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Background

Liposarcoma is a malignancy of fat cells (see Liposarcoma in the Pediatric Medicine section and Liposarcoma,
Soft Tissue in the Radiology section). In adults, it is the most common soft tissue sarcoma. Liposarcoma
normally appears as a slowly enlarging, painless, nonulcerated submucosal mass in a middle-aged person, but
some lesions grow rapidly and become ulcerated early. Virchow first described liposarcoma in the 1860s.
The development of a liposarcoma from a preexisting benign lipoma is rare. Most cases arise de novo.
Liposarcomas most frequently arise from the deep-seated stroma rather than the submucosal or subcutaneous
fat. Dermal lesions are rare and may resemble pleomorphic fibroma. [1]
The most recent World Health Organization classification of soft tissue tumors recognizes 5 categories of
liposarcomas: (1) well differentiated, which includes the adipocytic, sclerosing, and inflammatory subtypes; (2)
dedifferentiated; (3) myxoid; (4) round cell; and (5) pleomorphic.
A spindle-cell variant of well-differentiated liposarcoma is also described. The concept that round-cell
liposarcoma represents the high-grade counterpart of myxoid liposarcoma is generally accepted. Spindle-cell
liposarcoma is a rare variant of an atypical lipomatous tumor (ie, well-differentiated liposarcoma), and it must
be distinguished from a dedifferentiated liposarcoma with metastatic potential and a benign spindle-cell lipoma.
The advent of cytogenetic and molecular investigations has contributed to better categorization of this subset of
mesenchymal neoplasms. Not only have they provided new insights into the biology of these tumors, but they
have also validated the current classification schemes based on conventional morphologic observations. [2, 3, 4, 5]
Liposarcoma occurs in 3 main biologic forms: (1) well-differentiated liposarcoma; (2) myxoid and/or round cell;
and (3) pleomorphic. In rare circumstances, lesions can have a combination of morphologic types; these are
classified as combined or mixed-type liposarcomas.
The anatomical distribution of liposarcoma appears to be partly related to the histologic type. Well-differentiated
liposarcoma tends to occur in deep soft tissues of both the limbs and the retroperitoneum. Myxoid and/or
round-cell liposarcomas and pleomorphic liposarcomas have a striking predilection for the limbs, and
dedifferentiated liposarcoma occurs predominantly in the retroperitoneum. Although any liposarcoma subtype
occasionally arises in the subcutis, involvement of the dermis appears to be exceedingly rare.

Pathophysiology
Liposarcoma is a lipogenic tumor of large deep-seated connective tissue spaces. Fusion proteins created by
chromosomal abnormalities are key components of mesenchymal cancer development. An abnormality of band
12q13 has been associated with the development of liposarcomas. The most common chromosomal
translocation is the FUS-CHOP fusion gene, which encodes a transcription factor necessary for adipocyte
differentiation. These and other distinct genetic aberrations may aid in the diagnosis of particular liposarcoma
subtypes, and they can potentially be targets that can be exploited therapeutically. [6]

Epidemiology
Frequency
United States
Soft tissue sarcomas occur in approximately 5000 patients in the United States per year. Overall, liposarcomas
account for less than 20% of all soft tissue sarcomas, and the average patient age at presentation is 50 years.
However, in children, liposarcomas account for less than 5% of all soft tissue sarcomas; fewer than 60 cases in
children have been reported.
International
With an annual incidence of 2.5 cases per million population, liposarcoma is the most common soft tissue
sarcoma, accounting for approximately 17% of all soft tissue sarcomas and 3% of all liposarcomas in the head
and neck region (usually the neck and the cheek). Oral involvement is rare; as of the year 2000, fewer than 50
oral cases had been reported. The trunk and the lower extremities are the most likely sites of tumor
development.

Race

No association with race or geography is known.

Sex
Liposarcomas are slightly more common in males than in females.

Age
The mean patient age at onset is 50 years. Although liposarcomas account for about 17% of all soft tissue
sarcomas, they are involved in only 4% of childhood soft tissue sarcomas. Cases of liposarcoma are reported
in young adults and teenagers, but cases in children are rare. [7]

Clinical Features
Liposarcomas are most commonly found in the extremities; in the retroperitoneum; and, less often, in the head
and neck area. These tumors are most likely to arise from deep-seated, well-vascularized structures than from
submucosal or subcutaneous fat. Myxoid liposarcoma is usually evident as a deep-seated mass in the lower
extremity of adults, but it may be less commonly be first evident as a primary subcutaneous mass. [8]
Liposarcomas of all subtypes can occ ur in the cutis and the subcutis; however, their primary occurrence in the
skin is rare. Clinically, all cases of liposarcomas in the skin tend to grow in an exophytic manner, presenting as
either dome-shaped or polypoid lesions. In all patients, the neoplasm is centered in the dermis, and it has a
minimal tendency to grow downward into the underlying subcutaneous adipose tissue.
Most patients with liposarcoma have no symptoms until the tumor is large and impinges on neighboring
structures, causing tenderness, pain, or functional disturbances. In the retroperitoneal area, where liposarcoma
is detected at a late stage, the tumor may grow to a substantial size, weighing several pounds at the time of
diagnosis. In general, liposarcoma grows silently, and the patient's estimation of the clinical duration is often
unreliable. The patient eventually becomes aware of a swelling or a mass and reports this finding to the
physician.
Patients may report the following:

Associated episode of trauma to the region containing the mass


Painful swelling (occurs in one third of cases for as long as 6 mo)
Decreased function (ie, range of motion)
Numbness
Enlargement of varicose veins
Fatigue
Abdominal pain
Weight loss
Nausea
Vomiting

Physical
The 3 most common locations of involvement are the thighs, the retroperitoneum, and the inguinal region.
Liposarcoma usually appears as a well-circumscribed palpable mass as large as 10 cm in diameter. The mass
tends to grow slowly over time. The lesion is commonly not tender on palpation. Diffuse abdominal
enlargement may be observed in patients with retroperitoneal disease. Liposarcoma that resembles a skin tag
has been reported but is an exceptionally rare event. [9]
Fascial compartmentalization may cause liposarcomas to have awkward discoid and fusiform shapes rather
than smooth, round forms. Thus, liposarcoma can appear with an array of clinical morphologies and
manifestations. Other aspects to note on physical examination are neurologic involvement and
lymphadenopathy.

Pleomorphic liposarcoma is both uncommon and rarely occurs in the skin and subcutis. [10] They are most often
located on an extremity, trunk, and head and neck and more often involve the subcutaneous, less so the
subcutis or dermis. It may be evident as a painless pedunculated pink papulonodule. [11]

Causes
No well-established causative factor has been identified, although trauma has been implicated.

Diagnostic Considerations
Also consider the following:

Cellular angiofibroma
Solitary fibrous tumor
Cutaneous neurofibroma
Malignant schwannoma
Rhabdomyosarcoma
Leiomyosarcoma
Fibrous histiocytoma
Benign lipoblastoma in infants and children
Late granulomatous reactions from silicone may appear in a site different from that of the injection and may
cause an incorrect diagnosis of liposarcoma.[12] Silicone implants for chin augmentation may create a tissue
reaction that mimics a low-grade liposarcoma.[13]
Myxofibrosarcoma, one of the most common soft tissue sarcomas of elderly patients, may histologically
resemble pleomorphic liposarcoma.[14]
Primary liposarcoma may be evident as metastatic liposarcoma to the head and neck region, including the
gingival mucosa.[15, 16]
Spindle cell lipomas are benign lipomatous tumors that may require histological distinction from liposarcoma.
These lipomas are typically seen in the posterior neck, shoulder, or upper back of older males. [17]
Because cutaneous liposarcoma is extremely rare, the physician must rule out a metastatic lesion.

Laboratory Studies
Cytogenetics may be of value when diagnosing lipomatous tumors because different tumor types have different
more or less specific chromosomal abnormalities. [18] The lipoblastoma, for example, often exhibits
rearrangements of bands 8q11-13, and the gene PLAG1 has been implicated as the target of these
chromosomal changes.

Imaging Studies
CT scanning (see image below) is superior to MRI in detailing cortical bone erosion and tumor mineralization,
whereas MRI is useful in providing views of the long axis of the limb and in depicting the fatty nature of the
tumor.

Computed tomography (CT) scan of a left thigh


shows a huge mass (arrows) with predominant fat attenuation. The central soft-tissue component (asterisk) and thick,
internal septations are consistent with liposarcoma.

Most liposarcomas have well-defined and mostly lobulated margins. The well-differentiated liposarcomas are
composed of mainly fat with septa or nodules. These tumors are hyperintense on T2-weighted images, and
they demonstrate faint enhancement or no enhancement after the intravenous administration of contrast
material.
Myxoid liposarcomas are homogeneous or mildly heterogeneous, and a pseudocapsule can be present.
Pleomorphic types have a markedly heterogeneous internal structure. Both myxoid and pleomorphic lesions
have moderate or marked heterogeneous enhancement after the administration of contrast material. Welldifferentiated liposarcomas may be distinguished from the other types by their largely lipomatous appearance.
The malignancy grade increases with the degree of tumor heterogeneity and contrast enhancement.
Angiography may demonstrate tumor malignancy on the basis of prominent vascularity; thus, angiography may
be of value in planning surgical resection.
Chest radiography may be used as an initial screening for pulmonary metastases; however, the definitive test
for detection of pulmonary metastases is chest CT scanning.
An early-phase bone scan may show a marked increase of radioisotopic uptake.
Risk assessment in liposarcoma patients can be based on [(18)F]fluorodeoxyglucose (FDG) PET imaging.
[19]
Although tumor grade and subtype are considered standard parameters for risk assessment in patients with
liposarcoma, pretherapy tumor standardized uptake values obtained by FDG PET imaging was found to be a
more useful parameter for risk assessment in liposarcoma compared with tumor grade or subtype. A maximum
standardized uptake value of more than 3.6 was associated with significantly reduced disease-free survival and
identified patients at high risk for developing early local recurrences or metastatic disease.
Also see Liposarcoma, Soft Tissue.

Procedures
The diagnostic procedure of choice for liposarcoma is open biopsy. With superficial, small, fatty tumors,
excisional biopsy is recommended for diagnosis. In large (>3 cm) and deep tumors, diagnosis and treatment
may involve open incisional biopsy followed by definitive resection.
Fine-needle aspiration or biopsy should be followed by histologic and immunohistochemical examination.
Adjunctive tests for MDM2 (murine double minute 2) may be helpful to distinguish liposarcoma from benign
fatty neoplasms, but cutaneous and subcutaneous pleomorphic liposarcoma is less likely to demonstrate
amplification.[20, 21] Immunohistochemical examination aids in excluding other sarcomas. Lipid staining may be

helpful, although Sudan black or oil red O stains are generally insufficient for diagnosis. Helpful stains include
the following:

S-100 - Positive results in fat cells and lipoblasts


Alpha-1-antitrypsin - Positive results in malignant fibrous histiocytomas
Desmin - Positive results in leiomyosarcomas
Myoglobin - Positive results in rhabdomyosarcomas

Histologic Findings
The recognition of lipoblasts is the key finding in the diagnosis of liposarcoma. A lipoblast has the ability to
produce and accumulate nonmembrane-bound lipid within its cytoplasm. The key morphologic features are
well-demarcated cytoplasmic lipid that shifts, causes indentations in an irregular hyperchromatic nucleus, and
creates a characteristic scalloping of the nuclear membrane.
The stage and further differentiation into 1 of the 4 major types affect the prognosis.
Well-differentiated liposarcomas usually contain a predominance of mature fat cells with relatively few, widely
scattered lipoblasts. A misdiagnosis of lipoma can result from inadequate sampling. In the sclerosing subtype of
a well-differentiated liposarcoma, collagen fibrils that encircle fat cells and lipoblasts make up a prominent part
of the matrix.
Myxoid liposarcoma, the most common type, is diagnosed by the observation of a delicate plexiform capillary
network that is associated with both primitive mesenchymelike cells and a variable number of lipoblasts. The
stroma contains a large proportion of myxoid ground substance (ie, hyaluronic acid), in which numerous
microcysts may form.
In the round-cell type, lipoblasts are interspersed among sheets of poorly differentiated round cells.
Poorly differentiated pleomorphic liposarcoma is recognized by a mixture of bizarre, often multivacuolated
lipoblasts and atypical stromal cells, many of which contain highly abnormal mitotic figures. Hemorrhagic and
necrotic areas are common. Lipoblasts are present.

Staging
The Enneking oncologic staging system defines the biologic behavior of primary tumors. This system has
proven to be effective in planning surgery for limb lesions (eg, intralesional, marginal, wide, radical) and in
evaluating its results. Note the following:

The Enneking staging system divides benign tumors into 3 stages: S1, S2, and S3.
Localized malignant tumors are divided into 4 stages: IA, IB, IIA, and IIB.
Two other stages include metastatic high-grade intracompartmental tumors, or stage IIIA tumors, and
extracompartmental malignant tumors, or stage IIIB tumors.

This classification scheme was formerly used to describe long-bone tumors.

This staging system is based on a complete preoperative workup that includes an assessment of the
clinical features; the radiographic pattern and CT and MRI data regarding the extension of the tumor; the
peculiar imaging features of the tumor and its relationship to the neighboring tissues; the findings from
isotopic scanning, which provides information about local aggression and systemic diffusion; and the
histologic findings obtained at biopsy.
Surgical staging is appropriate only after the diagnosis is established and the oncologic stage is determined.