Pediatric Ependymoma: Biological Perspectives

Abstract

Pediatric ependymomas are enigmatic tumors that continue to present a clinical management challenge despite advances in neurosurgery, neuroimaging techniques, and radiation therapy. Difficulty in predicting tumor behavior from clinical and histological factors has shifted the focus to the molecular and cellular biology of ependymoma in order to identify new correlates of disease outcome and novel therapeutic targets. This article reviews our current understanding of pediatric ependymoma biology and includes a meta-analysis of all comparative genomic hybridization (CGH) studies done on primary ependymomas to date, examining more than 300 tumors. From this meta-analysis and a review of the literature, we show that ependymomas in children exhibit a different genomic profile to those in adults and reinforce the evidence that ependymomas from different locations within the central nervous system (CNS) are distinguishable at a genomic level. Potential biological markers of prognosis in pediatric ependymoma are assessed and the ependymoma cancer stem cell hypothesis is highlighted with respect to tumor resistance and recurrence. We also discuss the shifting paradigm for treatment modalities in ependymoma that target molecular alterations in tumor-initiating cell populations. (Mol Cancer Res 2009;7(6):765-86)

Supratentorial clear cell ependymomas with branching capillaries demonstrate characteristic clinicopathological features and pathological activation of nuclear factor-kappaB signaling

“…2 In children, 90% of ependymomas occur intracranially, with two thirds being located in the posterior fossa (PF) and one third in the supratentorial (ST) compartment. 3 In contrast, intracranial ependymomas are rare in adults. 4 Two factors are consistently prognostic across different series in the literature: age and extent of surgical excision.…”

Supratentorial parenchymal ependymomas of children: experience with 14 patients at a single institute

“…GTR (10 of 14 patients in our series) is the optimal therapy for symptomatic supratentorial parenchymal ependymomas (2,3,(5)(6)(7)(8)(9)12,15,(18)(19)(20)(21)23). In the present series, the postoperative care of patients depended on the operative procedure.…”

“…Most intracranial ependymomas develop within the ventricular system, but they may arise from the extraventricular parenchyma as well (2)(3)(4)(5)16). Supratentorial parenchymal ependymomas in children are a rarely seen pathological diagnosis.…”

Pediatric Thalamic Gliomas: An Updated Review

“…However, an estimated 40% of ependymomas are incurable, particularly when located in the lateral posterior fossa or deep gray structures such as the thalamus. 47 Additionally, a large percentage of supratentorial ependymomas, even those without clear cell histology, carry C11orf95-RELA fusion and CDKN2A (9p21.3) deletion. Although gross total resection is usually not possible in the thalamus, subtotal or partial resection of these relatively circumscribed tumors is occasionally possible and may improve prognosis.…”