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

Ellison DW, Kocak M, Figarella-Branger D, Felice G, Catherine G, Pietsch T, Frappaz D, Massimino M, Grill J, Boyett JM, Grundy RG - J Negat Results Biomed (2011)

Bottom Line: 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.Unfortunately, this appears to have utility in limited clinical settings.

View Article: PubMed Central - HTML - PubMed

Affiliation: Dept, of Pathology, St, Jude Children's Research Hospital, Memphis, USA. David.Ellison@stjude.org

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.

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Related in: MedlinePlus

Proportions of tumors in the three trial cohorts for which there was 4/5 or 5/5 agreement on grade among five pathologists during phase 1 of the study.
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Figure 5: Proportions of tumors in the three trial cohorts for which there was 4/5 or 5/5 agreement on grade among five pathologists during phase 1 of the study.

Mentions: Before any discussion of ependymoma grading, each pathologist independently evaluated tumors from children treated on the SFOP, CNS9204, and CNS9904 trials, allocating grade II or III. The proportions of ependymomas allocated grade II and grade III ranged from 19% to 59% and 41% to 81% respectively across the three trials. Figure 4 displays the ratios of grade II to grade III tumors grouped by trial (a) and pathologist (b), and Figure 5 displays agreement on grading by trial.


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

Ellison DW, Kocak M, Figarella-Branger D, Felice G, Catherine G, Pietsch T, Frappaz D, Massimino M, Grill J, Boyett JM, Grundy RG - J Negat Results Biomed (2011)

Proportions of tumors in the three trial cohorts for which there was 4/5 or 5/5 agreement on grade among five pathologists during phase 1 of the study.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3117833&req=5

Figure 5: Proportions of tumors in the three trial cohorts for which there was 4/5 or 5/5 agreement on grade among five pathologists during phase 1 of the study.
Mentions: Before any discussion of ependymoma grading, each pathologist independently evaluated tumors from children treated on the SFOP, CNS9204, and CNS9904 trials, allocating grade II or III. The proportions of ependymomas allocated grade II and grade III ranged from 19% to 59% and 41% to 81% respectively across the three trials. Figure 4 displays the ratios of grade II to grade III tumors grouped by trial (a) and pathologist (b), and Figure 5 displays agreement on grading by trial.

Bottom Line: 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.Unfortunately, this appears to have utility in limited clinical settings.

View Article: PubMed Central - HTML - PubMed

Affiliation: Dept, of Pathology, St, Jude Children's Research Hospital, Memphis, USA. David.Ellison@stjude.org

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.

Show MeSH
Related in: MedlinePlus