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Benign and Malignant
Tumors of Fat
M.H.A. 10.2012
Tumors of adipocytes are among the largest
group of primary soft tissue tumors.
The majority of these tumors occur in adults.
Liposarcomas (if atypical lipomas are included)
are the largest group of malignant soft tissue
tumors.
Benign Lipomatous Tumors
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Benign Lipoma
• Majority occur in adults over 30.
• Occurrence in childhood is uncommon
• No sex predilection is present in standard lipoma
• Most are subcutaneous
• Some are deep seated
Benign Lipoma, cont.
• Lipomas almost never occur in the retroperitoneum
• They can be single or multiple
• Recurrence rate is no more than 1% to 2%
• Most common cytogenetic changes
• Translocation involving 12q13-15
• Rearrangement 13q
• Rearrangement 6p21-33
Gross and Microscopic Appearance
• Most are well circumscribed
• There is a thin fibrous capsule
• Most are lobulated
• Size variable but rarely over 10cm.
• Cut surface has a mature fatty appearance. There can
be fibrous, vascular and myxoid areas and fat necrosis is
sometimes seen.
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Lipoma Gross
Benign lipoma
Prominent fibrous component
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Myxoid and spindle cell component of lipoma
Variants of Lipoma
Angiolipoma
• Most subcutaneous with trunk and upper extremity
favored.
• Often painful
• Often multiple, recurrence almost never occurs
however, new tumors are not uncommon.
• Male predominance
• Majority measure less than 2cm
Variants of Lipoma
Angiolipoma, cont.
• Small thin walled, capillary like vessels are present in
the lipoma
• Often the vessels are peripheral
• Number of vessels is variable and can be the majority
of the mass
• Often fibrin thrombi can be seen in the vessels
• Long standing tumors can have perivascular fibrosis
• Angiolipomas have a normal karyotype.
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angiolipoma
Angiolipoma
angiolipoma
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Angiolipoma thrombi
Synovial lipoma
• Also know as lipoma arborescens
• Mostly in adults
• Knee is favorite site
• Can cause degenerative articular pathology
• Consist of fat beneath synovial lining forming finger like
projections
Synovial lipoma AFIP
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Synovial lipoma JLP
Synovial lipoma JLP
Intramuscular / Intermuscular Lipoma
• These tumors are deeper
• Slow growing
• Poorly circumscribed
(only 10% are well circumscribed and non infiltrative)
• Often Infiltrative (20% recurrence rate)
• Blood vessels sparse
• No sex predilection
• Usually over 40-50 age group
• Most commonly in the trunk and thigh
• MDM2
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Intramuscular lipoma
Intramuscular lipoma
Intramuscular lipoma
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Intramuscular lipoma
Intramuscular lipoma
Bullet points intramuscular lipoma
• Make sure this is not an atypical lipoma/well differentiated
liposarcoma
• Some feel that the above is more common than benign
intramuscular lipoma
• Atypia should make you suspicious
• MDM2 FISH will differentiate between the two
• Some surgeons in some centers request MDM2 on all
intramuscular lipomas
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Hibernoma
• Arises in adults between age 20 and 50
• Commonest locations are the thigh, shoulder, interscapular
area or back of the neck
• Most are subcutaneous, 10% can be intramuscular
• Mostly 5 to 10cm in size
• No tendency to recur
• Cytogenetically 11q13 or 10q22
Hibernoma with
predominant
mature fat
Atypical Lipomatous Tumor
Small, central
bland nuclei in
vacuolated cells
Lipoblasts, if present, have atypical nuclei
Lacks atypical
nuclei
Contains atypical nuclei
Frequently
superifcial
Rarely superficial
MDM2, CDK4,
p16 negative
MDM2, CDK4, p16 most positive
hibernoma
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Hibernoma
Intramuscular hibernoma
hibernoma
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Lipoma like hibernoma
Lipomatosis
• A condition presenting with diffuse overgrowth of fatty tissue
• Predominance of cases occur in males
• Four types are recognized:
1. Multiple symetrical lipomas
2. Asymetrial lipomatosis
3. Pelvic lipomatosis
4. Mediastinoabdominal
Multiple symetrical lipomas
• Also called Madelung’s disease or Launois-Bensaude
adenolipomatosis
• Affects mainly the neck and shoulders and is the
commonest form
• Often associated with alcoholism and peripheral
neuropathy and hyperlipidemia.
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Multiple symmetrical lipomas
Cervical lipomatosis
Asymetrial lipomatosis
It is characterized by slowly
growing, usually asymptomatic,
subcutaneous masses of various
sizes in widespread distribution.
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Pelvic lipomatosis
•
Occurs around the bladder and rectum.
•
It has a characteristic radiologic appearance
•
Can be associated with urinary obstruction and
sequelae.
Mediastino-abdominal lipomatosis.
• All the above are composed of mature fat. Some may
have associated fibrosis.
Lipoblastoma
• Predominantly a tumor of infancy
• Mostly in males
• Usually before the age of 3
• Usually superficial slow growing masses in the limbs and
rarely exceeds 5 cm.
• Local recurrence is infrequent
• Associated with 8q11-13 gene abnormality.
lipoblastoma
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Lipoblastoma 10x
Lipoblastoma
20x
Note the lack of nuclear atypia,
myxoid stroma, and crow’s feet vessels.
Lipoblastoma
Chondroid lipoma
• Rare
• Can be mistaken for sarcoma
• Features to look for are mature adipocytes mixed with benign
lipoblasts, and hibernoma like cells in a psuedo-chondroid
matrix.
• 11q-13 abberations different from those in hibernoma
• No MDM2 FISH present
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Chondroid lipoma circumscribed masses
Chondroid lipoma AFIP
Chondroid lipoma, hibernoma like, benign lipoblasts
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Spindle Cell and Pleomorphic Lipoma
• Occurs predominantly in males
• Usually in mid to late adullts
• Over 80% originate in the upper back, shoulders or back of
the neck. Can occur in the head, oral cavity or anterior neck.
• Most are subcutaneous or dermal. These rarely recur.
• Some are deep and are likely to recur. Some authors classify
them as atypical lipomatous tumors for this reason.
Spindle Cell and Pleomorphic
Lipoma, cont.
• Well circumscribed and thinly encapsulated with firmer
consistency than ordinary lipoma.
• Histologically there is a mixture of mature fat cells with
spindle cells. Mitosis is very rare.
• Hyalin collagen (ropey collagen) bundles are frequent.
Floret cells can be seen.
• Myxoid change is not uncommon and thin vessels can be
seen.
• 13q and 16q gene abnormalities are consistent. Ringed
chromosomes are not seen. MDM2 gene marker is negative.
Spindle Cell Lipoma
Spindle Cell Variant Atypical
Lipomatous Tumor
Restricted to back of neck, upper
back, shoulders
Various locations
Bland spindle cells
Mild to moderate atypia of
spindle cells
Ropy collagen bundles
No ropy collagen
Circumscribed
May be infiltrative
Uniformly strong CD34
CD34 only occasionally reactive
MDM2 0-12% and CDK4 0-6%
MDM2 and CDK4 most positive
No areas of usual ALT pattern
Areas of usual ALT pattern
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typical admixture of mature adipocytes, bland, undifferentiated
spindle cells, and hyaline collagen bundles.
Spindle cell lipoma
Lesions showing spindle cell predominance may mimic schwannoma.
Spindle cell lipoma
Spindle cell lipoma
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Spindle cell lipoma
Ropey collagen in spindle cell lipoma
Spindle cell lipoma
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Prominent stromal myxoid change is quite common, sometimes leading to
confusion with myxoid liposarcoma.
Myxoid spindle cell lipoma
Marked myxoid degeneration may lead to a villiform,
lymph angiomatoid appearance
Spindle cell lipoma
Typical floret-type giant cells and hyperchromatic stromal cells and spindle cells.
Pleomorphic lipoma
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Liposarcoma
• Atypical lipomatous tumor/Well Differentiated Liposarcoma
• Myxoid liposarcoma
• Pleomorphic / Round Cell liposarcoma
• Dedifferentiated liposarcoma
Atypical lipomatous tumor /
Well differentiated liposarcoma
• Two variants lipoma like and sclerosing
• Account for 40-45% of all liposarcomas.
• Varying fibrous septa with cells with atypical nuclei. Classic
lipoblasts are rare and are not needed for diagnosis.
• Ocurr in the subcutis, deep soft tissues, and the
retroperitoneum
• By definition, it does not occur in the dermis or subcutis of
the posterior neck, upper back or shoulders
• Fatty tumors with atypia in those locations are termed
pleomorphic lipoma
• They do not recur aggressively or dedifferentiate
• Fat may appear grossly normal. Fat cell size may range
from smaller to larger than normal
• Atypical cells required for diagnosis
• Atypical cells frequently located in fibrous areas. May also
be located in fat, myxoid areas or in walls of blood vessels
usually scattered, not in nests or confluent
• Large irregular nuclei should be visible at low magnification
with dense, smudgy chromatin
• Lipoblasts sufficient but not required for diagnosis Atypical
nuclei indented or scalloped by vesicles containing fat
• Cytoplasmic vacuole(s) that indent and distort nucleus
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• Frequent floret cells, defined by a ring or semicircle of nuclei
• Frequently contains fibrous or myxoid areas
• Collagen may be fine or coarse. Frequently extends between
adjacent lipocytes at edge of fibrotic areas may predominate
• Has been termed sclerosing liposarcoma
or sclerosing variant
• No clinical significance
• Foci of moderately increased cellularity and mitotic activity
rarely may be seen. Non-lipogenic component with features
of fibromatosis, low grade fibrosarcoma or
hemangiopericytoma with mitotic rate <5/10 hpf
• Has been termed low grade dedifferentiated liposarcoma
• Cellular atypical lipomatous tumor may be a better
term(Evans 2007)
• When to suspect WDL/Atypical lipomatous tumor
• Large and deep fatty tumor. (When it comes in
buckets)
• Retroperitoneal fatty tumor.
• MRI heterogeneity (surgeon is suspicious)
• Fibrous bands
• Atypia (hyperchromasia) at low power.
• MDM2 is positive. Do fish if at all atypical. MDM2
immunocytochemistry not as sensitive.
• P16 very sensitive for ALT/WDL
FISH/PCR of lipomatous tumors
MDM2 FISH
MDM2
QPCR
CDK4
FISH
CDK4
QPCR
Atypical lipomatous tumor
90-100%
72100%
75100%
69-100%
Dedifferentiated liposarcoma
100%
100%
100%
100%
Myxoid liposarcoma
20%
Spindle cell / pleomorphic
lipoma
Negative
Negativ
e
Negativ
e
Negative
Angiolipoma
Negative
Lipoma, NOS
Negative
Negativ
e
Negativ
e
Negative
Sarcomas
0-40%
0%
0%
0%
Spindle cell / pleomorphic lipoma showed 89% chromosome 12 polysomy
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WDL/ATL Lipomatous variant
WDL/ALT Sclerosing variant
ALT/WDL
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WDL/ATL
WDL/ATL
WDL/ATL
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WDL/ATL
WDL/ATL
Myxoid Liposarcoma
• Is part of a continuum with the higher grade round cell variant
• Accounts for 30-35% of liposarcomas.
• Genetic abnormalities t(12;16)(q13;p11) or less often
T(12;22)(q13;q11-12) both show rearrangement of DDIT3 gene
• DDIT3 (CHOP) FISH is a sensitive and specific method for the
detection of DDIT3 gene rearrangements, which aid in the
diagnosis of round cell/myxoid liposarcoma.
• If no round cell variant this is a low grade tumor. Round cell
variant over 10% renders this an intermediate grade tumor. If
Over 25% this should be called high grade.
• Low grade tumors have lipoblastic differentiation and classic
chicken wire type blood vessels and some times focal
cartilagenous areas or multinucleated cells.
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Note crows feet vessels, small
undifferentiated cells and lipoblasts.
Myxoid liposarcoma
Myxoid liposarcoma Mucin pools not uncommon.
Myxoid liposarcoma chicken wire vessels
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Myxoid-liposarc pas
Myxoid liposarcoma with scattered round cells
Round cell liposarcoma with crows feet vessels
Round Cell Liposarcoma
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Myxoid/round cell liposarcoma
Myxoid and round cell areas often show sharp transition
Myxoid round cell liposarcoma with another area of sharp transition.
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Myxoid and round cell
Myxoid-round cell
Pleomorphic Liposarcoma
• Approximately 5% of liposarcomas
• Resembles Pleomorphic Undifferentiated Sarcoma (MFH family)
except for multivacuolated lipoblasts
• Lipoblasts may be focal and few in number
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Pleomorphic liposarcoma
The tumor is indistinguishable from so-called MFH except
for the scattered lipoblasts
Pleomorphic liposarcoma
Pleomorphic liposarcoma MFH area
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Pleomorphic liposarcoma, lipoblasts in MFH like area
Dedifferentiated Liposarcoma
• Accounts for approximately 10% of liposarcomas
• Must have well differentiated liposarcoma showing abrupt
transition to a high grade non-lipogenic sarcoma
• 90% are de novo with 10% originating in a recurrence
• Most commonly in the retroperitoneum.
• MDM2 positive in the well differentiated liposarcoma area.
Poorly differentiated sarcoma often is MFH type. Can have
rabdo, osteo or leiomyosarcomatous differentiation.
• No difference in survival among the dedifferentiated lesions
Dedifferentiated liposarcoma
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Dedifferentiated liposarcoma
Dedifferentiated liposarcoma, fibrosarcomatous area
Dedifferentiated liposarcoma, MFH type
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Dedifferentiated liposarcoma, spindle cell type
References:
Diagnostic Histopathology of Tumors, Third Edition,
Editor: Christopher Fletcher, M.D., FRCPath., 2007
Enzinger and Weiss’s Soft Tissue Tumors, 5th Edition
Editors: S.W.Weiss, M.D., J.R. Goldblum, M.D., 2008
19th Annual Seminar in Pathology, Pittsburgh 2012
Soft Tissue Pathology, J.R.Goldblum, M.D., Presenter
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