title: Primitive neuroectodermal tumors of the brainstem: investigation of seven cases.
abstract: OBJECTIVE
  We discuss the clinical aspects, pathology, and molecular genetics of 7 patients with primitive neuroectodermal tumors (PNETs) arising in the brainstem that were treated at our institution from 1986 through 1995. Most neuro-oncologists avoid performing biopsies in children with pontine tumors. This article raises the question as to whether biopsies should be performed, because treatment recommendations might differ if a PNET was diagnosed rather than a pontine glioma.
  
  
  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 PNETs arising in the brainstem among 146 pediatric brainstem tumors. The clinical, neuroradiological, and neuropathological data were reviewed. Postmortem 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). Magnetic resonance imaging (MRI) characteristics included a focal intrinsic exophytic nonenhancing brainstem lesion that had low T1-weighted and high T2-weighted signals. Hydrocephalus was present in 5 patients at diagnosis, 3 of whom had leptomeningeal dissemination. Meningeal dissemination occurred later in the course of the disease in 3 other patients. Five children required 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 than a diffuse intrinsic nonenhancing brainstem tumor. Like other PNETs, brainstem PNETs have a high predilection to disseminate within the central nervous system. The absence of p53 mutations is similar to other PNETs. Despite their origin close to the cerebellum, brainstem PNETs exhibit a more aggressive behavior and result in worse clinical outcomes than do cerebellar PNETs.
authors.affiliation: Department of Pathology, New York University Medical Center, New York, New York, USA. dz4@is3.nyu.edu
authors.forename: D
authors.initials: D
authors.lastname: Zagzag
authors.forename: D C
authors.initials: DC
authors.lastname: Miller
authors.forename: E
authors.initials: E
authors.lastname: Knopp
authors.forename: J P
authors.initials: JP
authors.lastname: Farmer
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: S
authors.initials: S
authors.lastname: Biria
authors.forename: A
authors.initials: A
authors.lastname: Pellicer
authors.forename: F J
authors.initials: FJ
authors.lastname: Epstein
authors.forename: J C
authors.initials: JC
authors.lastname: Allen
mesh_terms: D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D001933:Brain Stem / Q000737:chemistry / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D005910:Glioma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D008297:Male; D009154:Mutation; D017599:Neuroectodermal Tumors / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D011110:Polymorphism, Genetic