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]

History
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 occur 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]

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.

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. Well-differentiated
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.

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

Liposarcoma has a number of different subtypes (ie, well differentiated, dedifferentiated,

myxoid/round cell, pleomorphic), and their response to chemotherapy is not well
documented. [22] Thus, the response rates to chemotherapy of the different histological
subtypes and overall and progression free survival were investigated; survival according
to histological grade was also assessed. This retrospective analysis suggested that
myxoid liposarcoma is relatively chemosensitive in comparison to a combination of
other liposarcomas, in particular dedifferentiated and well-differentiated tumors.
In the case of well-differentiated liposarcoma, grade provides no incremental
information over other histological subtypes in terms of response to therapy. In
myxoid/round cell liposarcoma, the presence of a round cell component may be an
adverse prognostic sign. Tumor site, a high proliferative fraction noted with MIB-1
labeling, and TP53 missense mutations are also adverse prognostic factors in
myxoid/round cell tumors. [23]
For liposarcomas, radiation therapy may be a valuable adjunct to surgery, especially in
those of the myxoid variant.
The use of chemotherapy in liposarcomas remains experimental.
Although surgical resection is the mainstay of curative treatment, patients with large
high-grade liposarcomas may benefit from multimodality treatment with chemotherapy
and radiation. [24]
Treatment of an atypical lipoma using liposuction has been described. [25]
Trabectedin (Yondelis) was approved in November 2015 in the United States for
unresectable or metastatic liposarcoma or leiomyosarcoma in patients who have
received a prior anthracycline-containing regimen. It is an alkylating drug that binds
guanine residues in the minor groove of DNA. Approval was based on a phase 3 trial
(n=518) that showed a statistically significant improvement in progression-free survival
compared with dacarbazine (4.2 mo vs 1.5 mo; P <.0001). No improvement in overall
survival was observed. [26]
In January 2016, eribulin (Halaven) was approved by the US Food and Drug
Administration (FDA) for unresectable or metastatic liposarcoma in patients who
received a prior anthracycline-containing regimen. The FDA approval is based on the
results from the subgroup of 143 patients with liposarcoma. In this subgroup, the results
show a 7-month improvement in survival (15.6 months with eribulin compared with 8.4
months with dacarbazine). The median progression-free survival, a secondary endpoint,
was 2.9 months with eribulin compared with 1.7 months with dacarbazine. However,
eribulin was more toxic than dacarbazine. Treatment-emergent adverse events included
neutropenia (44% vs 24%), pyrexia (28% vs 14%), peripheral sensory neuropathy (20%
vs 4%), and alopecia (35% vs 3%) for eribulin compared with dacarbazine,
respectively. [27]

Surgical Care
The rationale for wide surgical excision of atypical lipomatous tumors is the prevention
of recurrence and dedifferentiation.
Wide and deep surgical excision, along with local radiation and/or chemotherapy, may
be necessary for high-grade lesions.
Given the favorable outcome with wide surgical excision alone, regardless of the
histologic type of the tumor, some authors believe that adjuvant radiation therapy is
unjustified.

Prognosis
The prognosis is affected by the type of liposarcoma present. In general, survival for
extremity tumors is favorable. [29] The histologic grade of localized liposarcomas of the
extremities may be the most important prognostic factor. [30]
The well-differentiated type and most myxoid types have favorable prognoses, with
100% and 88% 5-year survival rates, respectively. [31] However, these tumors are poorly
circumscribed and locally recur after incomplete excision. Although they rarely
metastasize, repeated local recurrences may cause the tumor to evolve into a higher
grade of sarcoma or to dedifferentiate, in which case metastasis is possible.
The form that a dermatologist is most likely to examine at biopsy is 1 of the 3 subtypes
of a well-differentiated liposarcoma, that is, the lipomalike liposarcoma or atypical
lipoma; the other 2, inflammatory and sclerosing, are less likely. The clinical outcome of
this subtype is best predicted by the anatomical location. In the subcutis, lipomalike
liposarcomas are often cured with local excision. Lipomalike liposarcomas rarely recur,
and they do not metastasize. Use of the term atypical lipomatous tumor, a less serious
designation for atypical lipoma, has been suggested.
Round-cell and poorly differentiated types have a poor prognosis. Each has a 5-year
survival rate of about 50% because they recur locally and tend to metastasize quickly
and widely, especially in poorly differentiated liposarcomas. The lungs and the liver are
the most common sites of metastasis. .
Despite high-grade morphology, cutaneous liposarcomas have a favorable clinical
prognosis.
For soft tissue sarcoma involving the popliteal fossa, despite a high rate of
microscopically positive margins, the local recurrence rate reported is only 7%. [32]
Cutaneous and subcutaneous pleomorphic liposarcomas have a more favorable
outcome compared with their deep-seated counterparts, a fact attributable to their small
size and superficial location. [10]