MDM2 Amplified Sarcomas: A Literature Review.

Raf Sciot

doi:10.3390/diagnostics11030496

Abstract

Murine Double Minute Clone 2, located at 12q15, is an oncogene that codes for an oncoprotein of which the association with p53 was discovered 30 years ago. The most important function of MDM2 is to control p53 activity; it is in fact the best documented negative regulator of p53. Mutations of the tumor suppressor gene p53 represent the most frequent genetic change in human cancers. By overexpressing MDM2, cancer cells have another means to block p53. The sarcomas in which MDM2 amplification is a hallmark are well-differentiated liposarcoma/atypical lipomatous tumor, dedifferentiated liposarcoma, intimal sarcoma, and low-grade osteosarcoma. The purpose of this review is to summarize the typical clinical, histopathological, immunohistochemical, and genetic features of these tumors.

Highlights

This group of tumors is called atypical spindle cell lipoma, since it has of Well-Differentiated Liposarcoma/Atypical Lipomatous Tumor (WDL/ATL) dedifferentiate into DDL
The transition to the nonlipogenic mally ALT” have been reported. These tumors, which do not fit neatly into the category of sarcoma is usually abrupt and the latter most often looks like undifferentiated pleolipoma or ALT, show prominent variation in adipocyte size, frequent single-cell adipocytic morphic or spindle cell sarcoma, but myxoid sarcoma-like pictures, or low grade desnecrosis, limited nuclear enlargement and hyperchromasia, and minimally thickened fimoid-like areas, can be seen as well (Figures 7 and 8)
DDL can mimic any6 of type of sarcoma and MDM2 immunohistochemistry/FISH should be part of the panel of tests in any sarcoma occurring at any site, certainly if it is undifferentiated and pleomorphic

Summary

Introduction

Mainly seen in the retroperitoneum, a lymphoplasmocytic inflammatory infiltrate predominates and obscures the adipocytic component, to the extent that it can mimic inflammatory myofibroblastic tumor, Castleman’s disease or even a lymphoma (Figure 3). These phenotypic variants can be admixed in the same tumor Whatever it looks like, WDL/ATL is characterized by giant marker and/or supernumerary ring chromosomes, both of which contain multiple copies of MDM2. Diagnostics 2021, 11, 496 of lipoma or ALT, show prominent variation in adipocyte size, frequent single-cell adipocytic necrosis, limited nuclear enlargement and hyperchromasia, and minimally thickened fibrous septa These tumors do not show MDM2 amplification as determined by FISH, but are positive for MDM2 RNA-ISH. A lack of MDM2Liposarcoma amplification does not entirely preclude the diagnosis of ALT/WDL

Dedifferentiated

Dedifferentiated Liposarcoma

Findings

Low-Grade Osteosarcoma