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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

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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.

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Authors and Affiliations

  1. Sarcoma Unit, The Royal Marsden NHS Foundation Trust, 203 Fulham Road, London, SW3 6JJ, UK

    Mustafa Mohamed, Charlotte Benson, Robin L. Jones, Cyril Fisher & Khin Thway

  2. Molecular Diagnostics, Royal Marsden Hospital, Surrey, Sutton, UK

    David Gonzalez & Dorte Wren

  3. Divisions of Anatomic Pathology and Laboratory Medicine & Pathology, Mayo Clinic, Rochester, MN, USA

    Karen J. Fritchie

  4. Clinical Cytogenetics, Royal Marsden Hospital, Surrey, Sutton, UK

    John Swansbury

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  1. Mustafa Mohamed
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  2. David Gonzalez
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  6. Charlotte Benson
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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.

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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.

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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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