title: The role of neuropathology in the management of patients with diffuse low grade glioma: A systematic review and evidence-based clinical practice guideline.
abstract: METHODS
  Adult patients (age ≥18 years) who have suspected low-grade diffuse glioma.
  
  
  OBJECTIVE
  What are the optimal neuropathological techniques to diagnose low-grade diffuse glioma in the adult?
  
  
  CONCLUSIONS
  LEVEL I: Histopathological analysis of a representative surgical sample of the lesion should be used to provide the diagnosis of low-grade diffuse glioma.
  
  
  METHODS
  Both frozen section and cytopathologic/smear evaluation should be used to aid the intra-operative assessment of low-grade diffuse glioma diagnosis. A resection specimen is preferred over a biopsy specimen, to minimize the potential for sampling error issues.
  
  
  METHODS
  Patients with histologically-proven WHO grade II diffuse glioma.
  
  
  OBJECTIVE
  In adult patients (age ≥18 years) with histologically-proven WHO grade II diffuse glioma, is testing for IDH1 mutation (R132H and/or others) warranted? If so, is there a preferred method?
  
  
  CONCLUSIONS
  
  
  
  METHODS
  IDH gene mutation assessment, via IDH1 R132H antibody and/or IDH1/2 mutation hotspot sequencing, is highly-specific for low-grade diffuse glioma, and is recommended as an additional test for classification and prognosis.
  
  
  METHODS
  Patients with histologically-proven WHO grade II diffuse glioma.
  
  
  OBJECTIVE
  In adult patients (age ≥18 years) with histologically-proven WHO grade II diffuse glioma, is testing for 1p/19q loss warranted? If so, is there a preferred method?
  
  
  CONCLUSIONS
  
  
  
  METHODS
  1p/19q loss-of-heterozygosity testing, by FISH, array-CGH or PCR, is recommended as an additional test in oligodendroglial cases for prognosis and potential treatment planning.
  
  
  METHODS
  Patients with histologically-proven WHO grade II diffuse glioma.
  
  
  OBJECTIVE
  In adult patients (age ≥18 years) with histologically-proven WHO grade II diffuse glioma, is MGMT promoter methylation testing warranted? If so, is there a preferred method?
  
  
  CONCLUSIONS
  There is insufficient evidence to recommend methyl-guanine methyl-transferase (MGMT) promoter methylation testing as a routine for low-grade diffuse gliomas. It is recommended that patients be enrolled in properly designed clinical trials to assess the value of this and related markers for this target population.
  
  
  METHODS
  Patients with histologically-proven WHO grade II diffuse glioma.
  
  
  OBJECTIVE
  In adult patients (age ≥18 years) with histologically-proven WHO grade II diffuse glioma, is Ki-67/MIB1 immunohistochemistry warranted? If so, is there a preferred method to quantitate results?
  
  
  CONCLUSIONS
  
  
  
  METHODS
  Ki67/MIB1 immunohistochemistry is recommended as an option for prognostic assessment.
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital, 32 Fruit Street, Yankey 9E, Boston, MA, 02114, USA. dcahill@partners.org.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Cahill
authors.affiliation: University Hospitals, Cleveland, OH, USA.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Sloan
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Brian V
authors.initials: BV
authors.lastname: Nahed
authors.affiliation: University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Aldape
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: David N
authors.initials: DN
authors.lastname: Louis
authors.affiliation: Department of Neurosurgery, Kansas University Medical Center, Kansas City, KS, USA.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Ryken
authors.affiliation: Department of Neurosurgery, Henry Ford Health System, Detroit, MI, USA.
authors.forename: Steven N
authors.initials: SN
authors.lastname: Kalkanis
authors.affiliation: Department of Neurosurgery, Emory Clinic, Atlanta, GA, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Olson
mesh_terms: D006801:Humans; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000628:therapy; D019468:Disease Management; D019317:Evidence-Based Medicine; D005910:Glioma / Q000175:diagnosis / Q000473:pathology / Q000628:therapy; D060787:Neoplasm Grading
keywords: 1p/19q loss-of-heterozygosity; Astrocytoma; Isocitrate dehydrogenase (IDH1, IDH2); Ki67/MIB1; Low-grade diffuse glioma; Methyl-guanine methyl-transferase (MGMT); Oligodendroglioma