Liposarcoma is a type of soft tissue sarcoma that begins in the fat cells. Types of liposarcoma include myxoid liposarcoma and pleomorphic liposarcoma.

Liposarcoma

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ZAKA CLINIC GULBERG LAHORE

Saad Ullah Siddiqui

Overview

Liposarcoma is derived from two words: lipo meaning fat, and sarcoma, which means a type of cancer that develops from soft tissues such as cartilage, blood vessels, fats, and connective and fibrous tissue1. Thus, liposarcoma means a type of cancer that develops in lipid cells. It is a rare cancer, with an overall age-adjusted incidence rate of 1.08 per 100,000 population2. 
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Moreover, studies have shown it is predominant in white people, with an incidence rate of 82%&ndash;86% of all tumours 2. Amongst the two sexes, it most commonly occurs in males, accounting for more than 60% of cases2. 
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The soft tissue cancer can develop in any part of the body but is most common in the abdomen, arms, and legs3. It then spreads to other parts of the body, targeting lipid cells and putting pressure on nearby organs. Liposarcoma is also called a &#39;lipomatous tumour&#39; and may be confused with lipomas, which are benign lumps under the skin. The two can be differentiated by an expert after conducting tests such as biopsy, MRI, and PET scans.&nbsp; 
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Liposarcoma can be divided into 5 categories based on histopathology. 
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<h5>1. Well-differentiated:</h5>

This is the most common type, accounting for nearly 50% of all liposarcomas4. The cells closely resemble mature adipose tissues except that it includes fibrous septa that have variable nuclear atypia5. Well-differentiated liposarcoma is also called a low-grade malignancy since it does not metastasize. In 2002, WHO classified it under atypical lipomatous tumours6. Moreover, it has an excellent prognosis, with a 5-year survival rate of 95.5%2. 
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<h5>2. Dedifferentiated:</h5>

This is a more aggressive type of liposarcoma, often occurring after a pre existing case of well-differentiated liposarcoma7. It accounts for 20% of liposarcoma cases2. Histologically, the cells resemble undifferentiated pleomorphic or spindle cell sarcoma5. Unfortunately, the prognosis for this type of liposarcoma is not good, with only 57.2% of patients surviving for 5 years or more after their diagnosis2. 
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<h5>3. Myxoid</h5>

Myxoid liposarcoma is most commonly found in the lower extremities8. It has a tendency to metastasize to distant bones, muscles, and skin, similar to the dedifferentiated form. This form can be recognized microscopically because of a distinct composition of bland spindle cells suspended in a myxoid stroma. It also has a characteristic vascular network that is often referred to as a &#39;chicken wire&#39; and &#39;crow&#39;s feet&#39; pattern9. The prognosis stands somewhere in the middle of the previously described types, with 85.7% of patients surviving 5 years or more2. 
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<h5>4. Round cell</h5>

Round cell liposarcoma is often poorly differentiated from myxoid liposarcoma. Since the two round cell types look similar histologically, it is difficult to distinguish whether an otherwise normal-looking myxoid liposarcoma may present a neoplasm that behaves like a high-grade sarcoma10. The only true difference between the two types is the fact that myxoid is low-grade while the round cell type is high-grade. 
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<h5>5. Pleomorphic</h5>

This type is, without doubt, the rarest, with only 7-8% of all liposarcomas being pleomorphic2. Moreover, it is the second worst type when it comes to prognosis, just 64% of patients survive 5 years after diagnosis, even less if upper extremities are involved2. Thus, it is categorized as a high-grade sarcoma and has a high chance of recurrence.&nbsp; 
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Signs and Symptoms

These can vary depending on the location of the lump, however, more generalised symptoms include:

1) &nbsp; &nbsp; Swelling

2) &nbsp; &nbsp; Constipation

3) &nbsp; &nbsp; Pain

4) &nbsp; &nbsp; Difficulty breathing

5) &nbsp; &nbsp; Blood in vomit

6) &nbsp; &nbsp; Weakness 
&nbsp;

If the tumour exists in the extremities, it can cause the following:

1) &nbsp; &nbsp; Pain

2) &nbsp; &nbsp; Swelling

3) &nbsp; &nbsp; Lump of tissue under your skin

4) &nbsp; &nbsp; Limb weakness 
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If tumour forms in the abdomen, it causes the following:

1) &nbsp; &nbsp; Abdominal pain and swelling

2) &nbsp; &nbsp; Constipation

3) &nbsp; &nbsp; Stool containing blood

4) &nbsp; &nbsp; Loss of appetite 
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Causes

The exact cause of this disease is still unknown; however, most experts agree that the disease begins as a result of gene mutation in the fat cells. These mutated genes then rapidly multiply and accumulate forming a lump, which can be palpated. The speed with which these cells grow depends on the type of liposarcoma. 
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<h5>1.Patients with a family history</h5>

Patients with a family history of liposarcoma or other cancers can take a genetic test to see if they carry a mutated allele or not. The test also focuses on noting any genetic defects that may increase the risk of developing soft tissue sarcomas. If any abnormality is observed in the test, the patient should consult their respective physician about the next steps to prevent cancer from developing. Moreover, with or without the test, they should still keep a note of any unexplained lumps and other symptoms associated with the sarcoma, and notify their healthcare provider immediately. 
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<h5>2.Patients without a family history</h5>

Currently, no screening tests exist for people who do not have a family history of liposarcoma, as the disease is so rare. Therefore, it is important to remain vigilant and have regular health checkups as frequently as possible. 
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Diagnosis

To diagnose the disease several tests must be performed to ensure clinical correlation with the symptoms. 
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<h5>1.Medical History and Physical Exam</h5>

The patient will first be asked a series of questions about past medical illnesses that they have been dealing with and a history of sarcomas or other carcinomas in their family. After this, they will be physically examined to note the lump(s), their location, and their size. 
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<h5>2.Imaging Tests</h5>

The next set of tests involves imaging to view the actual lump more clearly, see how deep it is and if it includes a metastatic activity or is benign. The doctor may ask to perform one or more of these tests. 
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<ul>
	<li>&nbsp;X-Ray: This is the most basic test and gives a general view of the lump. The doctor may also ask for a chest X-ray to rule out any possibility that the sarcoma has spread to the lungs. 
	&nbsp;</li>
	<li>&nbsp;CT Scan: Computed tomography (CT) scans work with X-rays to provide a detailed cross-sectional image of the body. It not only tells the exact location of the lumps, but also allows the doctor to see if the sarcoma has spread to other organs such as the liver, lungs, etc. This test is mostly performed for lumps in the abdomen or chest. The test can also be used to guide a biopsy needle into the tumour inside the body. CT-guided needle biopsy is performed by a radiologist. 
	&nbsp;</li>
	<li>MRI (magnetic resonance imaging) : MRI uses strong magnetic waves to generate an internal picture of the body. The procedure involves lying still on an MRI scanning table, while the machine takes a detailed image of your body. It is efficient in not just deducing whether the tumour is a sarcoma or not, but also how deep it is, and what other structures are involved. It can tell the doctors the exact condition of the spread if it&#39;s localized or has affected surrounding bones, muscles, cartilage, and organs. 
	&nbsp;</li>
	<li>Ultrasound: Unlike MRI or X-ray, this exam uses sound waves to view internal structures. It is mostly done for tumours in the abdomen and can differentiate whether the lump is a cyst, a fluid-filled pocket, or an actual tumour. 
	&nbsp;</li>
	<li>PET Scan: A PET scan may be performed alone or with CT. A radioactive sugar is injected into the blood shortly before the test. Since the rapidly multiplying cancer cells use glucose at a faster rate than normal cells, the image produced shows a higher concentration of the radioactive substance in the cancer site. This can help locate a very precise image of the extent of the spread.</li>
</ul>

<h5>3. Biopsy</h5>

If physical exams and imaging tests suggest any malignancy, the doctor may conduct a biopsy to confirm the suspicion. In this procedure, a surgical incision is made to cut out a small part of the tumour and view it under the microscope to observe if the cells are histologically different from normal cells and further identify the type of carcinoma. 
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Different types of biopsies exist based on the size and location of the tumour. However, fine needle aspiration is preferred by most physicians as the first step. 
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Staging and Grading 12

<ul>
	<li>Staging: How much the tumour has expanded or spread from its original location is used to determine the stage of malignancy. Your test and scan results will reflect this.</li>
	<li>Stage1- describes low-grade cancer that is less than 5 cm, and has not spread to other body parts</li>
	<li>Stage2- refers to any grade of cancer that is greater than grade one, but has not spread to other body parts.</li>
	<li>Stage3- High-grade cancer that has not spread to other body parts.</li>
	<li>Stage4- Any cancer, regardless of grade or size, that has migrated to another area of the body. 
	&nbsp;</li>
</ul>

Grading: The cancer grade identifies how different the malignant cells are from healthy cells. The grade will provide some insight into the potential rate of growth of the malignancy. 
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Low-grade: cancer cells are less aggressive, slower growing, bear resemblance to normal cells, and are less likely to spread. 
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Intermediate-grade: The cancer cells are developing a bit more quickly and exhibit a more abnormal appearance. 
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High-grade: The cancer cells are more aggressive, have an abnormal appearance, proliferate quickly, and are likely to spread faster. 
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Treatment

After diagnosis and staging, the next step is treating the sarcoma. Treatment options vary depending on the stage of cancer, size, and location of the tumour. There are four major treatment options: 
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<h5>1. Surgery:</h5>

Surgery is the preferred treatment option. The tumour can be removed surgically to control its growth, but it&#39;s important to ensure that all cancer cells are removed so that chances of relapse are minimal. However, retroperitoneal liposarcoma has a frequency of returning 2 years after surgical resection. Hence, a follow-up is critical to control any such incidences before they become aggressive13. Surgery is avoided in cases where cancer has spread to nearby organs. In that case, the oncologist suggests other treatments to control the size and shrink it before removing it once and for all by surgery. 
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Risks of uSrgery14

<ul>
	<li>Infection</li>
	<li>Blood clots</li>
	<li>Heavy bleeding</li>
	<li>Reactions to anesthesia</li>
	<li>Other organs are damaged</li>
	<li>Swelling</li>
	<li>Difficulty using arms or legs 
	&nbsp;</li>
</ul>

<h5>2. Chemotherapy:</h5>

This treatment involves the use of certain drugs that kill cancer cells, mostly by interfering with their metabolism pathways or reproductive pathways. Chemotherapeutic drugs vary in aggression, with some working faster and more aggressively than others. They can be taken orally, via capsules and tablets, or intravenously. It can be done as the first-line treatment or after surgery to ensure all cells are eliminated from the body and minimize the risk of recurrence. 
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Some new chemotherapeutic drugs include15

<ul>
	<li>Eribulin Mesylate (Halaven) - This drug is injected directly into the blood. It interferes with cell division, preventing mitosis. The microtubule polymerization is disrupted, which results in tubulin dimers being changed to aggregates that cannot be used by the cell during the prometaphase stage of mitosis. This results in cells being locked in a G2-M state and then ultimately being eliminated by apoptosis. 
	&nbsp;</li>
	<li>Trabectedin (Yondelis) - This drug interferes with the minor groove of the DNA helix, resulting in a change in the ladder-like double helix structure, such that it bends towards the major groove. This configuration change prevents DNA binding proteins and transcription factors from binding with the double helix. Thus, it affects the repair mechanism of the cell and eventually results in cell death.</li>
</ul>

Risks associated with chemotherapy14

<ul>
	<li>Hair loss</li>
	<li>Loss of appetite</li>
	<li>Low blood cell count</li>
	<li>Nausea and vomiting</li>
	<li>Weakness 
	&nbsp;</li>
</ul>

<h5>3. Radiation</h5>

It involves the use of high-energy rays to target and kill cancer cells by inhibiting cellular proliferation. Radiation is often suggested as a first-line treatment or along with chemotherapy. It can be used before and after surgery; before to shrink a tumour so that it can be removed, and after to kill any remaining cancer cells so that the sarcoma does not resurface. 
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A wide range of radiation therapies exists, which are grouped under two categories: external beam and internal beam. External beam, as the name suggests comes from a machine that aims radiation at your cancer cells. It is a local treatment targeting only specific parts of the body. Internal beam on the other hand involves putting a source of radiation within your body. The decision to choose which type of protocol to use depends on several factors such as the size of the tumour, place of tumour, type of tumour, the aggression of sarcoma, etc. 
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<h5>&nbsp; 4. Targeted cell therapy16</h5>

Targeted therapy goes after proteins that regulate the division and spread of cancer cells. Researchers are better able to develop cancer treatments that target these proteins as they gain knowledge about the DNA alterations and proteins that fuel cancer. The types are: 
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<ol>
	<li>Small Molecule Drugs:They are employed for targets inside cells since they are tiny enough to easily enter cells. 
	&nbsp;</li>
	<li>Monoclonal Antibodies:Also called therapeutic antibodies, these are created in the lab. These proteins bind to particular sites on the cancer cells. Some monoclonal antibodies identify cancer cells so that the immune system can more easily identify and eliminate them. Other monoclonal antibodies directly inhibit the growth of cancer cells or trigger their destruction. And some can deliver toxins to cancer cells. 
	&nbsp;</li>
</ol>

To treat liposarcoma, doctors occasionally have to amputate (remove) a whole limb. After surgery, patients in these situations might need an artificial limb or prosthetic.

Complications from liposarcoma therapy itself are possible. Chemotherapy and radiation therapy sometimes have unfavourable side effects. Once the treatment is over, these adverse effects frequently subside.

Serious complications from long-term esophageal liposarcoma include dysphagia, which can lead to anaemia and weight loss, regurgitation-related aspiration, asphyxiation, and respiratory failure. Liposarcoma of the extremities and retroperitoneum can also have local mass effects on the peritoneal cavity, retroperitoneal structures, and neurovascular bundles of the limbs17. 
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Some other complications are3

<ol>
	<li>Hairloss</li>
	<li>Neuropathy (nerve damage)</li>
	<li>Fever</li>
	<li>Fatigue</li>
	<li>Nausea 
	&nbsp;</li>
</ol>

While the cause remains unknown, a pattern of occurrence has been noted. Based on that the following people are considered to be the most at risk: 
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1.Prior history of radiation

2.Genetic predisposition, which means your family has a history of this disease

3.Long-term exposure to toxic chemicals such as vinyl chloride

4.Damage to the lymphatic system 
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Avoiding exposure to risk factors whenever possible is the only approach to stop some soft tissue sarcomas from developing. Nevertheless, the majority of sarcomas arise in adults with no identified risk factors. There is no known technique to stop this malignancy as of now. Additionally, radiation therapy patients typically have few options. 
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Doctors are attempting to gain a better understanding of sarcoma to better understand how to prevent it, treat it, and care for those who have been diagnosed with the condition. Through clinical trials, new treatment choices for patients may be found in the research areas listed below. Always discuss the best diagnostic and treatment options with your doctor. 
&nbsp;

<ol>
	<li>&nbsp;Immunotherapy - Immunotherapy takes many different forms.&nbsp; Research on immune checkpoint inhibitors has increased significantly. These medications work by disabling immune system defences to activate immunological responses in the body. They are targeted monoclonal antibodies (proteins). Blocking molecules include those with the designations CTLA-4, PD-1, PD-L1, OX40, LAG3, and TIM3. This method has been effective in the treatment of many cancers and sarcoma research studies. 
	&nbsp;</li>
</ol>

White blood cells from a patient&#39;s blood are used in T-cell receptor therapy and chimeric antigen receptor (CAR) T-cell therapy to kill cancer cells. After being extracted from the patient, the cells are modified to produce receptor-specific proteins. The T cells can identify the cancer cells thanks to their receptors. Large quantities of the modified T cells are produced and then put back into the patient&#39;s body. Once within the patient, these T cells hunt down and eliminate cancer cells. When there is a known target on the sarcoma, like in synovial sarcoma and myxoid-round cell liposarcoma, this approach is most effective. This fascinating yet challenging type of immunotherapy is being studied in clinical studies. 
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<ol start="2">
	<li>&nbsp;Improved Drug Delivery - To enhance the absorption and distribution of the medication in the patient&#39;s body, various chemotherapies are integrated into fat molecules known as liposomes. Researchers are exploring other novel approaches to deliver chemotherapy to cancer cells. For instance, chemotherapy can be linked to proteins, allowing them to enter cancer cells. As a result, chemotherapy is given only to cancer cells and not to healthy cells, which can increase efficiency and reduce adverse effects. In certain circumstances, these proteins are antibodies that target, or bind to, a specific marker on a cancer cell. The term &quot;antibody-drug conjugates&quot; refers to these. 
	&nbsp;</li>
	<li>&nbsp;New Drugs - Some kinds of soft-tissue sarcoma may be successfully treated by newly designed and tested drugs. Sarcoma research in this field is currently ongoing. 
	&nbsp;</li>
</ol>

Key Points

<ul>
	<li>Liposarcoma is a type of cancer that develops in lipid cells.</li>
	<li>Liposarcoma can develop in any part of the body, but most commonly affects the abdomen, arms, and legs. It then spreads to other parts of the body, mainly targeting lipid cells and putting pressure on nearby organs.</li>
	<li>Types of liposarcoma include dedifferentiated, well-differentiated, myxoid, round cell, and pleomorphic.</li>
	<li>Some of the generalized symptoms are abdominal swelling, <a href="https://merisehat.pk/disease/constipation">constipation</a>, abdominal pain, difficulty breathing, blood in vomit, and weakness.</li>
	<li>The exact cause of this disease is still a mystery for experts. However, most agree that the disease begins as a result of gene mutation in the fat cells.</li>
	<li>Diagnosis is based on medical history, physical exams, imaging tests and biopsy.</li>
	<li>Treatment includes surgery, chemotherapy, radiation, and targeted therapy.</li>
	<li>Common complications are fever, hair loss, fatigue, neuropathy, and nausea.</li>
	<li>Risk factors include genetic predisposition, history of exposure to radiation, long-term exposure to toxic chemicals, and damaged lymphatic system. 
	&nbsp;</li>
</ul>

[1] NCI Dictionary of Cancer terms. National Cancer Institute.

[2] Bock S, Hoffmann DG, Jiang Y, Chen H, Il'yasova D. Increasing Incidence of Liposarcoma: A Population-Based Study of National Surveillance Databases, 2001-2016. Int J Environ Res Public Health. 2020;17(8):2710. Published 2020 Apr 15. doi:10.3390/ijerph17082710

[3] Liposarcoma: Symptoms, causes, tests and treatments. Cleveland Clinic.

[4] Yamamoto N, Hayashi K, Tanzawa Y, et al. Treatment strategies for well-differentiated liposar

[5] Thway K. Well-differentiated liposarcoma and dedifferentiated liposarcoma: An updated review. Semin Diagn Pathol. 2019;36(2):112-121. doi:10.1053/j.semdp.2019.02.006

[6] Well-differentiated liposarcoma. Well Differentiated Liposarcoma - an overview | ScienceDirect

[7] Nascimento AG. Dedifferentiated liposarcoma. Semin Diagn Pathol. 2001;18(4):263-266.

[8] Myxoid liposarcoma - about the disease. Genetic and Rare Diseases Information Center.

[9] myxoid liposarcoma. Myxoid Liposarcoma - Surgical Pathology Criteria - Stanford University School of Medicine.

[10] JR; STAEKAG. Myxoid/round cell liposarcoma of the extremities. A clinicopathologic study of 29 cases with particular attention to extent of round cell liposarcoma. The American journal of surgical pathology.