The distinction of
atypical lipomatous tumor/
well-differentiated liposarcoma (ALT/WDL) from its benign counterpart,
lipoma, may represent a challenge. MDM2
DNA amplification is used as the gold standard as MDM2 immunohistochemistry lacks specificity and sensitivity. Herein, we investigate the diagnostic utility of MDM2
RNA in situ hybridization (
RNA-ISH) and compare the test with MDM2 immunohistochemistry and MDM2
DNA fluorescence in situ hybridization (FISH) in benign and malignant lipomatous
neoplasms. We evaluated 109
neoplasms including 27
lipomas, 25 spindle cell
lipomas, 32 ALTs/WDLs, and 25
dedifferentiated liposarcomas (DDL). The validation cohort included 14
lipoma-like
neoplasms that lacked unequivocal features of ALT/WDL and in which MDM2 immunohistochemistry was either equivocal, negative or falsely positive. Immunohistochemistry, automated
RNA-ISH and
DNA-FISH for MDM2 were performed.
Tumors with diffuse nuclear staining or >50 dots per cell on
RNA-ISH were considered positive. All
lipomas and
lipoma variants were negative for
RNA-ISH while all ALTs/WDLs and DDLs were positive. Eighty percent (24/30) and 92% (22/24) of ALTs/WDLs and DDLs were positive for MDM2 immunohistochemistry.
Lipomas and its variants were negative for MDM2 amplification; 92% and 100% of ALTs/WDLs and DDLs showed MDM2
DNA amplification. The mean percentage of ALT/WDL
tumor cells showing MDM2
RNA-ISH positivity was 73% compared with 24% on MDM2 immunohistochemistry.
RNA-ISH correctly classified all 10 ALTs/WDLs and all 4
lipomas in the validation cohort. The performance of MDM2
RNA-ISH and MDM2
DNA-FISH are equivalent. MDM2
RNA-ISH can be of diagnostic value in histologically challenging lipomatous
neoplasms. The automated MDM2
RNA-ISH assay should allow for more widespread use of MDM2 testing and for a more sensitive and specific diagnosis of ALT/WDL.