Clinical Pathology: Genetic Testing

1021) A 16-year-old girl presented with a right shoulder mass, which was submitted for cytogenetics work-up. The findings in surgical pathology identified tumor cells that were positive for CD99, beta-catenin, vimentin, and synaptophysin. Chromosome analysis performed after short-term cell culture showed a highly abnormal karyotype, as shown in Figure 1. Based on the breakpoint at 22q12, fluorescence in situ hybridization (FISH) analysis was performed using an EWSR1 dual-color break-apart probe. Based on the karyotype and FISH analysis, what is the most likely diagnosis of this tumor?

• Ewing sarcomas, also known as primitive neuroectodermal tumors (PNET), are highly aggressive tumors of neural crest derivation. The cytogenetic hallmark of Ewing sarcoma is t(11;22)(q24;q12), which is seen in approximately 90% of all histologic subtypes. This translocation is diagnostic of this entity.

• The t(11;22)(q24;q12) translocation results in rearrangement of the EWS gene at 11q24 and the FLI1 gene at 22q12. The translocation results in the formation of the ESW-FLI1 chimeric protein.

• Approximately 5% of Ewing sarcomas result from variant translocations involving the EWS gene at 11q24, resulting in t(21;22)(q12;q12)[EWS-ERG] and t(7;22)(p22;q12) [EWS-ETV1].

Mertens F, Mandahl N: Tumors of bone.In: Heim S, Mitelman F, eds. Cancer Cytogenetics. 3rd ed. Chap 22. Hoboken, NJ: John Wiley & Sons; 2009:655–674.

Atlas of Genetics and Cytogenetics in Oncology and Hematology.

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