Abstract
Dedifferentiated liposarcoma (DDL) is defined as the transition from well-differentiated liposarcoma (WDL)/atypical lipomatous tumor (ALT) to non-lipogenic sarcoma, which arises mostly in the retroperitoneum and deep soft tissue of proximal extremities. It is characterized by a supernumerary ring and giant marker chromosomes, both of which contain amplified sequences of 12q13-15 including murine double minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) cell cycle oncogenes. Detection of MDM2 (and/or CDK4) amplification serves to distinguish DDL from other undifferentiated sarcomas. Recently, CTDSP1/2-DNM3OS fusion genes have been identified in a subset of DDL. However, the genetic events associated with dedifferentiation of WDL/ALT remain to be clarified. The standard treatment for localized DDL is surgery, with or without radiotherapy. In advanced disease, the standard first-line therapy is an anthracycline-based regimen, with either single-agent anthracycline or anthracycline in combination with the alkylating agent ifosfamide. Unfortunately, this regimen has not necessarily led to a satisfactory clinical outcome. Recent advances in the understanding of the pathogenesis of DDL may allow for the development of more-effective innovative therapeutic strategies. This review provides an overview of the current knowledge on the clinical presentation, pathogenesis, histopathology and treatment of DDL.
Highlights
Adipocytic tumors are frequently encountered in routine practice
In the European and Treatment of Cancer (EORTC)-62012 phase 3 trial, post hoc subgroup analysis showed no improvement in objective response rate (ORR) or overall survival (OS) in patients with liposarcoma treated with combination therapy with doxorubicin and ifosfamide compared to doxorubicin alone [53]
dedifferentiated liposarcoma (DDL) typically arises in the retroperitoneum or proximal extremities of middle-aged and older adults and is defined as the transition from well-differentiated liposarcoma (WDL)/atypical lipomatous tumor (ALT) to non-lipogenic sarcoma, either in the primary tumor or in a recurrence of WDL/ALT
Summary
Adipocytic tumors are frequently encountered in routine practice. The 2020 World. Health Organization Classification of Tumors of Soft Tissue and Bone recognizes five major liposarcoma subtypes: well-differentiated liposarcoma (WDL)/atypical lipomatous tumor (ALT); dedifferentiated liposarcoma (DDL); myxoid liposarcoma; pleomorphic liposarcoma; and myxoid pleomorphic liposarcoma [1]. DDL is characterized as a typically non-lipogenic sarcoma that is juxtaposed to WDL/ALT. Dedifferentiation occurs in up to 10% of WDL/ALT cases [2]. DDL genetically overlaps with WDL/ALT; both entities are associated with high level amplifications of murine double minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4). Systemic treatment with chemotherapy and molecular targeted agents is one of the main therapeutic modalities in patients with advanced or metastatic disease. We review the key clinical, histopathological and genomic characteristics of DDL, summarize the current management and provide an overview of the ongoing research of novel therapeutic strategies.
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