MDM2 Amplified Sarcomas: A Literature Review

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.

Keywords: MDM2 amplification; dedifferentiated liposarcoma; intimal sarcoma low grade osteosarcoma; well-differentiated liposarcoma/atypical lipomatous tumor.

Figure 1

Lipoma-like variant of well-differentiated liposarcoma/atypical lipomatous tumor, showing the variation in adipocyte size, hyperchromatic nuclei and lipoblasts (a), detail of lipoblasts with the typical punched-out nucleus in (b).

Figure 2

Sclerosing variant of well-differentiated liposarcoma/atypical lipomatous tumor, highlighting the scattered lipoblasts in a sclerotic background.

Figure 3

Inflammatory variant of well-differentiated liposarcoma/atypical lipomatous tumor, dominated by a prominent lymphoplasmocytic infiltration. Note the atypical fat cells as well.

Figure 4

Ring chromosome in well-differentiated liposarcoma/atypical lipomatous tumor. The ring contains multiple copies of the MDM2 and CDK4 gene.

Figure 5

MDM2 expression in the lipoma-like (a), sclerosing (b), and inflammatory variant (c) of well-differentiated liposarcoma/atypical lipomatous tumor.

Figure 6

MRI pictures of a big retroperitoneal tumor in an 82-years-old male patient.

Figure 7

Abrupt transition of the well-differentiated lipoma-like liposarcoma part to the non-lipogenic sarcomatous part (a). Detail of both parts (b,c), and MDM2 expression in both parts (d,e).

Figure 8

Scar-like phenotype of a dedifferentiated liposarcoma, H&E (a), and MDM2 stain (b).

Figure 9

Meningothelial-like whorls and metaplastic bone formation in a retroperitoneal dedifferentiated liposarcoma (H&E).

Figure 10

Intimal sarcoma. Note the intravascular location (a), and the heterogeneous outlook of the tumor, ranging from bland spindled (b), to pleomorphic (c), to osteosarcoma-like (d). MDM2 expression is seen in (e).

Figure 10

Intimal sarcoma. Note the intravascular location (a), and the heterogeneous outlook of the tumor, ranging from bland spindled (b), to pleomorphic (c), to osteosarcoma-like (d). MDM2 expression is seen in (e).

Figure 11

Parosteal osteosarcoma, typically presenting as a mineralized mass at the back of the distal femur, X-ray (a), and whole mount section (b). At high power, the tumor consists of parallel bone trabeculae and a typical spindle cell proliferation (c). MDM2 expression is present as well (d).

Figure 11

Parosteal osteosarcoma, typically presenting as a mineralized mass at the back of the distal femur, X-ray (a), and whole mount section (b). At high power, the tumor consists of parallel bone trabeculae and a typical spindle cell proliferation (c). MDM2 expression is present as well (d).

Figure 12

Low-grade central osteosarcoma, showing a lytic lesion the distal femur on X-ray (a). On histology, the tumor strongly mimics fibrous dysplasia, with the very irregular bone trabeculae embedded in e fibrous stroma (b). The amplification of the MDM2 gene supports the diagnosis (c).

Figure 12

Low-grade central osteosarcoma, showing a lytic lesion the distal femur on X-ray (a). On histology, the tumor strongly mimics fibrous dysplasia, with the very irregular bone trabeculae embedded in e fibrous stroma (b). The amplification of the MDM2 gene supports the diagnosis (c).