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Ewing Sarcoma Treatment (PDQ®)

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Cellular Classification

Ewing sarcoma belongs to the group of neoplasms commonly referred to as small, round, blue-cell tumors of childhood. The individual cells of Ewing sarcoma contain round-to-oval nuclei with fine dispersed chromatin without nucleoli. Occasionally, cells with smaller, more hyperchromatic, and probably degenerative nuclei are present, giving a light cell/dark cell pattern. The cytoplasm varies in amount, but in the classic case, it is clear and contains glycogen, which can be highlighted with a periodic acid-Schiff stain. The tumor cells are tightly packed and grow in a diffuse pattern without evidence of structural organization. Tumors with the requisite translocation that show neuronal differentiation are not considered a separate entity, but rather, part of a continuum of differentiation.

The MIC2 gene product, CD99, is a surface membrane protein that is expressed in most cases of Ewing sarcoma and is useful in suggesting diagnosis of these tumors when the results are interpreted in the context of clinical and pathologic parameters.[1] MIC2 positivity is not unique to Ewing sarcoma, and positivity by immunochemistry is found in several other tumors including synovial sarcoma, non-Hodgkin lymphoma, and gastrointestinal stromal tumors. The detection of a translocation involving the EWSR1 gene on chromosome 22 band q12 and any one of a number of partner chromosomes is the key feature in the diagnosis of Ewing sarcoma.[2]

Cytogenetic Changes in Ewing Sarcoma

Cytogenetic studies of Ewing sarcoma have identified a consistent alteration of the EWSR1 locus (a member of the TET family [TLS/EWS/TAF15] of RNA binding proteins) on chromosome 22 band q12 that may involve other chromosomes, including 11 or 21.[3] Characteristically, the amino terminus of the EWSR1 gene is juxtaposed with the carboxy terminus of another gene. In most cases (90%), the carboxy terminus is provided by FLI1, a member of the Ets family of transcription factor genes located on chromosome 11 band q24. Other Ets family members that may combine with the EWSR1 gene in order of frequency are ERG, located on chromosome 21; ETV1, located on chromosome 7; and E1AF, located on chromosome 17; these result in the following translocations: t(21;22),[4] t(7;22), and t(17;22), respectively. Rarely, other TET family members can substitute for EWS.[5] Besides these consistent aberrations involving the EWSR1 gene at 22q12, additional numerical and structural aberrations have been observed in Ewing sarcoma, including gains of chromosomes 2, 5, 8, 9, 12, and 15; the nonreciprocal translocation t(1;16)(q12;q11.2); and deletions on the short arm of chromosome 6. Trisomy 20 may be associated with a more aggressive subset of Ewing sarcoma tumors.[6]

A molecular test (i.e., reverse transcriptase polymerase chain reaction [PCR] and restriction analysis of PCR products), currently available on a research basis only, now offers the opportunity to markedly simplify the definition of Ewing sarcoma.[7,8] The molecular assay can be performed on relatively small amounts of tissue obtained by minimally invasive biopsies and is capable of providing results faster than cytogenetic analysis.

References

  1. Parham DM, Hijazi Y, Steinberg SM, et al.: Neuroectodermal differentiation in Ewing's sarcoma family of tumors does not predict tumor behavior. Hum Pathol 30 (8): 911-8, 1999. [PUBMED Abstract]
  2. Delattre O, Zucman J, Melot T, et al.: The Ewing family of tumors--a subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med 331 (5): 294-9, 1994. [PUBMED Abstract]
  3. Urano F, Umezawa A, Yabe H, et al.: Molecular analysis of Ewing's sarcoma: another fusion gene, EWS-E1AF, available for diagnosis. Jpn J Cancer Res 89 (7): 703-11, 1998. [PUBMED Abstract]
  4. Hattinger CM, Rumpler S, Strehl S, et al.: Prognostic impact of deletions at 1p36 and numerical aberrations in Ewing tumors. Genes Chromosomes Cancer 24 (3): 243-54, 1999. [PUBMED Abstract]
  5. Sankar S, Lessnick SL: Promiscuous partnerships in Ewing's sarcoma. Cancer Genet 204 (7): 351-65, 2011. [PUBMED Abstract]
  6. Roberts P, Burchill SA, Brownhill S, et al.: Ploidy and karyotype complexity are powerful prognostic indicators in the Ewing's sarcoma family of tumors: a study by the United Kingdom Cancer Cytogenetics and the Children's Cancer and Leukaemia Group. Genes Chromosomes Cancer 47 (3): 207-20, 2008. [PUBMED Abstract]
  7. Meier VS, Kühne T, Jundt G, et al.: Molecular diagnosis of Ewing tumors: improved detection of EWS-FLI-1 and EWS-ERG chimeric transcripts and rapid determination of exon combinations. Diagn Mol Pathol 7 (1): 29-35, 1998. [PUBMED Abstract]
  8. Dagher R, Pham TA, Sorbara L, et al.: Molecular confirmation of Ewing sarcoma. J Pediatr Hematol Oncol 23 (4): 221-4, 2001. [PUBMED Abstract]
  • Updated: August 15, 2014