Can HMGI-C be used as an aid with MDM2 and CDK4 to differentiate liposarcoma subtypes from their mimics?

Abstract

Liposarcoma represents the most common soft tissue tumors in adults. The tumors are characterized by a high morphological diversity and a great variation in biological behavior. Atypical lipomatous tumors represent a distinctive subset of mesenchymal neoplasms featuring mature adipocytic differentiation. Histologically, atypical lipomatous tumor might be easily confused with lipoma. Conversely, dedifferentiated liposarcoma may be confused with other spindle cell/pleomorphic undifferentiated tumors. A group of liposarcomas was analyzed by investigating the MDM2, CDK4, and HMGI-C proteins. The study was extended to a group of lipomas and non-lipomatous sarcomas, to determine whether the immunohistochemical investigation of these proteins might play any diagnostic role. Our data suggest that ordinary lipomas may form a molecular genetic and morphological continuum with atypical lipomatous tumor. At one end of the spectrum are lipomas characterized by HMGI-C activation and at the other end are atypical lipomatous tumors with overrepresentation of the HMGI-C, CDK4, or MDM2 proteins. These findings not only provide insights into the molecular pathogenesis of lipomatous tumors, but also indicate that the immunohistochemical analysis of HMGI-C, CDK4, or MDM2 may help to increase diagnostic accuracy. HMGI-C is a useful adjunct in the diagnosis of atypical lipomatous tumor and dedifferentiated liposarcoma and differentiates them from their mimics. Therefore, in our experience, HMGI-C expression alone is of rather limited value in the differential diagnosis of liposarcoma subtypes.