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Ewing sarcoma and Ewing-like tumors

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Abstract

Ewing sarcoma (ES) and Ewing-like sarcomas are highly aggressive round cell mesenchymal neoplasms, most often occurring in children and young adults. The identification of novel molecular alterations has greatly contributed to a profound reappraisal of classification, to the extent that the category of undifferentiated round cell sarcoma has significantly shrunk. In fact, in addition to Ewing sarcoma, we currently recognize three main categories: round cell sarcomas with EWSR1 gene fusion with non-ETS family members, CIC-rearranged sarcomas, and BCOR-rearranged sarcomas. Interestingly, despite significant morphologic overlap, most of these entities tend to exhibit morphologic features predictive of the underlying molecular alteration. Ewing sarcoma is the prototype of round cell sarcoma whereas in CIC sarcomas, focal pleomorphism and epithelioid morphology can predominate. BCOR sarcomas often exhibit a spindled neoplastic cell population. NFATC2 sarcoma may exhibit remarkable epithelioid features, and PATZ1 sarcomas often feature a sclerotic background. The differential diagnosis for these tumors is rather broad, and among round cell sarcomas includes alveolar rhabdomyosarcoma, desmoplastic small round cell tumor, poorly differentiated round cell synovial sarcoma, small cell osteosarcoma, and mesenchymal chondrosarcoma. A combination of morphologic, immunohistochemical, and molecular findings allows accurate classification in most cases. A granular diagnostic approach to Ewing sarcoma and Ewing-like sarcomas is justified by significant differences in terms of both response to chemotherapy and overall survival. As all these entities are in part defined by specific fusion genes, a molecular diagnostic approach based on NGS technology should be considered. In consideration of the extreme rarity of many of these tumor entities, referral to expert rare cancer centers or to rare cancer networks represents the best strategy in order to minimize diagnostic inaccuracy, and allow proper patient management.

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Contribution statements

Marta Sbaraglia, Angelo Dei Tos, Marco Gambarotti, and Alberto Righi all contributed to the design of the manuscript, to the writing and corrections, and to the production of iconography.

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  1. Department of Pathology, Azienda Ospedaliera Universitaria di Padova, Padova, Italy

    Marta Sbaraglia & Angelo P. Dei Tos

  2. Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy

    Alberto Righi & Marco Gambarotti

  3. Department of Medicine, University of Padua School of Medicine, Padua, Italy

    Angelo P. Dei Tos

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  1. Marta Sbaraglia
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Correspondence to Angelo P. Dei Tos.

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Sbaraglia, M., Righi, A., Gambarotti, M. et al. Ewing sarcoma and Ewing-like tumors. Virchows Arch 476, 109–119 (2020). https://doi.org/10.1007/s00428-019-02720-8

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