>50 years old with a predominance in females. PLS tumors are rarely found in children. PLS tumors present in a leg or arm (65% of cases), retroperitoneum or abdomen (15% of cases), or in rare cases the trunk wall, spermatic cord, head and neck areas, chest wall, pelvic cavity, pulmonary pleurae, pericardium, and spine. These tumors are usually localized in deep soft tissues with only 25% of cases presenting in subcutaneous tissues. Rare cases of PLS have presented in individuals with the Li-Fraumeni or Muir–Torre syndromes, two hereditary genetic disorders that predispose affected persons to develop various types of cancer. Pathology The histopathology of PLS tumors often consists of areas resembling myxoid liposarcoma mixed with areas containing undifferentiated cells. These tumors are marked hypercellular and contain at least some variably shaped lipoblasts that have pleomorphic nuclei. Areas of necrosis are common, giant cells, some of which are multinucleated and/or contain engulfed neutrophils, are occasionally present, and hyaline droplets may be seen in some cells as well as scattered extracellularly throughout the tumor. The undifferentiated component of these tumors most often consists of spindle-shaped cells, with 25% of cases showing cells with an epithelioid cell morphology. These tumors have at least some foci with a histopathology similar to high-grade myxofibrosarcoma type histiocytomas, a tumor formerly termed malignant myxoid fibrous histiocytoma. Genetics PLS neoplastic cells contain various gene and chromosome abnormalities: the TP53 gene is deleted or mutated in 17–60% of cases; the RB1 gene is deleted in 60% of cases; and the Neurofibromin 1 gene is lost by inactivating mutations in 8% of cases or in rarer cases by a deletion around its location in band 11.2 on the long arm of chromosome 12. These cells can also show gains in the genetic material around: bands 12–15 on the short arm of chromosome 5; band 21 on the short arm of chromosome 1; and band 22 on the long arm of chromosome 7. The alterations in gene copy numbers induced by these abnormalities are similar to those seen in the myxofibrosarcoma type of the histiocytomas. The role(s) of these changes in gene copy numbers in promoting PLS has not been defined. Thus, PLS is unlike other liposarcomas in that its neoplastic cells have a complex genome without characteristic genomic alterations or identifiable genes that drive the disease. Detection of alterations in the expression of the TP53, RB1, and neurofibromin 1 genes,