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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p

Intracranial Ependymomas in Childhood - A Retrospective Review of Sixty-Two Children

Of the 818 tumours of the central nervous system diagnosed between 1972 and 1991, 62 patients (35 males and 27 females) with histopathologically confirmed ependymomas were treated and followed-up at the Children's Hospital of Hacettepe University during that period. The median age was 6 years (range 1-17 years). Headache, nausea and vomiting were the most frequent symptoms; papilledema was the most common sign in our patients. Tumour sites were in the posterior fossa in 47 patients and supratentorial in 15 patients. All patients underwent surgery. Gross- total resection was performed in 27 patients, subtotal resection in 32 patients and biopsy in the remaining 3 patients. Initially, 53 patients were given postoperative radiotherapy. Four patients did not receive radiotherapy because of their young age, whereas five patients died prior to starting radiotherapy. Two slightly different types of chemotherapy protocols were applied for an average of one year in 47 patients. Event-free and overall survival rates at 10 years were 36% and 50%, respectively. Twenty children suffered relapse 4 to 55 months after diagnosis (median 16 months). Relapses were distant in 3 cases and local in 17. Age was the only statistically significant prognostic factor, patients younger than 5 years of age having a poorer outcome. Sex, histopathologic type, localization of the tumour, extent of surgery, and chemotherapy did not influence the prognosis in our study. Because the majority of recurrences were local, better local tumour control is required. New treatment strategies should be developed in order to improve local control.WoSScopu