Summary Liposarcomas are a heterogeneous class of sarcomas with differentiation towards adipose tissue that consist of 5 different sub-types: well-differentiated, myxoid, round cell, pleomorphic, and dedifferentiated. The condition is typically seen in patients 50-80 years of age who present with a slow-growing, painless mass. Diagnosis is made with a biopsy showing immature lipoblasts with various cellular atypia depending on the sub-type. Treatment may be marginal excision for a well-differentiated liposarcoma. Wide surgical resection with radiation is indicated for intermediate and high-grade liposarcomas. Epidemiology Incidence liposarcomas are the second most common form of soft tissue sarcomas in adults Demographics occur in older individuals (50-80yrs) myxoid liposarcoma can present in younger adults affect more males than females Anatomic location almost always occurs deep to fascia 75% occur in the extremities more common in lower extremity than upper extremity common in retroperitoneum Etiology Pathophysiology the lipoblast (signet ring-type cell) is a hallmark of liposarcomas Genetics well-differentiated liposarcoma - amplification (MDM2) myxoid liposarcoma - translocation (12;16) well-differentiated and dedifferentiated liposarcomas have chromosome 12q13-15 amplification pleomorphic liposarcoma may have p53 mutation Malignant potential metastasis risk correlates with grade/sub-type of liposarcoma low grade (well-differentiated) has a metastasis rate of < 1% intermediate grade (myxoid) has a metastasis rate of about 10-30% high grade has a metastasis rate of > 50% Classification Histologic types liposarcoma types are related to the developmental stage of the lipoblasts from which they form all are from primitive mesenchymal cells types include well-differentiated (low grade) same entity as atypical lipomatous tumor can be sub-classified as lipoma-like, sclerotic, or inflammatory myxoid (intermediate grade) most common ~ 50% of all liposarcomas round cell (high grade) pleomorphic (high grade) < 5% of cases dedifferentiated (high grade) < 10% of cases Presentation History often an incidentally found mass Physical exam slow growing painless mass mass may be 10-20cm Imaging Plain Radiographs indications initial imaging modality findings may show soft tissue calcification or ossification in well-differentiated liposarcomas MRI with contrast indications best modality to characterize the lesion findings well-differentiated liposarcomas look similar to lipomas on MRI bright on T1, dark on T2 may show differences in rate of growth, stranding, size thicker (>2mm) and more irregular septa compared to lipomas on T2 suggests an area of dedifferentiation high-grade liposarcomas look similar to other sarcomas on MRI dark on T1, bright on T2 although high grade liposarcomas appear fibrogenic, they may have 10% fat composition, so they appear dark on T1 and bright on T2 unlike a lipoma which images iso-intense to subcutaneous fat on all sequences sensitivity and specificity sensitivity: 100% specificity: 71% positive predictive value: 100% CT Chest/Abd/Pelvis with contract indications staging for myxoid liposarcoma myxoid liposarcomas most commonly metastasize to the lungs, but also can spread to the abdomen and spine findings evidence of soft tissue within the fat mass invasion into mediastinal structures calcification Positron emission tomography may be used for staging and follow-up Histology Areas of the mass inconsistent with fat on imaging must be biopsied Characteristic histology immature lipoblasts (signet ring-type cells) mature adipocytes Atypical lipomatous tumor (ALT; located in extremities) referred to as well-differentiated liposarcoma (WDL) when located central/retroperitoneal WDLs have a higher risk of local recurrence and metastatic spread compared to ALTs low grade atypical lipoblasts, minimally cellular fatty stroma background stain for MDM2/CDK4 have ring chromosome 12 Myxoid liposarcoma low to intermediate grade proliferating lipoblasts upon a myxoid stroma matrix signet ring lipoblasts at the edge of the tumor lobules Round cell liposarcoma poorly differentiated liposarcoma with characteristic small round blue cells Pleomorphic liposarcoma high-grade pleomorphic tumor giant lipoblasts with bizarre nuclei eosinophilic giant cells Dedifferentiated liposarcoma often an ALT or WDL that transformed into a high-grade sarcoma Treatment Operative marginal resection without radiotherapy indications atypical lipomatous tumors (ALT) outcomes risk of local recurrence 10-50% over 10 yrs metastasis extremely rare dedifferentiation risk of 2% in extremities (ALTs) wide surgical resection with adjuvant radiotherapy indications well-differentiated liposarcoma intermediate grade liposarcomas high grade liposarcomas outcomes radiation decreases local recurrence wide surgical resection with adjuvant radiotherapy and chemotherapy indications myxoid liposarcoma with >5% round cells adequate surgical margins cannot be obtained outcomes myxoid liposarcoma is generally more responsive to chemotherapy and radiation therapy myxoid liposarcomas with >10% round cells have higher likelihood of metastasis Technique Marginal resection tumor is dissected out through the plane of the pseudocapsule Wide surgical resection & radiation therapy resection use of tourniquet without exsanguination maintain meticulous hemostasis meticulous dissection to ensure wide margins must confirm border free of disease with histology frozen section can be used to ensure margins are free of tumor consideration of nearby neurovascular and bony structures resection of neurovascular structures may be performed if bypass grafting is possible resection should only be performed if the resulting morbidity is acceptable to the patient radiation 50 Gy pre-operative and 66 Gy postoperative is the standard dose for soft-tissue sarcomas Complications Mass effect on surrounding structures location neurovascular bundles retroperitoneal structures peritoneal cavity Local recurrence depends on histology see prognosis section Prognosis Lipomas do not predispose a patient to a liposarcoma atypical lipomatous tumors (ALT) risk of local recurrence 10-50% over 10 yrs dedifferentiation occurs in 2% of ALTs almost 100% survival well-differentiated liposarcomas (WDL) WDLs have <1% chance of metastasis, but high rate of local recurrence dedifferentiation occurs in 20% of WDLs mortality 80% with mean survival is 6-11yrs intermediate and high grade liposarcomas ~ 20% risk of local recurrence 10-30% risk of metastasis for intermediate grade tumors >50% risk of metastasis for high grade tumors 5 year survival between 50-80%