S p e c i a l A r t i c l e • P i c t o r i a l E s s ay

O’Regan et al.
Imaging of Liposarcoma

Special Article
Pictorial Essay

Imaging of Liposarcoma:
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Classification, Patterns of Tumor

Recurrence, and Response to
Treatment
Kevin N. O’Regan1 OBJECTIVE. The purpose of this study was to illustrate the subtypes of liposarcoma (LPS)
Jyothi Jagannathan and the significance of the nonlipomatous tumor components using multiple imaging modalities.
Katherine Krajewski CONCLUSION. The subtypes of LPS with greater nonlipomatous soft-tissue compo-
Katherine Zukotynski nents on imaging studies tend to show less differentiation and are usually more aggressive
Frederico Souza both histologically and clinically. Imaging plays an important role in the diagnosis, surveil-
lance, and response assessment of LPS.
Andrew J. Wagner
Nikhil Ramaiya
O’Regan KN, Jagannathan J, Krajewski K, et al.

Keywords: CT, liposarcoma, MRI
DOI:10.2214/AJR.10.5824
Received September 10, 2010; accepted after revision
January 25, 2011.
This work was presented as an electronic exhibit at the
2010 annual meeting of the American Roentgen Ray
Society San Diego, CA, and was awarded a Certificate
of Merit.
1
All authors: Department of Imaging, Dana Farber Cancer
Institute, 450 Brookline Ave, Boston, MA 02215. Address
correspondence to K. N. O’Regan (kevin.oregan1@hse.ie).
WEB
This is a Web exclusive article.
AJR 2011; 197:W37–W43
0361–803X/11/1971–W37
© American Roentgen Ray Society
L
iposarcoma (LPS) is a histologi-
cally diverse group of tumors
arising from mesenchymal cells.
LPS accounts for 20–25% of
adult soft-tissue sarcomas, and the peak age
of onset is in the fifth to seventh decades [1–
3]. The clinical behavior of LPS ranges from
indolent nonmetastasizing disease to aggres-
sive subtypes that can recur and metastasize
rapidly. Therefore, accurate diagnosis and
staging, using a multidisciplinary approach,
are important to establish appropriate man-
agement and prognosis.
LPS can occur anywhere in the body but
occurs most frequently in the extremities
and retroperitoneum [4]. The presence of
intratumoral adipose tissue on CT or MRI
can suggest the diagnosis, but in some sub-
types macroscopic fat is not detectable with
imaging [4]. In the case of the pleomorphic
liposarcoma subtype, imaging features may
be indistinguishable from other aggressive
soft-tissue sarcomas. However, in the myx-
oid subtype, other features, such as site, MR
signal characteristics, CT appearance, and
enhancement pattern, can suggest the diag-
nosis. The challenge for radiologists dealing
with LPS is in recognizing the diverse im-
aging features that reflect its histologic het-
erogeneity. In our experience, the more dif-
ferentiated the tumor, the more its imaging
appearance will approach that of adipose
tissue. The aim of this article is to show the
multimodality imaging of LPS in our experi-
ence at a tertiary cancer center.
Liposarcoma Subtypes and Imaging
Characteristics
Although LPS can be classified into five
subtypes, recent developments in molecular bi-
ology and genetic mapping now support des-
ignation of three major categories. The first
category includes atypical lipomatous tumor
(ALT), well-differentiated LPS, and dediffer-
entiated LPS. The second category includes
myxoid LPS and round cell LPS. The third
category is composed of pleomorphic LPS.
Atypical Lipomatous Tumor, Well-Differentiated
Liposarcoma, and Dedifferentiated Liposarcoma
This category of LPS, which includes
ALT, well-differentiated LPS, and dediffer-
entiated LPS, is the most common subtype of
LPS, accounting for approximately 50% of
all cases. ALT and well-differentiated LPS
have a predilection for the extremities, retro-
peritoneum, and paratesticular and inguinal
regions [1]. ALT and well-differentiated LPS
are synonyms for the same pathologic entity,
but the difference in terminology is because
of the likelihood of curative resection for tu-
mors of the limbs and subcutaneous tissues
(ALT), whereas surgery for tumors arising in
the deep tissues of the trunk (well-differen-
tiated LPS) is rarely curative [1]. In fact, the
recurrence rate for retroperitoneal well-dif-
ferentiated LPS approaches 100% [1, 5]. The
different nomenclature also exists because of
the belief of some that a nonmalignant (i.e.,
nonmetastasizing) neoplasm is a “tumor” and
not a “sarcoma.” Well-differentiated LPS is

AJR:197, July 2011 W37


further subdivided into four pathologic sub-
types, including the more common adipocyt-
ic and sclerosing LPS and the rarer inflamma-
tory and spindle cell LPS [6]. Radiologically,
there is currently no reliable method to differ-
entiate these subtypes. On imaging, ALT and
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well-differentiated LPS are composed mostly
of fatty tissue on CT and MRI, but thick sep-
ta (> 2 mm), nodular soft-tissue elements, or
soft-tissue masses < 1 cm may also be seen
[3] (Figs. 1–3).
ALT and well-differentiated LPS are low-
grade neoplasms that do not metastasize.
However, dedifferentiation can occur in these
tumors, most often in a time-dependent man-
ner, and is most common in well-differentiat-
ed LPS of the retroperitoneum, seen in up to
15% of cases [5]. When dedifferentiated ele-
ments are present, the tumor is classified as
well-differentiated–dedifferentiated LPS, an
aggressive neoplasm with the potential to me-
tastasize. The presence of dedifferentiation is
suggested on imaging by a focal nodular non-
lipomatous region > 1 cm, often in the retro-
peritoneum [5]. In some cases, the nonlipo-
matous component predominates and can be
very large (Fig. 4).
Well-differentiated–dedifferentiated LPS
is characterized genetically by overexpres-
sion of the MDM2 protein [6, 7]. Histologi-
cally, the dedifferentiated tumor component
resembles undifferentiated high-grade pleo-
morphic sarcoma in 90% of cases. In con-
trast, in about 10% of dedifferentiated LPS,
there is heterologous differentiation, often
with rhabdomyosarcomatous, leiomyosarco-
matous, or osteosarcomatous elements [5].
Calcification on imaging may suggest the
presence of osteosarcomatous dedifferentia-
tion (Figs. 5 and 6).
Because of the heterogeneous appearance,
unpredictable growth patterns, and often in-
filtrative appearance of well-differentiated–
dedifferentiated LPS, it is difficult to apply
standard tumor response criteria such as Re-
sponse Evaluation Criteria in Solid Tumors
(RECIST). In our experience, when monitor-
ing patients with well-differentiated–dedif-
ferentiated LPS using serial CT or MRI, close
attention should be paid to the nonlipomatous
tumor components for evidence of tumor pro-
gression or recurrence (Figs. 7 and 8).
Distant metastases from dedifferentiat-
ed LPS occur in 15–20% of cases, and the
most common sites of spread are the liver and
lungs [5] (Fig. 9). LPS can metastasize to the
peritoneum, resulting in peritoneal sarcoma-
tosis, the radiologic findings of which have
W38 AJR:197, July 2011
O’Regan et al.
been recently reported in the literature by Oei
et al. [8] (Fig. 10).
Myxoid Liposarcoma and Round
Cell Liposarcoma
Myxoid LPS and round cell LPS were for-
merly classified as distinct entities but are
now recognized as a continuum of the same
entity on the basis of a common chromosom-
al translocation found in up to 90% of cases
[9]. This is the second most common subtype
of LPS, often occurring in young adults. Tu-
mors with a greater round cell component (>
5%) follow a more aggressive course with a
greater risk of metastases and death [9]. Tu-
mors in this category most often present as a
mass in the deep tissues of the thigh that con-
tains only small amounts of microscopic fat
(usually < 10% of the tumor volume) [3].
Myxoid LPS has a characteristic appearance
on MRI. Usually seen as a multilobulated in-
tramuscular mass, the high water content of
these tumors produces low signal intensity on
T1- and high signal intensity on T2-weighted
sequences [3]. Occasionally, such masses can
be mistaken for cystic lesions, but the differ-
entiating features, when present, include the
presence of fatty (T1-hyperintense) septa and
diffuse enhancement after contrast administra-
tion [5] (Fig. 11). The pure round cell variant
(round cell LPS) is a high-grade aggressive tu-
mor that has a nonspecific, heterogeneous ap-
pearance on MRI, often indistinguishable from
other high-grade soft-tissue sarcomas.
Myxoid LPS differs from other subtypes
of LPS in its unusual pattern of metastatic
spread. The most common metastatic sites in-
clude the paraspinal regions, bone, retroperi-
toneum, and opposite extremity [10] (Fig. 12).
Pleomorphic Liposarcoma
Pleomorphic LPS is the least common sub-
type of LPS, most often occurring in the deep
soft tissues of the extremities in elderly pa-
tients [3]. These are aggressive high-grade
sarcomas with a high incidence of recurrence
and metastasis [5]. On CT and MRI, the im-
aging appearance of pleomorphic LPS is of
a well-circumscribed mass containing little
or no fat. The MRI appearance is similar to
other aggressive soft-tissue sarcomas, often
showing internal hemorrhage and necrosis
(Fig. 13).
Management of Liposarcoma
Surgical resection is the mainstay of cura-
tive therapy. Neoadjuvant or adjuvant chemo-
therapy may be considered in patients with
large (> 5 cm) tumors or high-grade round
cell or pleomorphic subtypes, often with reg-
imens based on ifosfamide and anthracycline
[2]. Neoadjuvant or adjuvant radiation thera-
py may be used for local control in large high-
grade LPS [2]. Myxoid LPS can be quite sen-
sitive to the agent trabectedin (Yondelis ET
743, Johnson & Johnson), a marine-derived
alkaloid with reported response rates of up to
51% in one expanded access trial [11]. The
exact mechanism of action of trabectedin is
unclear, but there is evidence that it induces
differentiation of the tumor cells by inactivat-
ing the FUS-CHOP fusion oncogene, which
is present in approximately 90% of myxoid
LPS cases [9, 12]. In our experience with im-
aging of myxoid LPS in patients receiving
trabectedin, tumors can show transformation
from soft-tissue signal intensity on MRI (or
density on CT) to adipose-tissue signal inten-
sity, further supporting this theory of unique
tumor response to treatment [11] (Fig. 14).
Conclusion
LPS is a histologically diverse soft-tissue
sarcoma with a wide range of appearances on
imaging and unusual metastatic patterns. The
classification of LPS has been recently modi-
fied with advances in the molecular biology
of these tumors, and the radiologist should be
aware of the major subtypes. In well-differ-
entiated subtypes, adipose tissue predomi-
nates and is easily recognizable on imaging
studies. However, more aggressive LPS sub-
types show a progressively smaller lipoma-
tous composition. When monitoring patients
with LPS using serial imaging, careful atten-
tion must be paid to the nonlipomatous tumor
elements for evidence of disease progression
or recurrence and treatment response.
References
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11. Grosso F, Jones RL, Demetri GD, et al. Efficacy
of trabectedin (ecteinascidin-743) in advanced
pretreated myxoid liposarcomas: a retrospective
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France: IARC Press, 2002:330 tors and survival in a series of patients treated at a 12. Forni C, Minuzzo M, Virdis E, et al. Trabectedin
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36:358–371 tapuram S, Bredella M. Metastatic myxoid lipo­ 449–457

Fig. 1—78-year-old man with well-differentiated liposarcoma of retroperitoneum.

Contrast-enhanced CT image of abdomen shows predominantly fatty mass in left
retroperitoneum with sparse thin internal septa (arrow).

Fig. 2—58-year-old man with atypical lipomatous tumor of right thigh.

A–C, Axial proton density (A), axial T1-weighted fat-saturated (B), and coronal T1-weighted fat-saturated
(C) contrast-enhanced MR images show predominantly fat signal intensity mass (arrows) with thin internal
septations. There are no nodular or enhancing soft-tissue components.

Fig. 3—53-year-old man who presented with palpable left groin mass.
A and B, Coronal T2-weighted (A) and coronal T1-weighted (B) contrast-enhanced images from pelvic MRI
show soft-tissue mass in left spermatic cord (arrows) with fat-containing elements and enhancing soft-tissue
components. Histology showed well-differentiated liposarcoma of spermatic cord.

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Fig. 4—51-year-old woman who presented with abdominal mass. Contrast-

enhanced abdominal CT image shows large right-sided retroperitoneal mass
(arrow) that is predominantly of soft-tissue attenuation with faint enhancing septa.
Note displacement of adjacent liver and right kidney and paucity of fatty elements.
Histology showed well-differentiated liposarcoma/dedifferentiated liposarcoma.

Fig. 5—58-year-old man with dedifferentiated liposarcoma (LPS) of retroperitoneum.

A, Axial CT image of abdomen and pelvis at presentation shows predominantly calcified mass (arrow)
surrounding aortic bifurcation. Histology of this mass showed dedifferentiated LPS with chondrosarcomatous
and osteosarcomatous differentiation.
B, Follow-up axial CT image obtained after 3 months shows significant interval progression with enlargement
of calcified mass and new large soft-tissue component (arrow).

Fig. 6—55-year-old woman with recurrent dedifferentiated liposarcoma (LPS) of retroperitoneum. Patient
presented with abdominal fullness 2 years after initial resection of well-differentiated LPS.
A and B, Axial (A) and coronal reformatted (B) contrast-enhanced CT images of abdomen and pelvis show large
partially calcified mass in right lobe of liver (arrow) with multiple partially calcified masses in retroperitoneum
and peritoneum (arrowheads). Biopsy showed dedifferentiated LPS with heterologous osteosarcomatous
differentiation.

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Fig. 7—55-year-old woman with extensive well-differentiated liposarcoma/dedifferentiated liposarcoma of retroperitoneum.

A, Coronal reformatted contrast-enhanced CT image of abdomen and pelvis obtained at baseline study shows mixed fat (arrowheads) and soft tissue (asterisk)
attenuation masses throughout abdomen and pelvis.
B, Coronal reformatted contrast-enhanced CT image of abdomen and pelvis obtained at 3-month follow-up shows progressive enlargement of right perinephric soft-
tissue mass (asterisk) consistent with dedifferentiated component while fatty components (arrowheads) remain stable.
C, Coronal reformatted contrast-enhanced CT image of abdomen and pelvis obtained 3 months after B shows surgical debulking of right perinephric mass (asterisk). Fat
attentuation masses (arrowheads) in pelvis remain stable.
D, Coronal reformatted contrast-enhanced CT image of abdomen and pelvis obtained 3 months after C shows regrowth of right perinephric mass and several new soft-
tissue masses (asterisks). Note relative stability of fatty well-differentiated tumor components throughout (arrowheads).

Fig. 8—53-year-old man with asymptomatic incidentally detected mass in superior mediastinum. Biopsy of
lesion confirmed primary mediastinal well-differentiated liposarcoma/dedifferentiated liposarcoma.
A, Unenhanced CT image at diagnosis shows anterior mediastinal mass with mixed fatty (arrow) and soft-
tissue (asterisk) components.
B and C, Follow-up CT images obtained at 6 months (B) and 12 months (C) show progressive enlargement of
preaortic soft-tissue element (asterisk) that corresponds histologically to more malignant dedifferentiated
tumor component, whereas fat component (arrow) remains stable.

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Fig. 9—82-year-old man with history of resected left inguinal dedifferentiated liposarcoma 13 years previously Fig. 10—47-year-old man with recurrent
who presented with new left lower abdominal wall mass. dedifferentiated liposarcoma (LPS). Coronal
A, Coronal reformatted CT image shows recurrent soft-tissue mass deep in relation to left lower abdominal wall reformatted CT image of abdomen and pelvis shows
(arrow) and large metastasis on surface of right lobe of liver (arrowhead). multiple large masses throughout peritoneal cavity,
B, Chest CT image shows extensive left pleural metastasis evidenced by nodular pleural thickening and consistent with peritoneal sarcomatosis from
enhancement (arrow). metastatic dedifferentiated LPS.

Fig. 11—27-year-old woman with right thigh mass.

A, Coronal T2-weighted MR image shows characteristic high signal intensity of lesion (arrow).
B and C, T1-weighted fat-saturated axial MR images before (B) and after (C) administration of gadolinium show
intense enhancement of mass (arrows). Histology showed myxoid liposarcoma.

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Fig. 12—33-year-old man with metastatic myxoid liposarcoma/round cell liposarcoma.

A, Contrast-enhanced CT image through upper chest shows well-circumscribed mass in left periscapular
region, relatively hypoattenuating to muscle (arrow).
B, Axial T2-weighted MR image of thoracic spine shows multilobulated predominantly high-signal-intensity
mass (arrow) involving right paraspinal muscles.
C, Contrast-enhanced CT image through upper abdomen shows multiple lobulated low-density peritoneal
deposits (arrow).

Fig. 13—68-year-old man who presented with mass in right gluteal region.
A and B, Axial T2-weighted (A) and coronal STIR T2-weighted (B) MR images of pelvis show heterogeneous but
predominantly high-signal-intensity mass deep in relation to gluteal muscles (arrow). Biopsy of mass showed
pleomorphic liposarcoma.

Fig. 14—62-year-old man with metastatic myxoid liposarcoma in pelvis, treated with trabectedin (Yondelis ET
743, Johnson & Johnson).
A and B, Contrast-enhanced CT images through pelvis before (A) and after (B) treatment show change in
density (treatment response) of dedifferentiated component (arrow, A) from soft-tissue to well-differentiated
fat density (arrow, B).

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