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Test Catalog

Test ID: MDM2F    
MDM2 (12q15) Amplification, Well-Differentiated Liposarcoma/Atypical Lipomatous Tumor, FISH, Tissue

Useful For Suggests clinical disorders or settings where the test may be helpful

Supporting a diagnosis of well-differentiated liposarcoma/atypical lipomatous tumor

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This test does not include a pathology consult. If a pathology consultation is requested, PATHC / Pathology Consultation should be ordered and the appropriate fluorescence in situ hybridization (FISH) test will be ordered and performed at an additional charge.

 

This test includes a charge for application of the first probe set (2 FISH probes) and professional interpretation of results.

 

Additional charges will be incurred for all reflex probes performed. Analysis charges will be incurred based on the number of cells analyzed per probe set. If no cells are available for analysis, no analysis charges will be incurred.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Differential diagnosis of well-differentiated liposarcoma/atypical lipomatous tumor:

The histological discrimination of well-differentiated liposarcoma/atypical lipomatous tumor (WDL/ALT) from lipoma can be diagnostically challenging. However, standard cytogenetic identification of ring and giant rod chromosomes strongly support the diagnosis of WDL/ALT. These abnormal chromosomes are mainly composed of amplified sequences derived from chromosome bands 12q13-15, and contain several amplified genes including MDM2, CPM, CDK4, and TSPAN31. MDM2 is amplified in greater than 99% of WDL, and up to 30% of other types of sarcomas.

 

Differential diagnosis of osteosarcoma:

The histological discrimination of parosteal or low grade central osteosarcoma from other morphologically similar, but clinically distinct entities, can be difficult. Amplification of genomic material derived from chromosome 12q13-15, which contains several genes including MDM2, has been shown to be a recurrent finding in a large proportion (67-100%) of parosteal and central low-grade osteosarcomas. Therefore, the detection of MDM2 gene amplification by fluorescence in situ hybridization (FISH) may be a useful adjunct to support a diagnosis of low-grade central or parosteal osteosarcoma in the proper histopathologic context. Amplifications of 12q13-15 (including MDM2) are less common in conventional high-grade osteosarcoma, estimated to occur in approximately of 5% to 10% of tumors.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

Differential diagnosis of well-differentiated liposarcoma/atypical lipomatous tumor:

A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal reference range for the MDM2 fluorescence in situ hybridization (FISH) probe (positive result). A positive result is consistent with amplification of the MDM2 gene locus (12q15) and supports the diagnosis of well-differentiated liposarcoma/atypical lipomatous tumor (WDL/ALT). A negative result is consistent with absence of amplification of the MDM2 gene locus (12q15). However, negative results do not exclude the diagnosis of WDL/ALT. Amplification varies in individual tumors and among different cells in the same tumor.

 

Differential diagnosis of osteosarcoma:

A positive result is consistent with amplification of the MDM2 gene locus (12q15) and supports the diagnosis of parosteal osteosarcoma or low-grade central osteosarcoma. A negative result indicates an absence of amplification of the MDM2 gene locus (12q15). However, negative results do not exclude the diagnosis of low-grade central osteosarcoma or parosteal osteosarcoma.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test is not approved by the US Food and Drug Administration and it is best used as an adjunct to existing clinical and pathologic information.

 

Fixatives other than formalin (eg Prefer, Bouin) may not be successful for fluorescence in situ hybridization (FISH) assays; however non-formalin-fixed samples will not be rejected.

 

Paraffin-embedded tissues that have been decalcified may not be successful for FISH analysis. FISH studies will be attempted if sufficient tumor is present for analysis. However, if no FISH signals are observed post-hybridization, the case will be released indicating a lack of FISH results.

Supportive Data

Fluorescence in situ hybridization (FISH) analysis was performed on 10 formalin-fixed, paraffin-embedded, well-differentiated liposarcoma/atypical lipomatous tumors (WDL/ALT) tumor samples and 25 normal controls. Amplification of MDM2 was identified in the WDL/ALT samples and correlated with the CPM results. Amplification of MDM2 was not observed in any of the control samples tumors.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Erickson-Johnson MR, Seys AR, Roth CW, et al: Carboxypeptidase M: a biomarker for the discrimination of lipoma from liposarcoma. Mod Pathol. 2009 Dec;22(12):1541-1547

2. Jacob E, Erickson-Johnson MR, Wang X, et al: Assessment of MDM2 amplification using fluorescence in situ hybridization on paraffin-embedded tissue discriminates atypical lipomatous tumors from lipomas. Mod Pathol. 2006;19:13A

3. He X, Pang Z, Zhang X, et al: Consistent Amplification of FRS2 and MDM2 in Low-grade Osteosarcoma: A genetic study of 22 cases with clinicopathologic analysis. Am J Surg Pathol. 2018 Sept;42(9):1143-1155

4. Duhamel LAE, Ye H, Halai, D, et al: Frequency of Mouse Double Minute 2 (MDM2 ) and Mouse Double Minute 4 (MDM4) amplification in parosteal and conventional osteosarcoma subtypes. Histopathology. 2012 Jan;60(2):357-359

5. Dujardin F, Binh MBN, Bourvier C, et al.: MDM2 and CDK4 Immunohistochemistry Is a Valuable Tool in the Differential Diagnosis of Low-Grade Osteosarcomas and Other Primary Fibro-Osseous Lesions of the Bone. Mod Pathol. 2011 May;24(5):624-637

6. Fletcher DM, Bridge JA, Hogendoorn PCW, Mertens F eds. WHO Classification of Tumours of Soft Tissue and Bone. International Agency for Research on Cancer; 2013