by Bibianna Purgina, MD FRCPC
August 10, 2024
Well differentiated liposarcoma is a type of cancer that develops from fat cells. Unlike normal fat, the cells in a well differentiated liposarcoma have abnormal shapes and sizes, but they still resemble normal fat cells under the microscope. This type of cancer is usually slow-growing and less likely to spread to other parts of the body compared to other types of sarcomas. Well differentiated liposarcoma most commonly occurs in the deep soft tissues of the limbs, abdomen, or retroperitoneum (the space behind the abdominal organs).
The symptoms of well differentiated liposarcoma depend on the location of the tumour.
Common symptoms include:
Well differentiated liposarcoma is caused by genetic changes in fat cells that make them grow uncontrollably. The most common genetic change found in this type of cancer is the amplification (an increase in the number of copies) of a gene called MDM2. This genetic change plays a key role in the development of the tumour by interfering with the normal controls that keep cell growth in check. Well differentiated liposarcoma is usually not inherited, meaning it does not run in families.
The diagnosis of well differentiated liposarcoma is usually made after a biopsy or surgical removal of the tumour. A pathologist examines the tissue sample under a microscope to look for features that are characteristic of well differentiated liposarcoma. Additional tests, such as immunohistochemistry (IHC) or a special test called FISH, may also be performed to confirm the diagnosis by detecting the genetic changes associated with the tumour.
Under the microscope, well differentiated liposarcoma is made up of abnormal fat cells that still resemble normal fat cells to some extent. The tumour cells are often larger than normal fat cells and have more irregular shapes. The nuclei (the control centers of the cells) in these tumour cells may be enlarged and irregular, which is a key feature that pathologists look for when diagnosing this type of cancer. Immature fat cells called lipoblasts may also be seen. These cells have more prominent nuclei and can vary in size and shape. There may also be areas of fibrosis (thickening and scarring of connective tissue) within the tumour.
The French Federation of Cancer Centres Sarcoma Grading system, or FNCLCC, is a system that pathologists use to grade sarcomas, including well differentiated 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:
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). A higher grade indicates a more aggressive tumour.
Fluorescence in situ hybridization (FISH) is a special laboratory test that is used to detect specific genetic changes in tumour cells. For well-differentiated liposarcoma, FISH is commonly used to assess for the amplification of the MDM2 gene. In this test, fluorescent probes are used to attach to the MDM2 gene in the tumour cells. If the gene is amplified, the probes will show many copies of the gene, confirming the diagnosis of well-differentiated liposarcoma. This test is important because MDM2 amplification is a key feature that distinguishes well-differentiated liposarcoma from other types of tumours that may look similar under the microscope.
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).
Most well differentiated 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 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 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.
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.
If you have been diagnosed with well differentiated 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 well differentiated 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 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.
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.
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.
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.