Histopathological grading of pediatric ependymoma: Reproducibility and clinical relevance in European trial cohorts

David W. Ellison, Mehmet Kocak, Dominique Figarella-Branger, Giangaspero Felice, Godfraind Catherine, Torsten Pietsch, Didier Frappaz, Maura Massimino, Jacques Grill, James M. Boyett, Richard G. Grundy

Research output: Contribution to journalArticle

Abstract

Background: Histopathological grading of ependymoma has been controversial with respect to its reproducibility and clinical significance. In a 3-phase study, we reviewed the pathology of 229 intracranial ependymomas from European trial cohorts of infants (2 trials - SFOP/CNS9204) and older children (2 trials - AIEOP/CNS9904) to assess both diagnostic concordance among five neuropathologists and the prognostic utility of histopathological variables, particularly tumor grading. Results: In phase 1, using WHO criteria and without first discussing any issue related to grading ependymomas, pathologists assessed and independently graded ependymomas from 3 of 4 trial cohorts. Diagnosis of grade II ependymoma was less frequent than grade III, a difference that increased when one cohort (CNS9204) was reassessed in phase 2, during which the pathologists discussed ependymoma grading, jointly reviewed all CNS9204 tumors, and defined a novel grading system based on the WHO classification. In phase 3, repeat independent review of two cohorts (SFOP/CNS9904) using the novel system was associated with a substantial increase in concordance on grading. Extent of tumor resection was significantly associated with progression-free survival (PFS) in SFOP and AIEOP, but not in CNS9204 and CNS9904. Strength of consensus on grade was significantly associated with PFS in only one trial cohort (AIEOP). Consensus on the scoring of individual histopathological features (necrosis, angiogenesis, cell density, and mitotic activity) correlated with PFS in AIEOP, but in no other trial. Conclusions: We conclude that concordance on grading ependymomas can be improved by using a more prescribed scheme based on the WHO classification. Unfortunately, this appears to have utility in limited clinical settings.

Original languageEnglish
Article number7
JournalJournal of Negative Results in BioMedicine
Volume10
Issue number1
DOIs
Publication statusPublished - 2011

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Ellison, D. W., Kocak, M., Figarella-Branger, D., Felice, G., Catherine, G., Pietsch, T., Frappaz, D., Massimino, M., Grill, J., Boyett, J. M., & Grundy, R. G. (2011). Histopathological grading of pediatric ependymoma: Reproducibility and clinical relevance in European trial cohorts. Journal of Negative Results in BioMedicine, 10(1), [7]. https://doi.org/10.1186/1477-5751-10-7