Primitive neuroectodermal tumors of the brainstem: Investigation of seven cases

Objective. We discuss the clinical aspects, pathology, and molecular geneti cs of 7 patients with primitive neuroectodermal tumors (PNETs) arising in t he brainstem that were treated at our institution from 1986 through 1995. M ost neuro-oncologists avoid performing biopsies in children with pontine tu mors. This article raises the question as to whether biopsies should be per formed, because treatment recommendations might differ if a PNET was diagno sed rather than a pontine glioma. Patients and Methods. We reviewed the clinical neuro-oncology database and the files of the Division of Neuropathology at New York University Medical Center from 1986 through 1995 and identified 7 histologically confirmed PNE Ts arising in the brainstem among 146 pediatric brainstem tumors. The clini cal, neuroradiological, and neuropathological data were reviewed. Postmorte m examinations were performed in 2 cases. Formalin-fixed, paraffin-embedded tumor tissues were also available in 6 of 7 patients that were tested for p53 gene mutations using single-strand conformation polymorphism analysis. We also tested 9 cerebellar PNETs, 9 brainstem gliomas, and 3 normal brains for p53 gene mutations as controls. Results. All 7 patients presented with focal cranial nerve deficits, and 2 were also hemiparetic. The median age at diagnosis was 2.7 (1-8 years). Mag netic resonance imaging (MRI) characteristics included a focal intrinsic ex ophytic nonenhancing brainstem lesion that had low T1-weighted and high T2- weighted signals. Hydrocephalus was present in 5 patients at diagnosis, 3 o f whom had leptomeningeal dissemination. Meningeal dissemination occurred l ater in the course of the disease in 3 other patients. Five children requir ed shunts at diagnosis and another 2 at recurrence. Despite therapy, all 7 PNET patients died within 17 months of diagnosis with a mean survival of 8 (4-17) months. No mutation in the p53 gene was detected. Conclusions. Brainstem PNETs tend to arise at a younger age than brainstem gliomas and medulloblastomas. The MRI pattern suggests a localized rather t han a diffuse intrinsic nonenhancing brainstem tumor. Like other PNETs, bra instem PNETs have a high predilection to disseminate within the central ner vous system. The absence of p53 mutations is similar to other PNETs. Despit e their origin close to the cerebellum, brainstem PNETs exhibit a more aggr essive behavior and result in worse clinical outcomes than do cerebellar PN ETs.