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.
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.
Authors: Sara Dyer; Emma Prebble; Val Davison; Paul Davies; Pramila Ramani; David Ellison; Richard Grundy Journal: Am J Pathol Date: 2002-12 Impact factor: 4.307
Authors: Thomas E Merchant; Jesse J Jenkins; Peter C Burger; Robert A Sanford; Scot H Sherwood; Dana Jones-Wallace; Richard L Heideman; Stephen J Thompson; Kathleen J Helton; Larry E Kun Journal: Int J Radiat Oncol Biol Phys Date: 2002-05-01 Impact factor: 7.038
Authors: Richard J Gilbertson; Lyndsay Bentley; Roberto Hernan; Teemu T Junttila; Adrian J Frank; Hannu Haapasalo; Michele Connelly; Cynthia Wetmore; Tom Curran; Klaus Elenius; David W Ellison Journal: Clin Cancer Res Date: 2002-10 Impact factor: 12.531
Authors: D Figarella-Branger; M Civatte; C Bouvier-Labit; J Gouvernet; D Gambarelli; J C Gentet; G Lena; M Choux; J F Pellissier Journal: J Neurosurg Date: 2000-10 Impact factor: 5.115
Authors: Stefan Wolfsberger; Ingeborg Fischer; Romana Höftberger; Peter Birner; Irene Slavc; Karin Dieckmann; Thomas Czech; Herbert Budka; Johannes Hainfellner Journal: Am J Surg Pathol Date: 2004-07 Impact factor: 6.394
Authors: M Carter; J Nicholson; F Ross; J Crolla; R Allibone; V Balaji; R Perry; D Walker; R Gilbertson; D W Ellison Journal: Br J Cancer Date: 2002-03-18 Impact factor: 7.640
Authors: Roger E McLendon; Eric Lipp; Diane Satterfield; Melissa Ehinger; Alan Austin; Debra Fleming; Kathryn Perkinson; Michaela Lefaivre; David Zagzag; Benjamin Wiener; Sri Gururangan; Herbert Fuchs; Henry S Friedman; James E Herndon; Patrick Healy Journal: J Neurooncol Date: 2015-01-07 Impact factor: 4.130
Authors: Santhosh A Upadhyaya; Giles W Robinson; Arzu Onar-Thomas; Brent A Orr; Catherine A Billups; Daniel C Bowers; Anne E Bendel; Tim Hassall; John R Crawford; Sonia Partap; Paul G Fisher; Ruth G Tatevossian; Tiffany Seah; Ibrahim A Qaddoumi; Anna Vinitsky; Gregory T Armstrong; Noah D Sabin; Christopher L Tinkle; Paul Klimo; Danny J Indelicato; Frederick A Boop; Thomas E Merchant; David W Ellison; Amar Gajjar Journal: Neuro Oncol Date: 2019-10-09 Impact factor: 12.300