Clinicopathologic evaluation of dedifferentiated liposarcoma lacking MDM2 amplification.
1.6% of dedifferentiated liposarcomas lack MDM2 amplification yet still express CDK4.
Clinicopathologic evaluation of dedifferentiated liposarcoma lacking MDM2 amplification.
Dedifferentiated liposarcoma (dedifferentiated liposarcoma) is a typically non-lipogenic malignant neoplasm that arises from progression of an underlying atypical lipomatous tumour/well-differentiated liposarcoma (ALT/WDLPS) and is classically defined by amplification of chromosome 12q15, including MDM2 and frequently cyclin-dependent kinase 4 (CDK4).
Pathology archives from 2010 to 2025 were queried for cases diagnosed as dedifferentiated liposarcoma.
Despite the absence of MDM2 amplification, all cases showed strong CDK4 expression by immunohistochemistry.
Molecular analysis revealed recurrent alterations involving cell-cycle regulation, including CDK4 copy number gain in all cases and loss of CDKN2A in three.
Two cases harboured TP53 alterations.
Clinically, outcomes were heterogeneous, ranging from aggressive disease with rapid recurrence and death within months to prolonged disease-free survival exceeding 5 years.
MDM2 non-amplified dedifferentiated liposarcoma represents a rare subset of dedifferentiated liposarcoma that appear to be driven by alternative mechanisms of cell-cycle dysregulation, most commonly involving CDK4 gain and CDKN2A loss, with occasional TP53 alterations.
Awareness of this variant is critical to avoid misclassification as other high-grade sarcomas, particularly on limited biopsies, and underscores the importance of integrating morphology, immunohistochemistry and broad genomic profiling in diagnostically challenging retroperitoneal sarcomas.