Test ID: DDITF    
Myxoid/Round Cell Liposarcoma, 12q13 (DDIT3 or CHOP) Rearrangement, FISH, Tissue

Aiding in the diagnosis of myxoid/round cell liposarcoma by detecting a neoplastic clone associated with gene rearrangement involving the DDIT3 (CHOP) gene region at 12q13

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 application of 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.

Myxoid/round cell liposarcoma is the second most common subtype of liposarcoma, accounting for more than one-third of all liposarcomas and representing about 10% of all adult soft-tissue sarcomas. Myxoid/round cell liposarcoma is described as a malignant tumor composed of uniform round to oval shaped primitive nonlipogenic mesenchymal cells and a variable number of small signet-ring lipoblasts in a prominent myxoid stroma with a characteristic branching vascular pattern.

A unique chromosome translocation, t(12;16)(q13;p11), resulting in a fusion of the DDIT3 gene (also known as CHOP or GADD153) on chromosome 12 and the FUS gene (also referred to as TLS) on chromosome 16, is the key genetic aberration in myxoid/round cell liposarcoma. More than 90% of myxoid/round cell liposarcoma are cytogenetically characterized by this translocation. In rare cases, a variant t(12;22)(q13;q12) has been described in which DDIT3 (CHOP) fuses with EWS, a gene highly related to FUS.

An interpretive report will be provided.

A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal cutoff for the DDIT3 (CHOP) probe.

A positive result is consistent with a subset of myxoid/round cell liposarcoma.

A negative result suggests no rearrangement of the DDIT3 (CHOP) gene region at 12q13. However, this result does not exclude the diagnosis of myxoid/round cell liposarcoma.

This test is not approved by the U.S. 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's) may not be successful for FISH assays; however, nonformalin-fixed samples will not be rejected.

Paraffin-embedded tissues that have been decalcified are generally unsuccessful for FISH analysis. The pathologist reviewing the hematoxylin and eosin-stained slide may find it necessary to cancel testing.

FISH analysis was performed on 51 formalin-fixed, paraffin-embedded tissue samples including 26 myxoid/round cell liposarcomas and 25 normal soft tissue noncancerous control specimens (from various anatomic locations). The normal controls were used to generate a normal cutoff for this assay. A rearrangement of DDIT3 (CHOP) was identified in 18 of 26 (69%) of myxoid/round cell liposarcoma specimens.

1. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Soft Tissue and Bone. Edited by CDM Fletcher, K Unni, F Mertens: IARC: Lyon 2002, pp 40-43

2. Meis-Kindblom JM, Sjogren H, Kindblom LG, et al: Cytogenetic and molecular genetic analyses of liposarcoma and its soft tissue simulators: recognition of new variants and differential diagnosis. Virchows Arch 2001;439(2):141-51

3. Rabbitts TH, Forster A, Larson R, et al: Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma. Nat Genet 1993 Jun;4(2):175-180

4. Sandberg AA: Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: liposarcoma. Cancer Genet Cytogenet 2004 Nov;155(1):1-24

5. Downs-Kelly E, Goldblum JR, Patel RM, et al: The utility of fluorescence in situ hybridization (FISH) in the diagnosis of myxoid soft tissue neoplasms. Am J Surg Pathol 2008;32:8-13