title: Massive dissemination from spinal cord gangliogliomas negative for BRAF V600E: report of two rare adult cases.
abstract: OBJECTIVE
  Metastatic leptomeningeal spread from spinal cord gangliogliomas (GGs) is exceedingly rare.
  
  
  METHODS
  Two adult women, aged 27 and 51 years, died of massive disseminations of cervicothoracic GGs 4 and 6 years, respectively, after initial diagnoses; full autopsies were performed. BRAF status was assessed by VE1 immunohistochemistry (IHC), Sanger sequencing, and a single-nucleotide base extension assay (SNaPshot, Applied Biosystems, Princeton, NJ).
  
  
  RESULTS
  The 27-year-old underwent two biopsies, chemotherapy, radiation, and ventriculoperitoneal shunt placement; she developed craniospinal and peritoneal dissemination. Autopsy confirmed shunt-mediated peritoneal metastases, microscopic bone marrow involvement, and profuse spinal and supratentorial leptomeningeal and parenchymal spread. The 51-year-old underwent two resections, radiation, and chemotherapy and developed pancytopenia with biopsy-proven bony metastases 15 months before death. Autopsy demonstrated leptomeningeal, subpial, and subependymal metastases. The tumors in both primary and metastatic sites were BRAF negative by VE1 IHC and two different mutational analyses. This compared with negative BRAF results for an additional four nonmetastatic adult nonsupratentorial GGs and in our study.
  
  
  CONCLUSIONS
  We document two rare cases of massively metastatic spinal cord GGs in adult patients who were negative for BRAF V600E mutations via multiple methods.
authors.affiliation: From the Department of Pathology, Anschutz Medical Campus, University of Colorado at Denver, Aurora, CO;
authors.forename: Seth C
authors.initials: SC
authors.lastname: Lummus
authors.affiliation: From the Department of Pathology, Anschutz Medical Campus, University of Colorado at Denver, Aurora, CO;
authors.forename: Dara L
authors.initials: DL
authors.lastname: Aisner
authors.affiliation: From the Department of Pathology, Anschutz Medical Campus, University of Colorado at Denver, Aurora, CO;
authors.forename: Sharon B
authors.initials: SB
authors.lastname: Sams
authors.affiliation: Departments of Pathology and Neuro-Oncology, Children's Hospital Colorado, Aurora, CO;
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Foreman
authors.affiliation: Department of Neurosurgery, Anschutz Medical Campus, University of Colorado at Denver, Aurora, CO; and.
authors.forename: Kevin O
authors.initials: KO
authors.lastname: Lillehei
authors.affiliation: From the Department of Pathology, Anschutz Medical Campus, University of Colorado at Denver, Aurora, CO; Department of Neurosurgery, Anschutz Medical Campus, University of Colorado at Denver, Aurora, CO; and Department of Neurology, Anschutz Medical Campus, University of Colorado at Denver, Aurora, CO. bk.demasters@ucdenver.edu.
authors.forename: B K
authors.initials: BK
authors.lastname: Kleinschmidt-DeMasters
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D018303:Ganglioglioma / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013120:Spinal Cord Neoplasms / Q000175:diagnosis / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF V600E; Bone marrow; Ganglioglioma; Intramedullary; Metastasis; Spinal cord; VE1