Research
Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts
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* Corresponding author: David W Ellison David.Ellison@stjude.org
1 Dept. of Pathology, St. Jude Children's Research Hospital, Memphis, USA
2 Dept. of Biostatistics, St. Jude Children's Research Hospital, Memphis, USA
3 Dept. of Pathology, La Timone's Hospital, Marseille, France
4 Dept. of Experimental Medicine and Pathology, University of Rome, Rome, Italy
5 Laboratory of Pathology, St Luc Hospital, Bruxelles, Belgium
6 Neuropathology Institute, University Clinic, Bonn, Germany
7 Dept. of Oncology/Hematology, Centre Léon Berard, Lyon, France
8 Division of Pediatrics, National Tumor Institute, Milan, Italy
9 Dept. of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Institute, Paris
10 Children's Brain Tumor Center, University of Nottingham, Nottingham, UK
Journal of Negative Results in BioMedicine 2011, 10:7 doi:10.1186/1477-5751-10-7
Published: 31 May 2011Abstract
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.