The utility of MDM2 as a diagnostic adjunct for lipomatous tumors

Abstract

Background: Liposarcoma is one of the most common sarcomas among adults, accounting for about 20% of all sarcomas. Clinical presentations and histological morphologies remain the mainstay for differential diagnosis of liposarcoma but sometimes it is a challenge for pathologists to distinguish it from its mimickers. Recently, assessing the MDM2 (located in the 12q15) amplification status by fluorescence in situ hybridization (FISH) has become a standard diagnostic adjunct for differential diagnosis of atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and dedifferentiated liposarcoma (DDL). Although MDM2 immunohistochemistry (IHC) is less time-consuming and less expensive, opinions on its usefulness as a surrogate test are contradictory. Methodology: To examine the efficacy of MDM2 IHC as a marker for differential diagnosis of ALT/WDL and DDL, this study performed MDM2 IHC test on 42 cases of lipomatous and other soft tissue tumors. FISH had been previously performed on 33 cases to evaluate their MDM2 amplification status. The results of IHC and FISH were then compared. Results: The sensitivity and specificity of MDM2 IHC were 71% and 84% respectively. MDM2 expression and amplification were concordant for the five DDL cases but one case diagnosed as undifferentiated pleomorphic sarcoma showed false positive expression of MDM2 by IHC. We also observed discordance of MDM2 expression and amplification status in four out of nine ALT/WDL, one intramuscular lipoma and one angiomyolipoma. Conclusion: The sensitivity and specificity of MDM IHC cannot fulfil the requirements for a crucial diagnostic test in clinical settings. MDM2 FISH remains necessary for differential diagnosis of difficult cases with equivocal clinical and histological features. MDM2 IHC is only useful to confirm the diagnosis of DDL with well-defined clinical and histological features.