26460 MDM2 (12q15) Amplification, Well-Differentiated Liposarcoma/Atypical Lipomatous Tumor, FISH, Tissue (MDM2F)

​​ALT

Carboxypeptidase M (CPM)

Lipoma

WDL/ALT

Osteosarcoma

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

Preferred: Tissue block

Submit a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block. Blocks prepared with alternative fixation methods may be acceptable; provide fixation method used.

Acceptable: Slides

Four consecutive, unstained, 5 micron-thick sections placed on positively charged slides, and 1 hematoxylin and eosin-stained slide.

Specimen Minimum Volume:

Two consecutive, unstained, 5- micron-thick sections placed on positively charged slides and 1 hematoxylin and eosin-stained slide.

Necessary Information:

1. A pathology report is required in order for testing to be performed. Acceptable pathology reports include working drafts, preliminary pathology or surgical pathology reports.

2. A reason for testing must be provided. If this information is not provided, an appropriate indication for testing may be entered by Mayo Clinic Laboratories.

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

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.

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.

An interpretive report will be provided.

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.