Definition/General
Introduction:
Liposarcoma is the most common soft tissue sarcoma in adults
It represents 20% of all soft tissue sarcomas
Shows malignant transformation of adipocytic cells
FNAC reveals atypical lipoblasts and variable cellularity.
Origin:
Arises from primitive mesenchymal cells with adipocytic differentiation
Most commonly occurs in deep soft tissues
Retroperitoneum and thigh are common locations
Does not arise from pre-existing lipomas.
Classification:
WHO classification includes: Well-differentiated liposarcoma (atypical lipomatous tumor)
Myxoid liposarcoma
Round cell liposarcoma
Dedifferentiated liposarcoma
Pleomorphic liposarcoma.
Epidemiology:
Peak incidence in 5th-7th decades
Male predominance 1.5:1
Accounts for 15-20% of adult soft tissue sarcomas
Retroperitoneal location in 40-45% cases
Deep-seated tumors more common than superficial.
Clinical Features
Presentation:
Deep-seated mass (most common)
Painless swelling initially
Large size at presentation (>10 cm)
Firm to hard consistency
Mass effect symptoms
Rapid growth (high-grade variants).
Symptoms:
Initially asymptomatic
Pain in advanced cases
Abdominal distension (retroperitoneal)
Weight loss (large tumors)
Neurological symptoms (nerve compression)
Bowel obstruction (intra-abdominal).
Risk Factors:
Previous radiation exposure
Li-Fraumeni syndrome (TP53 mutations)
Neurofibromatosis type 1
Age >40 years
Genetic predisposition
Previous chemotherapy.
Screening:
Imaging studies for deep masses
MRI for retroperitoneal tumors
CT scan for staging
FNAC/Biopsy for diagnosis
Multidisciplinary evaluation
Genetic counseling if indicated.
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Gross Description
Appearance:
Large, lobulated mass
Variable consistency from soft to firm
Cut surface shows yellow areas (fat)
Myxoid areas (gelatinous)
Necrosis and hemorrhage common
Poor circumscription.
Characteristics:
Heterogeneous appearance
Yellow fatty areas mixed with solid regions
Myxoid components (gelatinous)
Areas of necrosis
Hemorrhage and cystic change
Infiltrative margins.
Size Location:
Retroperitoneum (40-45%)
Deep soft tissues of extremities (35%)
Intramuscular location common
Size: Usually >10 cm
Can reach massive sizes (>30 cm)
Paratesticular (5%).
Multifocality:
Usually solitary
Multifocal disease rare
Dedifferentiation in well-differentiated type
Satellite nodules possible
Local recurrence common
Metastatic potential varies by subtype.
Microscopic Description
Histological Features:
FNAC shows atypical lipoblasts with hyperchromatic nuclei
Uni/multivacuolated cytoplasm
Nuclear pleomorphism
Increased cellularity
Myxoid background (myxoid type)
Primitive round cells (round cell type).
Cellular Characteristics:
Lipoblasts with scalloped nuclei
Hyperchromatic nuclei
Prominent nucleoli
Vacuolated cytoplasm
Nuclear pleomorphism
Mitotic activity (high-grade).
Architectural Patterns:
Cellular smears with atypical cells
Myxoid background (myxoid subtype)
Monotonous round cells (round cell)
Pleomorphic pattern (pleomorphic type)
Mixed cellularity
Capillary pattern (myxoid).
Grading Criteria:
FNRS grading system: Differentiation
Mitotic count
Necrosis extent
Grade I: Well-differentiated
Grade II: Moderately differentiated
Grade III: Poorly differentiated.
Immunohistochemistry
Positive Markers:
S-100 protein (variable positivity)
Vimentin (positive)
MDM2 (well-differentiated/dedifferentiated)
CDK4 (well-differentiated/dedifferentiated)
p16 (myxoid type)
DDIT3 (myxoid type).
Negative Markers:
Cytokeratin (usually negative)
EMA (negative)
Desmin (negative)
Smooth muscle actin (negative)
CD68 (negative)
MyoD1 (negative).
Diagnostic Utility:
MDM2/CDK4 positive in well-differentiated/dedifferentiated
DDIT3 rearrangement in myxoid type
S-100 variable depending on subtype
Ki-67 correlates with grade
p53 overexpression in high-grade.
Molecular Subtypes:
Well-differentiated: MDM2+, CDK4+
Myxoid: DDIT3 rearrangement, FUS-DDIT3
Round cell: DDIT3 rearrangement, high-grade
Pleomorphic: Complex karyotype
Dedifferentiated: MDM2+, CDK4+.
Molecular/Genetic
Genetic Mutations:
MDM2 amplification (12q15) - well-differentiated/dedifferentiated
FUS-DDIT3 fusion t(12;16) - myxoid
EWSR1-DDIT3 fusion t(12;22) - myxoid
Complex karyotype - pleomorphic
TP53 mutations - high-grade.
Molecular Markers:
12q13-15 amplification (MDM2, CDK4, HMGA2)
DDIT3 rearrangement (myxoid/round cell)
FUS gene rearrangements
PIK3CA mutations
RB1 pathway alterations
Telomerase activation.
Prognostic Significance:
Subtype determines prognosis
Well-differentiated: Excellent (local disease)
Myxoid: Good (low-grade)
Round cell: Poor (high-grade)
Dedifferentiated: Poor
Pleomorphic: Poor prognosis.
Therapeutic Targets:
MDM2 inhibitors (well-differentiated/dedifferentiated)
CDK4/6 inhibitors
Trabectedin (myxoid type)
PI3K/mTOR inhibitors
Immunotherapy (selected cases)
Radiation therapy sensitivity varies.
Differential Diagnosis
Similar Entities:
Lipoma (benign adipocytic tumor)
Atypical lipomatous tumor (ALT)
Other sarcomas with lipoblasts
Hibernoma (brown fat tumor)
Spindle cell lipoma
Pleomorphic adenoma (lipomatous).
Distinguishing Features:
Liposarcoma: Atypical lipoblasts, nuclear atypia, MDM2+/DDIT3+
Lipoma: Mature adipocytes, no atypia, MDM2-
ALT: Atypical cells, MDM2+, low-grade
Hibernoma: Multivacuolated cells, UCP1+
Other sarcomas: Different lineage markers
Pleomorphic adenoma: Epithelial component.
Diagnostic Challenges:
Distinguishing well-differentiated from lipoma
Subtyping requires molecular studies
Sampling issues in heterogeneous tumors
Dedifferentiation recognition
Grading accuracy in FNAC
Myxoid background interpretation.
Rare Variants:
Inflammatory variant
Sclerosing variant
Spindle cell variant
Mixed-type liposarcoma
Epithelioid variant
Osteosarcomatous differentiation (dedifferentiated).
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Fine needle aspiration from [site], [size] cm deep soft tissue mass
Clinical History
[age]/[sex] with [duration] history of enlarging deep-seated mass at [site]. Imaging shows [findings].
Gross Examination
Aspirated material: [amount] of hemorrhagic material with fatty and solid components
Microscopic Examination
Smears show increased cellularity with atypical lipoblasts having hyperchromatic, pleomorphic nuclei and vacuolated cytoplasm. [Myxoid background/Round cell population/Pleomorphic cells] noted. Mitotic activity: [count]/10 HPF.
Immunocytochemistry
[MDM2]: [result], [CDK4]: [result], [S-100]: [result], [DDIT3]: [result]
Cytological Diagnosis
Cytological features consistent with LIPOSARCOMA, [subtype], Grade [I/II/III]
Comments
Histopathological examination recommended for subtyping and grading. Molecular studies may be helpful. Multidisciplinary management advised.