Predicting MDM2 Amplification in Well-Differentiated Liposarcomas

Background: Well-Differentiated Liposarcoma (WDLPS) is the most common subtype of malignant lipomatous tumours. This low-grade neoplasm carries a risk of local recurrence and dedifferentiation into higher-grade subtypes, and therefore requires aggressive treatment with wide local excision and neoadjuvant radiotherapy. WDLPS, however, shares overlapping features with its benign counterpart, lipoma. Diagnostically challenging cases can be resolved with molecular testing for Mouse Double Minute 2 (MDM2) amplification, which is found in almost all WDLPS. This study aimed to determine the predictors of MDM2 amplification to better inform the decision for tumours to undergo molecular testing. Methods: A retrospective study was performed on 173 lipomatous tumours. Demographic, clinical, radiology and pathology data were obtained from institutional records. Multivariate analysis was performed to determine the features of lipomatous tumours that correlate with MDM2 amplification. The relative strength of the associations between predictor variables and MDM2 amplification were measured via derivation of coefficients of determination (Pseudo-R2). Results: The significant predictors of MDM2 amplification were age of diagnosis ≥60 years (odds ratio (OR)=25.71; 95% confidence interval (CI)=4.47- 148.02); size ≥15cm (OR=11.68; 95% CI=2.70-50.59); presence of thick septa (OR=78.13; 95% CI=3.23-1890.71) on MRI; variable cell morphology (OR=22.19; 95% CI=4.03-122.20); and cytological atypia (OR=15.03; 95% CI=3.07-73.68). Conclusion: Molecular testing for MDM2 amplification should be considered for tumours 15cm or greater, in patients aged 60 years or older, with thick septa on MRI, even in the absence of concerning histological features.