What Is Liposarcoma

Overview

Liposarcoma is a type of cancer that arises from fat tissue.¹ It is the most common type of soft tissue sarcoma, and it is usually found in the abdomen, thigh, knee or head and neck region.¹

The name liposarcoma in itself is an umbrella term: recently, the World Health Organization (WHO) has divided this type of tumour into five categories.² Each type is related to different causes (like genetic mutations) and different presentations, with some being more aggressive than others.² Let’s understand more about these five types of liposarcomas and what challenges they represent to a patient.

Types of liposarcoma

Atypical lipomatous tumour (ATL) or well-differentiated liposarcoma (WDL)

This is the most common and more indolent form of liposarcoma, representing 40-45% of cases of fat tissue sarcomas, affecting mostly adults over the age of 40. They are more similar to a benign tumour like a lipoma.

• They can be found most commonly in the deep thigh area, followed by the retroperitoneum (inside the abdomen), head and neck region and spermatic cord.
• It is characterised by mature adipocytes (fat cells) with a lesser degree of atypia (abnormality).
• The nomenclature will depend on where the tumour is located: peripheral tumours will be called ATLs, while retroperitoneal tumours will be called WDL; this is because peripheral tumours can be surgically removed with clear margins and lesser risk of dedifferentiation (and this dedifferentiation results in a more aggressive and malignant presentation), meanwhile tumours in the abdomen will seldom be removed with clear margins and this increases risk of recurrence, dedifferentiation and results in a poorer prognosis.

Dedifferentiated liposarcoma (DDL)

This type is less common, and about 10% of them originate from a WDL that suffered mutations that lead to dedifferentiation (loss of original characteristics of the normal tissue). It affects older patients, with a slight preference towards males.

• Most commonly found in the retroperitoneum and spermatic head, very rare in the head and neck region. Characterised by areas of well-differentiated tissue (similar to a WDL) and areas of lesser differentiation where cells seem atypical and may not resemble adipocytes at all. The DDL can present dedifferentiated areas that start resembling other types of tissue, like muscle, nerve and bone.

Myxoid liposarcoma (MLS)

They represent about 30% of all liposarcomas.³ While having a preference for older individuals of the male sex, most liposarcomas of children and teenagers are MLS.³

• High predominance for the thighs and lower legs, with retroperitoneal lesions being rarer.³
• MLS has a particular pattern for metastasis that targets soft tissue (retroperitoneal and thoracic areas), bone and lungs.³
• Unlike the ATL, WDL and DDL, this tumour originates from the lipoblasts, precursor fat cells.³ Lipoblasts can assume a myriad of forms in this neoplasm, but one stands out, the round cell type: tumours that have a predominance of round cells are said to be high-grade and have a greater chance of metastasis.³

Pleomorphic liposarcoma (PLS)

This fast-growing tumour accounts for 5% of all liposarcomas, being highly malignant and aggressive.³ It occurs mostly in older patients as well, however, with a slight female preference over male.³

• The most common sites are the extremities of the body (legs and arms), followed by the retroperitoneum.³
• Similarly to the MLS, it also originates from lipoblasts, and it has areas that are similar to a myxoid liposarcoma with areas of undifferentiated cells; one of the most common variants of undifferentiated cells is the spindle-shaped cell.³

Myxoid pleomorphic liposarcoma (MPL)

Only recently recognized by the World Health Organization (WHO) in 2020, this tumour is very rare and quite different from other presentations of liposarcoma.³

• Unlike other types, the MPL usually affects children and teens and has a locational preference for the mediastinum.³
• Microscopically, the MPL has areas that are similar to the MLS due to the proliferation of round and spindle-shaped lipoblasts.³ However, the MPL has a greater content of rapid-growing, pleomorphic and irregular cells.³

Causes of liposarcoma

Liposarcoma is related to genetic mutations. 

• The subtypes ATL, WDL and DDL are due to chromosome abnormalities like an extra ring-shaped chromosome, or a giant rod-shaped chromosome 12. Chromosome 12 is where the proto-oncogenes (genes that can potentially cause cancer) MDM2 and CDK4 are located: overexpression of the MDM2 and CDK4 genes promotes excessive cell proliferation. Other genes that can be altered are FRS2, HMGA2, YEATS2, and NAV3.³ However, DLL has either a higher number of mutated genes or a higher level of mutation when compared to ATL and WDL, which results in a more malignant, aggressive progression.³
• Myxoid liposarcoma (MLS) is a result of the translocation of chromosomes 12 and 16, causing the fusion of genes FUS-DDIT3 (making it into an oncogene), or less commonly, the translocation of chromosomes 12 and 22 with fusion of genes EWSR1-DDIT3.
• Pleomorphic liposarcoma (PLS) has an even more complex list of associated mutations, without any characteristic marker.³ Some significant mutations that are worth mentioning are TP53, RB1, and NF1: these are called tumour suppressor genes, that inhibit excessive cell proliferation, and can be entirely absent in PLS cells.³
• Lastly, myxoid pleomorphic liposarcoma (MPL) has a wide range of genetic mutations that are still being studied. However, what has helped classify it as its own entity is that it lacks both the FUS-DDIT3 mutation characteristic of MLS and the absence of tumour suppressor genes of PLS.³ What has been found consistently in MPL cases is the inactivation of RB1, a tumour suppressor gene, but more studies are being done to understand this variation of sarcoma.³

Signs and symptoms of liposarcoma

The most common sign of liposarcoma is a hard mass or swelling in the extremities (especially thighs and lower legs), trunk or head and neck region, as well as masses on the nearby lymph nodes if there is local metastasis. They are usually painless and, unfortunately, most tumours grow from deeper tissues that cannot be easily seen or felt, such as the peritoneum, contributing to its quiet growth until it reaches a bigger size. More aggressive forms, such as MLS, PLS, and MPL can also present with metastatic tumours causing symptoms before the primary tumour is even located.³

Management and treatment for liposarcoma

The best course of treatment for this type of cancer is surgical resection of the tumour. More indolent, benign variants like the ATL can be removed surgically with clear margins more easily, and that can be the treatment on its own, but this is not the case for other variants.

A number of different therapies can be associated with surgery, like radiation therapy and chemotherapy.³ New ingenuous therapies have been studied to target the specific mutated genes, like MDM2 and CDK4, in order to inactivate them.³ PPAR-γ agonists are also being studied, as this molecule is responsible for cell differentiation in fatty tissue, being overexpressed in certain tumours like MLP.³ Immunotherapy to stimulate the patient’s own immune system to attack cancer cells is in its early stages of development, with promising results in the future.³ Metastatic tumours can be treated with surgery or chemotherapy if surgery is not viable or advised.

Although with a myriad of resources to treat this type of sarcoma, liposarcoma still has a high mortality rate without complete surgical resection with clear margins. Without clear margins, there is a risk of dedifferentiation of more benign forms like WDL, increasing aggressiveness. DDL is still mild compared to MLS, PLS and MPL, for example, but it has a 40-75% chance of recurrence, a 10-15% risk of metastasis and a 28% mortality rate: management and treatment are extremely important to reduce risk of recurrence and reduce mortality. More malignant forms like the myxoid and pleomorphic ones have poorer prognosis, with the survival rate in 5 years after diagnosis of PLS dropping to 29%.⁴

Diagnosis

An accurate diagnosis depends entirely on a biopsy, to properly identify subtypes of this particular cancer. A medical professional should look for hard masses or swelling, as well as lymph node involvement, in order to diagnose the patient. Complementary exams can and should be performed: medical ultrasonography or an MRI can determine the extension and relation to surrounding tissue.

Complications

Long-term survival is poor for more malignant tumours like PLS, MLS and MPL.⁴ Survival rates drop dramatically after five years due to increased risk of recurrence and metastasis, including bone, liver, and lung tumours.

FAQs

How can I prevent liposarcoma?

Unfortunately, due to the genetic cause of the disease, there is no way to prevent it for sure. If you have cases of liposarcoma in your family, especially close relatives, the risk of having or developing this cancer can be accessed by a medical professional.

How common is liposarcoma?

It is the most common type of soft tissue sarcoma, and it represents 20% of all sarcoma cases in adults.¹

Who is at risk of liposarcoma?

People who have had cases of liposarcoma in their families are more at risk of developing this disease, due to the genetic cause. There have been reports of cases of pleomorphic liposarcoma affecting patients with Li-Fraumeni syndrome and Muir-Torre syndrome, both genetic disorders that increase the risk of cancer.⁵

What can I expect if I have liposarcoma?

Well-differentiated tumours like ATL and WDS have a better prognosis and surgery is almost always enough to cure the patient. However, other malignant forms such as DDL, MLS, PLS and MPL can be harder to treat and might require additional surgeries, chemotherapy or radiotherapy, and have an increased risk of metastasis and recurrence, requiring life-long medical attention.³ Promising new therapies like immunotherapy and gene-targeting chemotherapy are being studied and though they still have a long way to go, they show promising results and better outcome for the patient.³

When should I see a doctor?

If you present with any hard masses in your extremities, trunk or head and neck area, especially if there is swelling or masses of the lymph nodes surrounding, you should seek medical advice. Prognosis of this type of cancer is much better at earlier stages and you can catch a well-differentiated tumour like WDL before a dedifferentiation/malignant transformation.

Summary

Liposarcoma is a category of cancers, more specifically sarcomas, that arise from fatty tissue cells. They can be categorised into five types, with some like ATL and WDL being more indolent, similar to benign tumours like a lipoma, and other types being infiltrative and aggressive. Common signs are hard masses and swelling, with or without lymph node involvement, and most retroperitoneal tumours are usually only felt once they reach a big size due to the deep localization. Treatment consists of surgery with complete resection along with clear margins, but radiotherapy and chemotherapy have been used to treat this type of cancer. Immunotherapy has been studied with promising results, although it’s in the early stages of development. The prognosis of indolent types is optimal, but usually poor for DDL, PLS, MLS, and MLP, with increased risk of recurrence and poor survival rates.