Adipose Tissue Tumors

#2
 Atypical Lipomatous Tumor/WDLS
CLINICAL ISSUES
Most common form of liposarcoma (40-45% of cases)
Middle-aged to elderly adults
Extremities, retroperitoneum, abdominal cavity,
paratesticular region, mediastinum
No metastatic potential
 Atypical Lipomatous Tumor/WDLS
MACROSCOPIC
Well-circumscribed, lobular
Variable yellow, fatty to tan-gray cut surface
Thickened fibrous bands may be evident grossly
Usually > 5 cm
 Atypical Lipomatous Tumor/WDLS
MICROSCOPIC
Sheets and lobules of relatively mature adipocytes of
varying sizes
Stromal &/or adipocyte nuclear atypia characteristic
Lipoblasts vary in number and may be absent
Subtypes: Sclerosing, inflammatory, spindle cell
IHC : Overexpression of nuclear MDM2 and CDK4
Atypical Lipomatous Tumor/WDLS

Well
circumscribed
Atypical stromal cells &
multivacuolated
lipoblasts
Atypical Lipomatous Tumor/WDLS

Atypical Stromal Cells

Floret Cells
Atypical Lipomatous Tumor/WDLS

Atypical Adipocyte
Fat Necrosis
Atypical Lipomatous Tumor/WDLS
Multivacuolated Lipoblasts

Cellular Fibrous Bands

Atypical Lipomatous Tumor/WDLS
Fibrosis

Sclerosing type
Atypical Lipomatous Tumor/WDLS

Myxoid Stroma

Rare Arborizing Capillary Vasculature

Atypical Lipomatous Tumor/WDLS

Inflammatory Subtype

Spindle Cell Subtype

Atypical Lipomatous Tumor/WDLS

Rare Brown Fat Component

MDM2 Amplification
 DD of Atypical Lipomatous
Tumor/WDLS
1. Lipoma
2. Pleomorphic lipoma
3. Dedifferentiated liposarcoma
4. Massive localized lymphedema
 DD of Atypical Lipomatous
Tumor/WDLS
Lipoma
Most are smaller than ALT/WDLPS
Lacks atypical stromal cells with irregular,
hyperchromatic, pleomorphic nuclei
Usually lacks significant variation in size and shape of
adipocytes
Generally no lipoblasts
Negative for MDM2 and CDK4 by
immunohistochemistry
 DD of Atypical Lipomatous
Tumor/WDLS
Lipoma
 DD of Atypical Lipomatous
Tumor/WDLS
Pleomorphic Lipoma
Usually small lesions, often subcutaneous
Variable number of floret-like cells
Ropey collagen and scattered mast cells common
Negative for MDM2 and CDK4 by IHC
 DD of Atypical Lipomatous
Tumor/WDLS
Pleomorphic Lipoma
 DD of Atypical Lipomatous
Tumor/WDLS
Dedifferentiated Liposarcoma
Nonlipogenic sarcoma + WDLPS component
MDM2(+), CDK4(+) by IHC
 DD of Atypical Lipomatous
Tumor/WDLS
Dedifferentiated Liposarcoma
 DD of Atypical Lipomatous
Tumor/WDLS
Massive Localized Lymphedema
Large superficial pseudotumor in morbidly obese
patients
Often show retention, but expansion, of overall
architecture of subcutaneous tissue
Reactive fibroblast nuclei may simulate atypical
stromal cells of ALT/WDLPS
No MDM2 amplification
 DD of Atypical Lipomatous
Tumor/WDLS
Massive Localized Lymphedema
 Dedifferentiated Liposarcoma
CLINICAL ISSUES
Middle-aged to elderly adults
Most common in retroperitoneum/abdominal cavity
Can be recurrence and metastases

MACROSCOPIC
Well-demarcated, large mass with variable cut surface
Important to sample thoroughly
 Dedifferentiated Liposarcoma
MICROSCOPIC
Abrupt or gradual transition from ALT/WDLPS to
nonlipogenic, cellular sarcoma
Nonlipogenic component shows broad morphologic
spectrum (often high grade)
Mitotic rate > 5 per 10 HPF
Diffuse nuclear MDM2(+) and CDK4(+)
 Dedifferentiated Liposarcoma

Lipogenic (yellowish white) and

nonlipogenic
(dedifferentiated) components (red) Mostly composed of fibrous or
fleshy nonlipogenic sarcoma
Dedifferentiated Liposarcoma

Abrupt Transition

Gradual Transition
Dedifferentiated Liposarcoma

Irregular Transition

Pleomorphic Morphology
 Dedifferentiated Liposarcoma

Myxofibrosarcoma Morphology

Low-Grade Fibromyxoid Morphology

Dedifferentiated Liposarcoma

Spindled Morphology

Fascicular Morphology
Dedifferentiated Liposarcoma

Storiform Morphology

Whorled Morphology
 Dedifferentiated Liposarcoma

Inflammatory Component

Abundant Neutrophils
 Dedifferentiated Liposarcoma

Hemangiopericytoma-Like Vasculature
Heterologous Elements
 Dedifferentiated Liposarcoma
Heterologous Elements

Homologous Lipoblastic Differentiation

 DD of Dedifferentiated Liposarcoma

1. Undifferentiated pleomorphic sarcoma

2. Pleomorphic liposarcoma
3. Myxoid liposarcoma
4. Myxofibrosarcoma
 DD of Dedifferentiated Liposarcoma

Undifferentiated Pleomorphic Sarcoma (UPS)

Very rare in retroperitoneum
Most retroperitoneal tumors with UPS morphology
are actually DDLPS
Lacks component of ALT/WDLPS
Generally less morphologically heterogeneous than
DDLPS
No MDM2 amplification
 DD of Dedifferentiated Liposarcoma

Undifferentiated Pleomorphic Sarcoma (UPS)

 DD of Dedifferentiated Liposarcoma

Pleomorphic Liposarcoma
May arise in retroperitoneum
Lacks component of ALT/WDLPS
No MDM2 amplification
 DD of Dedifferentiated Liposarcoma

Pleomorphic Liposarcoma
 DD of Dedifferentiated Liposarcoma

Myxoid Liposarcoma
Very rare in retroperitoneum/abdomen
Lacks component of ALT/WDLPS
No MDM2 amplification
 DD of Dedifferentiated Liposarcoma

Myxoid Liposarcoma
 DD of Dedifferentiated Liposarcoma

Myxofibrosarcoma
Very rare in retroperitoneum/abdomen
Lacks component of ALT/WDLPS
No MDM2 amplification
 DD of Dedifferentiated Liposarcoma

Myxofibrosarcoma
 Myxoid Liposarcoma
CLINICAL ISSUES
Accounts for ~ 30-35% of all liposarcomas
Most occur in young to middle-aged adults
Usually arise in deep soft tissue of the extremities
Local recurrence in ~ 30% of cases
Metastatic risk varies by histologic grade (< 10% up to
60%)
Presence of hypercellular (round cell) areas is most
important histologic predictor of outcome

MACROSCOPIC
Well circumscribed, multinodular
Usually large (median 10-12 cm)
 Myxoid Liposarcoma
MICROSCOPIC
Typically shows lobular growth pattern
Abundant myxoid stroma
Characteristic delicate, arborizing capillary
vasculature
Small spindled, stellate, and ovoid nonlipogenic tumor
cells
Uni-, bi-, and multivacuolated lipoblasts frequently
present
Mitoses generally scarce
Progression to hypercellular or "round cell" areas may
be present
 Myxoid Liposarcoma

Immunohistochemistry
Best utilized to exclude other entities
Variable S100 protein (+)
May highlight lipoblasts or show focal expression
in "round cell" areas
Negative for keratin, CD34, SMA, desmin
Usually negative for MDM2 and CDK4
 Myxoid Liposarcoma

Glistening, gelatinous cut

surface Lobular Growth
 Myxoid Liposarcoma

Abundant Myxoid Stroma

Bland Cytologic Features

 Myxoid Liposarcoma

Arborizing Capillary Vasculature

Arborizing Capillary Vasculature
 Myxoid Liposarcoma
Lipoblasts

Sparse Lipoblasts
 Myxoid Liposarcoma

Rare Multinucleated Cells

Hibernoma-Like Area
 Myxoid Liposarcoma

Stromal Mucin Pools

Stromal Mucin Pools
 Myxoid Liposarcoma

Mature Adipose Tissue

Stromal Hyalinization
 Myxoid Liposarcoma

S100 Protein Expression

Transitional Areas
 Myxoid Liposarcoma

Hypercellularity
Hypercellularity
 Myxoid Liposarcoma

Cytology of Hypercellular Areas

Mucin Pools in Hypercellular Areas

 Myxoid Liposarcoma

Round Cell Morphology

Round Cell Variations
 Differential Diagnoses of Myxoid
Liposarcoma
1. Atypical lipomatous tumor/well-differentiated
liposarcoma
2. Myxofibrosarcoma
3. Dermatofibrosarcoma Protuberans (Myxoid Variant)
4. Low-Grade Fibromyxoid Sarcoma
5. Intramuscular myxoma
 Differential Diagnoses of Myxoid
Liposarcoma
Atypical Lipomatous Tumor/Well-
Differentiated Liposarcoma
May contain zones of myxoid stromal change
Scattered enlarged, hyperchromatic stromal cells
(including floret-like cells)
Variably thickened fibrous bands
Absence of delicate, arborizing vasculature in most
cases
Most show MDM2(+) and CDK4(+) by IHC
 Differential Diagnoses of Myxoid
Liposarcoma
Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma
 Differential Diagnoses of Myxoid
Liposarcoma
Myxofibrosarcoma
Generally affects older age group than MLPS
Nuclear pleomorphism and atypia are characteristic
Lacks true lipoblasts
May contain pseudolipoblasts (vacuolated
fibroblastic tumor cells containing mucin)
Elongated curvilinear vessels of MFS are different from
delicate arborizing vasculature of MLPS
 Differential Diagnoses of Myxoid
Liposarcoma
Myxofibrosarcoma
 Differential Diagnoses of Myxoid
Liposarcoma
Dermatofibrosarcoma Protuberans (Myxoid
Variant)
Infiltrative dermal/subcutaneous neoplasm
Diffuse infiltration of preexisting structures and
adjacent soft tissue (honeycomb pattern)
Lacks lipoblasts
Vascular network and absence of nuclear
pleomorphism may somewhat resemble that of MLPS
Diffuse CD34(+) expression
 Differential Diagnoses of Myxoid
Liposarcoma
Dermatofibrosarcoma Protuberans (Myxoid Variant)
 Differential Diagnoses of Myxoid
Liposarcoma
Low-Grade Fibromyxoid Sarcoma
Bland fibrous zones punctuated by more cellular and
vascularized myxoid nodules
Lacks delicate arborizing capillary channels of MLPS
Lacks lipoblasts
 Differential Diagnoses of Myxoid
Liposarcoma
Low-Grade Fibromyxoid Sarcoma
 Differential Diagnoses of Myxoid
Liposarcoma
Intramuscular Myxoma
Often smaller, well-circumscribed tumors
Lacks lipoblasts and arborizing capillary vascular
pattern of MLPS
 Differential Diagnoses of Myxoid
Liposarcoma
Intramuscular Myxoma
 Pleomorphic Liposarcoma
CLINICAL ISSUES
Least common variant of liposarcoma (5% of cases)
Most common in patients > 50 years
Deep soft tissues of the extremities (75% of cases)
Also trunk, retroperitoneum, other sites
Aggressive sarcoma with poor prognosis
Metastases in 30-50% of cases

MACROSCOPIC
Well defined and multinodular or irregular and infiltrative
Usually large (median : 8-10 cm)
 Pleomorphic Liposarcoma
MICROSCOPIC
Lipoblasts (often pleomorphic) are characteristic and
requisite finding
Vary widely in number and distribution
Multiple morphologic patterns in varying proportions
Cellular pleomorphic sarcoma (most common),
myxofibrosarcoma-like, epithelioid
Mitoses and necrosis common in all patterns
IHC : Negative for MDM2 and CDK4
 Pleomorphic Liposarcoma

Intramuscular, partly necrotic

Lipoblasts & pleomorphic
lipoblasts
 Pleomorphic Liposarcoma

Pleomorphic Lipoblasts

Atypical Mitotic Figures

 Pleomorphic Liposarcoma

Cellular Morphology

Marked Nuclear Pleomorphism

 Pleomorphic Liposarcoma

Eosinophilic Globules

Coagulative Necrosis
 Pleomorphic Liposarcoma

Sheets of Lipoblasts

Sheets of Pleomorphic Lipoblasts

 Pleomorphic Liposarcoma

Myxofibrosarcoma-Like Pattern
Myxofibrosarcoma-Like Pattern
 Pleomorphic Liposarcoma

Spindled Morphology
Spindled Morphology
 Pleomorphic Liposarcoma

Epithelioid Morphology
Epithelioid Morphology
Pleomorphic Liposarcoma

Necrosis

S100 Protein Expression

 Differential Diagnoses of Pleomorphic
Liposarcoma

1. Dedifferentiated liposarcoma
2. Undifferentiated pleomorphic sarcoma
3. Myxofibrosarcoma
4. Poorly differentiated carcinoma
5. Metastatic Malignant Melanoma
 Differential Diagnoses of Pleomorphic
Liposarcoma

Dedifferentiated Liposarcoma
Much more common in retroperitoneum than PLS
ALT/WDL + nonlipogenic sarcoma
Pleomorphic lipoblasts rare (only seen in
"homologous dedifferentiation)
Presence of ALT/WDL component precludes diagnosis
of PLS
MDM2(+) and CDK4(+) by immunohistochemistry
 Differential Diagnoses of Pleomorphic
Liposarcoma

Dedifferentiated Liposarcoma
Homologous Lipoblastic Differentiation
 Differential Diagnoses of Pleomorphic
Liposarcoma

Undifferentiated Pleomorphic Sarcoma

Usually cellular, high grade, pleomorphic morphology
Can show significant morphologic overlap with PLS
No evidence of lipoblastic differentiation
Thorough gross sampling critical for correct
classification
 Differential Diagnoses of Pleomorphic
Liposarcoma

Undifferentiated Pleomorphic Sarcoma

 Differential Diagnoses of Pleomorphic
Liposarcoma

Myxofibrosarcoma
More common in subcutaneous than deep tissue
Multinodular growth
No true lipoblastic component
But may contain fibroblastic "pseudolipoblasts"
Can show significant morphologic overlap with PLS
However, myxofibrosarcoma lacks lipoblastic
differentiation
 Differential Diagnoses of Pleomorphic
Liposarcoma

Myxofibrosarcoma
 Differential Diagnoses of Pleomorphic
Liposarcoma

Poorly Differentiated Carcinoma

Renal cell and adrenocortical carcinomas are most
common types on differential of epithelioid PLS
No evidence of lipoblastic differentiation
More than focal expression of keratin, EMA, and other
epithelial markers
 Differential Diagnoses of Pleomorphic
Liposarcoma

Poorly Differentiated Carcinoma

 Differential Diagnoses of Pleomorphic
Liposarcoma

Metastatic Malignant Melanoma

No evidence of lipoblastic differentiation
S100 protein (+) in tumor cells
Expression of melanocytic markers
 Differential Diagnoses of Pleomorphic
Liposarcoma

Metastatic Malignant Melanoma

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