Thursday 9 October 2008
MDM2 and CDK4 amplification (#18551755#)
HMGA2 balanced rearrangement (#18551755#)
HMGA2-LPP fusion gene (#18551755#)
Adipose tissue tumors of the retroperitoneum showing no identifiable cytologic atypia are usually classified as lipomalike well-differentiated liposarcoma.
Whether a subset of these tumors represents true examples of retroperitoneal lipoma remains a controversial subject, because the diagnostic liposarcoma cells may be of difficult identification, even after extensive sampling.
The discrimination between ordinary lipoma and atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) is a common diagnostic challenge in diagnostic soft tissue pathology.
Histologic, cytogenetic, and molecular genetic data support the idea that these two major groups of adipose tissue tumors are distinct biologic entities in spite of overlapping histologic features. Careful tissue sampling and histologic examination are the major and simplest steps for the correct discrimination between a lipoma and an ALT/WDL.
Lipomas can be superficial or deep seated and are histologically characterized by mature fat cells with no cytologic atypia/hyperchromasia/pleomorphism. Occasionally, lipoblasts can be seen in lipomas, especially near blood vessels. However, they do not exhibit cytologic atypia/hyperchromasia/pleomorphism.
ALT/WDL are histologically characterized by the presence of mixed population of lipoblasts and lipocytes but more importantly by atypical hyperchromatic pleomorphic cells. These tend to be more commonly found near blood vessels and within fibrous septa. It is also important to note that the identification of lipoblasts is not a necessary criterion for the diagnosis of an ALT/WDL.
The discrimination between lipoma and ALT/WDL becomes challenging when the diagnostic atypical hyperchromatic pleomorphic cells are rare or have subtle atypical cytologic features.
Many cell types or tissue artifacts can simulate these cells, including lockhern artifact (intranuclear holes), activated fibroblasts/myofibroblasts, multinucleated giant cells, and degenerated skeletal muscle fibers. However, in most instances these cells can be correctly identified by careful examination. However, ALT/WDL cells with subtle cytologic features can be very difficult to recognize by histologic exam.
Lipoma and ALT/WDL have very distinct cytogenetic and molecular genetic characteristics:
Lipomas are mainly characterized by rearrangements of chromosome 12q13q15 with several partner chromosomes in approximately 50-60% of cases, especially chromosome 3. Lipomas without 12q13q15 rearrangements frequently show rearrangements of chromosome 6p21. Several lipoma fusion genes have been identified and the most common is LPP-HMGA2, product of the t(3;12)(q27-q28;q14-a15). Interestingly, lipomas grow relatively well in culture and, in our experience, 60-70% of them show abnormal karyotypes.
ALT/WDL usually exhibit supernumerary ring or giant maker chromosomes by standard cytogenetic analysis. These abnormal chromosomes are composed by amplified genomic material mainly derived from chromosome bands 12q13q15. These bands contain several cancer genes, including MDM2, SAS, CDK4 and HMGA2. MDM2 seems to be the most consistently amplified gene in ALT/WDL (>99% of cases). Amplification of these genes is not observed in lipoma.
no evidence of cytologic atypia.
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