DEFINITION AND PATHOGENESIS
- Takes origin from primitive mesenchymal cells rather than mature adipose cells
- A fairly common malignancy of fat most common in the thigh, retroperitoneum, and inguinal regions
- Most common in occurrence rates for soft-tissue sarcomas (20%)
- Retroperitoneal lesions may occur simultaneously or sequentially to extremity lesions
- 8 months to 87 years, mean 57 years, M:F = 3:2
- Rare in subcutaneous fat and GI subserosa
- Most common sites are thigh (25-30%) and retroperitoneum (?20%)
- Unusual locations
- Insidiously growing, deep-seated, ill-defined mass
- Pain, tenderness only in 10-15%
- Hemodynamic deteriorationin cardiac and abdominal locations reported
- Synchronous cardiac and abdominal metastases 13 yrs after a thigh liposarcoma reported
- Preexisting lipoma is extremely rare
- Liposarcoma associated with multiple intramuscular lipomas reported in a 71-year-old
- Has been reported in NF1
- Depend largely on histological type
- Well-delineated radiolucency to dense mass
- May have foci of calcification and ossification (esp well differentiated)
- Vascularity often seen on bone scan
- CT may show a low density mass with an area of higher density
- Myxoid liposarcoma may show a homogenous density between -40 to +30 Hounsfield units
- MRI shows inhomogeneic regions, some isointense with fat
- Intermediate T1 signal, bright on T2
- A liposarcoma of the pectoral muscle has been reported initially detected at mammography (heterogeneous without discrete margins) in a 76 yr-old man with painless gynecomastia
- Usually well encapsulated and distinctly lobulated (lobules can become separated)
- Can be the largest of neoplasms, esp in the retroperitoneal location
- Histological classification of liposarcoma
- Well-differentiated liposarcoma (atypical lipoma)
- Lipoma-like: scattered lipoblasts
- Sclerosing: inguinal prevalence
- Inflammatory: prominent inflammatory component
- Dedifferentiated: well and poorly differentiated together
- Myxoid liposarcoma (40-50%):lipoblasts, capillaries, myxoid matrix
- Round cell liposarcoma: tends more to metastasize
- Pleomorphic liposarcoma: bizarre cells
- Well-differentiated with a pleomorphic component
- Lipoblasts the characteristic cell
- Vacuolated tumor cell with single vacuole and eccentric nucleus or multiple vacuoles and a central nucleus; "signet ring" cell
- Vacuoles within the cell contain fat (+ oil red O)
- Cytogenetic studies
- t(12;16),(q13;p11) (in tumor lipoblasts)
- Other abnormalities reported include trisomy 8
- Chromosome 12 amplificationin well-differentiated and dedifferentiated liposarcomas
- MDM2 gene
- CDK4 gene
- ~10% do not amplify CDK4
- Alteration in CDKN2A/CDKN2B/CDK4/CCND1 pathwaydemonstrable
- Real-time genomic PCR
- Gene expression array
- Real-time RT-PCR
- Chromosome 1q21-1q23 is preferential partner of chromosome 12 amplicon in tumors with amplification/overexpression CDK4
- Over 40 microRNA expression alterations reporteddysregulated in dedifferentiated liposarcomas
- Upregulated microRNAs
- Downregulated microRNAs
- Restoring miR-143 expression:
- Inhibited proliferation
- Induced apoptosis
- Decreased expression of BCL2
- Decreased expression of topoisomerase 2A
- Decreased expression of protein regulator of cytokinesis (PRC1)
- Decreased expression of polo-like kinase 1 (PLK1)
- Tx with a PLK1 inhibitor potently induced G(2)-M growth arrest and apoptosis
DIFFERENTIAL CLINICOPATHOLOGIC DIAGNOSIS
- If lipoblasts are seen, the dx is made
- Lipid stains are positive in mesenchymal or epithelial neoplasms
- Myxoid chondrosarcoma and chordoma
- Vacuolated forms of lymphoma ("signet-ring" lymphoma)
- Rarely meningioma, malignant melanoma
- Intramuscular myxoma, myxoid MFH
DISEASE COURSE AND TREATMENT
- Wide resection, long course in some low grade lesions
- Lung metastases (most common) as well as viscera; check retroperitoneum (extrapulmonary metastases, esp with myxoid variant)
- +/- XRT; preoperative + postoperative boost in higher grade lesions
- XRT effective in preventing LR but not reported to impact survival
- Mediastinal and bone metastases have been reported
- 5-yr survivals (with appropriate tx)
- 74% overall 5-yr survival, all subtypes
- 80% myxoid liposarcoma, LR <10% with resection and XRT
- Oral and maxillofacial region
- Tumor size > 3.6 cm
- Histopathologic subtype
- Chemotx trials for lesions >8cm in diameter
- Characterized by the presence of ring or giant rod chomosomescontaining several amplified genes
- AKT activationin 27%
- Robust AKT phosphorylation
- BEZ235 (small molecule inhibitor of P13K and mammalian target of Rapamycin)
- Effectively inhibits AKT activation in culture
- Others derived from chromosome bands 12q13-15
- Characterized by chromosome 12q13-15 amplification
- Poorly responsive to XRT or chemotherapy
- ANIMAL MODEL
- Zebrafishexpressing constitutively active AKT2 in mesenchymal progenitors develop well-differentiated liposarcoma similar to the human counterpart
- p53 pathogenesis
- 8% in p53 wild-type zebrafish
- 6% in p53 heterozygotes
- 29% in p53-homozygous mutant zebrafis
- Consists of both well-differentiated liposarcoma and a transformed nonlipogenic sarcomatous component
- Histologic subtypes
- Extremely large tumors have been reported
- 46 kg tumor reported in the retroperitoneum
- 3/18 with lung metastasis at initial presentation reported
- 61.1% 5YS reported
- Poor prognostic findings
- Cell line
- Any grade or histological type may be found in this location
- Giant (50 cm and 52 kg) liposarcoma of the retroperitoneal spermatic cord reported
- Tumors in this location may become huge and simulate pregnancy
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