Liposarcoma

Liposarcoma
Key Facts
Clinical Issues
  • Rare tumor
  • Broad age range; from children to adults (mean age: 43 years)
  • Anterior and posterior mediastinum
  • Dyspnea
  • Chest pain
  • Recurrences in 33% of cases
  • Myxoid/round cell, dedifferentiated, and pleomorphic liposarcomas are associated with more aggressive behavior
Microscopic Pathology
  • Well-differentiated, lipoma-like liposarcoma/atypical lipomatous tumor
  • Myxoid/round cell liposarcoma
  • Dedifferentiated liposarcoma
  • Pleomorphic liposarcoma
Ancillary Tests
  • Lipoblasts and atypical cells in well-differentiated lipoma-like liposarcoma and dedifferentiated liposarcoma are positive for MDM2 and CDK4
  • Well-differentiated liposarcoma and dedifferentiated liposarcoma show amplification of MDM2 at 12q14-15 region
  • Myxoid liposarcoma shows TSL-CHOP translocation in t(12;16)(q13;p11)
Top Differential Diagnoses
  • Lipoma and thymolipoma
  • Low-grade spindle cell tumors
  • High-grade pleomorphic sarcomas
  • Small round blue cell tumors
Gross appearance of dedifferentiated liposarcoma of the mediastinum shows a well-circumscribed, lobulated mass with an admixture of fleshy white (dedifferentiated) and myxoid (well-differentiated) areas.
Histologic appearance of well-differentiated liposarcoma of the anterior mediastinum shows atypical lipoblast image surrounded by normal-appearing adipocytic cells.
TERMINOLOGY
Abbreviations
  • Liposarcoma (LS)
Synonyms
  • Atypical lipomatous tumor
Definitions
  • Malignant neoplastic proliferation of adipocytic cells
CLINICAL ISSUES
Epidemiology
  • Incidence
    • Rare tumor
  • Age
    • Broad age range; children to adults (mean: 43 years)
  • Gender
    • Slight predilection for males
Site
  • Anterior and posterior mediastinum
  • More common in anterior mediastinum
Presentation
  • Cough
  • Dyspnea
  • Chest pain
  • Asymptomatic in up to 1/3 of patients
  • May be an incidental finding on routine chest x-ray or at autopsy
Treatment
  • Surgical excision
Prognosis
  • Depends on stage and histologic type
  • Recurrences in 33% of cases
  • Large, infiltrative, and unresectable tumors are associated with worse prognosis
  • Myxoid/round cell, dedifferentiated and pleomorphic liposarcomas are associated with more aggressive behavior
  • Round cell and pleomorphic liposarcomas are associated with distant metastases and high mortality
  • Well-differentiated liposarcomas can recur 15-20 years after initial diagnosis
MACROSCOPIC FEATURES
General Features
  • Well-differentiated tumors are lobulated, well circumscribed, and thinly encapsulated with a soft, yellowish cut surface
  • Poorly differentiated tumors are irregular, infiltrative, with yellow-white firm cut surfaces and areas of hemorrhage and necrosis
Sections to Be Submitted
  • 1 section per centimeter of largest tumor diameter
  • Additional sections must be submitted in tumors suspected of corresponding to dedifferentiated liposarcomas to identify lipogenic elements
Size
  • 5-30 cm
MICROSCOPIC PATHOLOGY
Histologic Features
  • Well-differentiated, lipoma-like liposarcoma/atypical lipomatous tumor
    • Sheets of mature-appearing adipocytes ± scattered atypical lipoblastic cells
    • Areas of densely collagenized stroma containing atypical lipoblasts and spindle cells
    • Thymoliposarcoma is characterized by admixture of normal thymus with atypical lipomatous areas
    • Scattered lymphoid aggregates or lymphoid follicles
  • Myxoid/round cell liposarcoma
    • Scattered small, stellate or round cells embedded in abundant myxoid matrix
    • Prominent arborizing (“chicken wire”) vascular pattern of small branching vessels in stroma
    • Round cell variant characterized by increased cellularity with emergence of dense sheets of primitive, hyperchromatic small round cells
    • “Pulmonary-edema” pattern with dilated spaces filled with serum may be seen in these tumors
  • Dedifferentiated liposarcoma
    • Well-differentiated liposarcoma that shows emergence of nonlipogenic atypical spindle cell component
    • Low-grade dedifferentiated component shows bland-appearing spindle cell proliferation with low mitotic rate
    • High-grade dedifferentiated component shows pleomorphic tumor cells with atypical mitoses simulating malignant fibrous histiocytoma
    • Dedifferentiated component may be heterologous (i.e., rhabdo-, leio-, or osteosarcomatous)
    • Dedifferentiated component may show foci of spindle cells showing a distinctive whorling pattern that resembles meningioma
  • Pleomorphic liposarcoma
    • High-grade pleomorphic sarcoma with focal areas containing lipoblastic elements
    • Bizarre lipoblasts and multinucleated floret-type giant cells
  • Pleomorphic myxoid liposarcoma
    • Shows areas of myxoid liposarcoma admixed with pleomorphic tumor cells
    • More aggressive behavior than conventional myxoid liposarcoma
    • Rare morphologic variant more often seen in mediastinum
Cytologic Features
  • Majority of cells in well-differentiated liposarcoma resemble normal mature adipocytes
  • Well-differentiated liposarcoma may contain atypical, multinucleated adipocytes
  • Well-differentiated liposarcoma often contains floret-type multinucleated cells
  • Sclerosing areas in well-differentiated liposarcoma contain floret-type cells and bland-appearing spindle stromal cells
  • Lipoblasts may vary from small, signet-ring lipoblasts to multivacuolated adipocytes with multiple enlarged, atypical nuclei
  • Round cell liposarcoma shows primitive small round blue cells with scant cytoplasm
  • Pleomorphic liposarcoma contains bizarre, anaplastic and multinucleated atypical lipoblastic cells
ANCILLARY TESTS
Immunohistochemistry
  • Mature adipocytes are S100 protein positive
  • Lipoblasts and atypical cells in well-differentiated lipoma-like liposarcoma and dedifferentiated liposarcoma are MDM2 and CDK4 positive
Cytogenetics
  • Supernumerary ring and giant marker chromosomes are seen in well-differentiated and dedifferentiated liposarcoma
  • Random and nonrandom telomeric association can also be seen in well-differentiated liposarcoma
  • Characteristic t(12;16)(q13;p11) is present in > 90% of myxoid and round cell liposarcomas
    • t(12;16) in myxoid/round cell liposarcoma leads to fusion of CHOP and FUS genes with generation of a FUS/DDIT3 hybrid protein
  • Variant chromosomal translocation t(12;22)(q13;q12) is also present in myxoid liposarcoma in which DDIT3 fuses with EWS
  • No distinctive cytogenetic markers have been observed in pleomorphic liposarcoma
Molecular Diagnostics
  • FISH for MDM2 shows consistent amplification in 12q14-15 in well-differentiated and dedifferentiated liposarcomas
  • Neighboring genes such as CDK4, SAS, and HMGIC can also be amplified in well-differentiated and dedifferentiated liposarcomas
  • 12q14-15 amplification is not observed in benign tumors and may serve to distinguish well-differentiated liposarcoma from lipoma
  • FISH for detection of FUS/DDIT3 fusion product is helpful in confirming diagnosis of myxoid/round cell liposarcoma
  • Amplification of MDM2 can be observed in about 1/3 of pleomorphic liposarcomas
DIFFERENTIAL DIAGNOSIS
Lipoma and Thymolipoma
  • Mediastinal lipomas are small and well-circumscribed, completely encapsulated lesions
    • Absence of areas of sclerosis, lipoblasts, floret-type multinucleated cells, or signet ring lipoblastic cells
  • Thymolipoma shows admixture of mature adipose tissue with entrapped involuted thymic remnants
Low-Grade Spindle Cell Tumors
  • May be difficult to distinguish from low-grade dedifferentiated liposarcoma
    • Low-grade dedifferentiated liposarcoma is positive for MDM2 or CDK4
  • Low-grade spindle cell sarcomas of mediastinum lack well-differentiated adipocytic component
  • Solitary fibrous tumors are positive for CD34 and Bcl-2
  • Schwannomas and neurofibromas are S100 protein(+)
  • Spindle cell thymomas are positive for cytokeratin
  • Leiomyomas and low-grade leiomyosarcomas are positive for desmin and smooth muscle actin
High-Grade Sarcomas
  • May be difficult to distinguish from high-grade dedifferentiated liposarcoma or pleomorphic liposarcoma
  • Nonlipogenic high-grade sarcomas lack lipoblastic cells or well-differentiated adipocytic components
Small Round Blue Cell Tumors
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Jul 9, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Liposarcoma

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