Virchows Archiv

, Volume 455, Issue 5, pp 397–411 | Cite as

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

  • Antonio Llombart-Bosch
  • Isidro Machado
  • Samuel Navarro
  • Franco Bertoni
  • Patrizia Bacchini
  • Marco Alberghini
  • Apollon Karzeladze
  • Nikita Savelov
  • Semyon Petrov
  • Isabel Alvarado-Cabrero
  • Doina Mihaila
  • Philippe Terrier
  • Jose Antonio Lopez-Guerrero
  • Piero Picci
Original Article


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.


ESFT Histopathology Immunohistochemistry 


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Antonio Llombart-Bosch
    • 1
  • Isidro Machado
    • 1
  • Samuel Navarro
    • 1
  • Franco Bertoni
    • 2
  • Patrizia Bacchini
    • 2
  • Marco Alberghini
    • 2
  • Apollon Karzeladze
    • 3
  • Nikita Savelov
    • 3
  • Semyon Petrov
    • 4
  • Isabel Alvarado-Cabrero
    • 5
  • Doina Mihaila
    • 6
  • Philippe Terrier
    • 7
  • Jose Antonio Lopez-Guerrero
    • 8
  • Piero Picci
    • 2
  1. 1.Department of PathologyUniversity of ValenciaValenciaSpain
  2. 2.Institut Orthopedic RizzoliBolognaItaly
  3. 3.N.N. Blokhin National Cancer Research CenterMoscowRussia
  4. 4.Cancer Oncology CenterKazanRussia
  5. 5.Hospital General de Mexico DFMexicoMexico
  6. 6.Children’s HospitalIasiRomania
  7. 7.Institute Goustave RoussyVillejuifFrance
  8. 8.Instituto Valenciano OncologíaValenciaSpain

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