Liposarcoma: Dedifferentiated or

mixed-type? Thin Thin WIN @ Safiya YUNUS 1 and Mazita ISMAIL 2 1 Pathology Department, School of Medical Sciences, Universiti Sains Malaysia,

Kelantan, Malaysia and 2 Pathology Department, Hospital Raja Permaisuri Bainun,

Perak, Malaysia

ABSTRACT

Histopathological subtype of liposarcoma is one of the factors to assess biological behaviour of the tu-

mour. It can be challenging for histopathologists if it is composed of more than one histological subtype

or non-lipogenic dedifferentiated components. Two cases of liposarcoma with combined lipogenic and

various non-lipogenic components were reported. Both cases were male patients in their fifties with

deep seated soft tissue tumour in thigh. The first case was dedifferentiated liposarcoma; 30% of tu-

mour showed features of atypical lipomatous tumour, and 70% of tumour showed dedifferentiated fi-

brosarcoma like pattern and malignant fibrous histiocytoma like pattern with abrupt transition in be-

tween. The second case was mixed-typed liposarcoma with combination of typical myxoid liposarcoma

and dedifferentiated liposarcoma. Thorough sampling is necessary for identification of specific histologi-

cal subtypes and its combination in liposarcoma. Ancillary immunohistochemistry, cytogenetic and mo-

lecular studies may be needed in difficult cases for histological subtyping which can guide the develop-

ment of new therapeutic approach of targeted therapy.

Keywords: Liposarcoma, dedifferentiated liposarcoma, myxoid liposarcoma, mixed-typed

liposarcoma

Case Report

Correspondence: Thin Thin Win @ Safiya Yunus Pathology Department, School of Medical Sciences Universiti Sains Malaysia,16150, Kubang Kerian, Kelantan, Malaysia. Tel: 609 767 6445, Fax: 609 765 3370 E mail: drthinthinwin@gmail.com

Brunei Int Med J. 2013; 9 (5): 350-355

INTRODUCTION

Liposarcoma (LPS) is one of the most com-

mon malignant mesenchymal tumour and

account for approximately 20% of soft tissue

sarcoma. 1 According to the World Health Or-

ganisation (WHO) classification, liposarcomas

has five histological subtypes which include

atypical lipomatous tumour/ well-differ-

rentiated liposarcoma (ALT/WDLPS), dediffer-

entiated liposarcoma (DDLPS), myxoid/round

cell liposarcoma (MLPS/RLPS), pleomorphic

liposarcoma (PLPS) and mixed-typed liposar-

coma. 2 Based on the similarity of molecular

and cytogenetic abnormalities, it can be

grouped into three types; ALT (WDLPS)/

DDLPS, MLPS/RLPS and PLPS. 2, 3 MLPS is the

most common subtype. 2 However, some lit-

erature reported that ALT/WDLPS with or

without dedifferentiation (DDLPS) is the com-

monest accounting for 45% of all LPS. 4

Histopathological subtype of LPS is

one of the factors for assessing the biological

behaviour. Decision to make histological sub-

typing of LPS is sometimes challenging for

histopathologists if it is composed of more

than one histological subtype. We reported

two cases of liposarcoma with various non-

lipogenic dedifferentiated histopathologies.

CASE REPORTS

CASE 1: A 57-year-old Malay man presented

with a left thigh swelling of nearly 10 years. It

was painless and slow growing until a few

months before admission when it rapidly in-

creased in size within three months and be-

came painful. On examination, there was a

huge mass in the medial aspect of the left

thigh (30 x 20 x 11cm) with soft to cystic

consistency. Imaging was suggestive of a

high grade sarcoma. A trucut biopsy revealed

spindle cell lipoma but the pathologist advised

repeat sampling. The mass was widely ex-

cised. It was a huge soft tissue tumor mass

covered by fat and skeletal muscle measuring

30 x 27 x 20cm in diameter and weighing 7.5

kg. Serial cut sections showed fairly circum-

scribed, capsulated, and gray to yellowish,

multilobular appearance with myxoid areas,

haemorrhages and necrosis. Entrapped skele-

tal muscles were seen within the tumor mass.

Histological examination (Figures 1a

and b) revealed most of the sections were

composed of nodules divided by fibrous sep-

ta. Skeletal muscle fibers were entrapped in

the septa and some are atrophic. Some of the

nodules were composed of lipogenic cells with

variable pleomorphism from mild pleomorphic

cells to vacuolated lipoblasts. Some were

composed of loosely arranged round to oval

shape cells with mild pleomorphism, and easi-

ly seen mitoses in the background of myxoid

stroma. Rich capillary networks were seen

within the myxoid stroma. In the vicinity to

myxoid area with lipogenic cells, cellular are-

as were composed of pleomorphic spindle

Figs. 1: a) Lipogenic area composed of pleomorphic lipogenic cells (H&E, x20), b) Transition of lipogenic area

into non-lipogenic area composed of spindle shaped cells (H&E, x20), c) Lipogenic foci and non-lipogenic foci

intermingle each other giving rise to mosaic pattern. (H&E, x20), and d) Nodule composed of spindle shaped

cells with enhanced cellularity at the periphery (H&E, x10).

YUNUS and ISMAIL. Brunei Int Med J. 2013; 9 (5): 351

a b

c d

shaped cells. These spindle cells were ar-

ranged into interlacing fascicles which gave

rise to the pattern of fibrosarcoma. Some foci

show abrupt transition of lipogenic to non-

lipogenic spindle shaped cells with hypercellu-

larity. Some cellular areas were forming nod-

ules, and enhanced cellularity was seen at the

periphery of nodules in which spindle cells

were more pleomorphic. In areas, alternative

lipogenic and non-lipogenic cells were ar-

ranged into a mosaic pattern intermingling

each other. In non-lipogenic areas, some

showed fibroblastic area like fibrosarcoma

pattern, and some showed malignant fibrous

histiocytoma (MFH) like pattern with multinu-

cleate giant cells and floret cells. Some nod-

ules were composed of paucicelluar pleomo-

rohic non-lipogenic cells in the background of

myxoid stroma, giving rise to the features of

myxofibrosarcoma. All the surgical margins

were free of tumour. Immunohistochemical

staining showed only positive for vimentin.

Cytokeratin (CK) AE1&3, SMA, S100, desmin,

CD34, CD99 were negative. The histological

features were consistent with DDLPS.

CASE 2: A 50-year-old Arab man presented

with a painless left thigh mass of three year.

It had rapidly increased in size within the last

one year. A trucut biopsy that was done three

years previously was reported as intramuscu-

lar lipoma. On examination, there was a huge

mass at the lateral aspect of the left thigh

measuring 28 x 28 x 12cm diameter, firm in

consistency with ill defined border. A magnet-

ic resonance imaging (MRI) was consistent

with liposarcoma without bony invasion. A

repeat revealed myxoid liposarcoma. The pa-

tient proceeded to excision of the tumour.

The excised specimen consisted of a

huge soft tissue tumour weighing 9 kg and

measuring 28 x 29 x 15cm. The overlying

skin was ulcerated. Serial cut sections

showed well encapsulated tumour enclosing

lobulated fatty tissue without gross infiltration

Figs. 2; a) Pleomorphic

lipoblasts in lipogenic

area (H&E, x40), and

b) Pleomorphic spindle

shaped cells in non-

lipogenic area giving

rise to fibrosarcoma

pattern (H&E, x40),

c) Pleomorphic spindle

shaped cells in non-

lipogenic area giving

rise to MFH pattern

(H&E, x40), and d)

Pleomorphic cells in

the background of

myxoid stroma giving

rise to myxoid MFH

pattern (H&E, x40).

YUNUS and ISMAIL. Brunei Int Med J. 2013; 9 (5): 352

a b

c d

into the skeletal muscle. Most of the areas

were myxoid appearance with jelly like mate-

rials. Areas of necrosis, haemorrhage and

cystic degeneration were seen.

Histological examination (Figures 2a

& b) revealed most of the sections were myx-

oid appearance with some cystic like spaces.

Both univacuolated and multivacuolated lipo-

blasts were seen in the myxoid background.

Cystic spaces and myxoid stroma enclosing

lipogenic cells resembled pulmonary oedema

pattern. In some areas, stroma was more

cellular with pleomorphic spindle-shaped cells

without any lipogenic cells. These spindle-

shaped cells were arranged into storiform in-

terlacing pattern. In one foci of non-lipogenic

area, tumour cells were very plump and epi-

theloid looking with abundant eosinophilic

cytoplasm, vesicular nuclei and prominent

nucleoli. Foci of metaplastic cartilage and

bone formation were also seen. Immunohisto-

chemical profile of non-lipogenic spindle cell

area showed only vimentin positivity with

negative for S100, SMA, desmin, CD99 and

HMB45. Non-lipogenic epitheloid cell area was

strongly positive for vimentin and focally pos-

itive for CK AE1&3 and EMA. Based on histo-

logical findings, mixed-typed LPS with combi-

nation of MLPS and DDLPS was reported.

peritoneal and intra-abdominal locations with

tumour larger than 5 cm are of worse progno-

sis. 2 ALT/WDLPS does not recur after com-

plete wide excision. DDLPS, despite its high

grade morphology, is less aggressive clinically

than other types of high grade sarcoma. 2

MLPS and PLS have tendency to metastasize

distantly. Both of our cases were located in

the thigh which is a common site of most soft

tissue sarcoma, and both are larger size tu-

mour of more than 5 cm in diameter.

Among the five histological subtypes,

DDLPS was first described in 1979 by Evans. 7

It is defined as ALT/ WDLPS juxtaposed to

areas of high-grade non-lipogenic sarcoma,

usually resembling either fibrosarcoma or ma-

lignant fibrous histiocytoma (MFH). 5 The tran-

sition between lipogenic and non-lipogenic

area is abrupt, either in the primary or in a

recurrence, from ALT/WDLPS to non-lipogenic

sarcoma of variable histological grade. 2 Most

cases of DDLPS showed abrupt transition with

few gradual transitions, and occasional tu-

mours showed mosaic pattern. 8 Dedifferenti-

ation is the process in which differentiated

cell revert back to a less differentiated stage

within its own lineage. 9

In our first case, 70% of all tumours

composed of non-lipogenic DDLPS which in-

clude fibrosarcoma pattern, MFH pattern and

myxofibrosarcoma pattern. Only about 30%

of tumour nodules were composed of lipogen-

ic component which showed features of ALT,

lipoblasts and small foci of MLPS/RLPS with

prominent capillary networks. DDLPS with

prominent myxoid stroma resembling other

sarcoma such as MLPS and myxofibrosarcoma

were reported. 10 There were foci of abrupt

transition from myxoid lipogenic to non-

DISCUSSION

Although histopathological diagnosis of LPS is

based on finding of lipoblast(s), histopatho-

logical subtyping is also important to assess

biological behaviour. The behaviour ranges

from non-metastasising neoplasms (e.g ALT/

WDLPS) to high-grade sarcomas with full

metastatic potential (e.g PLPS). 5 Tumour lo-

cation, size and histological subtype are the

most important prognostic indicator. 6 Retro-

YUNUS and ISMAIL. Brunei Int Med J. 2013; 9 (5): 353

lipogenic dedifferentiated pattern, and also

mosaic pattern in this case. These features

were consistent for DDLPS. Foci of ALT/

WDLPS in this case were very scant, and it

was mixed with MLPS/RLPS pattern and LPS

of not otherwise specified pattern. We as-

sumed that the 10 years history of tumour

mass might be the period for transformation

of the ALT/WDLPS into higher grade liposar-

coma. Most of the dedifferentiated foci in the

first case were high grade. That features were

similar to findings of some previous litera-

tures. 8, 11

Mixed-type LPS is a very rare type

and it shows features of combined MLPS/RLPS

and ALT (WDLPS)/DDLPS or of MLPS/RLPS

and PLPS. 2 Most of the cases were reported

predominantly in retroperitoneal or intra-

abdominal locations. 2, 12 Mediastinum and

deep soft tissue of extremities are rare sites.

It is important for the prognosis to decide

whether it is combined MLPS and DDLPS

(mixed-typed), or myxoid degeneration of

DDLPS, and/or dedifferentiation with myxofi-

brosarcoma pattern. 2

In the second case, more than 70%

of the tumour was composed of MLPS pattern

characterized by loose myxoid stroma enclos-

ing uni- and multi-vacuolated lipoblasts. Cyst-

ic spaces with paucicellularity giving rise to

pulmonary oedema pattern were seen. From

lipogenic myxoid pattern, stroma gradually

transformed into more cellular myxoid which

resembled round cell LPS. Then it trans-

formed into the area composed of non-

lipogenic, spindle-shaped cells displaying in-

terlacing storiform pattern and small foci of

plump epitheloid cells. These epitheloid cells

were positive for cytokeratin AE1&3 and EMA

immunohistochemically. Epitheloid variant of

non-lipogenic cells are commonly seen in

PLPS. 2, 5 To the best of our knowledge, this is

the first case of combined MLPS with dediffer-

entiated epitheloid cells. MLPS with dediffer-

entiated non-lipogenic foci were previously

described as dedifferentiated MLPS. 13 Actual-

ly those dedifferentiated MLPS represents

mixed-type liposarcoma showing a combina-

tion of MLPS/RLPS and DDLPS. 2

Nowadays, more useful immunohisto-

chemical stains which are not available in our

center can be used for ALT/WDLPS, such as

MDM2 and CDK4. 3, 14 In recent years, ancil-

lary cytogenetic and molecular studies of

MLPS, detection of translocations of CHOP

and FUS genes has been introduced. 15

In conclusion, thorough sampling is

necessary for identification of specific histo-

logical subtypes and its combination in LPS.

Ancillary immunohistochemistry, cytogenetic

and molecular studies are useful tools for the

cases which are difficult for histological sub-

typing, and are helpful to develop new thera-

peutic approaches of targeted therapy.

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