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Tumors diagnosed as cerebellar glioblastoma comprise distinct molecular entities.

  • Reinhardt A Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
  • Stichel D Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
  • Schrimpf D Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
  • Koelsche C Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
  • Wefers AK Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
  • Ebrahimi A Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
  • Sievers P Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
  • Huang K Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
  • Casalini MB Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
  • Fernández-Klett F Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
  • Suwala A Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
  • Weller M Department of Neurology, University Hospital and University of Zuerich, Zuerich, Switzerland.
  • Gramatzki D Department of Neurology, University Hospital and University of Zuerich, Zuerich, Switzerland.
  • Felsberg J Institute for Neuropathology, Heinrich Heine University Duesseldorf, Duesseldorf, Germany.
  • Reifenberger G Institute for Neuropathology, Heinrich Heine University Duesseldorf, Duesseldorf, Germany.
  • Becker A Department of Neuropathology of the University of Bonn, Bonn, Germany.
  • Hans VH Institute for Neuropathology of the University of Essen, Essen, Germany.
  • Prinz M Institute of Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.
  • Staszewski O Institute of Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.
  • Acker T Institute of Neuropathology, University of Giessen, Giessen, Germany.
  • Dohmen H Institute of Neuropathology, University of Giessen, Giessen, Germany.
  • Hartmann C Department for Neuropathology, Institute for Pathology, Hannover Medical School, Hannover, Germany.
  • Paulus W Institute of Neuropathology, University Hospital Muenster, Muenster, Germany.
  • Heß K Institute of Neuropathology, University Hospital Muenster, Muenster, Germany.
  • Brokinkel B Institute of Neuropathology, University Hospital Muenster, Muenster, Germany.
  • Schittenhelm J Institute for Pathology and Neuropathology of the University of Tuebingen, Comprehensive Cancer Center Tuebingen, Tuebingen, Germany.
  • Buslei R Institute for Pathology, Sozialstiftung Bamberg, Bamberg, Germany.
  • Deckert M Department of Neuropathology, University Hospital of Cologne, Cologne, Germany.
  • Mawrin C Institute for Neuropathology of the University of Magdeburg, Magdeburg, Germany.
  • Hewer E Institute of Pathology, University of Bern, Bern, Switzerland.
  • Pohl U Department of Cellular Pathology, Queen's Hospital, Romford, UK.
  • Jaunmuktane Z Department of Molecular Neuroscience, UCL Queen Square Institute of Neurology, Queen Square, London, UK.
  • Brandner S Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London, UK.
  • Unterberg A Clinic for Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany.
  • Hänggi D Clinic for Neurosurgery, University of Mannheim, Mannheim, Germany.
  • Platten M Department of Neurology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Pfister SM Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Wick W Neurology Clinic, University of Heidelberg Medical Center, Heidelberg, Germany.
  • Herold-Mende C Division of Experimental Neurosurgery, Department of Neurosurgery, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany.
  • Korshunov A Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
  • Reuss DE Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
  • Sahm F Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
  • Jones DTW Hopp Children's Cancer Center Heidelberg (KiTZ), 69120, Heidelberg, Germany.
  • Capper D Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
  • von Deimling A Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany. andreas.vondeimling@med.uni-heidelberg.de.
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  • 2019-10-30
Published in:
  • Acta neuropathologica communications. - 2019
Anaplastic astrocytoma with piloid features
Anaplastic pilocytic astrocytoma
Cerebellar glioblastoma
Copy number variation load
Integrated diagnosis
Methylation-based classification
Adolescent
Adult
Aged
Aged, 80 and over
Cerebellar Neoplasms
Child
Child, Preschool
Cyclin-Dependent Kinase Inhibitor p16
ErbB Receptors
Female
Glioblastoma
Humans
Infant
Infant, Newborn
Infratentorial Neoplasms
Male
Methylation
Middle Aged
Retrospective Studies
Telomerase
Young Adult
English In this multi-institutional study we compiled a retrospective cohort of 86 posterior fossa tumors having received the diagnosis of cerebellar glioblastoma (cGBM). All tumors were reviewed histologically and subjected to array-based methylation analysis followed by algorithm-based classification into distinct methylation classes (MCs). The single MC containing the largest proportion of 25 tumors diagnosed as cGBM was MC anaplastic astrocytoma with piloid features representing a recently-described molecular tumor entity not yet included in the WHO Classification of Tumours of the Central Nervous System (WHO classification). Twenty-nine tumors molecularly corresponded to either of 6 methylation subclasses subsumed in the MC family GBM IDH wildtype. Further we identified 6 tumors belonging to the MC diffuse midline glioma H3 K27 M mutant and 6 tumors allotted to the MC IDH mutant glioma subclass astrocytoma. Two tumors were classified as MC pilocytic astrocytoma of the posterior fossa, one as MC CNS high grade neuroepithelial tumor with BCOR alteration and one as MC control tissue, inflammatory tumor microenvironment. The methylation profiles of 16 tumors could not clearly be assigned to one distinct MC. In comparison to supratentorial localization, the MC GBM IDH wildtype subclass midline was overrepresented, whereas the MCs GBM IDH wildtype subclass mesenchymal and subclass RTK II were underrepresented in the cerebellum. Based on the integration of molecular and histological findings all tumors received an integrated diagnosis in line with the WHO classification 2016. In conclusion, cGBM does not represent a molecularly uniform tumor entity, but rather comprises different brain tumor entities with diverse prognosis and therapeutic options. Distinction of these molecular tumor classes requires molecular analysis. More than 30% of tumors diagnosed as cGBM belong to the recently described molecular entity of anaplastic astrocytoma with piloid features.
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  • English
Open access status
gold
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https://sonar.ch/global/documents/279132
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