INTERPRETATION (Dr. PS)
Entire tumor is submitted
for microscopic examination. Sections show a multilobular tumor with
a pseudocapsule. The tumor lobules are composed of spindle shaped
cells that are arranged in short and long interlacing fascicles. The
tumor exhibits hypocellular and hypercellular areas with prominent
fine vasculature. The cells are relatively bland with elongated
nuclei in hypocellular areas. Hypercellular areas show cells with
moderate atypia and pleomorphic multinucleated giant cells. Mitotic
count ranges from 2-6 per 10 high power fields. Foci of mature bone
and calcifications are identified within the tumor. Tumor necrosis
is not identified. Lymphovascular invasion is identified. Upon
extensive sampling, a well differentiated intramuscular lipomatous
component is seen adjacent to the tumor.
Vimentin - positive.
Smooth muscle actin - weakly positive.
p16 - positive
GFAP - weakly positive.
BCL2 - weak focal positivity.
Desmin - negative.
Myogenin - negative.
CD68 - negative.
AE1/AE3 - negative.
EMA - negative.
S100 - negative.
MART-1 - negative.
CD57 - negative.
Neuron specific enolase - negative.
CD31 - negative.
CD34 - negative.
CD117 - negative.
Ki-67 immunostain reveals proliferation index of approximately 8-15
ELECTRON MICROSCOPY (Dr. WJH)
Ultrastructurally, the neoplasm consists of sheets of roughly
spindle shaped cells embedded in a patently granular matrix with
abundant long space collagen. The neoplastic cells contain irregular
and angulated nuclei with prominent chromatin clumping and
occasional prominent nucleoli. No mitotic figures are noted. The
nuclei are quite large relatively to the cytoplasm. The cytoplasm of
many of these cells contain areas of abundant rough endoplasmic
reticulum. Many of the cells appear to contain long thin cytoplasmic
processes. There are focal collections of intermediate filaments and
in an occasional cell, appear to condense at the plasma membrane.
Many of these cells appear to be classic myelofibroblasts. Pinocyto-vesicles
at the plasma membrane are occasionally seen but are a prominent
feature. In several areas, there is some intertwining of the thin
cellular processes. The neoplastic cells do not appear to be
producing significant basal lamina like material. No lipid material
is noted. No osteoid is noted
CYTOGENETICS (MMI, UNMC)
Molecular cytogenetic (FISH and M-FISH) studies revealed the ring
chromosomes observed in the G-band from chromosome 12. Additional
studies were negative for a t(17;22)(q21.3;q13.1)(COL1A1-PDGFB
fusion) and for a disruption of the FUS gene region at 16p11.2.
liposarcoma, grade 3/3 (FNCLCC system).
General Futures of Liposarcoma
Account for about
10-16% of all soft
tissue sarcomas, 4% of childhood soft tissue sarcomas, most
common soft tissue sarcoma in adults. The mean age 50 years.
Most cases arise de novo. Liposarcomas most frequently arise
from the deep-seated stroma rather than the submucosal or
The most recent WHO
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. Well differentiated liposarcoma and
dedifferentiated liposarcoma may comprise on subgroup since they
are closely related. Round cell liposarcoma is a poorly
differentiated myxoid liposarcoma.
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 (75%) and the retroperitoneum. Myxoid and/or
round-cell liposarcomas and pleomorphic liposarcomas have a
striking predilection for the limbs (75%), and dedifferentiated
liposarcoma occurs predominantly in the retroperitoneum (75%).
Although any liposarcoma subtype occasionally arises in the
subcutis, involvement of the dermis appears to be exceedingly
rare, and despite
high-grade morphology, cutaneous liposarcomas have a favorable
The recognition of lipoblasts is the
key finding in the diagnosis of liposarcoma. The earliest cells
arise as pericapillary spindle adventitial cells resembling
fibroblasts. As fat accumulates in the cytoplasm, the cells lose
ER and assume round shape. Gradually, the nuclei become indented
and pushed to aside. Criteria for identifying lipoblasts: (1),
hyperchromatic indented or sharply scalloped nuclei; (2),
well-demarcated cytoplasmic lipid (neutral) droplet; and (3), an
appropriate histological background since lipoblasts or
lipoblast-like cells are present in other conditions. Presence
of lipoblasts is not diagnostic of liposarcoma.
Lipoblasts are noted in benign adipocytic
tumors, including chondroid lipoma, lipoblastoma, pleomorphic lipoma.
General: Also named atypical lipoma and
atypical lipomatous tumor. Represents 40-45% of all liposarcoma,
most common liposarcoma in late adult life.
Tends to occur in deep soft tissues of both the limbs and the retroperitoneum. and rarely in the spermatic cord and the
mediastinum. Grossly, large multilobular, deep yellow to
Four histopathological subtypes:
Adipocytic (Lipoma like
): the most common form. Grossly, large well
circumscribed and coarsely
Microscopically, the tumor predominantly
consists of mature adipocytes with a variable
number of spindle lipoblasts with hyperchromatic
nuclei and multivacuolated cytoplasm. Lipoma-like liposarcomas rarely recur,
and they do not metastasize.
Sclerosing: These are
relatively pale and firm lesions occur most
frequently in the retroperitoneum and the
Microscopically, tumor contains dense fibrotic
zones alternating with mature adipocytes. The
fibrotic areas contain collagen fibrils of
variable thickness and scattered hyperchromatic
spindle or multipolar stromal cells. Multivacuolated
lipoblasts are rarely present. Therefore, the
diagnosis of this subtype more depends on the
identification of the atypical stromal cells
than on the identification of the diagnostic
Inflammatory: There is
a dense chronic inflammatory infiltrate almost
obscuring the lipogenic areas. Prominent
aggregates of lymphoid cells and plasma cells
are noted simulating inflammatory pseudotumor.
Spindle cell: There
is proliferation of bland spindle cells in a
fibrous or myxoid background together with
atypical lipomatous component including
lipoblasts. The differential diagnosis include:
malignant peripheral nerve sheath tumour,
spindle cell lipoma , neurofibroma (S100
positive), dermatofibrosarcoma protuberans
(diffuse CD34 positive) , well differentiated
sclerosing liposarcoma and low grade fibromyxoid
Fat necrosis: foamy
Lipoma with lochkern;
Fatty atrophy: lobular pattern, uniform size of
Spindle cell lipoma/pleomorhpic lipoma;
Atypical lipoma: only diagnosed in skin;
Cytogenetics: Ring or giant marker
chromosome (RGC) derived from 12(q13-q15). Several
tumor-associated genes, localized to 12q13-q21, are amplified,
in particular MDM2, but also SAS, CDK4, and HMGI-C. Another
characteristic feature, seen in the majority of these tumors, is
the high frequency of telomeric associations, showing a
non-random pattern with a preferential involvement of the 11p
Prognosis: The well-differentiated
type and most myxoid types have favorable prognoses, with 100%
and 88% 5-year survival rates, respectively. However, these
tumors are poorly circumscribed and oftn 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
General: Myxoid liposarcoma is the
most common form of liposarcomas, constituting about half of the
cases, and the much less common and more aggressive round
cell liposarcoma is regarded as a poorly differentiated variant
of myxoid liposarcoma. Myxoid and round cell liposarcomas
commonly occur in the limbs (75%) usually between third and
fifth decade. grossly, multinodular, gelatinous masses devoid of
necrosis. Areas with round cell predominance reveal opaque white
nodules in the myxoid mass.
Multilobular with central hypocellarity and enhanced cellularity
peripherally. Each lobule consists of bland fusiform or round
cells in myxoid background composed of hyaluronic acid. A delicate plexiform capillary
network is present throughout the tumor that is distinguish from the
myxoma. Purely myxoid liposarcoma (low grade tumour) is
characterised by hypocellular bland spindle cells in a
myxoid background. Univacuolated lipoblasts are noted around
the vessels. Multivacuolated lipoblasts are present in the
peripheral subcapsular zone. There are thin walled
branching vessels arranged in a plexiform pattern ('crow's feet'
or 'chicken wire pattern' ). Mitotic figures are rare.
Transition to hypercellular (round cell) areas are noted in
myxoid liposarcoma. Myxoid/round cell liposarcoma is
characterised by hypercellular areas with undifferentiated round
cells. These cells are larger with hyperchromatic and more
rounded configuration, in contrast to the spindle cells in the
myxoid variant . Mitotic figures are more frequent in these
(myxoid MFH): marked nuclear atypia and a
small, distinctive eosinophilic cells in small
clusters, cords or pseudoacini in a pale-blue
Intramuscular or cutaneous
electron microscopy: Electron microscopy:
non-membrane bound lipid droplets.
Undifferentiated round cells and bland spindle cells in myxoid
and round cells display cytoplasmic and nuclear positivity with
S100 protein. The lipoblasts stain positively with S100 protein.
Plexiform vascular areas may be demonstrated by CD31 and CD34
stains. Antibody to aP2 protein (adipocyte
Cytogenetics: t(12;16)(q13;p11) is found in about 90% of myxoid/round
cell liposarcomas, involving FUS (TLS)
in 16p11 and
in 12q13, encoding a chimerical protein. The
CHOP protein belongs to the C/EBP family of basic leucin zipper
group of transcription factors. The most common secondary
aberration, in 6-7% of the
cases, is trisomy 8. The alternative t(12;22)(q13;q12) has been
identified in about 5% of the cases. The t(12;22)(q13;q12) results in
and EWS genes. Thus, the two closely related genes FUS and EWS seem
to be interchangeable when fused to CHOP; both FUS and EWS carry a
central RNA-binding RNP-1 motif.
Prognosis: Pure round cell
liposarcoma is rare (more than 80% round cells and with a
relatively favorable prognosis;). More than 10% round cell areas
- increased potential for metastasis. More than 25% round cell
areas - High grade tumour.
General: Pure round cell liposarcomas are very rare, and more often the
tumors represent mixed liposarcomas with both myxoid and round cell
components at different proportions. In recurrences the round cell
component may increase. In the round-cell type, lipoblasts are
interspersed among sheets of poorly differentiated round cells.
Differential diagnosis: Metastatic
carcinoma, lymphoma, melanoma, Ewing's sarcoma.
Cytogenetics: Among the few reported
cases as pure round cell liposarcoma , t(12;16) is rare and the
majority of cases have had fairly complex, unspecific aberrations
Prognosis: 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. The lungs are particularly affected
Least common form of liposarcoma (5% of liposarcomas), equally
located in the limbs and retroperitoneum of older adults.
appearances: Two subtypes. A high grade pleomorphic MFH-like
form: disorderly growth pattern and extensive cellular
pleomorphism, containing a mixture of scattered bizarre and often multivacuolated
lipoblasts and atypical stromal cells, many of which contain highly
abnormal mitotic figures. Hemorrhagic and necrotic areas are common.
Numerous intracytoplasmic eosinophilic globules may be present.
Sometimes a heavy neutrophilic infiltrate is present, which may
be confused with well differentiated inflammatory liposarcoma.
Another form is less common and mainly consists of sheets of
large pleomorphic giant cells associated with smaller
mononuclear cells. A new variant of pleomorphic liposarcoma
characterised by sheets of epithelioid cells and focal
Few cases have been cytogenetically characterized; they
invariably show complex karyotypic changes, with no
characteristic changes identified.
Aggressive tumors showing distant metastasis and about 40%
- General: Characterised by
abrupt transition from low grade to high grade non lipogenic
morphology within a well differentiated liposarcoma. 90% cases
occur in primary tumour and 10% cases occur in recurrent
Microscopic appearances: Tumor consists
of well-differentiated areas and non-lipogenic
(dedifferentiated) areas. Dedifferentiated areas are
characterised by spindle and pleomorphic cells exhibiting
various patterns, including storiform-pleomorphic MFH,
myxofibrosarcoma, osteochondrosarcomatous and angiosarcomatous
features. New variant has been described exhibiting neural-like,
meningothelial-like whorls of spindle cells, or rarely
paraganglioma-like histologic pattern. Sometimes the tumour
exhibits fascicles of bland spindle cells these are described as
Spindle cell liposarcoma
(lipogenic lesion) must be distinguished from
low grade dedifferentiated liposarcoma which is
non lipogenic in nature and has a relatively
liposarcoma must be differentiated from high
grade dedifferentiated liposarcoma (non
Sarcoma infiltrating fat.
- There is no difference in biological
behavior of low and high grade dedifferentiated liposarcomas.
These are associated with 20-25% metastasis. Recurrence rate is