Acta Neuropathologica Communications (Jan 2022)
Pleomorphic xanthoastrocytoma is a heterogeneous entity with pTERT mutations prognosticating shorter survival
- Azadeh Ebrahimi,
- Andrey Korshunov,
- Guido Reifenberger,
- David Capper,
- Joerg Felsberg,
- Elena Trisolini,
- Bianca Pollo,
- Chiara Calatozzolo,
- Marco Prinz,
- Ori Staszewski,
- Leonille Schweizer,
- Jens Schittenhelm,
- Patrick N. Harter,
- Werner Paulus,
- Christian Thomas,
- Patricia Kohlhof-Meinecke,
- Marcel Seiz-Rosenhagen,
- Till Milde,
- Belén M. Casalini,
- Abigail Suwala,
- Annika K. Wefers,
- Annekathrin Reinhardt,
- Philipp Sievers,
- Christof M. Kramm,
- Nima Etminam,
- Andreas Unterberg,
- Wolfgang Wick,
- Christel Herold-Mende,
- Dominik Sturm,
- Stefan M. Pfister,
- Martin Sill,
- David T. W. Jones,
- Daniel Schrimpf,
- David E. Reuss,
- Ken Aldape,
- Zied Abdullaev,
- Felix Sahm,
- Andreas von Deimling,
- Damian Stichel
Affiliations
- Azadeh Ebrahimi
- Department of Neuropathology, Institute of Pathology, University of Heidelberg
- Andrey Korshunov
- Department of Neuropathology, Institute of Pathology, University of Heidelberg
- Guido Reifenberger
- Institute of Neuropathology, Heinrich Heine University
- David Capper
- German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ)
- Joerg Felsberg
- Institute of Neuropathology, Heinrich Heine University
- Elena Trisolini
- Pathology Unit, Maggiore Della Carità Hospital
- Bianca Pollo
- Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta
- Chiara Calatozzolo
- Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta
- Marco Prinz
- Institute of Neuropathology, Faculty of Medicine, University of Freiburg
- Ori Staszewski
- Institute of Neuropathology, Faculty of Medicine, University of Freiburg
- Leonille Schweizer
- Department of Neuropathology, Charité-Universitaetsmedizin Berlin, Corporate Member of Freie Universitaet Berlin, Humboldt-Universitaet Zu Berlin, and Berlin Institute of Health
- Jens Schittenhelm
- Department of Neuropathology, Institute of Pathology and Neuropathology, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen
- Patrick N. Harter
- Institute of Neurology (Edinger Institute), Goethe University
- Werner Paulus
- Institute of Neuropathology, University Hospital Muenster
- Christian Thomas
- Institute of Neuropathology, University Hospital Muenster
- Patricia Kohlhof-Meinecke
- Department of Pathology, Katharinenhospital Stuttgart
- Marcel Seiz-Rosenhagen
- Department of Neurosurgery, Hospital Memmingen
- Till Milde
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Belén M. Casalini
- Department of Neuropathology, Institute of Pathology, University of Heidelberg
- Abigail Suwala
- Department of Neuropathology, Institute of Pathology, University of Heidelberg
- Annika K. Wefers
- Department of Neuropathology, Institute of Pathology, University of Heidelberg
- Annekathrin Reinhardt
- Department of Neuropathology, Institute of Pathology, University of Heidelberg
- Philipp Sievers
- Department of Neuropathology, Institute of Pathology, University of Heidelberg
- Christof M. Kramm
- Division of Pediatric Hematology and Oncology, University Medical Center Göttingen
- Nima Etminam
- Department of Neurosurgery, Medical Faculty Mannheim, University Hospital Mannheim, University of Heidelberg
- Andreas Unterberg
- Division of Experimental Neurosurgery, Department of Neurosurgery, Heidelberg University Hospital
- Wolfgang Wick
- Department of Neurology and Neurooncology Program, National Center for Tumor Diseases, Heidelberg University Hospital
- Christel Herold-Mende
- Division of Experimental Neurosurgery, Department of Neurosurgery, Heidelberg University Hospital
- Dominik Sturm
- Division of Pediatric Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ)
- Stefan M. Pfister
- Division of Pediatric Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ)
- Martin Sill
- Division of Pediatric Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ)
- David T. W. Jones
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
- Daniel Schrimpf
- Department of Neuropathology, Institute of Pathology, University of Heidelberg
- David E. Reuss
- Department of Neuropathology, Institute of Pathology, University of Heidelberg
- Ken Aldape
- Laboratory of Pathology, National Cancer Institute, Centre for Cancer Research
- Zied Abdullaev
- Laboratory of Pathology, National Cancer Institute, Centre for Cancer Research
- Felix Sahm
- Department of Neuropathology, Institute of Pathology, University of Heidelberg
- Andreas von Deimling
- Department of Neuropathology, Institute of Pathology, University of Heidelberg
- Damian Stichel
- Department of Neuropathology, Institute of Pathology, University of Heidelberg
- DOI
- https://doi.org/10.1186/s40478-021-01308-1
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 10
Abstract
Abstract Pleomorphic xanthoastrocytoma (PXA) in its classic manifestation exhibits distinct morphological features and is assigned to CNS WHO grade 2 or grade 3. Distinction from glioblastoma variants and lower grade glial and glioneuronal tumors is a common diagnostic challenge. We compared a morphologically defined set of PXA (histPXA) with an independent set, defined by DNA methylation analysis (mcPXA). HistPXA encompassed 144 tumors all subjected to DNA methylation array analysis. Sixty-two histPXA matched to the methylation class mcPXA. These were combined with the cases that showed the mcPXA signature but had received a histopathological diagnosis other than PXA. This cohort constituted a set of 220 mcPXA. Molecular and clinical parameters were analyzed in these groups. Morphological parameters were analyzed in a subset of tumors with FFPE tissue available. HistPXA revealed considerable heterogeneity in regard to methylation classes, with methylation classes glioblastoma and ganglioglioma being the most frequent mismatches. Similarly, the mcPXA cohort contained tumors of diverse histological diagnoses, with glioblastoma constituting the most frequent mismatch. Subsequent analyses demonstrated the presence of canonical pTERT mutations to be associated with unfavorable prognosis among mcPXA. Based on these data, we consider the tumor type PXA to be histologically more varied than previously assumed. Histological approach to diagnosis will predominantly identify cases with the established archetypical morphology. DNA methylation analysis includes additional tumors in the tumor class PXA that share similar DNA methylation profile but lack the typical morphology of a PXA. DNA methylation analysis also assist in separating other tumor types with morphologic overlap to PXA. Our data suggest the presence of canonical pTERT mutations as a robust indicator for poor prognosis in methylation class PXA.
Keywords
- Pleomorphic xanthoastrocytoma
- Ganglioglioma
- Epithelioid glioblastoma
- BRAF V600E
- pTERT mutation
- DNA methylation array profiling
