Also known as:
There are five types of liposarcoma according to the World Health Organisation (2020).
- Atypical lipomatous tumour /Well-differentiated liposarcoma (WDLS)
- Dedifferentiated liposarcoma (DDLS)
- Myxoid liposarcoma/round cell liposarcoma (MLS/RCL)
- Pleomorphic liposarcoma (PLS/PLPS)
- Myxoid-Pleomorphic liposarcoma (MPL)
It is also called lipoma sarcomatodes (an alternative name for liposarcoma, not often used).
Contents
How rare is liposarcoma?
In the UK and Europe the usual definition of a rare cancer is one that occurs in less than 6 people out of every 100,00 each year. Because there are around 200 rare cancers, this means that they make up about 24% (nearly a quarter) of all cancers. In the UK, there are around 391 cases of liposarcoma each year, an incidence rate of 0.58 per 100,000 people.
Of the different types, the most common is the well-differentiated liposarcoma, which accounts for around 50% of cases (~196 a year). The next most common is myxoid/round cell liposarcoma which makes up around 35% of liposarcomas (~137 cases a year). Dedifferentiated liposarcoma is about 10% (~39) of cases, whilst pleomorphic liposarcoma is the rarest at 5-10% of cases with only 20-40 cases a year in the UK.
What is liposarcoma?
Liposarcomas are a type of sarcoma, a cancer that forms from the soft tissues that surround and support our organs. As with other sarcomas, liposarcoma comes from a type of cell called a mesenchyme cell which formed in the first few days of an embryo’s life. Mesenchymal cells develop into tissues such as bone, cartilage, tendon and fat (adipose).
In liposarcoma the cancer forms from the adipose, or fatty tissues that are found through the body. Fatty tissue is not just a store for excess energy from our food, but is an essential for cushioning and protecting our organs, regulating our metabolism and hunger and even producing some of our sex hormones.
When we think about fat or fatty tissue, we might imagine the fat you see on a piece of meat. It looks like a smooth, uniform, greasy substance with no real structure to it – just a lump of fat. But biology is never so untidy as to leave anything just lying around inside a body. The fat is stored in billions of individual cells called adipocytes that are supplied with nerves and blood vessels like other tissues.
When you look at fatty tissue under a microscope it looks like the pictures below. On the left is a cartoon to give a clearer idea of what you can see in the picture on the right, which is a micrograph (microscope photograph) of some real adipocytes. The really noticeable feature of these cells is that they have what looks like a large empty space in the middle, but this is actually a large droplet of fat. All the other parts of the cell are squashed against the edge and can be seen as the darker areas, including the very dark nucleus (where the DNA is found).
Although the different liposarcomas start in the adipocytes, that is where most of their similarities end. The World Health Organisation has defined the five types of liposarcoma and they can be thought of as five almost entirely separate cancers. Each has a different pattern of cells to the normal ones when seen under a microscope. DNA or genetic testing will also show particular genetic changes that are different for each type. The different liposarcomas also behave differently in how aggressive they are and how they respond to different treatments.
The rest of this information pack outlines what each type is and the way they are treated.
1. Atypical lipomatous tumour /Well-differentiated liposarcoma (ALT-WDLS)
A short summary of ALT/WDS:
A slow growing, mostly painless tumours of fatty tissue that appear mostly in the arms and legs (ALT) or the trunk of the body (WDLS). Cancer cells mostly appear as an overgrowth of fat cells with some immature fat cells called lipoblasts. Genetically there are extra copies of genes for mdm2 and cdk4 which are used to confirm the diagnosis and are targets for potential treatments. The main current treatment is surgery to remove the tumour.
More detailed information about ALT/WDS:
Whilst these two liposarcomas have different names, they are essentially the same disease, but the tumours are found in different places. Atypical lipomatous tumours are usually found in the arms or legs, whilst the well-differentiated liposarcomas are found mostly in the trunk of the body – the retroperitoneum (the space at the very back of the abdomen), the mediastinum (the space in the chest that contains the heart, major blood vessels and the trachea and gullet), near the testicles or in the neck.
This type of liposarcoma is most common in men aged between 50 and 60.
They are usually a slow growing, soft, fleshy lump that only causes pain if they press on nerves or internal organs. Tumours in the retroperitoneum can cause pain and changes in bowel habits. Large tumours can sometimes cause additional swelling (oedema) as they affect the body’s ability to drain fluid from the tissues. This type of liposarcoma tends not to become metastatic (grow new tumours in new places) and the worst consequences are usually the effect of the tumour pushing on, and damaging organs inside the abdomen.
Confirming a diagnosis
ALT/WDLS is diagnosed by a combination of scans, and looking at tissue samples taken by biopsy for histology and genetics.
X-rays, CT or MRI scans can help doctors understand more about the size and location of a tumour, any blood vessels and nerves it has and how it sits within normal tissues.
A biopsy is a small sample of tissue taken from the tumour that can be used to find out exactly what type of cancer it is and the best way to treat it.
When looked at by a histologist (someone who studies cells) these tumours will often look like a large, overgrown mass of normal adipocytes, or fat cells with patches of more unusual cells that look rather like adipocytes or immature fat cells called lipocytes. This is why this liposarcoma is described as well differentiated, because it looks a lot like its original cell type. Well differentiated cancers tend to be slower growing and less aggressive than ones where the cells have changed a lot.
The unusual patches are used to help divide this sarcoma into three different types: a) adipocyte like- which has groups of a type of cancer cell, called spindle cells b)sclerosing- which has cells that look like ones that would normally make connective tissue and c) inflammatory – which has cells that look like immune cells.
Genetics
Most cancers are caused by changes, called mutations in their genetic material, the DNA. Chromosomes are structures in the cell that are used to organise the DNA. One feature of many cancers is that the cancer cells have large changes to their chromosomes. Normally there will be 46 chromosomes most in almost identical pairs. When cells become cancerous, the changes to the DNA are sometimes small, but significant, sometimes the changes are on a much bigger scale. In ALT/WDLS an extra copy of a large piece of one of the chromosomes has been made. This piece is called a small supernumerary marker chromosome (which means a small extra chromosome that is a sign of a particular cancer). Sometimes the extra copied material is so big it is seen as a giant extra chromosome, far bigger than even the largest normal chromosome.
This extra bit of chromosome is what causes the problem in this particular cancer. Chromosomes contain many genes which are the instructions for cells to make particular things it needs. The extra bit of chromosome here has extra copies of several genes that affect how cells divide.
The most important of these is called mdm2, which makes a protein called MDM2 (unfortunately genes don’t often have helpful or memorable names). Mdm2 helps destroy a very important protein called p53. P53 is sometimes called the guardian of the genome because it repairs damage to the DNA that might lead to cancer and if a cell is too damaged it makes it self-destruct. So extra MDM2 stops p53 doing its job properly, allowing cells to survive with dangerous damage to their DNA.
The second important gene is called CDK4. This one is part of the switch that controls whether and when cells divide. Too much CDK4 means cells divide when they shouldn’t – uncontrolled cell division is the hallmark of cancer.
The combination of the extra piece of chromosome seen using special microscope techniques and too much mdm2 and cdk4, confirmed by gene analysis, are used to confirm that a sarcoma is ALT/WDL, or its close relative DDLS (see next section) rather than anything else.
What are the current treatments?
The main treatment for ALT/WDLS is surgery. The tumour is removed along with a border of normal tissue to make sure that all of the cancer cells are gone, including any that can’t easily be seen. This is called an R0 surgery. This is usually most successful for ALT tumours as they are easy to get to in the arms and legs. In this case the cancer will usually be gone and no further treatment is needed. WDLS tumours can be harder to remove if they are in an awkward place in the abdomen and there is a 30-50% chance that the tumour will grow again. Sometimes they develop into the more aggressive dedifferentiated liposarcoma, DDLS.
Radiotherapy is occasionally used to support the surgery, but in spite of several clinical trials, chemotherapy seems to make little difference and is not usually used for this cancer unless it progresses to the next type, a dedifferentiated liposarcoma (DDLS).
2. Dedifferentiated liposarcoma (DDLS)
A short summary of DDLS:
A faster growing and more aggressive form which may develop from ALT/WDLS where the cancer cells no longer look like fat cells, but can resemble many cell types. DDLS is often found in the back of the abdomen (tummy) and can form where earlier ALT/WDLS tumours have been removed. It has the same set of genetic mutations as ALT/WDLS of extra mdm2 and cdk4 genes, which is why they are thought to be related, but DDLS has extra changes that make it more aggressive. Although it can respond to some chemotherapy and new drugs are being tested that work against some of the genetic changes, the main treatment is still surgery.
More detailed information about DDLS
Dedifferentiated liposarcomas are thought to be connected to a previous or existing ALT/WDLS tumour. Tumours will often contain a mixture of both types and the response to treatment and the outcome depends on how much of each type is present. They are also most common in adults over 50, and very rare in young people. They may develop at the site where a previous tumour was removed, develop within an existing tumour or develop when an ALT/WDLS tumour was not noticed because of its location in the body. They may have been underdiagnosed in the past as other types of liposarcoma.
Most DDLS tumours are found in the retroperitoneum – the area at the back of the abdomen, which can make surgery difficult. They can also be found in other places in the abdomen, as well as the chest, limbs, head and neck.
It is noticeably different to ALT/WDLS as the cancer cells no longer look like adipocytes, and can look like many other types of cells. This is why it is described as dedifferentiated. In scans it will appear as a mix of fatty tissue and other types.
It is more aggressive than ALT/WDLS, is considered a higher grade tumour and is more likely to recur after surgery. Around 40% of tumours regrow and also, unlike ALT/WDLS, up to 15% of DDLS will become metastatic.
The same genetic changes, extra chromosomes and extra copies of genes called cdk4 and mdm2 are seen as for ALT/WDLS which adds support to the idea that it is a progression from ALT/WDLS. In DDLS extra genetic changes are seen, including ones that encourage further cell division, and these are still being studied. These are potentially ways into finding new drugs for DDLS as many of these changes affect the activity of cell messengers called tyrosine kinases. Scientists have been studying tyrosine kinases for over twenty years as we have discovered that drugs that affect their action can slow or kill cancer cells.
What are the current treatments?
Surgery is the main and most effective treatment. Sometimes it is not possible to remove all of the tumour because of its location (described as R1 – some cancer is still visible under a microscope, or R2 – some of the tumour is still visible to the naked eye).
Radiotherapy can be used to treat any remaining cancer cells if the tumour is still visible or the margin (amount of normal tissue taken around the tumour) is less than 1cm.
Chemotherapy: In the past several types of common chemotherapy drugs have been the standard treatment for patients with DDLS that could not be removed completely or had become metastatic (spread). The cytotoxic drugs (that kill dividing cells) doxorubicin, ifosfamide, gemcitabine, and docetaxel have been used in combination and can slow the progression of the disease.
Trabectedin, (Yondelis), is a drug that was discovered from a sea squirt after a project searching for new medicines in the natural world in the 1960s. This will only be given after a patient has tried conventional chemotherapy. It works by stopping DNA being copied, stopping cells dividing.
Eribulin (Halaven) is a drug discovered in a sea sponge that stops the final process of cells dividing into two. This will also only be given after other chemotherapy has not worked.
Targeted Therapies: As with ALT/WDLS scientists are using the genetic differences that have appeared in the cancer cells as a target for new drugs to treat the cancer.
The most important of these is MDM2 which is amplified in several cancers and it is predicted that reducing its effect will stop the cancer cells dividing. As yet there are no licensed drugs, but there are several in clinical trials that are starting to show promising results.
The other major target for new drugs is the amplified CDK4 gene. This gene makes a protein, also called CDK4 that is partly responsible for allowing cells to divide. Proteins like CDK4 are called tyrosine kinases and have been studied for many years. There are several potential drugs that can affect it including palbociclib, ribociclib and abemaciclib which have already been licensed for DDLS and others are being considered.
Immunotherapy: Many DDLS cells have a marker (a kind of cell “flag”) on their surface that helps to stop the immune system attacking cancer cells. Immunotherapy such as pembrolizumab (Keytruda) uses molecules called antibodies that stop immune cells recognising the cancer cells “don’t destroy me” flag and allows the immune system to attack the cancer instead.
3. Myxoid liposarcoma/ round cell liposarcoma (MLS/RCL)
A short summary of MLS/RCL:
The myxoid form of this liposarcoma is slow growing, often in the arms and legs, with cells that appear to be full of mucous. The presence of round cells in the tumour is a more aggressive development and metastases are often found in the trunk of the body. MLS has characteristic genetic changes that create a new gene called FUS-CHOP that is used to help diagnose it. The first treatment is usually surgery, although MLS does respond to chemotherapy.
More detailed information about MLS/RCL:
The second most common liposarcoma, Myxoid liposarcoma, usually affects young and middle-aged adults, typically between the ages of 35 and 55. It often occurs in the legs, especially the thigh, but it can also form in the arms. Unlike other liposarcomas myxoid liposarcoma is usually seen in other places such as the abdominal wall, retroperitoneum (back of the abdomen), spine and armpit (axilla) if it has become metastatic (spread). Like most sarcomas it is mostly slow growing and painless unless it is affecting nerves or other organs.
Myxoid means “containing mucous” which describes the soft, gel-like appearance of the cells of this tumour under the microscope. This is the low-grade form of the cancer. The second part of the name describes a type of small, blue staining round cells that are seen when the cancer becomes a higher grade, that is, more likely to spread. The higher the number of round cells in the tumour, the more likely it is to spread. This is why a biopsy of the tumour is usually needed to confirm how much of each type of cell is there.
In general, myxoid liposarcoma has a better prognosis than other types of liposarcoma, with a five-year survival rate of about 80%.
One of the key genetic features of myxoid liposarcoma is a characteristic mutation. This is a large-scale change that involves the fusion of two genes: FUS and DDIT3, sometimes called CHOP or GADD145. Genes are the instructions for the cell to make particular proteins. If they get fused, some of the properties of each protein get added to create something which behaves differently to the “parent” proteins, in this case it leads to the development of a tumour. This mutation is seen in more than 9 out of 10 cases. We’re not sure exactly how the FUS-DDIT3 protein affects cells as experiments have found it is involved with many different processes. One of these may be a previously unknown way of bringing together the machinery to help produce other proteins that lead to uncontrolled cell division.
Most of the rest of the myxoid liposarcomas have another similar mutation. In this case it is a gene called EWSR1, that has fused to CHOP. EWSR1 was originally associated with Ewing’s sarcoma, but has now been found in many different sarcomas.
What are the current treatments?
The main treatment for myxoid liposarcoma is surgery to remove the tumour and some surrounding normal tissue, called taking a margin, or an R0 resection. Depending on the location and size, radiotherapy is sometimes used alongside surgery. If the tumour is a low grade and is entirely removed, the cancer is unlikely to return. Even if surgery has not cleared the whole of the tumour, if there are no round cells present only 15% of the tumours will have recurred after three years.
However, recurrence and metastasis is more common in tumours with high round cell content.
Chemotherapy and targeted therapy are used when the tumour is difficult to remove or has spread or is in danger of recurring. Usually the treatment to be used is the chemotherapy drug doxorubicin (Adriamycin). Ifosfamide is sometimes used as well, although studies are still being done to confirm if it is effective. Both of these work by sticking to DNA and affecting its ability to be copied when cells divide or to produce the messages that tell cells what to make.
Another drug that is used if conventional chemotherapy isn’t working is trabectedin (Yondelis). It is thought to work in myxoid liposarcoma by somehow interfering with the way FUS-CHOP affects a cell’s DNA. Whilst eribulin (Halaven) is used in other liposarcomas its effectiveness in myxoid liposarcoma is still being studied, so it is not a standard treatment yet.
“Targeted” drugs for myxoid liposarcoma.
As we are still unsure exactly how the genetic changes in myxoid liposarcoma lead to the cells becoming cancerous there are no obvious targets yet for developing targeted drugs. Several current targeted drugs are still being tested in myxoid liposarcoma because they can affect the processes involved in cell division or the development of new blood vessels that have been overactivated by the original mutation. These new drugs include pazopanib, sirolimus and troglitazone and efatutazone.
4. Pleomorphic liposarcoma (PLMS)
A short summary of PLMS:
This rare and aggressive liposarcoma produces tumours in the limbs or abdomen. Although the original cells were adipocytes (fat cells), pleomorphic liposarcomas contain cells with many different appearances and have many different genetic mutations. Whilst surgery is the first line of treatment it does respond to conventional chemotherapy.
More detailed information about PLMS:
This is a very rare type of liposarcoma, and makes up only 5-10% of the total number of cases. It is unusual for a liposarcoma because it is always high grade, fast growing and more than half become metastatic, often spreading to the lungs. Patients tend to be older, 90% are over 50, most are around 70 and cases are exceptionally rare in younger people. The first symptoms are a firm lump growing deep within a limb or sometimes the abdomen or chest wall which may cause swelling, numbness if it presses on nerves, or digestive problems if the tumour affects the organs in the abdomen.
Diagnosis usually involves scans (CT, X-ray, MRI etc) to confirm the size and exact location of the tumour. A biopsy is needed to confirm the cancer cells that are present. Pleomorphic means “occurring in various distinct forms” which means that when seen down a microscope there will be an almost chaotic and highly variable mix of cells of different sizes and types. PLMS has cells that look like adipocytes (fat cells), lipoblasts (immature fat cells), spindle cells, immune cells and epithelioid cells (cells that form the lining of organs).
Pleomorphic liposarcoma is also different from the other types because it doesn’t have a characteristic genetic mutation that can be used for a clear diagnosis or a target for treatment. Nor does it have the mdm2 or FUS-CHOP mutations that are used to help diagnose other liposarcomas. Instead it has a complicated mix of genetic changes that are different between patients. Scientists looking for mutations have found ones linked to several tumour suppressors – proteins that help protect the cell from damage that might lead to cancer. These often become mutated in many cancers so they can no longer carry out their protective function. As some of these are shared with other cancers, drugs that are designed to act on these mutations may potentially be used for patients with the same mutations in PLMS.
What are the current treatments?
Surgery is the main treatment.The success of surgery depends on the location and size of the tumour. Tumours in the limbs are much easier to remove than ones that are deep inside the body. Radiotherapy or chemotherapy might be given before surgery to make them smaller. Sometimes surgery can be followed by further radiotherapy if there is a chance that some cancer cells remain.
Chemotherapy is used when surgery has not, or could not remove the tumour, or it has become metastatic. PLMS is more sensitive to chemotherapy than other liposarcomas. The first one to be given is usually doxorubicin (Adriamycin) or Ifosfamide, sometimes in combination. Eribulin can also be effective.
5. Myxoid - pleomorphic liposarcoma (MPLS)
A short summary of MPLS:
A relatively newly discovered liposarcoma, MPLS produces tumours that start from fat cells, mostly deep in the torso of younger adults. It has cells that resemble the mucus containing ones of myxoid liposarcoma and the chaotic mixture of pleomorphic liposarcoma cells. Currently surgery is the only established treatment for MPLS, but doctors are now reporting some effect for chemotherapy in individual patients.
More detailed information about MPLS:
Only finally classified in 2020 by the World Health Organisation, this is an exceptionally rare form of liposarcoma that has not been well studied yet. It has also been described as a mixed liposarcoma because tumours contain cells that resemble both myxoid and pleomorphic liposarcomas.
It is most commonly found in the area of the upper chest called the mediastinum (between the lungs, including the heart, major blood vessels, trachea and oesophagus) as well as the abdomen and thigh. It tends to be quite large when diagnosed because it is often deep in the body.
Patients tend to be younger, typically in their 30s although some patients have been over 70. There is a link with patients who have an inherited condition called Li-Fraumeni syndrome which means radiotherapy must be used with caution as it can trigger other tumours.
Diagnosis may uses a combination of scans, biopsy where the histologist (person who studies cells for disease) will look for a characteristic mix of cell types, and genetics to rule out other liposarcomas that have particular mutations (mdm2 which are found in well differentiated and dedifferentiated liposarcoma and FUS-CHOP which is a marker for myxoid liposarcoma).
What are the current treatments?
At the moment surgery is the only way of treating these tumours. With the recent confirmation of MPL as a unique cancer and very few patients being diagnosed with it, our understanding of suitable chemotherapy or other treatments is still in its early stages.
What are the current clinical trials for liposarcoma?
Information current as of: 12/04/23.
In the UK there are only four clinical trials currently recruiting patients, one looking at whether chemotherapy before surgery improves outcomes for patients with certain liposarcomas, one looking at a drug that affects tumours with mdm2 mutations, another that affects cell division and one immunotherapy treatment.
Where can I find GIST support groups?
Name
Website
Notes
Sarcoma support groups
A list of local and online groups for general sarcoma or more specific conditions
Awareness and symbols
All sarcomas have July as their awareness month. The ribbon for sarcomas is yellow
