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Desmoplastic small round cell tumor: evaluation of reverse transcription-polymerase chain reaction and fluorescence in situ hybridization as ancillary molecular diagnostic techniques

Abstract

Desmoplastic small round cell tumor (DSRCT) is a rare, biologically aggressive soft tissue neoplasm of uncertain differentiation, most often arising in the abdominal and pelvic cavities of adolescents and young adults with a striking male predominance. Histologically, it is characterized by islands of uniform small round cells in prominent desmoplastic stroma, and it has a polyimmunophenotypic profile, typically expressing WT1 and cytokeratin, desmin, and neural/neuroendocrine differentiation markers to varying degrees. Tumors at other sites and with variant morphology are more rarely described. DSRCT is associated with a recurrent t(11;22)(p13;q12) translocation, leading to the characteristic EWSR1-WT1 gene fusion. Fluorescence in situ hybridization (FISH), to detect EWSR1 rearrangement, and reverse transcription-polymerase chain reaction (RT-PCR) to assess for EWSR1-WT1 fusion transcripts are routine diagnostic ancillary tools. We present a large institutional comparative series of FISH and RT-PCR for DSRCT diagnosis. Twenty-six specimens (from 25 patients) histologically diagnosed as DSRCT were assessed for EWSR1 rearrangement and EWSR1-WT1 fusion transcripts. Of these 26 specimens, 24 yielded positive results with either FISH or RT-PCR or both. FISH was performed in 23 samples, with EWSR1 rearrangement seen in 21 (91.3%). RT-PCR was performed in 18 samples, of which 13 (72.2%) harbored EWSR1-WT1 fusion transcripts. The sensitivity of FISH in detecting DSRCT was 91.3%, and that of RT-PCR was 92.8% following omission of four technical failures. Therefore, both methods are comparable in terms of sensitivity. FISH is more sensitive if technical failures for RT-PCR are taken into account, and RT-PCR is more specific in confirming DSRCT. Both methods complement each other by confirming cases that the other method may not. In isolation, FISH is a relatively non-specific diagnostic adjunct due to the number of different neoplasms that can harbor EWSR1 rearrangement, such as Ewing sarcoma. However, in cases with appropriate morphology and a typical pattern of immunostaining, FISH is confirmatory of the diagnosis.

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Acknowledgments

We acknowledge support from the NIHR Royal Marsden/ICR Biomedical Research Centre.

Author information

Correspondence to Khin Thway.

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Research involving human participants and/or animals

No research involving human participants or animals. All materials were formalin-fixed, paraffin-embedded archival surplus biopsy or excision material from the pathology archive.

Informed consent

All specimens were formalin-fixed, paraffin-embedded archival surplus biopsy or excision material from the pathology archive. No patient informed consent was required for this study, and there is no identifiable patient information.

Funding

No funding to disclose.

Conflict of interest

The authors declare that they have no conflict of interest.

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Mohamed, M., Gonzalez, D., Fritchie, K.J. et al. Desmoplastic small round cell tumor: evaluation of reverse transcription-polymerase chain reaction and fluorescence in situ hybridization as ancillary molecular diagnostic techniques. Virchows Arch 471, 631–640 (2017). https://doi.org/10.1007/s00428-017-2207-y

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Keywords

  • Desmoplastic small round cell tumor
  • Reverse transcription-polymerase chain reaction
  • Fluorescence in situ hybridization
  • Sarcoma