Dedifferentiated Liposarcoma
Dedifferentiated liposarcoma is a rare and fast-growing cancer that develops from well-differentiated liposarcoma, most commonly affecting adults over 50 and requiring specialized treatment and long-term monitoring.
Table of contents
- What is dedifferentiated liposarcoma?
- How common is this condition?
- Signs and symptoms
- What causes dedifferentiated liposarcoma?
- How is it diagnosed?
- Treatment options
- After treatment
What is dedifferentiated liposarcoma?
Dedifferentiated liposarcoma, often shortened to DDLS, is a fast-growing tumor that develops from another type of cancer called well-differentiated liposarcoma (a slower-growing tumor that forms in fat cells)[1]. This transformation from one type to another is what doctors call dedifferentiation.
This cancer most commonly occurs in adults over the age of 50, with the typical person diagnosed at around 68 years old[1]. DDLS tends to affect more males than females[1][4]. The tumor usually appears in the back of the abdomen (an area called the retroperitoneum) or in the deep soft tissue of the upper arms and legs[2][4].
Unlike well-differentiated liposarcoma, DDLS is considered a high-grade and aggressive tumor. This means it has a greater chance of coming back in the same area after treatment (called local recurrence) and spreading to other parts of the body (called metastasis)[1][4]. Studies show that recurrence occurs in 40 to 75 percent of DDLS cases, and metastasis occurs in about 10 to 15 percent of cases[1].
In about 90 percent of cases, dedifferentiated liposarcoma develops on its own. In the remaining 10 percent, it occurs when a previously treated well-differentiated liposarcoma returns in a more aggressive form[4]. The tumor is made up of two types of tissue: one that looks like well-differentiated liposarcoma and another that is a non-fatty sarcoma[4].
How common is this condition?
There are an average of 107 cases of DDLS diagnosed every year in England[1]. DDLS makes up just under a quarter of all liposarcoma diagnoses[1]. Although DDLS can affect anyone of any age, it most commonly occurs in middle-aged and older adults, with a slight predominance in men[4].
The location of the tumor plays an important role in the outcome. Studies suggest that DDLS cases that occur in the arms or legs tend to have better outcomes than those that develop in the retroperitoneum (the back of the abdominal cavity)[4].
Signs and symptoms
The main symptom of dedifferentiated liposarcoma is a lump or swelling. Symptoms can vary depending on the size and location of your tumor[1]. Dedifferentiated liposarcoma typically appears as a large, painless lump that may have grown slowly over several years[4].
When the tumor forms in the arms and legs, you may notice a lump that grows persistently, often on the arm, leg, or torso. Other symptoms in these areas can include swelling or numbness around the lump, or weakness of the affected arm or leg[1].
When the tumor forms in the torso (the abdomen or retroperitoneum), it can cause stomach pain or cramping, and a gradually increasing tummy. When located in the abdominal cavity, it is often discovered accidentally during imaging tests done for other reasons[1][4]. Other symptoms in the abdomen may include digestive issues such as constipation, blood in the stool or vomit, difficulty breathing, or a persistent cough[4].
What causes dedifferentiated liposarcoma?
Dedifferentiated liposarcoma often shares the same genetic abnormalities as well-differentiated liposarcoma. The cancer is characterized by specific changes in chromosomes, which are structures that carry genetic information. Specifically, DDLS has extra copies of a section of chromosome 12, in a region called 12q13-15[2][4].
This chromosomal region contains important genes called MDM2 and CDK4. When there are too many copies of these genes (a process called amplification), they help the tumor grow by disrupting normal cell processes[2][4]. The detection of MDM2 (and sometimes CDK4) amplification helps doctors distinguish DDLS from other types of undifferentiated sarcomas[2].
Researchers have recently found specific gene fusions (when two or more genes join together to form a new gene) in some DDLS cases. However, it is still unclear exactly what genetic events cause well-differentiated liposarcoma to progress to dedifferentiated liposarcoma[2][4].
How is it diagnosed?
Liposarcomas are usually found by a patient when a lump appears on the arms, legs, or torso. They can also be found during an investigation of other symptoms or during a routine operation[1]. Diagnosing DDLS involves a thorough evaluation using multiple methods to understand the tumor’s nature and location[4].
A diagnosis of dedifferentiated liposarcoma may start with a visit to your GP, who will examine you and then refer you to a specialist doctor. A specialist doctor will diagnose the cancer through a series of tests[1].
The first step is usually a physical examination, where the doctor looks at and feels any lump by examining the affected area[1][4].
Imaging tests such as CT scans or MRIs (machines that take pictures of the inside of the body) help assess the tumor’s size, location, and extent. These scans also determine if the tumor has spread to nearby tissues or other parts of the body[1][4].
A biopsy (taking and testing a tissue sample) is usually needed to confirm the diagnosis. This often involves using an image-guided needle biopsy, where a sample is taken and analyzed under a microscope to identify the tumor’s characteristics[1][4].
Treatment options
Surgery is the main treatment used for dedifferentiated liposarcoma and is the most common and most reliable option for treatment of DDLS[1]. The surgeon will remove the tumor and will aim to take out an area of normal tissue around it too. This is known as taking a margin. It allows any cancer cells that are not visible to the naked eye to be removed along with the tumor, which can reduce the risk of the cancer coming back[1]. In rare cases, surgical amputation may be performed[1].
Radiotherapy (treatment using high-energy rays) is sometimes used in patients with margins of less than 10 millimeters after surgical removal of the tumor[1]. The standard treatment for localized DDLS is surgery, with or without radiotherapy[2].
In advanced disease, the standard first-line therapy is an anthracycline-based regimen, which is a type of chemotherapy drug. This can be given as a single drug or in combination with another drug called ifosfamide[2]. Unfortunately, this regimen has not always led to a satisfactory clinical outcome[2].
It is not yet clear how suitable chemotherapy is as a treatment for DDLS, but an ongoing clinical trial is investigating this[1]. Studies have shown that combination chemotherapy can yield a response rate of 24 percent and a clinical benefit rate (which includes complete response, partial response, or stable disease lasting more than 6 months) of 44 percent[9].
After treatment
After treatment, you will have regular follow-up appointments for several years. You should receive a follow-up schedule from your sarcoma clinical nurse specialist[1].
The usual practice will include a chance to discuss symptoms and an examination to look for any signs of the sarcoma returning. This may include an MRI (magnetic resonance imaging) or ultrasound if required[1].
