Acta Neuropathologica Communications (Oct 2019)
Tumors diagnosed as cerebellar glioblastoma comprise distinct molecular entities
- Annekathrin Reinhardt,
- Damian Stichel,
- Daniel Schrimpf,
- Christian Koelsche,
- Annika K. Wefers,
- Azadeh Ebrahimi,
- Philipp Sievers,
- Kristin Huang,
- M. Belén Casalini,
- Francisco Fernández-Klett,
- Abigail Suwala,
- Michael Weller,
- Dorothee Gramatzki,
- Joerg Felsberg,
- Guido Reifenberger,
- Albert Becker,
- Volkmar H. Hans,
- Marco Prinz,
- Ori Staszewski,
- Till Acker,
- Hildegard Dohmen,
- Christian Hartmann,
- Werner Paulus,
- Katharina Heß,
- Benjamin Brokinkel,
- Jens Schittenhelm,
- Rolf Buslei,
- Martina Deckert,
- Christian Mawrin,
- Ekkehard Hewer,
- Ute Pohl,
- Zane Jaunmuktane,
- Sebastian Brandner,
- Andreas Unterberg,
- Daniel Hänggi,
- Michael Platten,
- Stefan M. Pfister,
- Wolfgang Wick,
- Christel Herold-Mende,
- Andrey Korshunov,
- David E. Reuss,
- Felix Sahm,
- David T. W. Jones,
- David Capper,
- Andreas von Deimling
Affiliations
- Annekathrin Reinhardt
- Department of Neuropathology, University Hospital Heidelberg
- Damian Stichel
- Department of Neuropathology, University Hospital Heidelberg
- Daniel Schrimpf
- Department of Neuropathology, University Hospital Heidelberg
- Christian Koelsche
- Department of Neuropathology, University Hospital Heidelberg
- Annika K. Wefers
- Department of Neuropathology, University Hospital Heidelberg
- Azadeh Ebrahimi
- Department of Neuropathology, University Hospital Heidelberg
- Philipp Sievers
- Department of Neuropathology, University Hospital Heidelberg
- Kristin Huang
- Department of Neuropathology, University Hospital Heidelberg
- M. Belén Casalini
- Department of Neuropathology, University Hospital Heidelberg
- Francisco Fernández-Klett
- Department of Neuropathology, University Hospital Heidelberg
- Abigail Suwala
- Department of Neuropathology, University Hospital Heidelberg
- Michael Weller
- Department of Neurology, University Hospital and University of Zuerich
- Dorothee Gramatzki
- Department of Neurology, University Hospital and University of Zuerich
- Joerg Felsberg
- Institute for Neuropathology, Heinrich Heine University Duesseldorf
- Guido Reifenberger
- Institute for Neuropathology, Heinrich Heine University Duesseldorf
- Albert Becker
- Department of Neuropathology of the University of Bonn
- Volkmar H. Hans
- Institute for Neuropathology of the University of Essen
- Marco Prinz
- Institute of Neuropathology, Medical Faculty, University of Freiburg
- Ori Staszewski
- Institute of Neuropathology, Medical Faculty, University of Freiburg
- Till Acker
- Institute of Neuropathology, University of Giessen
- Hildegard Dohmen
- Institute of Neuropathology, University of Giessen
- Christian Hartmann
- Department for Neuropathology, Institute for Pathology, Hannover Medical School
- Werner Paulus
- Institute of Neuropathology, University Hospital Muenster
- Katharina Heß
- Institute of Neuropathology, University Hospital Muenster
- Benjamin Brokinkel
- Institute of Neuropathology, University Hospital Muenster
- Jens Schittenhelm
- Institute for Pathology and Neuropathology of the University of Tuebingen, Comprehensive Cancer Center Tuebingen
- Rolf Buslei
- Institute for Pathology, Sozialstiftung Bamberg
- Martina Deckert
- Department of Neuropathology, University Hospital of Cologne
- Christian Mawrin
- Institute for Neuropathology of the University of Magdeburg
- Ekkehard Hewer
- Institute of Pathology, University of Bern
- Ute Pohl
- Department of Cellular Pathology, Queen’s Hospital
- Zane Jaunmuktane
- Department of Molecular Neuroscience, UCL Queen Square Institute of Neurology
- Sebastian Brandner
- Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology
- Andreas Unterberg
- Clinic for Neurosurgery, University Hospital Heidelberg
- Daniel Hänggi
- Clinic for Neurosurgery, University of Mannheim
- Michael Platten
- Department of Neurology, Medical Faculty Mannheim, Heidelberg University
- Stefan M. Pfister
- Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ)
- Wolfgang Wick
- Neurology Clinic, University of Heidelberg Medical Center
- Christel Herold-Mende
- Division of Experimental Neurosurgery, Department of Neurosurgery, Ruprecht-Karls-University Heidelberg
- Andrey Korshunov
- Department of Neuropathology, University Hospital Heidelberg
- David E. Reuss
- Department of Neuropathology, University Hospital Heidelberg
- Felix Sahm
- Department of Neuropathology, University Hospital Heidelberg
- David T. W. Jones
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- David Capper
- Department of Neuropathology, University Hospital Heidelberg
- Andreas von Deimling
- Department of Neuropathology, University Hospital Heidelberg
- DOI
- https://doi.org/10.1186/s40478-019-0801-8
- Journal volume & issue
-
Vol. 7,
no. 1
pp. 1 – 12
Abstract
Abstract 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.
Keywords
- Cerebellar glioblastoma
- Methylation-based classification
- Copy number variation load
- Anaplastic pilocytic astrocytoma
- Anaplastic astrocytoma with piloid features
- Integrated diagnosis
