MLS tumors are located in deep-seated soft tissues of the thighs (65–80% of cases), lower legs (10–15% of cases), retroperitoneum (8% of cases), and arms (5% of cases). In about one-third of cases, these tumors metastasize to other soft tissue sites (e.g. retroperitoneum, thorax, or other extremity), skeletal bone, and/or lung. Individuals may present with these metastasis, particularly those in bone; it has been recommended that patients should be tested at presentation for bone metastasis by medical imaging, including X-rays, CT scans, and/or magnetic resonance imaging. Pathology Histopathologic analyses of MLS (see Figs. 3 and 4 in the below Histopathology of liposarcomas section) reveals cells scattered throughout a myxoid matrix (i.e. a connective tissue background that appears more blue or purple than the red color of normal connective tissue when these tissues are properly prepared, H&E stained, and viewed microscopically). These cells are lipoblasts, some of which are signet ring-shaped (a shape suggesting that the cell may be neoplastic), oval-shaped, or round-shaped. MLS tumors may be hypercellular and contain solid sheets of round cells that comprise at least 5% of all cells or low cellularity populated with cells that have bland nuclei and <5% round cells in a background of curving capillaries resembling a chicken-wire pattern. Tumors that contain at least 5% round cells are classified as high-grade while those with <5% round cells are classified as low-grade. High-grade MLS tumors typically take a more aggressive clinical course than low-grade MLS tumors. Genetics MLS tumor cells are virtually defined by their expression of a FUS-DDIT3 fusion gene (also termed a chimeric gene) which occurs in >95% of cases or a EWSR1-DDIT3 fusion gene which occurs in the remaining <5% of cases. The FUS-DDIT3 fusion gene forms as a result of a translocation (termed t(12:16)(q13:p11)) between the site of the DDIT3 gene at band 12 of chromosome 12's q arm and the site of the FUS gene at band 11 on chromosome 16's short arm (also termed the p arm). The fusion protein (also termed chimeric protein) product of this chimeric oncogene gene, FUS-DDIT3, is known to arrest fat cell maturation and promote neoplasia. The EWSR1-DDIT3 fusion gene (termed t(12;22)(q13;q12)) results from a translocation of the EWSR1 gene located at band 12.2 on chromosome 22's q arm with the DDIT2 gene. The fusion protein product of the EWSR1-DDIT3 gene, like the FUS-DDIT3 fusion protein, promotes neoplasia. In spite of these fusion