Well differentiated liposarcoma

by Bibianna Purgina, MD FRCPC
March 25, 2023

What is a well-differentiated liposarcoma?

Well-differentiated liposarcoma is a type of cancer made up of adipose tissue (fat). It is a slow-growing tumour that can start almost anywhere in the body. Another name for this tumour is an atypical lipomatous tumour.

What is the difference between a well-differentiated liposarcoma and an atypical lipomatous tumour?

Well-differentiated liposarcoma and atypical lipomatous tumour (ALT) are two names given to the same tumour. Doctors use the term ALT when describing tumours that start in a superficial part of the body such as the arm or leg and where the tumour can be fully removed by surgery. The term well-differentiated liposarcoma is used for tumours starting in deeper locations such as the back of the abdomen and for those that cannot be fully removed by surgery alone.

How is the diagnosis of well-differentiated liposarcoma made?

The diagnosis of a well-differentiated liposarcoma is usually after a small sample of the tumour is removed in a procedure called a biopsy. The biopsy tissue is then sent to a pathologist who examines it under a microscope. The diagnosis can also be made after the entire tumour is removed as an excision or resection specimen.

What does well-differentiated liposarcoma look like under the microscope?

When examined under the microscope, well-differentiated liposarcoma can look like normal fat. However, unlike normal fat, well-differentiated liposarcoma contains abnormal-looking cells fat cells, known as lipoblasts.

What is MDM2 and why is it tested?

MDM2 is a gene that promotes cell division (the creation of new cells). Normal cells and those in non-cancerous tumours have two copies of the MDM2 gene. In contrast, well-differentiated liposarcomas have more than two copies of the MDM2 gene.

A test called fluorescence in situ hybridization (FISH) is commonly used to count the number of MDM2 genes in a cell. An increased number of genes (more than two) is called amplification and supports the diagnosis of well-differentiated liposarcoma.

What is the FNCLCC grade and why is it important for well-differentiated liposarcoma?

Pathologists divide well-differentiated liposarcoma into three grades based on a system created by the French Federation of Cancer Centers Sarcoma Group (FNCLCC). This system uses three microscopic features to determine the tumour grade: differentiation, mitotic count, and necrosis. These features are explained in more detail below. The grade can only be determined after a sample of the tumour has been examined under the microscope.

Points (from 0 to 3) are assigned for each of the microscopic features (0 to 3) and the total number of points determines the final grade of the tumour. According to this system, well-differentiated liposarcomas may be either low or high-grade tumours. The tumour grade is important because high-grade tumours (grades 2 and 3) are more aggressive and are associated with a worse prognosis.

Points associated with each grade:

• Grade 1 – 2 or 3 points.
• Grade 2 – 4 or 5 points.
• Grade 3 – 6 to 8 points.

Microscopic features used to determine the grade:

1. Tumour differentiation – Tumour differentiation describes how closely the tumour cells look like normal fat cells. Tumours that look very similar to normal fat cells are given 1 point while those that look very different from normal fat cells are given 2 or 3 points.
2. Mitotic count – A cell that is in the process of dividing to create two new cells is called a mitotic figure. Tumours that are growing fast tend to have more mitotic figures than tumours that are growing slowly. Your pathologist will determine the mitotic count by counting the number of mitotic figures in ten areas of the tumour while looking through the microscope. Tumours with no mitotic figures or very few mitotic figures are given 1 point while those with 10 to 20 mitotic figures are given 2 points and those with more than 20 mitotic figures are given 3 points.
3. Necrosis – Necrosis is a type of cell death. Tumours that are growing fast tend to have more necrosis than tumours that are growing slowly. If your pathologist sees no necrosis, the tumour will be given 0 points. The tumour will be given 1 point if necrosis is seen but it makes up less than 50% of the tumour or 2 points if necrosis makes more than 50% of the tumour.

What does it mean if a well-differentiated liposarcoma shows dedifferentiation?

Some well-differentiated liposarcomas will change over time so that some of the cells no longer look like normal fat. This process is called dedifferentiation. Finding dedifferentiation in a well-differentiated liposarcoma changes the diagnosis to dedifferentiated liposarcoma. This change is important because dedifferentiated liposarcoma is a more aggressive cancer that is more likely to grow back after surgery and spread to other parts of the body.

Why is the size of the tumour important for well-differentiated liposarcoma?

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

What is a margin?

A margin is any tissue that was cut by the surgeon to remove the tumour from your body.  Depending on the type of surgery you have had, the margins can include bones, muscles, blood vessels, and nerves that were cut to remove the tumour from your body. Margins will only be described in your report after the entire tumour has been removed.

A negative margin means that no tumour cells were seen at any of the cut edges of tissue. A margin is called positive when there are tumour cells at the very edge of the cut tissue. A positive margin is associated with a higher risk that the tumour will recur in the same site after treatment.

What is the pathologic stage for well-differentiated liposarcoma?

​The pathologic stage for well-differentiated 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 well-differentiated liposarcoma

The tumour stage for well-differentiated 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 that surrounds the organ from which is 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 well-differentiated liposarcoma

Well-differentiated 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.

Metastatic stage (pM) for well-differentiated liposarcoma

Well-differentiated liposarcoma is given a metastatic stage of 0 or 1 based on the presence of tumour cells at a distant site in the body (for example the lungs). The metastatic stage can only be assigned if tissue from a distant site is submitted for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as MX.