Liposarcoma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]; Ammu Susheela, M.D. [3]

Liposarcoma is a uncommon cancer of connective tissues. Liposarcoma is a malignant tumor that arises in fat cells in deep soft tissue, such as that inside the thigh or in the retroperitoneum.

They are typically large bulky tumors which tend to have multiple smaller satellites extending beyond the main confines of the tumor.

Liposarcoma was first described by Dr. Rudolph Virchow, a German pathologist, in 1857. Virchow reported a “myxoma lipomatoides malignum”, highlighting the malignant nature of the tumor. Between 1954 and 1979, several authors reported cases of liposarcoma and suggested that liposarcoma should be classified according to histopathological analysis into well-differentiated, myxoid, and dedifferentiated subtypes.

Liposarcoma may be classified into well-differentiated, de-differentiated, myxoid, round cell, or pleomorphic liposarcoma.

The pathogenesis of liposarcoma depends on the histological subtype. The role of proto-oncogenes has been implicated in the development of well-differentiated liposarcoma

There are no established causes for liposarcoma.

Liposarcoma must be differentiated from other diseases that cause a painless, growing mass such as spindle cell lipoma, neurofibroma, dermatofibrosarcoma protuberans, and malignant peripheral nerve sheath tumor.

Liposarcoma is the second most common type of all soft tissue sarcomas in adults. The annual incidence is 0.25 cases per 100,000 individuals. Men are slightly more affected with liposarcoma than women. It is most frequent in middle-aged and older adults.

Common risk factors in the development of liposarcoma include chemical carcinogens, radiation, immunodeficiency, genetic disorders, and viral infections.

Common complication of liposarcoma include metastasis. Mass may compress adjacent structures causing different clinical manifestations. Metastasis is the most important aspect to assess in the prognosis of liposarcoma. The prognosis will depend on the histopathological subtype, being the well differentiated liposarcoma the subtype with the best prognosis, and the pleomorphic liposarcoma with the worst prognosis.

The staging of liposarcoma is based on the TNM classification, which includes primary tumor spread, lymph node involvement, and presence of metastasis.

Liposarcoma usually presents as a painless mass. The most common location of a liposarcoma is the lower extremities. Patients with retroperitoneal liposarcoma remain asymptomatic until the mass invades adjacent structures, which may cause pain or obstructive symptoms.

Physical examination findings of liposarcoma depend on the location of the tumor. Since most liposarcomas are located in the lower extremities, liposarcoma is commonly associated with the findings of palpable firm nontender mass in one lower extremity. Physical examination of retroperitoneal liposarcomas is usually unremarkable, but other pertinent findings on physical examination of retroperitoneal liposarcomas include palpation of an abdominal mass, abdominal distension, and tenderness.

There are no specific laboratory tests for the diagnosis of liposarcoma. The pertinent laboratory findings of liposarcoma include anemia and elevated BUN due to GI bleeding and elevated creatinine among patients with obstructive nephropathy.

The definitive diagnosis of liposarcoma is made by biopsy, which also provides histopathological classification of the liposarcoma’s subtype.

CT imaging is crucial for the diagnosis of liposarcoma. CT scan may detect regions of lipid and non-lipid components that correlate with histological subtypes of liposarcoma. CT imaging may demonstrate the size, location, and depth of a liposarcoma, as well as lymph node involvement and distant metastasis. CT findings may be correlated with the histopathological subtype.

MRI is the optimal imaging test for the diagnosis of liposarcoma. MRI findings for a well-differentiated liposarcoma include a mass with at least 75% of adipose content with thin irregular septa. MRI also evaluates the size, location, and depth of the mass. MRI findings help to differentiate between the different subtypes of liposarcoma and help to assess distant metastasis.

Positron emission tomography (PET) scan is useful in cases where the liposarcoma is firm, deep, and has a size greater than 3 cm.^[1] PET scan may also help evaluate the grade and prognosis of the tumor,as well as its shrinkage following chemotherapy.

Li-Fraumeni syndrome is associated with liposarcoma. Mutations in the TP53 gene that encodes the tumor suppressor gene p53 cause Li-Fraumeni syndrome.^[1]

Medical therapy for liposarcoma includes Chemotherapy, chemoradiation, immunotherapy and targeted therapy.

The predominant therapy for liposarcoma is surgical resection. Adjunctive chemotherapy and radiation may be required.

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]

Liposarcoma was first described by Rudolph Virchow, a German pathologist, in 1857. Virchow reported a “myxoma lipomatoides malignum”, highlighting the malignant nature of the tumor. Between 1954 and 1979, several authors reported cases of liposarcoma and suggested that liposarcoma should be classified according to histopathological analysis into well-differentiated, myxoid, and dedifferentiated subtypes.

• Liposarcoma was first discovered in 1857 by Rudolph Virchow, a German pathologist, who described a tumor arising from fat tissue. Originally, Virchow called the tumor “myxoma lipomatodes malignum”.^[1]
• Virchow demonstrated that the tumor has a malignant nature.
• In 1859, Delamater reported a “mammoth” retroperitoneal tumor with lipomatous aspect.^[2]

• Several lesions similar to lipoma myxomatodes were reported by Robertson in 1916.^[3]
• In 1921, Von Wahlendorf demonstrated that retroperitoneal tumors of the adipose tissue that are dangerous in a collective review of liposarcomas (14%) of 168 collected cases.^[4]
• The malignant component of the liposarcoma was described in 1927 by Seids et al., who reported malignant lesions with a myxoid component.^[5]
• Ewing described adipose tumors that arise from the embryonal tissue in adults in 1935.^[6]
• In 1942 and 1944, liposarcoma was described in different anatomical locations and with different clinical manifestations that were associated with the disease prognosis. ^[7][8]
• Between 1954 and 1979, several authors reported cases of liposarcoma and suggested that liposarcoma should be classified according to histopathological analysis into well-differentiarted, myxoid, and dedifferentiated subtypes. ^[9][10][11]

• In 2014, Rob Ford, the mayor of Toronto, was diagnosed with an abdominal pleomorphic liposarcoma.

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Liposarcoma may be classified into well-differentiated, de-differentiated, myxoid, round cell, or pleomorphic liposarcoma.

Liposarcoma is a type of soft tissue sarcoma, which accounts for approximately 20% of the mesenchymal malignancies. Liposarcomas may be classified into different subtypes, according to their histologic, cytogenetic, biologic, and molecular features. The World Health Organization proposed the following classification of liposarcomas:^[1][2][3]

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]Sabawoon Mirwais, M.B.B.S, M.D.[3]

Liposarcoma is the most common sarcoma of soft tissue. The pathogenesis of liposarcoma depends on the histological sub-type. The two sub-types, well differentiated and dedifferentiated, are the two most commonly occurring liposarcomas. The majority of well differentiated liposarcomas arise in the retroperitoneum. The chromosome region 12q13-15, is rich in protooncogenes, including the CHOP, CDK4, MDM2, HMGI-C, GLI, SAS, OS1, and the OS9, all of which play an important role in the pathogenesis of many neoplasms. Liposarcoma is associated with genetic conditions like Li-Fraumeni syndrome. Liposarcoma usually presents as a mass which often resembles lipoma and is multinodular. Microscopic pathological findings of liposarcoma depend on the sub-type.

• Liposarcoma is the most common sarcoma of soft tissue.^[1]
• The two sub-types, well differentiated and dedifferentiated, are the two most commonly occurring liposarcomas.^[2]
• The majority of well differentiated liposarcomas arise in the retroperitoneum.^[3][4]

• The tumor can also arise in the deep soft tissue of the thigh, mediastinum, and paratesticular area.^[5][6]

• Retroperitoneal tumors are more likely to recur.^[7][8]
• The dedifferentiated sub-type arises as a primary or de novo lesion in majority of the cases.^{[9][10][11][12]}

• The dedifferentiated sub-type is clinically more aggressive than the well differentiated liposarcoma.^{[13][14][15][16]}

• The chromosome region 12q13-15, is rich in protooncogenes, including the CHOP, CDK4, MDM2, HMGI-C, GLI, SAS, OS1, and the OS9, all of which play an important role in the pathogenesis of many neoplasms.
• Amplification of some of these regions, with concomitant amplification of their proteins, has clearly been demonstrated in liposarcoma.^[17]
• The difference between malignant and benign masses resides in the amount of rearranged gene present in each tissue.^[17]

• Liposarcoma is associated with genetic conditions like Li-Fraumeni syndrome.

• Liposarcoma usually presents as a mass which often resembles lipoma and is multinodular.
• Cut surface may be soft or firm and is yellow in color.
• Focal mucinous area may be seen.
• Areas of necrosis may be noted.

Each liposarcoma sub-type has specific characteristics:

• The particular histological finding in this type of well differentiated liposarcoma is the identification of distinctive stromal cells distributed across the tissue, which are associated with lipoblasts filled with multiple vacuoles.
• This association forms a collagenous background of fibrillary appearance.
• In certain cases, the fibrous component of the neoplasm may occupy most of its mass.^[18]

• Frequently composed by adipocytes with different cell sizes, hyperchromasia, and nuclear atypia.
• Fibrous septa may be identified surrounding adipocytes, containing hyperchromatic stromal cells.
• Besides these two types of cells, mono- or multi-vacuolated lipoblasts may also be identified.
• Lipoblasts are characterized by the presence of single (mono) or multiple (multi) peripheral cytoplasmic vacuoles that press on the hyperchromatic nucleus.^[18]
• In general, adipocytic neoplasms are often identified by the presence of these lipoblasts.
• Additionally, lipoblasts may infrequently be absent, which makes the diagnosis of adipocytic neoplasm more difficult but possible with the help of other histological features.^[18]

• Its adipocytic nature may be misidentified due to the heavy chronic inflammatory infiltrate.
• The inflammatory component is frequently composed of different lympho–plasmacytic aggregates. These tend to be predominantly formed by a specific type of B-cell, or less commonly T-cells may populate the inflammatory aggregate.^[18][19][20]

• This is a rare adult-type of well-differentiated liposarcoma.
• It results from the proliferation of neural-like spindle cells, which are organized in a fibrous structure, that contains lipoblasts.^[21][22]

• In this form of liposarcoma, there is a transition from a low-grade differentiation to a high-grade differentiation within the same mass of well-differentiated liposarcoma.^[18][23][24]
• 90% of dedifferentiation from well-differentiated liposarcomas occur in primary tumors, while the remaining 10% occur in recurrent neoplasms.^{[25][26][27][28]}

• They have a non-homogenous appearance with cystic and solid components.

• It is a high-grade liposarcoma which is a poorly differentiated form of myxoid sarcoma.
• It has a very poor prognosis and often metastasizes to the retroperitoneum, pleural cavity, soft tissue, or pelvis and very rarely to the lungs.
• Microscopically, it consists of small, round, or spindle cells with sparse eosinophilic and granular cytoplasm and large nuclei.
• It may have scattered lipoblasts and areas of necrosis.

• Pleomorphic cells may be identified with enlarged round to bizarre nuclei.

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

There are no established causes for liposarcoma.

There are no established causes for liposarcoma.

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Liposarcoma must be differentiated from other diseases that cause a painless, growing mass such as spindle cell lipoma, neurofibroma, dermatofibrosarcoma protuberans, and malignant peripheral nerve sheath tumor.

Differential diagnosis of liposarcoma includes nonadipocytic lesions such as:^[1]

• Inflammatory myofibroblastic tumor
• Castleman’s disease
• Spindle cell lipoma
• Neurofibroma
• Dermatofibrosarcoma protuberans
• Malignant peripheral nerve sheath tumor

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Liposarcoma is the second most common type of all soft tissue sarcomas in adults. The incidence of liposarcoma was estimated to be 0.25 cases per 100,000 individuals. Men are slightly more affected with liposarcoma than women. It is most frequent in middle-aged and older adults. The incidence of liposarcoma was estimated to be 0.25 cases per 100,000 individuals. Liposarcoma affects people of all ethnic groups but slightly more in the people from black ethnic background.

• The incidence of liposarcoma was estimated to be 0.25 cases per 100,000 individuals.^[1]

• Liposarcoma most frequently occurs in the middle-aged and older adults (age 40 and above).
• Tumors of adult life have a median age of 55 – 60 years.

• Men are slightly more affected with liposarcoma than women.

• Liposarcoma affects people of all ethnic groups but slightly more in the people from black ethnic background.

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Liposarcoma is the second most common type of all soft tissue sarcomas in adults. The incidence of liposarcoma was estimated to be 0.25 cases per 100,000 individuals. Men are slightly more affected with liposarcoma than women. It is most frequent in middle-aged and older adults. The incidence of liposarcoma was estimated to be 0.25 cases per 100,000 individuals. Liposarcoma affects people of all ethnic groups but slightly more in the people from black ethnic background.

• The incidence of liposarcoma was estimated to be 0.25 cases per 100,000 individuals.^[1]

• Liposarcoma most frequently occurs in the middle-aged and older adults (age 40 and above).
• Tumors of adult life have a median age of 55 – 60 years.

• Men are slightly more affected with liposarcoma than women.

• Liposarcoma affects people of all ethnic groups but slightly more in the people from black ethnic background.

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]

The natural history of liposarcoma depends on the histopathological sub-type and location of the tumor. If left untreated, liposarcomas may remain silent for a long time, especially if they are located in the retroperitoneum. Liposarcoma may metastasize to other organs. Lung is the most common location for metastatic disease. Retroperitoneal liposarcomas may affect adjacent organs and structures, that can lead to kidney disease or vascular compression. The prognosis of liposarcoma will depend on the histopathological sub-type. Atypical lipomatous neoplasm/well-differentiated liposarcoma has a low metastasis risk, but may recur locally. The prognosis for this sub-type is better than for other sub-types of liposarcoma. The 5-year disease free survival rate for liposarcoma located in the extremities is 74%.

• The natural history of liposarcoma depends on the histopathological sub-type and location of the tumor.
• If left untreated, liposarcomas may remain silent for a long time, especially if they are located in the retroperitoneum.^[1]
• The most common presentation of a liposarcoma located in the extremities is a painless growing mass without additional symptoms.

• Liposarcoma may metastasize to other organs.
• Lung is the most common location for metastatic disease.
• A myxoid liposarcoma metastasizes more commonly to extrapulmonary locations, such as retroperitoneum, pericardium, chest wall, pleura, and pelvic soft tissue.^[1]
• Retroperitoneal liposarcomas may affect adjacent organs and structures, that can lead to kidney disease or vascular compression.^[2]
• A case of pancreatitis has been reported due to a dedifferentiated retroperitoneal liposarcoma.^[3]
• Other complications can include:

• Intestinal obstruction, ischemia, and/or perforation^[4]
• Hydronephrosis^[5]
• Ureteric fistula
• Aortic rupture

• The prognosis of liposarcoma will depend on the histopathological sub-type.
• Atypical lipomatous neoplasm/well-differentiated liposarcoma has a low metastasis risk, but may recur locally. The prognosis for this sub-type is better than for other sub-types of liposarcoma.^[1]
• The pleomorphic liposarcoma has a high metastasis potential and a high recurrence rate. The 5-year disease free survival rate for pleomorphic liposarcoma is 40%.^[6]
• The 5-year disease free survival rate for liposarcoma located in the extremities is 74%.^[7]

Template:WikiDoc Sources