in middle-aged and older individuals as slowly enlarging masses that tend to be larger and at a more advanced stage when located in deep tissues. These tumors usually are not painful and if located superficially, readily apparent; they can also cause extensive edema (i.e. swelling due to the local accumulation of fluid) in involved areas such as the thigh (see adjacent figure) due to their invasion into the blood and/or lymphatic vessels draining the tumor's site. Deep-seated ALT/WDL tumors may be asymptomatic but, depending on their location, produce serious signs and/or symptoms of disfunction in any one of the various organs which they infiltrate. These organs include those close to or in the retroperitoneum (e.g. intestines, kidney, and the kidney's ureters); the paratesticular region; the mediastinum (e.g. trachea and lung's major bronchi); and the head (e.g. the retrobulbar space behind the globe of the eye). Pathology Histopathologically, ALT/WDL tumors are divided into adipocytic/lipoma-like, sclerosing, and inflammatory variants with adipocyte/lipoma-like being the most common. Adipocytic/lipoma-like ALT/WDL tumors consist of lobules of mature fat cells variably intersected with irregular fibrous septa (see the adjacent H&E stained photomicrograph). Sclerosing ALT/WDL tumors, the second most common variant, develop primarily in the retroperitoneal and paratesticular areas; it consists of scattered, atypical stromal cells within a collagenous (i.e. collagen-containing) stromal tissue background. Rare vacuole-containing lipoblasts populate this tissue. Inflammatory ALT/WDL tumors are the rarest variant. they occur most frequently in the retroperitoneum and consists of chronic inflammatory cells, e.g. lymphocytes and plasma cells plus occasional lymph node-like follicles interspersed throughout a tissue background containing fat cells. Genetics The neoplastic cells in ALT/WDL tumors contain one or more extra ring-shaped small supernumerary marker chromosome (sSMC) or an abnormal giant marker chromosome (i.e. a formerly normal chromosome that is made abnormal by having a duplication of parts of its own or one or more other chromosome's genetic material). These abnormal chromosomes contain extra copies of chromosome 12's long arm (also termed the q arm) at bands 13 through 15. This stretch of chromosome 12 includes the MDM2 proto-oncogene (a potentially tumor-causing gene when overexpressed) located at band 15 and CDK4 (a gene that when overexpressed promotes the development of various tumors) located at band 14.1. The amplificiation (i.e. increased copies of a gene without a proportional increase in other genes) of these two genes is a highly sensitive and specific indicator that a liposarcoma is either an ALT/WDL