the myxoid as well as the other three liposarcoma forms. Presentation Myxoid pleomorphic liposarcoma (MPL) is an exceptionally rare and highly aggressive form of the liposarcomas that develops in children, adolescents, young adults, and, in a more recent study, individuals >50 years old. MPL tumors present as deep soft-tissue masses that are often located in the mediastinum and, less often, the extremities, head and neck, abdominal cavity, or trunk. At least two case of MPL have presented in individuals with the Li–Fraumeni syndrome, an inherited genetic disorder that predisposes individuals to develop various cancers. Pathology On histopathologic analyses, MPL tumors consist of areas resembling conventional myxoid liposarcoma; these areas, which represent 30–50% of the total tumor areas, have an abundant myxoid matrix, a well-developed capillary vasculature, bland cells that are round and/or slightly spindle-shaped, vacuolated lipoblasts, and multinucleated cells shaped like small flowers. However, these areas also contain a scattering of highly pleomorphic cells that show greater degrees of nuclear enlargement and irregularity than the cells seen myxoid liposarcoma tumors. Other areas of MPL tumors are more cellular and consist of rapidly growing and highly pleomorphic lipoblasts. Genetics The neoplastic cells in MPL do not express the FUS-DDIT3 or EWSR1-DDIT3 fusion genes that are expressed by the neoplastic cells in >95% or <5%, respectively, of myxoid fibrosarcoma cases. Inactivation of the RB1 tumor suppressor gene due to its deletion or pathological suppression is found in all cases MPL. MPL neoplastic cells also commonly have other alterations in their chromosomes. They may show abnormal gains in some of the genetic material normally found on chromosomes 1, 6, 7, 8, 19, 21, and/or X and losses in the genetical material normally found on chromosomes 2, 3, 4, 5, 10, 11, 12, 13, 14, 15, 16, 17 and/or 22. The genetic material lost in band 14 on the long arm of chromosome 13 includes not only the RP1 gene but also the RCBTB2, DLEU1, and ITM2B genes. Due to its rarity and more recent definition, the molecular characteristics and importance of these genetic abnormalities have yet to be fully defined. Nonetheless, studies have suggested that Losses in any one or more of the RB1, RCBTB2, DLEU1, and ITM2B genes, but particularly the RP1 gene, may be involved in contributing to the development and/or progression of MPL. Diagnosis The diagnosis of MPL depends on its tumors clinical presentation, histopathological resemblance to myxoid liposarcoma, and,