From the Guidelines
Complete en bloc resection, preserving adjacent neurovascular structures, is the recommended treatment for MDM2 amplified well-differentiated liposarcoma, as it affords long-term local control 1.
Diagnosis and Treatment
MDM2 amplification is a key genetic alteration in well-differentiated liposarcoma (WDLPS), serving as both a diagnostic marker and potential therapeutic target. The amplification of the MDM2 gene can be detected through fluorescence in situ hybridization (FISH), immunohistochemistry, or molecular techniques. Diagnosis typically requires core needle or excisional biopsy with MDM2 testing to distinguish WDLPS from benign lipomas. Some key points to consider in the diagnosis and treatment of MDM2 amplified well-differentiated liposarcoma include:
- MDM2 amplification is present in nearly all cases of WDLPS 1
- MRI with expert review can differentiate between large, deep lipomas and ALT/WDL in up to 69% of cases, but the defining diagnostic test is the molecular demonstration of amplification of the MDM-2 cell cycle oncogene 1
- Surgical resection is the usual treatment for ALT, and the prognosis is mostly excellent 1
- Marginal resections as a complete en bloc specimen, even if classified histopathologically as R1, will give excellent rates of long-term local control 1
Management
The management of MDM2 amplified well-differentiated liposarcoma involves:
- Complete surgical resection with preservation of adjacent neurovascular structures 1
- No attempt to gain wide surgical margins, as this can increase morbidity without improving outcomes 1
- Consideration of radiological surveillance in older patients or those with significant comorbidities, if surgery is likely to be morbid 1
- Adjuvant radiotherapy may occasionally be considered in larger tumors or those where clear margins are difficult to achieve 1
From the Research
Mdm2 Amplification in Well-Differentiated Liposarcoma
- MDM2 amplification is a genetic mutation typically present in well-differentiated liposarcomas (WDLS) and absent in benign lipomas (BL) 2.
- A study found that 33 out of 282 patients with lipomatous tumors showed MDM2 amplification (11.7%), and 2 of them had local recurrence (6.1%) 2.
- The study suggested that an initial marginal excision is a reasonable surgical approach for WDLS, as recurrences are rare and can be managed with re-excision when they occur 2.
Diagnosis and Treatment
- Fluorescence in situ hybridization (FISH) testing for MDM2 amplification can be used to discriminate lipomas from atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) 3.
- A study recommended FISH testing for recurrent lesions, deep extremity lesions >10 cm in patients over 50 years of age, cases with equivocal atypia, and lesions of the retroperitoneum/pelvis/abdomen 3.
- MDM2 inhibition using the antagonist RG7112 can activate the P53 pathway and decrease cell proliferation in MDM2-amplified liposarcoma 4.
Prognosis and Progression
- The MDM2 amplification ratio can be used to characterize progression to high-grade tumors, with a ratio of 16 showing optimal sensitivity and specificity as a cutoff point for progression to dedifferentiated liposarcoma (DDL) 5.
- Borderline areas with increased cellularity and atypia but preserved lipomatous differentiation showed a significantly higher MDM2 ratio compared to WDL 5.
- Central (retroperitoneal and intra-abdominal) tumors also showed a significantly higher MDM2 ratio than peripheral ones 5.