Pleomorphic liposarcoma

By Jason Wasserman MD PhD FRCPC
August 10, 2024

Background:

Pleomorphic liposarcoma is a rare and aggressive type of cancer that develops from fat cells. Unlike well differentiated liposarcoma, which still resembles normal fat tissue, pleomorphic liposarcoma is made up of very abnormal cells that look nothing like normal fat cells. This type of cancer can grow quickly and has a higher risk of spreading (metastasizing) to other parts of the body. Pleomorphic liposarcoma can occur in various parts of the body, but it most commonly affects the limbs and the deep tissues of the trunk.

What are the symptoms of pleomorphic liposarcoma?

The symptoms of pleomorphic liposarcoma depend on the location and size of the tumour.

Common symptoms include:

• A rapidly growing lump: Often, the first sign of pleomorphic liposarcoma is a lump or mass that increases in size over a short period.
• Pain or tenderness: As the tumour grows, it may cause pain or discomfort, especially if it presses on nearby nerves or muscles.
• Swelling: The area around the tumour may become swollen.
• Difficulty moving: If the tumour is located in a limb, it may interfere with normal movement.

What causes pleomorphic liposarcoma?

Pleomorphic liposarcoma is caused by genetic changes in fat cells that make them grow uncontrollably. Unlike well differentiated liposarcoma, pleomorphic liposarcoma usually does not have the amplification of the MDM2 gene. Instead, other genetic changes are involved, although these changes are less well understood. Pleomorphic liposarcoma is not inherited, meaning it does not run in families.

How is this diagnosis made?

The diagnosis of pleomorphic liposarcoma is usually made after a biopsy or surgical removal of the tumour. A pathologist examines the tissue sample under a microscope to identify features that are characteristic of pleomorphic liposarcoma. Additional tests, such as FISH (fluorescence in situ hybridization), may be used to assess for genetic changes and to help distinguish pleomorphic liposarcoma from other types of sarcomas.

What does pleomorphic liposarcoma look like under the microscope?

Under the microscope, pleomorphic liposarcoma is made up of varying numbers of pleomorphic lipoblasts (immature fat cells with abnormal shapes) in a background of high grade undifferentiated spindle cells (elongated cells that do not resemble normal fat cells). The tumour cells are highly variable in appearance, with some areas of the tumour looking like myxofibrosarcoma, another type of high grade sarcoma. Mitotic figures (cells in the process of dividing) are common, indicating that the tumour cells are dividing rapidly. Areas of necrosis (dead tumour cells) are also often seen, which suggests that the tumour is aggressive and fast-growing.

French Federation of Cancer Centres Sarcoma Grading System (FNCLCC)

The French Federation of Cancer Centres Sarcoma Grading system, or FNCLCC, is a system that pathologists use to grade sarcomas, including pleomorphic liposarcoma. The grade helps predict how the tumour is likely to behave, including how fast it might grow and whether it might spread to other parts of the body.

The FNCLCC system assigns a score to the tumour based on three components:

• Mitotic activity: This refers to the number of cells that are actively dividing in the tumour. Pathologists count the number of mitotic figures in an area measuring 10 high-powered fields under the microscope. The score for mitotic activity can range from 1 to 3, with a higher score indicating more frequent cell division and a potentially more aggressive tumour.
• Necrosis: Necrosis refers to areas of the tumour where the cells have died. The score for necrosis also ranges from 1 to 3, with a higher score indicating more extensive necrosis, which usually suggests a more aggressive tumour.
• Differentiation: Differentiation refers to how much the tumour cells look like normal cells. In the FNCLCC system, all pleomorphic liposarcomas are given a differentiation score of 3 because the tumour cells look very different from normal fat cells and are highly abnormal in appearance.

The scores from these three components are added together to give the tumour an overall grade, which can range from Grade 1 (low grade) to Grade 3 (high grade). Pleomorphic liposarcomas are typically high-grade tumours.

Fluorescence in situ hybridization (FISH)

FISH (fluorescence in situ hybridization) is a special laboratory test that is used to detect specific genetic changes in tumour cells. For pleomorphic liposarcoma, FISH is often used to assess for the absence of MDM2 amplification. The absence of MDM2 amplification helps distinguish pleomorphic liposarcoma from well differentiated liposarcoma and dedifferentiated liposarcoma, which typically show MDM2 amplification. This distinction is important because it can affect the diagnosis and treatment plan.

Tumour size

Tumour size is important because tumours less than 5 cm are less likely to spread to other body parts and are associated with a better prognosis. Tumour size is also used to determine the pathologic tumour stage (pT).

Tumour extension

Most pleomorphic liposarcomas arise in an area of the body containing normal fat. However, over time the tumour can grow into surrounding organs and tissues. This is called tumour extension. Your pathologist will examine samples of the surrounding organs and tissues under the microscope to look for tumour cells. Any surrounding organs or tissue that contain tumour cells will be described in your report. Tumour extension into surrounding organs or tissues increases the pathologic tumour stage (pT).

Perineural invasion

Perineural invasion means that tumour cells were seen attached to a nerve. Nerves are found all over the body and are responsible for sending information (such as temperature, pressure, and pain) between the body and the brain. Perineural invasion is important because tumour cells that have become attached to a nerve can spread into surrounding tissues by growing along the nerve. This increases the risk that the tumour will regrow after treatment.

Lymphovascular invasion

Lymphovascular invasion means that tumour cells were seen inside a blood vessel or lymphatic vessel. Blood vessels are long, thin tubes that carry blood around the body. Lymphatic vessels are similar to small blood vessels except that they carry a fluid called lymph instead of blood. Lymphovascular invasion is important because it increases the risk that the tumour will metastasize or spread to other body parts, such as lymph nodes or the lungs.

Margins

In pathology, a margin is the edge of tissue removed during tumour surgery. The margin status in a pathology report is important as it indicates whether the entire tumour was removed or if some was left behind. This information helps determine the need for further treatment.

Pathologists typically assess margins following a surgical procedure, like an excision or resection, that removes the entire tumour. Margins aren’t usually evaluated after a biopsy, which removes only part of the tumour. The number of margins reported and their size—how much normal tissue is between the tumour and the cut edge—vary based on the tissue type and tumour location.

Pathologists examine margins to check if tumour cells are present at the tissue’s cut edge. A positive margin, where tumour cells are found, suggests that some cancer may remain in the body. In contrast, a negative margin, with no tumour cells at the edge, suggests the tumour was fully removed. Some reports also measure the distance between the nearest tumour cells and the margin, even if all margins are negative.

Treatment effect

If you have been diagnosed with pleomorphic liposarcoma on a biopsy, you may be offered chemotherapy and/or radiation therapy before the operation to remove the tumour. If you have received either of these treatments before your surgery, your pathologist will examine all the tissue sent to pathology to see how much of the tumour is still alive (viable).

Different systems are used to describe the treatment effects for pleomorphic liposarcoma. Most commonly, your pathologist will describe the percentage of dead tumour. Pathologists use the word necrosis to describe dead (non-viable) tumours. A tumour showing 90% or more therapy response (meaning 90% of the tumour is dead and 10% or less of the tumour is still alive) is considered a good response to therapy and is associated with a better prognosis.

Lymph nodes

Lymph nodes are small immune organs found throughout the body. Cancer cells can spread from a tumour to lymph nodes through small lymphatic vessels. For this reason, lymph nodes are commonly removed and examined under a microscope to look for cancer cells. The movement of cancer cells from the tumour to another part of the body, such as a lymph node, is called a metastasis.

Cancer cells typically spread first to lymph nodes close to the tumour, although lymph nodes far away from the tumour can also be involved. For this reason, the first lymph nodes removed are usually close to the tumour. Lymph nodes further away from the tumour are only typically removed if they are enlarged and there is a high clinical suspicion that there may be cancer cells in the lymph node.

If any lymph nodes were removed from your body, they will be examined under the microscope by a pathologist, and the results of this examination will be described in your report. The examination of lymph nodes is important for two reasons. First, this information determines the pathologic nodal stage (pN). Second, finding cancer cells in a lymph node increases the risk that cancer cells will be found in other parts of the body in the future. As a result, your doctor will use this information when deciding if additional treatment, such as chemotherapy, radiation therapy, or immunotherapy, is required.

Some helpful definitions:

• Positive: Positive means that cancer cells were found in the lymph node being examined.
• Negative: Negative means that no cancer cells were found in the lymph node being examined.
• Deposit: The term deposit describes a group of cancer cells inside a lymph node. Some reports include the size of the largest deposit. A similar term is “focus”.
• Extranodal extension: Extranodal extension means that the tumour cells have broken through the capsule on the outside of the lymph node and have spread into the surrounding tissue.

Pathologic stage (pTNM)

​The pathologic stage for pleomorphic liposarcoma is based on the TNM staging system, an internationally recognized system originally created by the American Joint Committee on Cancer. This system uses information about the primary tumour (T), lymph nodes (N), and distant metastatic disease (M)  to determine the complete pathologic stage (pTNM). Your pathologist will examine the tissue submitted and give each part a number. In general, a higher number means a more advanced disease and a worse prognosis.

Tumour stage (pT) for pleomorphic liposarcoma

The tumour stage for pleomorphic liposarcoma varies based on the body part involved. For example, a 5-centimetre tumour that starts in the neck will be given a different tumour stage than a tumour that starts deep in the back of the abdomen (the retroperitoneum). However, in most body sites, the tumour stage includes the tumour size and whether the tumour has grown into surrounding body parts.

Head and neck

• T1 – The tumour is no greater than 2 centimetres in size.
• T2 – The tumour is between 2 and 4 centimetres in size.
• T3 – The tumour is greater than 4 centimetres in size.
• T4 – The tumour has grown into surrounding tissues such as the bones of the face or skull, the eye, the larger blood vessels in the neck, or the brain.

Chest, back, or stomach and the arms or legs (trunk and extremities)

• T1 – The tumour is no greater than 5 centimetres in size.
• T2 – The tumour is between 5 and 10 centimetres in size.
• T3 – The tumour is between 10 and 15 centimetres in size.
• T4 – The tumour is greater than 15 centimetres in size.

Abdomen and organs inside the chest (thoracic visceral organs)

• T1 – The tumour is only seen in one organ.
• T2 – The tumour has grown into the connective tissue surrounding the organ from which it started.
• T3 – The tumour has grown into at least one other organ.
• T4 – Multiple tumours are found.

Retroperitoneum (the space at the very back of the abdominal cavity)

• T1 – The tumour is no greater than 5 centimetres in size.
• T2 – The tumour is between 5 and 10 centimetres in size.
• T3 – The tumour is between 10 and 15 centimetres in size.
• T4 – The tumour is greater than 15 centimetres in size.

Tissue around the eye (orbit)

• T1 – The tumour is no greater than 2 centimetres in size.
• T2 – The tumour is greater than 2 centimetres in size but has not grown into the bones surrounding the eye.
• T3 – The tumour has grown into the bones surrounding the eye or other bones of the skull.
• T4 – The tumour has grown into the eye (the globe) or the surrounding tissues such as the eyelids, sinuses, or brain.

Nodal stage (pN) for pleomorphic liposarcoma

Pleomorphic liposarcoma is given a nodal stage of 0 or 1 based on the presence of tumour cells in a lymph node. If no tumour cells are seen in any of the lymph nodes examined, the nodal stage is N0. If tumour cells are seen in any of the lymph nodes examined, the nodal stage becomes N1.