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Histological heterogeneity of Ewing’s sarcoma/PNET: an immunohistochemical analysis of 415 genetically confirmed cases with clinical support

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Abstract

Ewing’s sarcoma (ES)/peripheral neuroectodermal tumor (PNET) are malignant neoplasms affecting children and young adults. We performed a study to typify the histological diversity and evaluate antibodies that may offer diagnostic/prognostic support. In total, 415 cases of genetically confirmed paraffin-embedded ES/PNET were analyzed on whole sections and in tissue microarrays. This study confirms the structural heterogeneity of ES/PNET, distinguishing three major subtypes: conventional ES (280 cases); PNET (53 cases); and atypical ES/PNET (80), including large cells, vascular-like patterns, spindle pattern, and adamantinoma-like configuration. All cases presented positivity for at least three of the four tested antibodies (CD99, FLI1, HNK1, and CAV1). CAV1 appeared as a diagnostic immunomarker of ES/PNET being positive in CD99-negative cases. Hence, the immunohistochemical analysis confirmed the diagnostic value of all four antibodies, which together cover more than 99% of the tumors, independently of the histological variety. The univariate analysis for survival revealed atypical ES as the only histological parameter apparently associated with less favorable clinical outcome, particularly in the subgroup of patients treated with surgery. In conclusion, the diagnosis of atypical ES is a challenge for the pathologist and needs support from molecular techniques to perform an optimal differential diagnosis with other small round cell tumors.

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Acknowledgements

This study was supported by and performed within the project Prognosis and Therapeutic Targets in the Ewing Family of Tumors (PROTHETS), European Community 6FP contract no. 503036.

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We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, University of Valencia, Ave. Blasco Ibañez, 17, 46010, Valencia, Spain

    Antonio Llombart-Bosch, Isidro Machado & Samuel Navarro

  2. Institut Orthopedic Rizzoli, Bologna, Italy

    Franco Bertoni, Patrizia Bacchini, Marco Alberghini & Piero Picci

  3. N.N. Blokhin National Cancer Research Center, Moscow, Russia

    Apollon Karzeladze & Nikita Savelov

  4. Cancer Oncology Center, Kazan, Russia

    Semyon Petrov

  5. Hospital General de Mexico DF, Mexico, Mexico

    Isabel Alvarado-Cabrero

  6. Children’s Hospital, Iasi, Romania

    Doina Mihaila

  7. Institute Goustave Roussy, Villejuif, France

    Philippe Terrier

  8. Instituto Valenciano Oncología, Valencia, Spain

    Jose Antonio Lopez-Guerrero

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  1. Antonio Llombart-Bosch
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Correspondence to Antonio Llombart-Bosch.

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Llombart-Bosch, A., Machado, I., Navarro, S. et al. Histological heterogeneity of Ewing’s sarcoma/PNET: an immunohistochemical analysis of 415 genetically confirmed cases with clinical support. Virchows Arch 455, 397–411 (2009). https://doi.org/10.1007/s00428-009-0842-7

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