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

Tags:
Jul 9, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Liposarcoma

Full access? Get Clinical Tree
Get Clinical Tree app for offline access