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Glioblastoma

Diffuse Astrocytic and Oligodendroglial Tumors
  • Serge Weis
  • Michael Sonnberger
  • Andreas Dunzinger
  • Eva Voglmayr
  • Martin Aichholzer
  • Raimund Kleiser
  • Peter Strasser
Chapter
  • 370 Downloads

Abstract

Glioblastoma (GBM) is a high-grade glioma with predominantly astrocytic differentiation; featuring nuclear atypia, cellular pleomorphism (in most cases), mitotic activity, and typically a diffuse growth pattern, as well as microvascular proliferation and/or necrosis, and which lacks mutations in the IDH genes.

GBM is the most frequent tumor of the CNS affecting predominantly persons between 40-80 years of age. All regions of the brain and spinal cord are susceptible; a preferential involvement of the telencephalon is noted with a characteristic involvement of the white matter.

On imaging, GBM presents as an irregular, heterogeneous, ring enhancing mass of variable size with central necrosis and surrounding vasogenic edema. GBMs are normally FDG-avid. Results obtained for MET-PET are similar to FET-PET enabling non-invasive tumor grading. Sensitivity of FET - PET for glioblastoma is about 95% (gliomatosis cerebri can be false negative).

GBM is a large tumor which involves several lobes. The tumor is usually not sharply demarcated presenting with a broad and diffuse zone of infiltration. Tumors spread to the contralateral hemisphere through the corpus callosum displaying a symmetrical tumor growth into both hemispheres, i.e. butterfly GBM.

GBM shows a high diversity of cell forms (thus, the former term of “glioblastoma multiforme”) which include high density of small, poorly differentiated cells with marked polymorphism of tumor cells including multinucleated giant cells, anaplastic cells displaying astrocytic features, atypical mitoses, vascular endothelial cell proliferation. Typical tumor necroses, i.e. palisading with cells arranged side by side in rows and their processes directed towards a central area of necrosis and large areas of necroses.

Genome-wide analyses revealed that the TP53 (tumor protein 53) pathway, the RTK (receptor tyrosine kinase)/RAS/PI3K (phosphoinositide 3-kinase) pathway, both involved in the regulation of cellular growth, apoptosis and proliferation, and the RB1 (retinoblastoma) pathway, controlling the G1 to S phase transition in the cell cycle are affected by genetic aberrations in GBM.

Mutations of IDH1 involved in cytosolic NADPH production at codon 132 are found in secondary GBM while IDH1 wildtype is characteristic for primary GBM. Mutations in the IDH2 gene at chromosome position 15q26.1, encoding the mitochondrial isoenzyme isocitrate dehydrogenase 2 (IDH2), are found at a considerably lower frequency. Further mutations of the TERT promoter and ATRX, mutations affecting oncogenes/tumor suppressor genes and chromosomal aberrations are described. Primary and secondary glioblastomas can be characterized on genetic grounds. The molecular classification of GBM distinguishes four distinct subtypes, i.e. proneural, neural, classical, and mesenchymal. Further changes include changes in DNA methylation (especially of the MGMT gene), microRNAs and gene expression.

State of the art therapy is given by the STUPP scheme including after the surgical intervention focal radiation therapy (RT) (total of 60 Gy delivered as 30 sessions with 2 Gy dose for a duration of 6 weeks) and temozolomide (TMZ). Mean survival is around 18 months with a range between 2 and 92 months. Prognostic factors include among others age of the patient, Karnofsky performance score, amount of resected tumor tissue, MGMT methylation status (methylated promotor → better response to TMZ → better overall survival), IDH-1 mutation status (mutation → better overall survival), polymorphisms in genes including EGFR, TP53, carcinogen-metabolizing gene, immune function (e.g. interleukin-4), DNA repair, telomerase hTERT, and microRNA expression.

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  • Serge Weis
    • 1
  • Michael Sonnberger
    • 2
  • Andreas Dunzinger
    • 3
  • Eva Voglmayr
    • 2
  • Martin Aichholzer
    • 4
  • Raimund Kleiser
    • 2
  • Peter Strasser
    • 5
  1. 1.Division of Neuropathology, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  2. 2.Department of Neuroradiology, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  3. 3.Department of Neuro-Nuclear Medicine, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  4. 4.Department of Neurosurgery, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  5. 5.PMU University Institute for Medical & Chemical Laboratory DiagnosticsSalzburgAustria

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