Introduction 

Liposarcoma (pronounced li-po-sar-co-ma) is a cancerous tumour that forms from adipocytes (fat cells) or primitive mesenchymal cells (undifferentiated cells that may become adipocytes).¹ These growths often occur deep within the tumour, and can grow larger than 5 cm long.² Although liposarcomas are malignant, they are often slow-growing and usually do not cause pain. This can make them difficult to detect, as individuals may not seek medical attention if the tumour does not cause discomfort. However, if a liposarcoma grows and starts to interfere with nerves or other organs, this can cause symptoms. 

Liposarcoma is a rare form of soft tissue sarcoma, with fewer than 500 cases diagnosed each year in the UK ³. Although liposarcoma can affect anyone, it tends to be diagnosed in people aged 40-60 years old, and more commonly in men than women.  Liposarcomas tend to develop in the extremities, particularly the thighs, or in the abdomen, specifically in the retroperitoneum (the lower sides of the abdomen). Symptoms may include weakness or numbness in the affected limb or abdominal cramping if the tumour is located in the abdomen.⁴ The World Health Organisation recognises four main subtypes of liposarcoma, each with its own prognosis, treatment approach, and likelihood of metastasis.

Well-differentiated liposarcoma 

Well-differentiated liposarcoma (WDLS) is the most common subtype of liposarcoma. It is a low-grade tumour that is locally aggressive but rarely spreads to distant organs.⁵ WDLS is composed of well-differentiated fat cells and usually occurs due to an MDM2 or CK4 gene amplification.⁶

If diagnosed with WDLS, comprehensive imaging will be requested to determine the extent of the tumour. This will often be done via MRI.⁷ A diagnostic criterion of having a variety of sizes in adipose cells, as well as atypicality in these cells. WDLS tumours often present as painless masses that reside deep in soft tissue. WLDS are usually found in extremities, but also in the retroperitoneum (lower left and right of the abdomen).⁸ It is important to have imaging of the tumour to assess its extent. Not only does it help guide surgeons if excision is required, but it also allows the clinical team to confirm that the tumour is graded correctly. WDLS does not typically respond to chemotherapy, known as being chemoinsensitive.

Therefore, the most common treatment is surgery. To prevent recurrence, a large area is taken out, including areas which have healthy cells. This is because if any cancer cells remain, this increases the risk of the tumour coming back. WDLS is the most common type of liposarcoma to occur. Of all the liposarcomas, WDLS are considered the most locally aggressive but have the least potential to metastasise. This means that they're likely to recur, with up to 40% of recurrence happening for retroperitoneum tumours. WDLS is considered a low-grade tumour and has the best survival rate, of 82% over 5 years.⁹

Dedifferentiated liposarcoma 

Dedifferentiated liposarcoma can contain a well-differentiated (WDLS) component as well as a dedifferentiated portion. DDLS make up ¼ of all liposarcoma diagnoses. It can occur de novo or can be formed if WDLS dedifferentiates. 

This means that the more times the WDLS recurs, the greater the possibility that it has a 20% chance of happening in first-time local recurrence tumours (first reappearance of the tumour) and a 44% chance of happening in second-time local recurrences. becomes dedifferentiated and therefore is more likely to metastasise.¹⁰

DDLS have a lower survival rate compared to WDLS, of 49% over 5 years. They also have a much higher metastatic potential, or 15 to 20%. DDLs commonly metastasise to the lungs. Metastasis has also been documented to the liver and bone, but less frequently. In order to treat DDLS, surgery is often used, but occasionally radiotherapy is used alongside. 

Myxoid liposarcoma

Myxoid Liposarcoma (MLS) is the third subsection of liposarcoma. MLS are formed from round cells embedded in a myxoid matrix with many capillaries.  It is characterised by chromosomal translocation that results in a fusion protein that has cancer-promoting (oncogenic) properties.¹¹

MLS properties are dependent on their percentage of round cell components. Round cell components refer to dense areas made up of undifferentiated tumours. This contrasts with the usual make-up of a loose, gelatinous myxoid background that is usually found in MLS. If they comprise more than 5%, the risk increases to about 50%. However, if the round cell components are over 5%, then there is a 50% chance of metastasis.¹²

In MLS, extrapulmonary metastases often occur before lung involvement. This differentiates it from other forms of liposarcoma, which tend to metastasise into the lungs.¹³ Therefore, those diagnosed with MLS should have regular CT scans, which include the abdomen and pelvis, or full-body MRIs done regularly.  MLS have a 70-80% 5-year survival rate, making it the 2nd least fatal of the liposarcoma subtypes. 

Pleomorphic liposarcoma 

Pleomorphic liposarcoma (PLS) is a high-grade tumour comprised of undifferentiated cells. The cells have nuclear atypia and do not usually resemble usual adipocytes. These tumours are due to genome-wide instability. 

PLS are the most aggressive liposarcoma subtype. They metastasise early, resulting in a poor prognosis.¹⁴ These tumours have a high metastatic potential of 50% and exhibit rapid progression and early dissemination. The most common sites of metastasis are the lungs, liver, brain and bone. 80% of metastasis cases end up in the lungs. Even if the tumour is removed via surgery, recurrence is common, usually occurring between 4 and 20 months after surgery.¹⁵

Metastasis  

Metastasis occurs when a tumorous cell is removed from the primary tumour and moves to another part of the body. These detached cells enter surrounding tissues and the bloodstream. While many of these cells are destroyed by the immune system, some survive, adhere to distant tissues, and begin to form new tumours.

They also use chemicals to produce new blood vessels. This allows the new tumour to have a good blood supply, which will provide it with oxygen, allowing it to grow. This is done by the tumour cells expressing a growth factor called VEGF, which aids vascular invasion. High-grade tumours typically express a greater degree of VEGF.¹⁶  This is because new blood vessel formation helps support tumour growth and facilitates spread. 

There are subtype-specific mechanisms that might make a tumour more prone to metastasis than others. For example, MLS have chemokine (chemical) receptors that cause the cancer cells to end up in the bone, rather than in other locations such as the lung. PLS exhibits high genomic instability, which aids its aggressiveness and increases its chance of metastasis.  

Lungs are the most common metastatic site for liposarcoma, with approximately 38.3% of metastases located in the lungs. This is due to the cells circulating in the blood; the cells will travel to the lungs first, which act as a filter system. The cells can then exit the capillaries and colonise the lung tissue. Myxoid liposarcomas (MLS) express CXCR4, a chemokine receptor, to a great extent (heavily). Therefore, these cells have an easier time metastasising to areas rich in CXCL12, which binds to the CXCR4 receptor. The lung and bone marrow are two metastatic sites rich in CXCL12. 

Round cell components are associated with higher expression of CXCR4, resulting in a greater risk of metastasis in MLS with high round cell components. This CXCR4 receptor also attracts MLS tumour cells to fat-rich environments such as bone marrow.¹⁷ Other soft tissue areas or metastasis can occur in the liver or lymph nodes. Although the liver is less common than the lungs or bone, it is noted with dedifferentiated liposarcoma (DDLS) or pleomorphic liposarcoma (PLS). Lymph nodes are very rare for liposarcomas, but common for other carcinomas. 

Summary 

Overall, the higher the grade of the tumour, the higher the metastatic risk. In addition, the larger the tumour, the greater the risk of metastasis. This means it is important to diagnose liposarcoma early and implement a treatment plan. 

To diagnose and then further surveillance of the liposarcoma, multiple different methods can be used. MRI can be used to obtain a full body scan or have a local assessment to monitor growth. CT scans are routinely done in the thorax area to catch any lung metastases.  Biopsies are also carried out to produce accurate typing, as many histological and molecular markers help differentiate the different subtypes.