor cells are found inside a blood vessel or a lymphatic vessel. Blood vessels carry blood throughout the body, and lymphatic vessels carry lymph, a fluid that contains immune cells and waste products.

Lymphovascular invasion is significant because it provides a pathway for tumor cells to travel to other parts of the body, such as lymph nodes or lungs. When lymphovascular invasion is present, the risk of metastasis (spread) is higher.

Margins

A margin is the edge of the tissue removed during surgery. Pathologists examine all margins to determine whether the tumor was removed entirely.

• A negative margin means there are no tumor cells at the cut edge, suggesting the tumor has been entirely excised.

• A positive margin means tumor cells are present at the edge, raising concern that some tumor remains in the body.

Your report may also state the distance between the nearest tumor cells and the margin. Margin status helps your surgeon and oncologist decide if additional treatment, such as more surgery or radiation, is needed.

Treatment effect

If you received chemotherapy and/or radiation therapy before surgery (called neoadjuvant therapy), your pathologist will look for signs of treatment effect.

They will estimate the percentage of the tumor that is dead (necrotic) versus alive (viable). A tumor with 90% or more necrosis is considered a good response to therapy and is generally associated with a better prognosis. This information can help your doctors evaluate how well the treatment worked and plan next steps.

Lymph nodes

Lymph nodes are small immune organs located throughout the body. Cancer cells sometimes spread to nearby lymph nodes through lymphatic vessels. Although well differentiated liposarcoma more commonly spreads locally than to lymph nodes, lymph nodes may be removed and examined if they are enlarged or suspicious.

If lymph nodes are removed, the pathology report will describe:

• The number of lymph nodes examined.

• How many contain tumor cells.

• Whether there is extranodal extension, meaning tumor cells have broken through the lymph node capsule into surrounding tissue.

Finding tumor in a lymph node changes the nodal stage (pN):

• pN0 – no tumor cells in any lymph node.

• pN1 – tumor cells present in at least one lymph node.

Lymph node involvement is important because it increases the risk of tumor spread to other parts of the body and may influence recommendations for additional therapy.

Tumor stage (pT) for well differentiated liposarcoma

The tumor stage (pT) describes the size of the tumor and how far it has grown into nearby body structures. Because well differentiated liposarcoma can develop in many different parts of the body, the T stage depends on the tumor’s location.

Head and neck

• T1 – The tumor is 2 cm or smaller.

• T2 – The tumor is between 2 cm and 4 cm.

• T3 – The tumor is larger than 4 cm.

• T4 – The tumor has grown into nearby structures, including facial bones, the skull, the eye socket, major blood vessels, or the brain.

Chest, back, abdomen, arms, and legs (trunk and extremities)

• T1 – The tumor is 5 cm or smaller.

• T2 – The tumor is between 5 cm and 10 cm.

• T3 – The tumor is between 10 cm and 15 cm.

• T4 – The tumor is larger than 15 cm.

Thoracic visceral organs (organs inside the chest)

These tumors start in organs such as the lung, esophagus, or heart coverings.

• T1 – The tumor is found only in the organ where it started.

• T2 – The tumor has grown into the connective tissue around that organ.

• T3 – The tumor has grown into at least one additional organ.

• T4 – Multiple tumors are present.

Retroperitoneum (space deep in the back of the abdomen)

• T1 – 5 cm or smaller.

• T2 – Between 5 cm and 10 cm.

• T3 – Between 10 cm and 15 cm.

• T4 – Larger than 15 cm.

Orbit (tissue around the eye)

• T1 – 2 cm or smaller.

• T2 – Larger than 2 cm, but the tumor has not invaded bone.

• T3 – The tumor has grown into the bones around the eye socket or the bones of the skull.

• T4 – The tumor has grown into the eye itself or other nearby tissues such as the eyelids, sinuses, or brain.

The T stage helps guide treatment decisions and provides information about prognosis. Higher T stages generally reflect larger tumors or tumors that have grown into important structures, making complete removal more difficult.

What happens after the diagnosis?

After a diagnosis of well differentiated liposarcoma is made, your healthcare team will use the information in your pathology report—such as the tumor’s size, location, margins, and genetic findings—to plan the most appropriate treatment. Surgery is the main form of treatment because removing the tumor completely offers the best chance of long-term control. If the tumor could not be removed entirely or if tumor cells were seen at the edge of the surgical specimen, additional treatment such as radiation therapy may be recommended to lower the risk of recurrence.

Some tumors grow in places where complete removal is difficult, especially those in the retroperitoneum. In these situations, recurrence is more common, so careful follow-up is very important. Chemotherapy is not routinely used for well differentiated liposarcoma because these tumors tend to grow slowly and are less responsive to chemotherapy. However, treatment plans are individualized, and therapy may be considered if the tumor shows more aggressive features or if part of the tumor has “dedifferentiated,” meaning it has changed into a higher-grade sarcoma.

After treatment, regular follow-up appointments are required to look for any signs that the tumor has returned. The schedule for follow-up imaging depends on your specific situation, but may include periodic CT or MRI scans and physical examinations. Recurrence can happen months or even years later, so ongoing monitoring is an important part of your care.

Questions to ask your doctor

• Was the tumor completely removed, and were the margins negative?

• Did the molecular testing confirm MDM2 amplification?

• What was the FNCLCC grade for my tumor?

• Do I need radiation therapy after surgery?

• How likely is this tumor to come back based on its size and location?

• What kind of follow-up schedule do you recommend?

• Are there symptoms I should watch for that may suggest the tumor has returned?

• How will treatment affect my daily activities and long-term health?