bb5_3.qxd 13.9.2006 9:40 Page 19
CHAPTER 1
Adipocytic Tumours
Adipocytic tumours represent the largest single group of
mesenchymal tumours, due to the high prevalence of lipomas
and angiolipomas. Liposarcomas represent the single most
common type of soft tissue sarcoma. Its principal histological
subtypes (well differentiated, myxoid, and pleomorphic) are
entirely separate diseases with different morphology, genetics,
and natural history. Most types of adipocytic neoplasm have
distinctive karyotypic aberrations which can be of considerable
help in diagnosis.
Principal changes and advances since the 1994 WHO classifi-
cation have been
> the recognition that atypical lipomatous tumour and well
differentiated liposarcoma are essentially synonymous and that
site-specific variations in behaviour relate only to surgical
resectability,
> the inclusion of two newly characterized entities, myolipoma
and chondroid lipoma, and
> the renaming of fibrolipomatous hamartoma of nerve as lipo-
matosis of nerve.
Descriptions of angiomyolipoma and myelolipoma are provided
in the Urogenital and Endocrine volumes, respectively.
bb5_3.qxd 13.9.2006 9:40 Page 20
G.P. Nielsen
Lipoma
N. Mandahl
Definition 1982}. Imaging studies show a homoge- Immunophenotype
Lipoma is a benign tumour composed of neous soft tissue mass that is isodense Mature adipocytes stain for vimentin,
mature white adipocytes and is the most to the subcutaneous tissue and demon- S100 protein and leptin {1610}.
common soft tissue mesenchymal neo- strates fat saturation. Attenuated fibrous
plasm in adults. strands can be seen but they are not as Ultrastructure
prominent as seen in the atypical lipo- Lipoma is composed of cells that have a
ICD-O code 8850/0 mas. Intramuscular lipomas are more large, single lipid droplet compressing a
variably circumscribed, and lipoma peripherally situated nucleus.
Epidemiology arborescens shows diffuse fatty infiltra-
Conventional lipoma occurs over a wide tion of the synovium.
age range but is most common between
the ages of 40 and 60 years and is more Aetiology
frequent in obese individuals {601}. Unknown. Lipomas are more common in
Lipomas are rare in children. obese individuals.
Approximately 5% of patients have multi-
ple lipomas. Macroscopy
Grossly, lipomas are well circumscribed
Sites of involvement and have a yellow, greasy cut surface.
Conventional lipoma can arise within Different types are basically similar in
subcutaneous tissue (superficial lipoma) appearance, however bone formation
or within deep soft tissues (deep lipoma) can be seen in osteolipoma and grey
or even on the surfaces of bone glistening nodules may be seen in chon-
(parosteal lipoma) {1079,1800}. Deep drolipoma. Intramuscular and intermus-
seated lipomas that arise within or cular lipoma do not show any specific
between skeletal muscle fibres are gross features except that a portion of
called intramuscular or intermuscular skeletal muscle is often attached to the
Fig. 1.01 Image of a deep seated conventional lipo-
lipomas, respectively {685,1113}. periphery of the tumour. In lipoma arbor-
ma showing a well circumscribed, homogenous
Intramuscular lipoma arises during mid escens the entire synovium assumes a
tumour with the same characteristics as the adja-
to late adulthood and involves skeletal nodular and papillary appearance and
cent subcutaneous fat.
muscle in a variety of locations including has a bright yellow cut surface.
the trunk, head and neck region, upper
and lower extremities {685,1113}. Histopathology
Intermuscular lipoma arises between Conventional lipoma is composed of lob-
muscles most frequently in the anterior ules of mature adipocytes. The cells are
abdominal wall, and involves a similar identical to the surrounding adipose tis-
age group as the intramuscular lipoma. sue except for slight variation in the size
So-called lipoma arborescens (villous and shape of the cells in lipomas.
lipomatous proliferation of synovial mem- Lipomas can occasionally have areas of
brane) is characterized by fatty infiltra- bone formation (osteolipoma), cartilage
tion of the subsynovial connective tissue (chondrolipoma), abundant fibrous tis-
and may represent a reactive process. sue (fibrolipoma), or extensive myxoid
change (myxolipoma). Intramuscular
Clinical features lipoma may be either well demarcated
Lipomas usually present as a painless from the surrounding skeletal muscle or,
soft tissue mass, except for larger ones more often, shows an infiltrative growth
that can be painful when they compress pattern with mature adipocytes infiltrat-
peripheral nerves. Superficial lipomas ing and encasing skeletal muscle fibres
are generally smaller (<5cm) than the that often show evidence of atrophy. In
deep seated ones (>5cm). Patients with lipoma arbor-escens the subsynovial
lipoma arborescens are usually adult connective tissue is infiltrated by mature
Fig. 1.02 Synovial lipoma (lipoma arborescens)
men that complain of gradual swelling of adipocytes; scattered inflammatory cells
demonstrating a fatty infiltration of the synovium
the affected joint {324,837,875,1343, are also usually present. that assumes papillary appearance.
20 Adipocytic tumours
bb5_3.qxd 13.9.2006 9:40 Page 21
Tumours without 12q13-15 aberrations
Among these tumours, constituting one-
third of lipomas with acquired chromo-
some aberrations, all chromosomes
except 20 have been involved, but the
only distinct clustering of breakpoints
seen is to 6p21-23, 13q11-22, and, less
often, 12q22-24, together constituting
about half of this group of tumours.
Involvement of 6p21-23, mostly in the
A B
form of seemingly balanced transloca-
Fig. 1.03 Conventional lipoma. A Grossly, the tumour is well circumscribed and has a homogenous yellow cut
tions, has been found in more than 20%
surface. B The mature adipocytes vary only slightly in size and shape and have small eccentric nuclei.
of these tumours. The only recurrent
translocation partner has been 3q27-28
in two cases. Aberrations affecting the
long arm of chromosome 13 are domi-
nated by deletions, which have been
found in slightly less than 20% of the
cases. Most aberrations are interstitial
deletions with breakpoints in 13q12-14
and 13q22, respectively. There is an
overlap between 6p21-23 rearrange-
ments and 13q deletions, with some
tumours showing both aberrations, but
A B more often these aberrations occur as
sole anomalies.
Fig. 1.04 Intramuscular lipoma. A This intramuscular lipoma appears well circumscribed from the adjacent
Simultaneous involvement of 6p21-23
skeletal muscle (right). B Mature adipocytes infiltrate and encase skeletal muscle fibres.
and 12q13-15 is uncommon, in contrast
to the coexistence of 12q13-15 aberra-
Pinocytotic vesicles are present and with respect to age distribution and gen- tions and 13q losses. In tumours with
external lamina is seen surrounding the der. The frequency of abnormal kary- combinations of 6p, 12q, and 13q aber-
cells {1110}. otypes seems to be higher among older rations, 13q is mostly involved in bal-
patients {2020,2271}. Otherwise, no
clear, consistent correlations between
Genetics clinical and cytogenetic data have been
Cytogenetics identified.
Lipomas have been analysed extensive-
ly by chromosome banding. In larger Tumours with 12q13-15 aberrations
cytogenetically investigated series, chro- About two-thirds of tumours with abnor-
mosome aberrations have been found in mal karyotypes show aberrations of
55-75% of the cases {1320,2020,2271}. 12q13-15, which has been found to
Among the abnormal tumours, about recombine with a large number of bands
75% show seemingly balanced kary- in all chromosomes except 16 and Y. The
A
otypes and in more than 50% there is a preferred rearrangement, seen in more
single abnormality in at least one clone than 20% of tumours with 12q13-15 aber-
{1477}. On average, signs of clonal evo- rations, is t(3;12)(q27-28;q13-15). Other
lution is found in every sixth tumour. recurrent recombination partner regions,
Numerical chromosome changes are present in 3-7% of these tumours, are
rare and randomly distributed, and chro- 1p36, 1p32-34, 2p22-24, 2q35-37, 5q33,
mosome numbers deviating from 46 are 11q13, 12p11-12, 12q24, 13q12-14,
exceedingly rare. The pattern of cytoge- 17q23-25, and 21q21-22. The majority of
netic aberrations is quite heterogeneous, these aberrations originate through
but three cytogenetically defined sub- translocations or insertions. One in six of
groups have been distinguished: 1) the these tumours show more or less com-
B
major subgroup consisting of tumours plex intrachromosomal rearrangements -
Fig. 1.05 A Synovial lipoma (lipoma arborescens).
with aberrations involving 12q13-15, 2) including primarily inversions, but also
The entire synovium is bright yellow and has a
tumours with aberrations involving 6p21- deletions and duplications - leading to
nodular or papillary appearance. B Synovial lipoma
23, and 3) tumours with loss of material recombination between 12q13-15 and
(lipoma arborescens). The subsynovial connective
from 13q. Patients with and without aber- other segments of chromosome 12, pri-
tissue has been replaced by mature adipocytes.
rations of 12q13-15 show no differences marily 12p11-12 and 12q24.
Note also scattered chronic inflammatory cells.
Lipoma 21
bb5_3.qxd 13.9.2006 9:40 Page 22
A B
Fig. 1.06 A Karyotype from a lipoma showing the most common structural rearrangement, a translocation t(3;12)(q27;q15). B Lipoma with t(12;21)(q15;q22) as the sole chro-
mosomal aberration. Arrowheads indicate breakpoints.
anced translocations when recombining mates the frequency of tumours with 12q13-15 and 12p11, due to inversion,
with 6p21-23 or 12q13-15, whereas dele- recombination between these two chro- fusion of putative but yet unidentified
tions in 13q are predominating when mosome segments {1696}. In all cases, gene sequences in 12p11 with HMGIC
aberrations of 6p21-23 or 12q13-15 are the chimeric HMGIC/LPP transcript is was found {1081}, and ectopic
present but recombine with other chro- expressed, whereas the reciprocal sequences mapping to chromosome 15
mosome segments. LPP/HMGIC transcript is expressed only have been implicated {90}. Possibly, the
Among tumours without rearrangements occasionally. Alternative fusion tran- related HMGIY (HMGA1B) gene is the
of 12q13-15 or 6p21-23 or loss of 13q scripts, encoding the three DNA binding target, directly or indirectly, in lipomas
sequences, one-fifth of the breakpoints AT-hook domains of HMGIC and two or with 6p21-23 aberrations; split FISH sig-
coincide with those recurrently recom- three LIM domains of LPP have been nals, using probes covering HMGIY,
bining with 12q13-15. reported, thus excluding the 3´ acidic, have been reported in cases with translo-
protein-binding domain and the N-termi- cations involving 6p {1082,2083}.
Molecular genetics nal leucine-zipper motif, respectively. Transcriptional activation of HMGIC or
The HMGIC (a.k.a. HMGA2) gene, The preferred breakpoints are in the HMGIY is indicated by immunohisto-
encoding a family member of the high large intron 3 of HMGIC and LPP intron 8. chemical studies, and correlates well
mobility group of proteins, located in The chimeric transcript is not unique for with cytogenetic findings of breakpoints
12q15 is affected in at least some lipo- lipomas of the soft tissues but has also in the regions where these two gene loci
mas with rearrangements of 12q13-15 been detected in parosteal lipoma and are located {2083}.
{90,1890}. In tumours with t(3;12)(q27- pulmonary chondroid hamartoma
28;q13-15), the consequence at the {1698,1803}. Prognostic factors
molecular level is the formation of a Rearrangement of HMGIC has been The subclassification of conventional
fusion gene involving HMGIC and LPP in detected also in tumours with changes lipoma does not have any prognostic sig-
3q27-28, a member of the LIM protein involving 12q13-15 and other chromo- nificance except for the infiltrating intra-
gene family {1696}. In addition, this some segments. In a single case of lipo- muscular lipoma that has a higher local
fusion gene has been observed in a few ma with t(12;13)(q13-15;q12), an recurrence rate, therefore total removal of
cases with complex karyotypic changes HMGIC/LHFP fusion transcript has been the involved muscle or a compartmental
including 12q13-15 but not 3q27-28 and reported {1697}. Also in this case, the resection has been suggested for these
in cases with normal karyotypes, indicat- breakpoint was in HMGIC intron 3. In infiltrating tumours in order to minimize
ing that cytogenetic analysis underesti- lipomas with recombination between local recurrence {206}.
22 Adipocytic tumours
bb5_3.qxd 13.9.2006 9:40 Page 23
G.P Nielsen
Lipomatosis
A.E. Rosenberg
Definition Epidemiology vena cava. Patients with pelvic lipomato-
Lipomatosis is a diffuse overgrowth of Diffuse lipomatosis usually occurs in sis frequently complain of urinary fre-
mature adipose tissue. It occurs in a vari- individuals under 2 years of age but it quency, perineal pain, constipation, and
ety of clinical settings and can affect dif- may also arise in adults {1574}. Pelvic abdominal and back pain. Bowel
ferent anatomic regions of the body. lipomatosis most frequently affects black obstruction and hydronephrosis may
males who range in age from 9 to 80 eventually develop. Imaging studies in
ICD-O code 8850/0 {839,944,1135}. Symmetric lipomatosis all forms of lipomatosis show accumula-
develops in middle aged men of tion of fat and are only helpful in deter-
Synonyms Mediterranean origin. Many patients mining the extent of its accumulation and
Madelung disease, Launois-Bensaude have a history of liver disease or exces- excluding other processes.
syndrome. sive alcohol consumption. Steroid lipo-
matosis manifests in patients on hormon- Aetiology
al therapy or have increased endoge- The basic mechanism underlying lipo-
nous production of adrenocortical matosis is not well understood. In sym-
steroids. HIV lipodystrophy is frequently metric lipomatosis point mutations in
seen in AIDS patients treated with pro- mitochondrial genes have been implicat-
tease inhibitors but is also seen in ed in its pathogenesis {1140}. The simi-
patients receiving other forms of anti- larity between HIV lipodystrophy and
retroviral therapy {234,1175}. benign symmetric lipomatosis suggests
a similar pathogenesis in that mitochon-
Sites of involvement drial DNA damage may be induced by
Diffuse lipomatosis involves the trunk, the drugs being used to treat HIV
large portion of an extremity, head and {153,400}.
neck, abdomen, pelvis or intestinal tract.
It may be associated with macrodactyly Macroscopy
Fig. 1.07 Lipomatosis presenting as diffuse
or gigantism of a digit {836,1365,1616}. The gross appearance of lipomatosis is
enlargement of the lower leg in an infant
Symmetric lipomatosis manifests as the same for all of the different subtypes.
symmetric deposition of fat in the upper The lesions consist of poorly circum-
part of the body particularly the neck. In scribed aggregates of soft yellow fat that
pelvic lipomatosis there is diffuse over- is identical in appearance to normal fat.
growth of fat in the perivesical and The only differences are the site of
perirectal areas. Steroid lipomatosis is involvement and the distribution of the
characterized by the accumulation of fat fat.
in the face, sternal region or the upper
middle back (buffalo hump). HIV-lipody- Histopathology
strophy typically shows the accumulation All of the different types of lipomatosis
of visceral fat, breast adiposity, cervical have identical morphologic features,
fat pads, hyperlipidemia, insulin resist- consisting of lobules and sheets of
ance as well as fat wasting in the face mature adipocytes that may infiltrate
and limbs {400,1461}.
Clinical features
In most forms of lipomatosis the patients
present with massive accumulation of fat
in the affected areas that may mimic a
neoplasm. Additionally patients with
symmetric lipomatosis can have neu-
ropathy and central nervous system
involvement {1541,1712}. Accumulation
of fat in the lower neck areas in these
patients can also cause laryngeal
Fig. 1.08 Patient showing typically symmetrical, Fig. 1.09 Diffuse lipomatosis showing extensive
massive expansion of the neck. obstruction, and compression of the skeletal muscle infiltration of mature adipocytes.
Lipomatosis 23
bb5_3.qxd 13.9.2006 9:40 Page 24
other structures such as skeletal muscle. Genetics The treatment is palliative surgical
Immunophenotype An association with several genetic dis- removal of excess fat. Massive accumu-
The adipose tissue stains for vimentin orders has been reported, and an auto- lation of fat in the neck region may cause
and S-100, similar to normal fat. somal dominant inheritance is suggested death due to laryngeal obstruction. The
{1377}. fat in steroid lipomatosis regresses after
Ultrastructure steroid levels have been lowered.
The adipocytes have the features of Prognostic factors Experimental drugs such as recombinant
white fat. All idiopathic forms of lipomatoses have growth hormones have been used to
a tendency to recur locally after surgery. treat HIV-lipodystrophy.
G.P. Nielsen
Lipomatosis of nerve
Definition patients may not present for treatment Sites of involvement
Lipomatosis of nerve is characterized by until early or mid adulthood. In the The median nerve and its digital branch-
infiltration of the epineurium by adipose largest reported series the patients es are most commonly affected followed
and fibrous tissue. The tissue grows be- ranged in age from 11 to 39 years. by the ulnar nerve {189,1952}. The
tween and around nerve bundles thereby Because the constituent tissues are process has also been reported to
causing enlargment of the affected nerve. normal components of the epineurium, involve unusual sites such as the cranial
some have considered this lesion to be nerves and the brachial plexus
ICD-O code 8850/0 a hamartoma of the nerve sheath {445, {176,1726}.
2103}. In some cases it is associated
Synonyms and historical annotations with macrodactyly of the digits inervat- Clinical features
Fibrolipomatous hamartoma, lipofibro- ed by the affected nerve. Patients present with a gradually enlarg-
ma, fibrolipomatosis, intraneural lipoma Associated macrodactyly was present ing mass in the affected area that may be
of the median nerve, perineural lipoma, in approximately 1/3 of patients, asymptomatic or associated with motor
median nerve lipoma, macrodystrophia including 5 females and 2 males or sensory deficits. Patients with macro-
lipomatosa, neural fibrolipoma. {1952}. Females predominate when dactyly have symmetrical or asymmetri-
lipofibroma is accompanied by macro- cal enlargement of the affected finger(s)
Epidemiology dactyly, whereas males are more com- with enlargement of the involved bones.
Lipomatosis of nerve is frequently first monly affected when macrodactyly is Imaging studies show fusiform enlarge-
noted at birth or in early childhood, but absent. ment of the nerve with fatty infiltration
A B C
Fig. 1.10 Lipomatosis of nerve. A A clinical picture showing macrodactyly of the second and third fingers. B An intraoperative view of lipomatosis of nerve showing
a transition between the normal nerve (left) and the affected area (right). C Cross section reveals nerve bundles entrapped within fibroadipose tissue.
24 Adipocytic tumours
bb5_3.qxd 13.9.2006 9:40 Page 25
{474} and MRI findings are virtually
pathognomonic {1336}.
Aetiology
The aetiology is unknown. Lipomatosis of
nerve is not associated with any syn-
drome nor is there any known hereditary
predisposition.
Macroscopy
Grossly there is fusiform enlargement of
the nerve by yellow fibrofatty tissue,
which is generally confined within the
epineurial sheath.
Histopathology
The epineurial and perineurial compart-
ments of the enlarged nerve are infiltrat-
ed by mature adipose tissue admixed
with fibrous tissue which dissects
A
between and separates individual nerve
bundles {1952}. Concentric perineurial
fibrous tissue is a prominent feature. The
affected nerve may also show other
changes such as perineural septation,
microfascicle formation and pseudo-
onion bulb formation mimicking an intra-
neural perineurioma {1882}. Metaplastic
bone formation is rarely present {551}.
Immunophenotype
Immunohistochemical studies are not
helpful in diagnosing this lesion as all of
its components are seen in normal
nerves.
Ultrastructure
There are no characteristic ultrastructur-
al findings. The nerve bundles demon-
strate onion bulblike formations with one
or two nerve fibres and peripheral per-
B
ineural cells {99}.
Fig. 1.11 A Epineural infiltration of fibroadipose tissue separating nerve bundles. B The nerves show pseudoo-
nion bulb formation and perineural fibrosis.
Prognostic factors
Lipomatosis of nerve is a benign lesion
with no effective therapy. Surgical exci-
sion usually causes severe damage of
the involved nerve. Division of the trans-
verse carpal ligament may relieve neuro-
logical symptoms.
Lipomatosis of nerve 25
bb5_3.qxd 13.9.2006 9:40 Page 26
R. Sciot
Lipoblastoma / Lipoblastomatosis
N. Mandahl
Definition Macroscopy whelming fat component with lipoblasts,
A lobulated, localized (lipoblastoma) or Notwithstanding exceptions, lipoblas- help to separate lipoblatoma(tosis) from
diffuse (lipoblastomatosis) tumour, tomas are relatively small lesions (2-5 these lesions.
resembling fetal adipose tissue. cm), showing fatty looking tissue with
gelatinous areas. Ultrastructure
ICD-O code 8881/0 Lipoblastoma(tosis) strongly resembles
Histopathology normal developing fat, with a spectrum
Synonyms Lipoblastoma shows a lobulated appear- ranging from primitive mesenchymal
Foetal lipoma, embryonic lipoma, infan- ance with an admixture of mature and cells to multivacuolated lipoblasts and
tile lipoma. immature adipocytes, the latter corre- mature lipocytes {223}.
sponding to lipoblasts in various stages
Epidemiology of development. Depending on the age Genetics
Both tumours are most commonly found of the patient, lipoblasts may be very Typically, lipoblastomas have simple,
in the first three years of life. They may scarce. Connective tissue septa sepa- pseudodiploid karyotypes with structural
occasionally be present at birth or in rate the lobules. The lobulation is less chromosome aberrations. The character-
older children. There is a male predilec- prominent in lipoblastomatosis, in which istic cytogenetic feature is rearrange-
tion {348,391,1410,2196}. entrapped muscle fibres frequently ment of 8q11-13, which has been found
occur. The matrix can be quite myxoid, in the vast majority of cases. The only
Sites of involvement with a plexiform vascular pattern, thus chromosome segments that, so far, have
The extremities are most commonly mimicking myxoid liposarcoma. The lat- been found to be involved in recurrent
involved, but locations in the medi- ter tumour, which is exceptionally rare recombinations with 8q11-13 are 3q12-
astinum, retroperitoneum, trunk, head & under the age of 10, usually shows 13, 7p22, and 8q24, but several other
neck, and various organs (lung, heart, nuclear atypia and does not show the chromosome segments have been the
parotid gland) have been described pronounced lobulated pattern of translocation partners in single cases.
{273,500,525,1002,1010,1177,1192, lipoblastoma {223}. However, in rare Numerical changes are rare, but gain of
1352,1654,1713,1720,1762,2134,2149}. cases molecular genetic analysis may chromosome 8 has been found in cases
be required for definitive distinction. with or without simultaneous rearrange-
Clinical features Occasionally, lipoblastoma(tosis) may ment of 8q11-13.
Most patients present with a slowly growing show extramedullary haematopoiesis or To date, two different fusion genes have
soft tissue nodule/mass, well circumscribed cells resembling brown fat. Cellular mat- been reported to result from the chromo-
and confined to the subcutis in case of uration has been described, leading to a somal rearrangements, HAS2/PLAG1 in
lipoblastoma, infiltrating the deeper muscle lipoma-like picture. When fascicles of three cases and COL1A2/PLAG1 in a
in case of lipoblastomatosis. Depending on primitive mesenchymal cells are present single case {945}. The PLAG1 gene is
the location, the tumour may compress in the septa, lipoblastoma resembles located in 8q12, HAS2 in 8q24 and
adjacent structures, such as the trachea. infantile lipofibromatosis or infantile fibro- COL1A2 in 7q22. The genomic break-
Imaging reveals a mass with adipose tis- matosis {658}. The lobulated aspect, the point of PLAG1 seems to be in intron1,
sue density, but does not allow distinction at least focal myxoid stroma and plexi- resulting in loss of exon 1. The entire
from lipoma and liposarcoma {1777}. form capillaries, as well as the over- HAS2 5´ untranslated region is involved
in the fusion gene, which is probably
under control of the HAS2 promoter,
leading to transcriptional up-regulation
of PLAG1 and production of a full-length
PLAG1 protein. The COL1A2-PLAG1
fusion gene encodes a chimeric protein
containing the first amino acids of
COL1A2 and full-length PLAG1. These
fusion genes seem to act through a pro-
moter-swapping mechanism {105,945}.
An alternative mechanism associated
A B with lipoblastoma tumourigenesis may
act through excess copies of chromo-
Fig. 1.12 Lipoblastoma. A Grossly, the tumour shows vague lobularity and fibrous / gelatinous areas.
B Low power view. Note the prominent lobulation. some 8 {792}. Since +8 may be present
26 Adipocytic tumours
bb5_3.qxd 22.9.2006 9:24 Page 27
A B
Fig. 1.13 A Admixture of multivacuolated lipoblasts and mature adipocytes. B 315 Delicate plexiform vascular pattern and myxoid changes in lipoblastoma.
in tumours both with and without and lipoma-like lipoblastomas as well as does not occur. Recurrences are
changes of 8q12, the effect of PLAG1 in a variety of mesenchymal cell compo- described in 9% to 22% of cases, mainly
rearrangement might be reinforced by nents, indicating the mutation to occur in in lipoblastomatosis. Therefore wide total
gain of chromosome 8 in some cases. a progenitor cell that then differentiates excision of diffuse lesions is advised
Whether the extra copies of the PLAG1 {792}. {348,391,1410,2196}.
gene are normal or have point mutations
is not known. By in situ hybridization it Prognostic factors
has been shown that split PLAG1 signals Lipoblastoma(tosis) is fully benign and
are present in both classical, myxoid, malignant transformation or metastasis
Lipoblastoma / Lipoblastomatosis 27
bb5_3.qxd 13.9.2006 9:40 Page 28
R. Sciot
Angiolipoma
N. Mandahl
Definition coma and Kaposi sarcoma {983}. cally investigated tumours have had a
A subcutaneous nodule consisting of Interstitial mast cells may be prominent normal karyotype {1905}.
mature fat cells, intermingled with small and in older lesions, increased fibrosis is
and thin-walled vessels, a number of present. Prognostic factors
which contain fibrin thrombi. Angiolipomas are always benign and
Genetics show no tendency to recur. Malignant
ICD-O code 8861/0 With a single exception, all cytogeneti- transformation does not occur.
Epidemiology
Angiolipomas are relatively common and
usually appear in the late teens or early
twenties. Children and patients older
than 50 years are rarely involved. There
is a male predominance and an
increased familial incidence has been
described (5% of all cases) {230,357,
942,977,1062,1232}. The mode of inheri-
tance is not clear.
Sites of involvement
The forearm is the most common site, fol-
lowed by the trunk and upper arm.
Spinal angiolipomas and intramuscular
haemangiomas, previously also called
 infiltrating angiolipomas , are different
lesions {878,2148}.
Clinical features
Angiolipomas most frequently present as
A
multiple subcutaneous small nodules,
usually tender to painful. There is no cor-
relation between the intensity/occur-
rence of pain and the degree of vascu-
larity {527}.
Macroscopy
Angiolipomas appear as encapsulated
yellowish to reddish nodules, most often
less than 2 cm in diameter.
Histopathology
Angiolipomas typically consist of two
mesenchymal elements: mature
adipocytes and branching capillary
sized vessels, which usually contain fib-
rin thrombi. The vascularity is more
prominent in the subcapsular area {527}.
The relative proportion of adipocytes and
vessels varies and some lesions are
almost completely composed of vascular B
channels. These  cellular angiolipomas
Fig. 1.14 Angiolipoma. A The tumour consists of mature adipocytes and capillaries, some of which contain
should be distinguished from angiosar- microthrombi. B Cellular angiolipoma, in which the vessels predominate.
28 Adipocytic tumours
bb5_3.qxd 13.9.2006 9:40 Page 29
J.M. Meis-Kindblom
Myolipoma of soft tissue
L.G. Kindblom
Definition Macroscopy
Myolipoma of soft tissue is a benign Deep-seated myolipomas of soft tissue
tumour exhibiting features of mature range between 10 and 25 cm in size; the
smooth muscle and mature adipose tis- average size is 15 cm. Smaller lesions
sue. are seen in the subcutis. A completely or
partially encapsulated lipomatous
ICD-O code 8890/0 tumour intermingles with strands and
nodules of firm white-tan, fibrillary to
Synonym whorled areas corresponding to smooth
Extrauterine lipoleiomyoma. muscle.
Fig. 1.15 An encapsulated myolipoma of the pelvis with
Epidemiology Histopathology
clear fatty and smooth muscle components.
Myolipoma of soft tissue is an extremely The smooth muscle component usually
rare lesion occurring in adults, with a dominates with a muscle to fat ratio of
male to female ratio of 1:2 {1393}. 2:1. Smooth muscle tends to be evenly seen in angiomyolipoma. Sclerosis and
distributed and arranged in short fasci- focal inflammation may be present in
Sites of involvement cles, resulting in a sieve-like pattern as it the fat.
The majority of cases are deeply located traverses the fat. Individual smooth mus-
and involve the abdominal cavity, cle fibres have deeply acidophilic fibril- Immunophenotype
retroperitoneum, and inguinal areas. The lary cytoplasm that becomes Diffusely and strongly positive smooth
trunk wall and extremities may also be fuchsinophilic with the Masson trichrome muscle actin and desmin immunostain-
involved; such cases are subcutaneous stain. Nuclear chromatin is evenly dis- ing confirm the presence of smooth mus-
and may grow deeply to involve the persed, nucleoli are inconspicuous and cle in myolipoma.
superficial muscular fascia {1393}. no appreciable mitotic activity is seen.
Equally important is the absence of any Prognostic factors
Clinical features atypia in the mature lipomatous compo- Myolipoma does not recur. Complete
Most lesions present as a palpable nent of myolipoma. Floret cells and surgical resection is curative.
mass; the remainder are incidental lipoblasts are not seen, nor are medium
findings. calibre thick-walled blood vessels as
A B
Fig. 1.16 A,B Mature adipose tissue and mature smooth muscle arranged in short fascicles are seen in a myolipoma of the distal extremity.
Myolipoma of soft tissue 29
bb5_3.qxd 13.9.2006 9:40 Page 30
L.G. Kindblom
Chondroid lipoma
J.M. Meis-Kindblom
N. Mandahl
Definition may be significantly larger {1396}. Ultrastructure
Chondroid lipoma is a unique and Tumours are typically well circumscribed Primitive cells sharing features of embry-
recently recognized benign adipose tis- and yellowish, suggesting fatty differenti- onal fat and embryonal cartilage are
sue tumour containing lipoblasts, mature ation. seen, as well as lipoblasts,
fat, and a chondroid matrix. It bears a preadipocytes and mature fat.
strikingly close resemblance to myxoid Histopathology Cytoplasmic knobby protrusions are
liposarcoma and extraskeletal myxoid Chondroid lipoma is often encapsulated often seen. The matrix has features
chondrosarcoma. and occasionally multilobular. Its histo- resembling cartilage, including thin fila-
logic hallmarks are nests and cords of ments, thin collagen fibres and numer-
ICD-O code 8862/0 abundant uni- and multivacuolated ous proteoglycan particles {1116,1559}.
lipoblasts embedded in a prominent
Epidemiology myxoid to hyalinized chondroid matrix
Chondroid lipoma is rare and affects pri- admixed with a variable amount of
marily adults with a male:female ratio of mature adipose tissue. The lipoblast
1:4 {1396} without racial predilection. nuclei are small and uniform, ranging
from oval, reniform to multilobated in
Sites of involvement shape, with evenly dispersed chromatin
This tumour occurs most commonly in and small nucleoli. The cytoplasm is fine-
the proximal extremities and limb girdles. ly vacuolated, containing small lipid
However, the trunk and head and neck droplets and PAS positive glycogen.
areas may also be affected. Chondroid Cells may have granular eosinophilic Fig. 1.18 EM of lipoblasts arranged in cords and a
prominent chondroid matrix.
lipoma is often deep-seated, involving cytoplasm. Chondroid lipoma is highly
skeletal muscle or deep fibrous connec- vascular and not infrequently contains
tive tissues. Those cases involving the haemorrhage and fibrosis. Cytogenetics
subcutis tend to impinge on the superfi- Toluidine blue and alcian blue stains at Two chondroid lipomas reported have
cial muscular fascia. controlled pHs confirm the typical pres- displayed a seemingly balanced translo-
ence of chondroitin sulfates in the matrix cation, t(11;16)(q13;p12-13), in one case
Clinical features {1116}. as the sole anomaly {1477}. Recurrent
The majority of patients present with a involvement of 11q13 has been found
painless mass of variable duration. There Immunophenotype also in ordinary lipoma and hibernoma.
is a recent history of enlargement in Lipoblasts are weakly S100 protein posi- However, in these tumour entities, 11q13
roughly one-half of cases. tive whereas stronger staining is seen has never been found to recombine with
Reports of imaging studies of this lesion with increasing adipocytic maturation 16p12-13 {1477}.
are exceedingly sparse {1277,2320}. {1116}. Vimentin is uniformly positive in
all cells; cytokeratins are detected in rare Prognostic factors
Macroscopy cases, corresponding ultrastructurally to Chondroid lipoma does not recur locally
Most chondroid lipomas are 2 7 cm in tonofilaments. EMA is uniformly negative. or metastasize. Surgical excision is
size, although cases with haemorrhage Proliferative index with MIB1 is <1%. curative.
A B C
Fig. 1.17 Chondroid lipoma. A Mature fat and nests of small lipoblasts. B High magnification shows cellular details. C Mature fat and nests of small lipoblasts in chon-
droid lipoma showing a more prominent myxoid matrix.
30 Adipocytic tumours
bb5_3.qxd 13.9.2006 9:40 Page 31
M.M. Miettinen
Spindle cell lipoma /
N. Mandahl
Pleomorphic lipoma
Definition spindled cells, hyperchromatic rounded Sites of involvement
Spindle cell and pleomorphic lipoma, cells, and multinucleate giant cells asso- Spindle cell / pleomorphic lipomas occur
ends of a common histological spec- ciated with ropey collagen. predominantly in the posterior neck and
trum, are circumscribed subcutaneous shoulder area. Face, forehead, scalp,
lesions occurring typically on the neck ICD-O codes buccal-perioral area and upper arm are
and back usually of males and com- Spindle cell lipoma 8857/0 less common sites, and occurrence in
posed of a variable admixture of bland Pleomorphic lipoma 8854/0 the lower extremity is distinctly rare.
Clinical features
Spindle cell / pleomorphic lipomas typi-
cally present in older men with a median
age of over 55 years, and only 10% of
patients are women {60,102,595,684,
1944}. The tumour forms an asympto-
matic, mobile dermal or subcutaneous
mass, and there is often a long history.
Rare patients have multiple lesions, and
familial occurrence has been reported,
mostly in men {633}. Spindle cell / pleo-
morphic lipomas have benign behaviour
and conservative local excision is con-
sidered sufficient.
Macroscopy
Grossly spindle cell lipoma / pleomor-
phic lipoma forms an oval or discoid yel-
lowish to greyish-white mass depending
on the relative extent of the fatty and
A
spindle cell components. The tumour
often has a firmer texture than ordinary
lipoma, but some examples have a
gelatinous texture.
Histopathology
Histologically, at one end at the histolog-
ical spectrum, spindle cell lipoma is
composed of bland mitotically inactive
B
Fig. 1.19 Spindle cell lipoma. A The relative proportions of the adipocytic and spindle cell components are vari- Fig. 1.20 Spindle cell lipoma. Typical case with bland
able. B Some lesions are almost devoid of adipocytes and show vague nuclear palisading. Note the typically spindle cells in a background with thick collagen
ropey collagen bundles. fibres and a small number of adipocytes.
Spindle cell lipoma / Pleomorphic lipoma 31
bb5_3.qxd 13.9.2006 9:40 Page 32
Fig. 1.22 Immunopositivity for CD34 is a consistent
feature of the spindle cell component.
vascular slits ("pseudoangiomatoid vari-
ant") {911}.
A
At the opposite end of the spectrum,
pleomorphic lipoma is characterized by
small spindled and rounded hyperchro-
matic cells and multinucleated giant cells
with radially arranged nuclei in a"floret-
like" pattern, like petals of flowers. Cases
with features intermediate between clas-
sic spindle cell lipoma and pleomorphic
lipoma quite often occur.
Immunophenotype
The spindle cells in both spindle cell and
pleomorphic lipomas are strongly posi-
tive for CD34 and may rarely be positive
for S100 protein {626,2059,2102}.
B
Cytogenetics
Spindle cell lipomas and pleomorphic
lipomas show similar cytogenetic aberra-
tions. The karyotypes are, on average,
more complex than those found in ordi-
nary lipomas and are frequently
hypodiploid, often with multiple partial
losses, no gain of sequences, and few
balanced rearrangements. Monosomy or
partial loss of chromosomes 13 and/or 16
have been found in seven to eight out of
ten cases. Half of the tumours with
involvement of chromosome 16 have had
a breakpoint in 16q13, and all of them
have had loss of 16q13-qter. The most
frequently lost segments of chromosome
C 13 include 13q12 and 13q14-q22. Other
chromosome segments lost in two to
Fig. 1.21 Pleomorphic lipoma. A Prominent myxoid change of the stroma is not an uncommon feature.
B Classical example showing numerous floret-like multinucleate cells. C Some pleomorphic lipomas consist three of the ten cases are 6pter-p23,
almost entirely of mature adipocytes with admixed multinucleated stroma cells, often having floret-like nuclei.
6q15-q21, 10pter-p15, 10q23-qter, and
17pter-p13 {442}.
spindled cells arranged in parallel regis- spindle cells, and lymphocytes and plas- Prognostic factors
ters between the fat cells and associated ma cells may occur, especially in pleo- These are benign lesions which only
with thick rope-like collagen bundles. morphic lipoma. Some spindle cell lipo- rarely recur locally.
{60,595,684,1944}. Large numbers of mas show myxoid stromal change or dis-
mast cells are often seen in between the play slit-like cleavage spaces resembling
32 Adipocytic tumours
bb5_3.qxd 13.9.2006 9:40 Page 33
M.M. Miettinen
Hibernoma
J.C. Fanburg-Smith
N. Mandahl
Definition patients over 60 years. There is a slight Aetiology
Hibernoma is a rare benign adipose male predominance {747}. The aetiology of hibernoma is unknown,
tumour composed at least in part of although many lesions arise at the sites
brown fat cells with granular, multivacuo- Sites of involvement where brown fat is normally found in
lated cytoplasm. This brown fat compo- Hibernoma occurs in a wide variety of hibernating animals and human fetus-
nent is admixed in variable proportion locations. The most common site is the es/newborns {754}.
with white adipose tissue. Residual thigh, followed by the trunk, upper
brown fat, mostly seen around cervical extremity, and head and neck. The myx- Macroscopy
and axillary lymph nodes, should not be oid and spindle cell variants tend to be The median size for hibernoma is 9.3
classified as hibernoma. located in the posterior neck and shoul- centimeters, range 1-24 centimeters
ders, similar to spindle cell lipoma {747}. {747}. Hibernomas are lobular, well-
ICD-O codes 8880/0 Less than 10% occur in the intra-abdom- demarcated, and vary in colour from yel-
inal or thoracic cavities {19}. low to brown. They have a greasy, soft,
Epidemiology and spongy cut surface {747,1113}.
Recognized since around the turn of the Clinical features
century {1424}, hibernoma comprises Hibernoma is a relatively slow growing Histopathology
1.6% of benign lipomatous tumours and tumour of the subcutis. At least 10% of Histologically, hibernomas vary in the
approximately 1.1% of all adipocytic cases are intramuscular. Hibernomas are content and appearance of the polygo-
tumours in AFIP files. Based on AFIP usually painless. MRI reveals non-fat nal brown fat cells, the associated small
data on 170 cases {747}, hibernoma septations in hibernoma, not found in capillary proliferation, and the stromal
occurs predominantly in young adults, lipoma. By CT scan, hibernoma has a tis- background, resulting in six variants.
with a mean age of 38 years. 60% occur sue attenuation intermediate between fat Most tumours contain large numbers of
in the third and fourth decades, only 5% and skeletal muscle and enhances with multivacuolated brown fat cells with
occur in children 2-18 years, and 7% in contrast {1172}. abundant, granular cytoplasm and a
Fig. 1.23 Hibernoma. The eosinophilic variant is Fig. 1.24 Hibernoma. Detail of the eosinophilic vari- Fig. 1.25 Hibernoma. The pale cell variant has a pale
composed mostly of granular-appearing, multivac- ant with granular, multivacuolated brown fat cells tinctorial quality of the multivacuolated brown fat
uolated brown fat cells with prominent nucleoli. and prominent nucleoli. cells.
Hibernoma 33
bb5_3.qxd 13.9.2006 9:40 Page 34
del(11) der(11) der(17) 17
Fig. 1.28 Hibernoma. Partial G-banded karyotype
showing a translocation t(11;17)(q13;p13).
Immunophenotype
Hibernoma cells are variably, sometimes
strongly, positive for S100 protein. The
spindle cell variant has a CD34 positive
spindle cell component, similar to spin-
dle cell lipoma, whereas the other hiber-
noma variants are negative for CD34
{747}.
Fig. 1.26 Hibernoma. The myxoid variant has a myxoid background with floating brown fat cells.
Genetics
Although hibernomas frequently show
somewhat more complex chromosome
changes than ordinary lipomas and
lipoblastomas, the karyotypes are near-
or pseudodiploid. The only recurrent
aberration is the involvement of 11q13-
21, most often 11q13, in structural
rearrangements, which in the majority of
cases affect three or more chromo-
somes. No chromosome band has been
involved more than once as a transloca-
tion partner.
Metaphase FISH analyses have demon-
strated that the chromosomal rearrange-
ments are more complex than can be
detected by chromosome banding
analysis {793}. The aberrations not only
affect the obviously rearranged chromo-
some 11, but also the seemingly normal
homologue. Both heterozygous and
homozygous deletions have been
Fig. 1.27 Hibernoma. The spindle cell variant, a hybrid tumour between hibernoma and spindle cell lipoma,
detected, with deletions comprising seg-
shows brown fat cells, mature white fat cells, scattered mast cells, bland spindled cells.
ments up to 4 Mb. Homozygous deletion
of the multiple endocrine neoplasia type
small, central nucleus, the granular or component, with thick bundles of colla- I tumour suppressor gene MEN1 has
eosinophilic variant. The brown fat cells gen fibres, scattered mast cells, and been found in four of five tumours,
vary from pale staining to variably mature adipose tissue (spindle cell vari- whereas all five hibernomas investigated
eosinophilic, and some cases have a ant), a hybrid between hibernoma and showed heterozygous loss of PPP1A
mixture of pale and eosinophilic cells, the spindle cell lipoma, have been {793}. Yet, no conclusive evidence of the
mixed variant, while other cases have described. Mitoses are exceptional and pathogenetically important event is avail-
pure pale brown fat cells, the pale vari- cytological atypia is unusual. Such fea- able.
ant. Some hibernomas contain small tures should not be equated with malig-
clusters of brown fat amidst ordinary nancy as the biologic behaviour of hiber- Prognostic factors
white fat, the "lipoma-like" variant. noma is invariably benign. However, Hibernoma is a benign tumour that does
Multivacuolated lipoblast-like cells are scattered normal brown fat cells may be not recur with complete local excision
often seen. Rare variants with myxoid found in an otherwise classic myxoid or {747}. All morphologic variants have the
stroma (myxoid variant), or a spindle cell well differentiated liposarcoma. same good prognosis.
34 Adipocytic tumours
bb5_4.qxd 13.9.2006 9:49 Page 35
A.P. Dei Tos
Atypical lipomatous tumour /
F. Pedeutour
Well differentiated liposarcoma
Definition Terminology in clinical practice kept separated from the atypical lipoma
Atypical lipomatous tumour (ALT) / well- The fact that WD liposarcoma shows no category as it is morphologically as well
differentiated (WD) liposarcoma is an potential for metastasis unless it under- as cytogenetically distinct, rarely recurs
intermediate (locally aggressive) malig- goes dedifferentiation led, in the late and has no potential to dedifferentiate
nant mesenchymal neoplasm composed 1970s, to the introduction of terms such (see page 31).
either entirely or in part of a mature as atypical lipoma or atypical lipomatous
adipocytic proliferation showing signifi- tumour {626}, particularly for lesions aris- Synonyms
cant variation in cell size and at least ing at surgically amenable locations in Atypical lipoma, adipocytic liposarcoma,
focal nuclear atypia in both adipocytes the limbs and on the trunk since, at these lipoma-like liposarcoma, sclerosing
and stromal cells. The presence of scat- sites, wide excision should usually be liposarcoma, spindle cell liposarcoma,
tered hyperchromatic, often multinucle- curative and hence the designation  sar- inflammatory liposarcoma.
ate stromal cells and a varying number coma is not warranted. However, the
of monovacuolated or multivacuolated variable, sometimes controversial appli- Epidemiology
lipoblasts (defined by the presence of cation of this new terminology has repre- ALT/WD liposarcoma accounts for about
single or multiple sharply marginated sented a source of potential diagnostic 40-45% of all liposarcomas and therefore
cytoplasmic vacuoles scalloping an confusion {620, 1112, 2246}. Atypical represents the largest subgroup of
enlarged hyperchromatic nucleus) may lipomatous tumour and WD liposarcoma aggressive adipocytic neoplasms. These
contribute to the morphologic diagnosis. are synonyms describing lesions which lesions mostly occur in middle aged
Use of the term  atypical lipomatous are identical both morphologically and adults with a peak incidence in the 6th
tumour is determined principally by karyotypically (see below) and in terms decade. Convincing examples in child-
tumour location and resectability. of biologic potential. The choice of termi- hood are extremely rare. Males and
nology is therefore best determined by females are equally affected with the
ICD-O code 8851/3 the degree of reciprocal comprehension obvious exception of those lesions affect-
between the surgeon and the pathologist ing the spermatic cord {588,678, 2242}.
to prevent either inadequate or exces-
sive treatment {486}. However, in sites Sites of involvement
such as the retroperitoneum and medi- ALT/WD liposarcoma occurs most fre-
astinum it is commonly impossible to quently in deep soft tissue of the limbs,
obtain a wide surgical excision margin especially the thigh, followed by the
and, in such cases, local recurrence retroperitoneum, the paratesticular area
(often repeated and ultimately uncon- and the mediastinum {588, 678, 2242}.
trolled) is almost inevitable and often These lesions may also arise in subcuta-
leads to death, even in the absence of neous tissue and, very rarely, in skin.
dedifferentiation and metastasis  hence,
at these sites, retention of the term WD Clinical features
Fig. 1.29 Atypical lipomatous tumour / Well differ-
liposarcoma can readily be justified. ALT/WD liposarcoma usually presents as
entiated liposarcoma. Surgical specimen showing
Spindle cell/pleomorphic lipoma must be a deep-seated, painless enlarging mass
a well circumscribed, lobulated mass.
A B C
Fig. 1.30 Atypical lipomatous tumour / Well differentiated liposarcoma. A Marked variation in adipocytic size is one of the most important diagnostic clues for the diag-
nosis. B The presence of atypical, hyperchromatic stromal cells represents a common finding. C A varying number of lipoblasts can be seen in well-differentiated liposar-
coma but their presence does not make (nor is required for) a diagnosis of liposarcoma.
Atypical lipomatous tumour / Well differentiated liposarcoma 35
bb5_4.qxd 13.9.2006 9:49 Page 36
A B C
Fig. 1.31 Atypical lipomatous tumour / Well differentiated liposarcoma. A The presence of scattered bizarre stromal cells, exhibiting marked nuclear hyperchromasia
set in a fibrillary collagenous background represent the most important diagnostic feature of sclerosing variant. B Neural-like spindle cell proliferation in a fibrous and /
or myxoid background, associated with an atypical lipomatous component that usually includes lipoblasts, characterize the spindle cell variant. C Bizarre, often multinu-
cleate cells in the stroma are an important diagnostic clue in the inflammatory variant. Note the accompanying inflammatory component.
that can slowly attain a very large size, hallmark of any liposarcoma subtype; which the adipocytic component is
particularly when arising in the retroperi- however, it is important to emphasise that scarce the presence of bizarre multinu-
toneum. Retroperitoneal lesions are often the mere presence of lipoblasts does not cleate stromal cells represents a useful
asymptomatic until the tumour has make (nor is required for) a diagnosis of diagnostic clue and should raise the sus-
exceeded 20 cm in diameter and may be liposarcoma. picion of inflammatory liposarcoma.
found by chance. Sclerosing liposarcoma ranks second in The spindle cell variant of ALT/WD
frequency among the group of ALT/WD liposarcoma {490} is composed morpho-
Macroscopy liposarcoma. This pattern is most often logically of a fairly bland neural-like spin-
ALT/WD liposarcoma consists usually of seen in retroperitoneal or paratesticular dle cell proliferation set in a fibrous
a large, usually well-circumscribed, lobu- lesions. Microscopically, the main histo- and/or myxoid background and is asso-
lated mass. In the retroperitoneum there logical finding is the presence of scat- ciated with an atypical lipomatous com-
may be muliple discontiguous masses. tered bizarre stromal cells, exhibiting ponent which usually includes lipoblasts.
Rarely an infiltrative growth pattern may marked nuclear hyperchromasia and An interesting albeit rare finding in
be encountered. Colour varies from yel- associated with rare multivacuolated ALT/WD liposarcoma, is the presence of
low to white (and firm) depending on the lipoblasts set in an extensive fibrillary heterologous differentiation. In addition
proportion of adipocytic, fibrous and/or collagenous stroma. As occasionally the to metaplastic bone formation, a well dif-
myxoid areas. Areas of fat necrosis are fibrous component may represent the ferentiated smooth or striated muscle
common in larger lesions. majority of the neoplasm, lipogenic areas component can rarely be seen and
(which are often limited in extent) can be should be distinguished from heterolo-
Histopathology easily overlooked or even missed in a gous differentiation arising in the context
ALT/WD liposarcoma can be subdivided small tissue sample. Extensive sampling of dedifferentiated liposarcoma (see
morphologically into four main subtypes: of the surgical specimen is therefore page 38) {2063}.
adipocytic (lipoma-like), sclerosing, mandatory, and blocks should be taken
inflammatory {2234} and spindle cell from any area showing variation in gross Immunophenotype
{490}. The presence of more than one appearance. Immunohistochemistry plays a very
morphological pattern in the same lesion Inflammatory liposarcoma represents a minor role in the differential diagnosis of
is common, particularly in retroperitoneal rare variant of ALT/WD liposarcoma, ALT / WD liposarcoma. Adipocytic cells
tumors. occurring most often in the retroperi- usually exhibit S-100 protein immunore-
Microscopically, ALT/WD liposarcoma is toneum, in which a chronic inflammatory activity that may be helpful in highlighting
composed of a relatively mature infiltrate predominates to the extent that the presence of lipoblasts {493}. HMB-45
adipocytic proliferation in which, in con- the adipocytic nature of the neoplasm immunonegativity has proved useful in
trast to benign lipoma, significant varia- can be obscured. In such instances, the the differential diagnosis with angiomy-
tion in cell size is easily appreciable. differential diagnosis is mainly with non olipoma that occasionally may mimic
Focal adipocytic nuclear atypia as well adipocytic lesions such as inflammatory liposarcoma.
as hyperchromasia also contributes to myofibroblastic tumour, Castleman dis-
the usual morphologic picture and scat- ease and Hodgkin as well as non- Genetics
tered hyperchromatic as well as multinu- Hodgkin lymphomas {78, 1174}. The The defining genetic features of ALT/WD
cleate stromal cells are often identified. inflammatory infiltrate is usually com- liposarcoma cells are supernumerary cir-
Hyperchromatic stromal cells tend to be posed of polyphenotypic lymphoplasma- cular ("ring") and giant rod chromo-
more numerous within fibrous septa. A cytic aggregates in which a B-cell phe- somes. These rings and giant markers
varying number (from many to none) of notype tends to predominate. Cases contain amplification of the 12q14-15
monovacuolated or multivacuolated exist in which a polyclonal T-cell popula- region, including the MDM2 gene, asso-
lipoblasts may be found. It is commonly tion represents the main inflammatory ciated with co-amplification of various
believed that lipoblasts represent the component. When dealing with cases in other chromosomal regions; they most
36 Adipocytic tumours
bb5_4.qxd 13.9.2006 9:49 Page 37
often lack alpha-satellite centromeric 1889}. Another striking feature of
sequences. ALT/WDLPS supernumerary chromo-
somes is that they have a functional cen-
Cytogenetics tromere, as indicated by positive labeling
The supernumerary ring and giant mark- with anti-CENPC antibodies that bind to
er chromosomes have been observed as the kinetochore, but they do not contain
the sole change or concomitant with a alpha-satellite sequences, and C-band-
few other numerical or structural abnor- ing is often negative {1962}.
malities {1477}. Metaphase cells are usu-
ally near-diploid but often near-tetraploid. Prognostic factors
Random and non-random telomeric The most important prognostic factor for
associations are frequently observed ALT/WD liposarcoma is anatomic loca-
and may give a false impression of com- tion. Lesions located in surgically
plexity to ALT/WD liposarcoma kary- amenable soft tissue do not recur follow-
A
otypes {1322}. Cells containing either ing complete (preferably wide) excision
rings or giant markers or both can be with a clear margin. Tumours occurring in
observed in the same tumour sample. deep anatomic sites such as retroperi-
Varying stages of complexity are toneum, spermatic cord or mediastinum
observed, from the simple, classical pic- tend to recur repeatedly to the extent that
ture of a supernumerary ring or giant they may cause the patient s death as a
marker in addition to 46 apparently nor- result of uncontrolled local effects or they
mal chromosomes up to more complex may dedifferentiate and metastasise. The
patterns showing several copies of rings ultimate risk of dedifferentiation varies
and giant markers, telomeric associa- according to site and lesional duration
tions, and other structural alterations. and is probably >20% in the retroperi-
toneum but < 2% in the limbs. Overall
Molecular cytogenetics and genetics mortality ranges from essentially 0% for
The combination of fluorescence in-situ ALT of the extremities to more than 80%
hybridisation (FISH) using whole chromo- for WD liposarcomas occurring in the
some painting probes and comparative retroperitoneum if the patients are fol-
B
genomic hybridisation indicates that lowed up for 10-20 years. Median time to
Fig. 1.32 Atypical lipomatous tumour / Well differ-
both supernumerary rings and giant death ranges between 6 and 11 years
entiated liposarcoma. A Lipoma-like subtype. B In
markers are composed of interspersed {1290, 2246}.
the inflammatory subtype, the inflammatory infil-
amplified sequences consistently origi- trate often predominates and may obscure the
nating from the 12q14-15 region. A vari- adipocytic nature of the neoplasm.
ety of other chromosomal regions, the
most frequent of which are 12q21-22 and
1q21-25, have been shown to be co-
amplified with 12q14-15 {434, 1678,
1680, 2053, 2072}. Investigations using
FISH with unique probes and Southern
blotting showed that MDM2, located in
12q14-15, was consistently amplified,
usually accompanied by amplification of
neighbouring genes, such as SAS,
CDK4, and HMGIC. This 12q14-15
amplification is not observed in lipomas
and its detection may therefore serve to
distinguish ALT/WD liposarcoma from
benign adipose tumours. More cen-
tromeric genes, located in 12q13, such
as GLI or DDIT3 (CHOP), have not been
shown to be amplified. Nuclear blebs,
anaphase bridges, and strings or
micronuclei containing the amplified
regions are frequently observed. The
TP53 gene is usually not subject to muta-
tions in ALT/WD liposarcoma {1706, Fig. 1.33 Metaphase spread from an atypical lipomatous tumour, showing characteristic ring chromosome.
Atypical lipomatous tumour / Well differentiated liposarcoma 37
bb5_4.qxd 13.9.2006 9:49 Page 38
A.P. Dei Tos
Dedifferentiated liposarcoma
F. Pedeutour
Definition Macroscopy 10% of cases which apparently does not
Malignant adipocytic neoplasm showing Dedifferentiated liposarcoma usually affect the clinical outcome. Most often
transition, either in the primary or in a consists of large multinodular yellow the line of heterologous differentiation is
recurrence, from atypical lipomatous masses containing discrete, solid, often myogenic or osteo/chondrosarcomatous
tumour/well differentiated liposarcoma to tan-grey non-lipomatous (dedifferentiat- but angiosarcomatous elements have
non-lipogenic sarcoma of variable histo- ed) areas. Dedifferentiated areas often also been reported. A peculiar "neural-
logical grade, usually at least several show necrosis. The transition between like" or "meningothelial-like" whorling pat-
milimeters in diameter. the lipomatous and the dedifferentiated tern of dedifferentiation has recently
areas sometimes may be gradual. been described {636, 1538}. This pattern
ICD-O code 8858/3 is often associated with ossification.
Histopathology Dedifferentiated liposarcoma appears to
Epidemiology The histological hallmark of dedifferenti- exhibit less aggressive clinical behaviour
Dedifferentiation occurs in up to 10% of ated liposarcoma is represented by the when compared with other high grade
well differentiated (WD) liposarcomas of transition from ALT/WD liposarcoma of pleomorphic sarcomas. Careful and
any subtype, although the risk of dedif- any type to non-lipogenic sarcoma extensive sampling is therefore manda-
ferentiation appears to be higher when which, in most cases, is high grade. The tory, particularly in large retroperitoneal
dealing with deep seated (particularly extent of dedifferentiation is variable but lesions, as the well differentiated compo-
retroperitoneal) lesions and is significant- most often this component is evident to nent may be overlooked. Additionally, it
ly less in the limbs. the naked eye. The prognostic signifi- should be noted that local recurrences of
This most probably represents a time- cance of microscopic foci of dedif- dedifferentiated liposarcoma may be
dependent more than a site-dependent ferentation is uncertain. The transition entirely well differentiated {1374, 2246}.
phenomenon. Dedifferentiated liposar- usually occurs abruptly. However in
coma affects basically the same patient some cases this can be more gradual Immunophenotype
population as WD liposarcoma (see and, exceptionally, low grade and high Immunohistochemistry plays its main
page 35). grade areas appear to be intermingled. role in permitting the recognition of diver-
No sex predilection is observed. About Dedifferentiated areas exhibit a variable gent differentiation and in excluding
90% of dedifferentiated liposarcomas histological picture but most frequently other tumour types.
arise "de novo" while 10% occur in recur- they resemble unclassified  MFH -like
rences {678, 2242}. pleomorphic sarcoma or intermediate to Genetics
high grade myxofibrosarcoma {1374, Cytogenetics
Sites of involvement 2246}. Similar to ALT/WD liposarcoma, dediffer-
The retroperitoneum represents the most Although, originally, dedifferentiation was entiated liposarcoma most often has ring
common anatomic location, outnumber- characterized definitionally by high or giant marker chromosomes {680,794,
ing the soft tissue of the extremities by at grade morphology {617}, the concept of 1389,1425,1706,1962}. However, the
least 3:1. Other locations include the low grade dedifferentiation has increas- number of karyotyped cases is presently
spermatic cord and, more rarely, the ingly been recognized {578,937}. Low too small to establish whether significant
head and neck and trunk. Occurrence in grade dedifferentiation is characterized
subcutaneous tissue is extremely rare most often by the presence of uniform
{678, 2242}. fibroblastic spindle cells with mild
nuclear atypia, often organized in a fas-
Clinical features cicular pattern and exhibiting cellularity
Dedifferentiated liposarcoma usually intermediate between WD sclerosing
presents as a large painless mass, which liposarcoma and usual high grade areas.
may be found by chance (particularly in Low grade dedifferentiation should not
the retroperitoneum). be confused with WD spindle cell
In the limbs, the history of a long-stand- liposarcoma which is invariably a
ing mass exhibiting recent increase in lipogenic lesion (i.e. it contains atypical
size often indicates dedifferentiation. adipocytes or lipoblasts), whereas dedif-
Fig. 1.34 Dedifferentiated liposarcoma. Note the
Radiological imaging shows coexistence ferentiated areas, both low and high
solid, fleshy areas with haemorrhage, indicating the
of both fatty and non-fatty solid compo- grade are generally non lipogenic.
presence of a high grade component in this other-
nents which, in the retroperitoneum, may Dedifferentiated liposarcoma may exhib-
wise well differentiated retroperitoneal liposarcoma.
be discontiguous. it heterologous differentiation in about 5-
38 Adipocytic tumours
bb5_4.qxd 13.9.2006 9:49 Page 39
A B
Fig. 1.35 Dedifferentiated liposarcoma. A Abrupt transition between well differentiated liposarcoma and high grade non lipogenic area is seen. B The morphology of the
dedifferentiated component usually overlaps with so called storiform and pleomorphic MFH.
differences between the well differentiat- amplification were found to have TP53 ed by anatomic location, with retroperi-
ed and dedifferentiated types exist. A mutations, whereas in another series of toneal lesions exhibiting the worst clinical
peculiarity of dedifferentiated liposarco- 14 dedifferentiated liposarcoma, a major- behaviour. The extent of dedifferentiated
ma might be the presence of multiple ity of which expressed MDM2, TP53 areas does not seem to predict the out-
abnormal clones, with one or more con- mutation was detected only in the dedif- come. Interestingly, dedifferentiated
taining supernumerary rings or large ferentiated component of a single case liposarcoma, despite its high grade mor-
markers {1389,1425}. {487}. phology, exhibits a less aggressive clini-
cal course than other types of high grade
Molecular cytogenetics and genetics Prognostic factors pleomorphic sarcoma, although the
Comparative genomic hybridization and Dedifferentiated liposarcoma is charac- basis for this difference is unknown {937,
fluorescence in situ hybridisation analy- terized by a tendency to recur locally in 1374, 2246}. Relative absence of com-
ses revealed amplification of the 12q13- at least 40% of cases. However, almost plex karyotypic aberrations as well as
21 region associated with the co-amplifi- all retroperitoneal examples seem to integrity of the TP53 gene in most cases
cation of other regions, as also observed recur locally if the patients are followed (at variance with what is observed in high
in WD liposarcomas {794, 1389, 1706, for 10-20 years. Distant metastases are grade pleomorphic sarcomas) may at
1962, 2072}. Southern blot studies observed in 15-20% of cases with an least in part explain the discrepancy
showed MDM2 amplification in 5/5 overall mortality ranging between 28 and between morphology and clinical out-
retroperitoneal, but not in 4/4 non- 30% at 5 years follow-up {937, 1374, come {399,487}.
retroperitoneal dedifferentiated liposar- 2246}, although this figure is undoubted-
coma cases {1706,1889}. These 4 non- ly much higher at 10-20 years. The most
retroperitoneal cases negative for MDM2 important prognostic factor is represent-
A B C
Fig. 1.36 Dedifferentiated liposarcoma. A Often the dedifferentiated component exhibits morphologic features indistinguishable from myxofibrosarcoma. B Rarely, ded-
ifferentiated liposarcoma features a peculiar whorling growth pattern reminiscent of neural or meningothelial structures. C Approximately 5% of cases exhibit heterolo-
gous differentiation, most often myogenic. This example shows rhabdomyosarcomatous differentiation.
Atypical lipomatous tumour / Well differentiated liposarcoma 39
bb5_4.qxd 13.9.2006 9:49 Page 40
C. Antonescu
Myxoid liposarcoma
M. Ladanyi
Definition Sites of involvement sise to unusual soft tissue (such as
A malignant tumour composed of uni- MLS occurs with predilection in the deep retroperitoneum, opposite extremity, axil-
form round to oval shaped primitive non- soft tissues of the extremities, and in la, etc) or bone (with predilection to
lipogenic mesenchymal cells and a vari- more than two-thirds of cases arises spine) locations, even before spread to
able number of small signet-ring within the musculature of the thigh. MLS lung. In a significant number of cases,
lipoblasts in a prominent myxoid stroma rarely arises primarily in the retroperi- MLS patients present clinically with syn-
with a characteristic branching vascular toneum or in subcutaneous tissue. chronous or metachronous multifocal
pattern. Included in this category are disease {73}. This unusual clinical phe-
lesions formerly known as round cell Clinical features nomenon most likely represents a pat-
liposarcoma. MLS typically occurs as a large painless tern of haematogenous metastases to
mass within the deep soft tissues of the other sites by tumour cells seemingly
ICD-O codes limbs. MLS is a disease of young adults, incompetent to seed the lungs.
Myxoid liposarcoma 8852/3 with the age at presentation on average
Round cell liposarcoma 8853/3 a decade younger than with other histo- Macroscopy
logical subtypes of liposarcoma. It has a Grossly, MLS are well-circumscribed,
Synonyms peak incidence in the 4th and 5th multinodular intramuscular tumours,
Myxoid / round cell (RC) liposarcoma, decades of life and, although very rare, it showing a tan, gelatinous cut surface in
round cell liposarcoma. is the commonest form of liposarcoma in predominantly low-grade tumours. In
patients younger than 20 years old. contrast, areas of RC component, repre-
Epidemiology There is no gender predilection. MLS is senting high-grade sarcoma, have a
Myxoid liposarcoma (MLS) is the second prone to recur locally and one-third of white fleshy appearance. Gross evi-
most common subtype of liposarcoma, patients develop distant metastases, but dence of tumour necrosis is uncommon.
accounting for more than one third of this is dependent on the histological
liposarcomas and representing about grade. In contrast to other types of Histopathology
10% of all adult soft tissue sarcomas. liposarcoma or other myxoid sarcomas At low-power MLS has a nodular growth
of the extremities, MLS tends to metasta- pattern, with enhanced cellularity at the
A
B
Fig. 1.38 Myxoid liposarcoma. Gross appearance of
A B
MLS with (A) a gelatinous cut surface in low grade
Fig. 1.37 A,B Myxoid liposarcoma. CT images of multifocal myxoid liposarcoma, showing synchronous soft myxoid areas and (B) a yellow-white appearance in
tissue masses, likely representing multiple soft tissue metastases. the high grade round cell component.
40 Adipocytic tumours
bb5_4.qxd 13.9.2006 9:49 Page 41
A B C
Fig. 1.39 Histological spectrum of myxoid liposarcoma (MLS). A Uniform round to oval shaped primitive nonlipogenic mesenchymal cells and a variable number of
small lipoblasts in a prominent myxoid stroma. B Signet-ring lipoblasts with multivacuolated cytoplasm. C Delicate arborizing vasculature.
periphery of the lobules. There is a mix- so-called "pulmonary oedema" growth areas are characterized by solid sheets
ture of uniform round to oval shaped pattern. Interstitial haemorrhage is com- of back-to-back primitive round cells with
primitive nonlipogenic mesenchymal mon. Typically, MLS lacks nuclear pleo- a high nuclear/cytoplasmic ratio and
cells and small signet-ring lipoblasts in a morphism, giant tumour cells, prominent conspicuous nucleoli, with no interven-
prominent myxoid stroma, rich in a deli- areas of spindling, or significant mitotic ing myxoid stroma {677}. The RC (hyper-
cate, arborising, "chicken-wire" capillary activity. A subset of MLS shows histolog- cellular) areas may be composed of
vasculature. Frequently the extracellular ical progression to hypercellular or RC close-packed relatively small cells simi-
mucin forms large confluent pools, creat- morphology, which is associated with a lar to those in the myxoid areas or may
ing a microcystic lymphangioma-like or significantly poorer prognosis. The RC less often consist of larger rounded cells
A B
C D
Fig. 1.40 Histological spectrum of myxoid liposarcoma (MLS). A Characteristic "pulmonary oedema" growth pattern due to pools of stromal mucin. B Low power view of
a low grade MLS showing focal areas of increased cellularity. C High power view of a "transitional area", showing increased cellularity. Tumour cells are not closely
packed, retaining a small amount of intercellular myxoid stroma. D Round cell MLS characterized by solid sheets of back-to-back primitive round cells with a high nuclear
/ cytoplasmic ratio and conspicuous nucleoli, with no intervening myxoid stroma.
Myxoid liposarcoma 41
bb5_4.qxd 13.9.2006 9:49 Page 42
Immunophenotype
Although, for most MLS cases, immuno-
histochemical studies are not needed for
establishing a correct diagnosis, it can
be useful in cases showing predominant-
ly round cell morphology. In the majority
of cases this shows a diffuse staining for
S100 protein.
Ultrastructure
Ultrastructurally the proportion of undif-
Fig. 1.41 Myxoid liposarcoma. Ultrastructural
ferentiated cells, devoid of lipid droplets
appearance of signet ring lipoblast, with
and rich in clusters of vimentin-type inter-
microvesicular fat droplets.
mediate filaments, and signet-ring
lipoblasts vary from case to case.
with variable amounts of eosinophilic Lipoblasts in variable stages of adipocyt- Fig. 1.42 Myxoid liposarcoma. Schematic illustra-
cytoplasm. These two morphologic pat- ic maturation can be identified, contain- tion of the breakpoints involved in the specific
translocations of myxoid/round cell liposarcoma,
terns show no clear difference in progno- ing either relatively few small lipid
t(12;16)(q13;p11) and t(12;22)(q13;q12).
sis but have been responsible for some droplets, or large confluent lipid droplets
of the confusion regarding definition of that displace the nucleus to the periph-
the round cell variant. The presence of ery. Flocculent mucoid stromal material
gradual transition from myxoid to hyper- coating the cells and extracellular t(12;22)(q13;q12) has been described,
cellular/ RC areas, commonly observed spaces is common. in which DDIT3 fuses instead with EWS,
in MLS, provides strong evidence that a gene highly related to FUS {1641}.
myxoid and RC liposarcoma represent a Genetics FUS/DDIT3 fusion transcripts occur as
histological continuum of MLS. The so- The karyotypic hallmark of myxoid and different recurrent structural variants
called areas of transition are defined as round cell liposarcoma is the based on the presence or absence of
areas of increased cellularity, not reach- t(12;16)(q13;p11) present cytogenetical- FUS exons 6 to 8 in the fusion product.
ing the level of RC component and still ly in more than 90% of cases {2018, Of the possible FUS genomic break-
retaining small amount of intercellular 2145}. The translocation leads to the points, only breaks in FUS introns 5, 7,
myxoid stroma. The existence of a mor- fusion of the DDIT3 (a.k.a. CHOP) and and 8 give rise to in-frame fusion tran-
phologic spectrum, in which purely myx- FUS (a.k.a. TLS) genes at 12q13 and scripts joining FUS exons 5, 7, and 8,
oid and RC liposarcoma represent the 16p11, respectively, and the generation respectively, to exon 2 of DDIT3 {1061,
well and poorly differentiated compo- of FUS/DDIT3 hybrid protein {104, 410, 1642}. Thus, three major recurrent fusion
nents is supported by the same recurrent 1687, 1741}. In rare cases of MLS a transcript types have been reported:
genetic alteration in both. variant chromosomal translocation type 7-2 (a.k.a. type I), seen in about
20% of cases, type 5-2 (a.k.a. type II),
seen in approximately two-thirds of
cases, and type 8-2 (a.k.a. type III), seen
in about 10% {73, 1143, 1642}.
Sequence analysis of the genomic
t(12;16) breakpoints in FUS and DDIT3
and associated functional studies sug-
gest the involvement of translin and
topoisomerase II in the process of
translocation {971,1061}.
The monoclonal origin of the synchro-
nous and/or metachronous multifocal
MLS has been confirmed by comparing
FUS/DDIT3 or EWS/DDIT3 genomic
rearrangement structure in tumours from
different sites {66}.
The presence of the FUS/DDIT3 fusion is
highly sensitive and specific for the MLS
entity, and is absent in other morpholog-
ic mimics, such as the predominantly
myxoid well differentiated liposarcomas
of the retroperitoneum and myxofibrosar-
comas {67}. No convincing genetic evi-
Fig. 1.43 Myxoid liposarcoma. Karyotype showing the characteristic translocation t(12;16)(q13;p11) in a
myxoid liposarcoma. Arrowheads indicate breakpoints. dence has been provided to date to
42 Adipocytic tumours
bb5_4.qxd 13.9.2006 9:49 Page 43
support the concept of mixed type
liposarcoma composed of MLS and ded-
ifferentiated liposarcoma.
Prognostic factors
High histological grade, often defined as
5%RC areas, presence of necrosis, and
TP53 overexpression are predictors of
unfavourable outcome in localized MLS
{73, 1103, 1976}. The prognostic signifi-
cance of more limited hypercellularity
(transitional areas) is less certain. The
clinical outcome of multifocal MLS is
poor, regardless of its often bland or "low
grade" histological appearance. In con-
trast with some other translocation-asso-
ciated sarcomas, the molecular variabili-
ty of fusion transcripts in MLS does not
appear to have a significant impact on
histological grade or clinical outcome
{73}.
Fig. 1.44 Myxoid liposarcoma. Kaplan-Meier curve showing a correlation between high histological grade
( 5%RC) and disease specific survival in patients with localized MLS (From C.R. Antonescu et al. {73}).
Myxoid liposarcoma 43
bb5_4.qxd 13.9.2006 9:49 Page 44
T. Mentzel
Pleomorphic liposarcoma
F. Pedeutour
Definition or rare purely dermal pleomorphic of necrosis are noted. The majority of
Pleomorphic liposarcoma is a pleomor- liposarcomas have been reported {489, neoplasms are large with a median
phic, high grade sarcoma containing a 548, 774}. greatest diameter of more than 10 cm.
variable number of pleomorphic
lipoblasts. No areas of atypical lipoma- Clinical features Histopathology
tous tumour (well differentiated liposar- As in other deep seated sarcomas, most Histologically, well circumscribed, non-
coma) or another line of differentiation patients complain of a firm, enlarging encapsulated cases as well as ill defined
(malignant mesenchymoma) are evident. mass; many cases have a notably short and infiltrative neoplasms composed of a
preoperative history. In general, pleo- varying number of pleomorphic
ICD-O code 8854/3 morphic liposarcoma is an aggressive lipoblasts in a background of a high
mesenchymal neoplasm showing a 30% grade, pleomorphic sarcoma are seen.
Epidemiology to 50% metastasis rate and an overall The majority of neoplasms consist of
Pleomorphic liposarcoma represents the tumour associated mortality of 40% to pleomorphic spindle shaped tumour
rarest subtype of liposarcoma, account- 50% {548, 1445, 2332}. Many patients cells and fascicles of spindled and
ing for approximately 5% of all liposarco- die within a short period of time {1445}, smaller, round cells admixed with multin-
mas {101} and 20% of pleomorphic sar- and the lung represents the preferred ucleated giant cells (similar to so called
comas {675}. The majority of neoplasms site of metastases {548}. In contrast, malignant fibrous histiocytoma), as well
arise in elderly patients (>50 years) with dedifferentiated liposarcomas and high- as pleomorphic, multivacuolated
an equal sex distribution. grade myxofibrosarcomas have a pro- lipoblasts, with bizarre, hyperchromatic
longed clinical course, whereas pleo- and scalloped nuclei. In some cases
Sites of involvement morphic myogenic sarcomas of deep only scattered pleomorphic lipoblasts
Pleomorphic liposarcoma tends to occur soft tissues show an even more aggres- are found, whereas sheets of pleomor-
on the extremities (lower>upper limbs), sive clinical course emphasising the phic lipoblasts are evident in other
whereas the trunk and the retroperi- need for subclassification of pleomor- examples. Frequently, intra- and extra-
toneum are less frequently affected; rare phic sarcomas. cellular eosinophilic hyaline droplets or
sites of involvement include the medi- globules are noted, that most likely rep-
astinum, the paratesticular region, the Macroscopy resent lysosomal structures. Rarely a
scalp, the abdominal/pelvic cavities, and Grossly, the neoplasms are typically prominent inflammatory infiltrate is evi-
the orbit {290, 489, 548, 1139, 1445, described as firm, often multinodular dent. In a number of cases, areas with
1609}. Although most cases arise in lesions with white to yellow cut surfaces. morphological features of pleomorphic
deep soft tissues, examples in subcutis In many cases myxoid areas and areas sarcoma resembling intermediate to high
Fig. 1.45 Pleomorphic liposarcoma. Deep Fig. 1.46 Pleomorphic liposarcoma. Pleomorphic spindle and giant cells as well as pleomorphic lipoblasts
seated tumour with grey-white cut surface. which contain enlarged and hyperchromatic nuclei scalloped by cytoplasmic vacuoles.
44 Adipocytic tumours
bb5_4.qxd 13.9.2006 9:49 Page 45
grade myxofibrosarcoma associated
with pleomorphic lipoblasts are noted.
The recently described epithelioid vari-
ant of pleomorphic liposarcoma {1445} is
composed predominantly of solid, cohe-
sive sheets of epithelioid tumour cells
with distinct cell borders, eosinophilic
cytoplasm and round to oval nuclei with
prominent nucleoli separated by narrow
fibrous septa with thin-walled
A B
capillaries; at least focally, lipogenic dif-
Fig. 1.47 Pleomorphic liposarcoma. In some neoplasms sheets of pleomorphic lipoblasts are seen (right part,
ferentiation with pleomorphic lipoblasts is
A), whereas only scattered lipoblasts are present in other cases (B).
noted also in these neoplasms. The
mitotic rate is higher in the epithelioid
variant, but areas of tumour necrosis are
seen in the majority of cases irrespective
of the morphological subtype. Most
recently a small round cell variant con-
taining pleomorphic lipoblasts and small
round cells virtually indistinguishable
from round cell liposarcoma has been
proposed {1389}.
Immunophenotype A B
The tumour cells stain positively for
Fig. 1.48 This retroperitoneal neoplasm shows features of a myxoid sarcoma resembling myxofibrosarcoma (A),
vimentin, but despite unequivocal
however, focally, lipoblasts with hyperchromatic and scalloped nuclei were noted (B)
lipogenic differentiation S-100 protein is
seen in less than half of the cases. Some
cases of the epithelioid variant of pleo-
morphic liposarcoma show focal expres- been reported in 6 of the 11 cases. The
sion of epithelial markers, an important cytogenetic profile of pleomorphic
finding in the differential diagnosis of liposarcoma appears therefore to be
these lesions {774, 1445}. closer to other pleomorphic sarcomas
than to well differentiated liposarcoma.
Ultrastructure
Neoplastic cells of pleomorphic liposar- Molecular genetics
coma contain abundant and coalescing In contrast to well differentiated liposar-
lipid droplets, numerous cytoplasmic comas, amplification of the 12q14-15
organelles and surrounding plasma region and the MDM2 gene does not
membranes {2231}. occur consistently in pleomorphic
Fig. 1.49 Epithelioid variant of pleomorphic liposar-
liposarcomas. A number of varied chro-
coma, characterized by sheets and clusters of
Genetics mosomal gains and losses but no ampli-
atypical epithelioid tumour cells associated with
Cytogenetics fication of the 12q14-15 region were
pleomorphic lipoblasts (upper part).
All 11 pleomorphic liposarcomas from found in two cases studied by compara-
which karyotypic data exist have shown tive genomic hybridisation {2072}. The
high chromosome counts and complex amplification of MDM2 was observed in
structural rearrangements {1425,2018}. approximately one third of the cases,
This complexity, represented by numer- and could be associated with the pres- Prognostic factors
ous unidentifiable marker chromosomes, ence of ring chromosomes {1568, 1889}. Although no single morphological factor
non-clonal alterations, polyploidy and TP53 alterations, such as mutations in predicts the clinical prognosis reliably,
intercellular heterogeneity has made the exons 7 or 8 or loss of heterozygosity, tumour depth and size, more than 20
detection of specific rearrangements dif- have been observed in 4/9 studied mitoses in 10 HPFs, and areas of tumour
ficult. The presence of ring, large marker, cases; all these 4 cases were negative necrosis are associated with a worse
or double minute chromosomes has for MDM2 amplification {1889}. clinical prognosis {548,1408,1445}.
Pleomorphic liposarcoma 45
bb5_4.qxd 13.9.2006 9:49 Page 46
T. Mentzel
Mixed-type liposarcoma
F. Pedeutour
Definition painless tumour mass, that is noted lipoblasts, and round cells set in a myx-
Liposarcomas showing features of com- sometimes incidentally. oid matrix with mucin pooling and a
bined myxoid/round cell liposarcoma prominent plexiform capillary pattern),
and atypical lipomatous tumour (well dif- Macroscopy pleomorphic liposarcoma (features of
ferentiated liposarcoma)/dedifferentiated Given the location, most cases of mixed- pleomorphic sarcoma with a variable
liposarcoma or of myxoid/round cell type liposarcoma are large, and often number of pleomorphic lipoblasts),
liposarcoma and pleomorphic liposarco- present as multinodular masses with and/or atypical lipomatous tumour (well
ma. cystic and solid areas and grey-yellow differentiated liposarcoma) (adipocytes
cut surfaces. with marked variation in size and shape,
ICO-O codes nuclear atypia). Cases of so called ded-
Mixed type liposarcoma 8855/3 Histopathology ifferentiated myxoid liposarcoma may
Liposarcoma, NOS 8850/3 The occurrence of myxoid areas in the represent mixed-type liposarcomas
group of atypical lipomatous tumour showing a combination of myxoid/round
Epidemiology (well differentiated liposarcoma)/dedif- cell liposarcoma and dedifferentiated
True mixed-type liposarcomas are ferentiated liposarcoma is well recog- liposarcoma.
exteremely rare and occur predominant- nized and especially in retroperitoneal
ly in elderly patients {1416}. and intraabdominal location quite com- Genetics
mon. However, in most cases, this In the three karyotyped cases of mixed-
Sites of involvement reflects either myxoid degeneration or type liposarcoma, the presence of ring or
Most cases of mixed-type liposarcoma dedifferentiation with myxofibrosarcoma- giant marker chromosomes was
appear to arise in retroperitoneal or intra- like features in atypical lipomatous observed either as the sole abnormality
abdominal locations. More rarely, exam- tumour (well differentiated liposarcoma) {680} or in association with complex
ples in the mediastinum and in deep soft instead of a true mixed-type liposarcoma rearrangements {794, 1389}.
tissue of the extremities have been {67, 955, 1389}. Rare mixed-type liposar- Amplification of the 12q14-15 region
reported {1114, 1139, 1389, 1416}. comas show a combination of morpho- and, more specifically, of the MDM2
logical features of myxoid/round cell gene has been found, but not TP53
Clinical features liposarcoma (small undifferentiated mes- mutations {794, 1389, 1889}.
The patients usually present with a large enchymal cells, often univacuolated
A B
Fig. 1.50 This case of a mixed type liposarcoma shows morphological features of lipoma-like atypical lipomatous tumour (well differentiated liposarcoma) (right) and myx-
oid liposarcoma (left) (A). High power view reveals small undifferentiated mesenchymal cells and lipoblasts set in a myxoid matrix with a plexiform vascular pattern in the
myxoid liposarcoma areas (B).
46 Adipocytic tumours