Dedifferentiated liposarcoma is a fast-growing type of cancer that develops from a slower-growing tumor in fat cells. This rare disease most commonly affects adults over 50 and often appears in the abdomen or the upper arms and legs, requiring specialized treatment and long-term monitoring.
What Is Dedifferentiated Liposarcoma?
Dedifferentiated liposarcoma, often shortened to DDLS, is a type of soft tissue cancer that begins in fat cells. What makes this condition unique is that it does not start on its own. Instead, it develops when a less aggressive tumor called well-differentiated liposarcoma (a slow-growing fatty tumor) transforms into a more aggressive form. This transformation is called dedifferentiation, and it means the tumor changes from one that looks and behaves more like normal fat tissue into one that looks very different and grows much faster.[1]
When doctors look at dedifferentiated liposarcoma under a microscope, they see two different types of tissue side by side. One part still looks like the original well-differentiated liposarcoma, with fat cells that appear somewhat normal. The other part looks completely different and does not resemble fat tissue at all. This non-fatty part is what makes the tumor more dangerous, as it tends to grow faster and has a higher chance of spreading to other parts of the body.[2]
The transformation from well-differentiated to dedifferentiated liposarcoma happens over time. In about 90% of cases, the dedifferentiated tumor appears on its own without any prior treatment. In the remaining 10% of cases, it develops when a previously treated well-differentiated liposarcoma comes back in a more aggressive form.[4]
Epidemiology: How Common Is This Disease?
Dedifferentiated liposarcoma is a rare disease. In England, about 107 new cases are diagnosed each year on average. This makes DDLS responsible for just under a quarter of all liposarcoma diagnoses in that country.[1]
The disease mainly affects older adults. The typical age at diagnosis is 68 years old, though it most commonly occurs in people over 50. It can affect anyone at any age, but finding it in younger people is uncommon. Unlike some cancers that affect men and women equally, dedifferentiated liposarcoma tends to affect more men than women.[1][6]
Because dedifferentiated liposarcoma is so rare, many people may never have heard of it before their diagnosis. To put it in perspective, liposarcoma as a whole affects only about 1 in 100,000 people in the United States each year, and dedifferentiated liposarcoma represents just a portion of those cases.[3]
Causes: Why Does This Happen?
The exact reasons why well-differentiated liposarcoma transforms into dedifferentiated liposarcoma are not fully understood. However, researchers have identified certain genetic changes that are present in these tumors and help explain why they grow and behave the way they do.[2]
Dedifferentiated liposarcoma shares the same genetic abnormalities as well-differentiated liposarcoma. The most important of these is a change in a specific region of chromosome 12, labeled as 12q13-15. In this region, certain genes become amplified, meaning there are extra copies of them. Two key genes involved are called MDM2 and CDK4. These genes help control how cells grow and divide, and when they are amplified, they can push cells to grow uncontrollably, leading to tumor formation.[2]
These genetic changes appear as ring-shaped or giant marker chromosomes when doctors examine the tumor cells. Detecting the amplification of MDM2 and CDK4 genes is very helpful for diagnosis because it allows doctors to distinguish dedifferentiated liposarcoma from other similar-looking cancers.[2][7]
Researchers have also recently discovered specific gene fusions in some cases of dedifferentiated liposarcoma. A gene fusion occurs when two separate genes join together to form a new, abnormal gene. However, scientists still do not fully understand what triggers the transformation from well-differentiated to dedifferentiated liposarcoma, and research is ongoing.[2][4]
Risk Factors: Who Is More Likely to Develop This Disease?
Unlike some other cancers, there are no clearly identified lifestyle or environmental risk factors that increase the chance of developing dedifferentiated liposarcoma. This means that actions such as diet, exercise, smoking, or sun exposure do not appear to play a role in causing this disease.[2]
The most significant risk factor is having a pre-existing well-differentiated liposarcoma. Since dedifferentiated liposarcoma develops from this slower-growing tumor, anyone diagnosed with well-differentiated liposarcoma has a risk that it may transform over time into the more aggressive form.[4]
Age is another factor. Because the disease most commonly affects people over the age of 50 and peaks around age 68, being in this older age group is associated with a higher likelihood of diagnosis. Men are also slightly more likely to be diagnosed than women, though the reasons for this are not well understood.[1][6]
There is no evidence that dedifferentiated liposarcoma runs in families, and genetic testing for hereditary risk is not currently recommended. The genetic changes found in the tumor are specific to the cancer cells and are not passed down through generations.[2]
Symptoms: What Do Patients Experience?
The symptoms of dedifferentiated liposarcoma depend largely on where the tumor is located in the body and how large it has grown. Many patients do not notice any symptoms in the early stages, which means the tumor can grow quite large before it is discovered.[1]
The most common symptom is a noticeable lump or swelling. This lump is often painless, especially at first, and may appear on the arm, leg, or torso. Patients sometimes describe noticing a bump that grows steadily over time and does not go away on its own. Because the lump is usually not painful, some people delay seeking medical attention, thinking it is harmless.[1][4]
When dedifferentiated liposarcoma develops in the arms or legs, it can cause additional symptoms. As the tumor grows, it may press on nearby nerves, leading to pain, swelling, or numbness in the area around the lump. Some patients notice weakness in the affected limb, making it harder to use the arm or leg normally.[1]
Dedifferentiated liposarcoma often develops in the retroperitoneum, which is the space at the back of the abdominal cavity. Tumors in this location can become very large before causing any symptoms because the abdomen has more room for the tumor to grow. When symptoms do appear, they may include stomach pain or cramping, a feeling of fullness or bloating, and a gradually increasing belly size. Some patients experience digestive problems such as constipation, or they may notice blood in their stool or vomit.[1][4]
In some cases, dedifferentiated liposarcoma in the abdomen is discovered accidentally during imaging tests done for other reasons, such as a routine check-up or investigation of unrelated symptoms.[4]
Prevention: Can This Disease Be Avoided?
Because the exact causes of dedifferentiated liposarcoma are not well understood and there are no known lifestyle or environmental risk factors, there are no proven strategies to prevent the disease from developing. This can be frustrating for patients and families, but it is important to remember that nothing a person did or did not do caused the tumor to form.[2]
For individuals already diagnosed with well-differentiated liposarcoma, regular follow-up with a healthcare provider is important. Close monitoring can help detect any changes or transformation to dedifferentiated liposarcoma at an earlier stage, when treatment may be more effective. Follow-up typically includes regular physical examinations and imaging tests such as MRI or ultrasound scans.[1]
There is no vaccine, supplement, or dietary change currently known to prevent dedifferentiated liposarcoma. Research into the biology of the disease continues, and scientists hope that a better understanding of the genetic changes involved may one day lead to preventive strategies or early detection methods.[2]
Pathophysiology: What Happens in the Body?
Understanding what happens inside the body when dedifferentiated liposarcoma develops helps explain why the disease behaves the way it does. At its core, this cancer involves cells that have lost their normal ability to control growth and division.[2]
Normally, fat cells grow and divide in a controlled way. They respond to signals from the body that tell them when to grow, when to stop growing, and when to die. In well-differentiated liposarcoma, this control system is partially broken. The cells grow more than they should, but they still look somewhat like normal fat cells and grow slowly.[2]
When dedifferentiation occurs, the tumor cells undergo additional changes that make them lose even more of their normal characteristics. The dedifferentiated part of the tumor no longer looks like fat tissue at all. These cells grow much faster and are more likely to invade nearby tissues or spread to other parts of the body. This is why dedifferentiated liposarcoma is considered more aggressive than its well-differentiated counterpart.[2][6]
The genetic changes driving this process involve the amplification of the MDM2 and CDK4 genes. MDM2 normally helps regulate a protein called p53, which acts as a brake on cell growth and can trigger damaged cells to die. When MDM2 is amplified, it interferes with p53, removing this brake and allowing cells to grow unchecked. CDK4 helps push cells through the cycle of growth and division, and when it is amplified, cells divide more rapidly than they should.[2][7]
Dedifferentiated liposarcoma has a higher risk of local recurrence, meaning the tumor can come back in the same area after treatment. Studies show recurrence happens in 40% to 75% of cases. The disease also has a higher risk of spreading to distant parts of the body (metastasis), though this is less common, occurring in about 10% to 15% of patients. The disease-related mortality rate is around 30%, meaning that while dedifferentiated liposarcoma is serious, many patients can live for years with appropriate treatment.[1][4][6]
The location of the tumor also plays an important role in how the disease behaves. Dedifferentiated liposarcoma in the arms or legs tends to have better outcomes than tumors in the retroperitoneum. This is partly because tumors in the limbs are easier to remove completely with surgery, while tumors in the abdomen can be large and difficult to fully excise without affecting nearby organs.[4]
