Anaplastic ganglioglioma-A diagnosis comprising several distinct tumour types

Annekathrin Reinhardt; Kristin Pfister; Daniel Schrimpf; Damian Stichel; Felix Sahm; David E Reuss; David Capper; Annika K Wefers; Azadeh Ebrahimi; Martin Sill; Joerg Felsberg; Guido Reifenberger; Albert Becker; Marco Prinz; Ori Staszewski; Christian Hartmann; Jens Schittenhelm; Dorothee Gramatzki; Michael Weller; Adriana Olar; Elisabeth Jane Rushing; Markus Bergmann; Michael A Farrell; Ingmar Blümcke; Roland Coras; Jan Beckervordersandforth; Se Hoon Kim; Fabio Rogerio; Petia S Dimova; Pitt Niehusmann; Andreas Unterberg; Michael Platten; Stefan M Pfister; Wolfgang Wick; Christel Herold-Mende; Andreas von Deimling

doi:10.1111/nan.12847

Anaplastic ganglioglioma-A diagnosis comprising several distinct tumour types

Neuropathol Appl Neurobiol. 2022 Dec;48(7):e12847. doi: 10.1111/nan.12847. Epub 2022 Sep 16.

Authors

Annekathrin Reinhardt^{1

2}, Kristin Pfister^{1

2

3}, Daniel Schrimpf^{1

2}, Damian Stichel^{1

2}, Felix Sahm^{1

2}, David E Reuss^{1

2}, David Capper^{4

5}, Annika K Wefers^{1

2

6}, Azadeh Ebrahimi^{1

2

7}, Martin Sill^{8

9}, Joerg Felsberg¹⁰, Guido Reifenberger^{10

11}, Albert Becker⁷, Marco Prinz^{12

13

14}, Ori Staszewski¹², Christian Hartmann¹⁵, Jens Schittenhelm¹⁶, Dorothee Gramatzki¹⁷, Michael Weller¹⁷, Adriana Olar¹⁸, Elisabeth Jane Rushing¹⁹, Markus Bergmann²⁰, Michael A Farrell²¹, Ingmar Blümcke²², Roland Coras²², Jan Beckervordersandforth²³, Se Hoon Kim²⁴, Fabio Rogerio²⁵, Petia S Dimova²⁶, Pitt Niehusmann²⁷, Andreas Unterberg²⁸, Michael Platten^{29

30}, Stefan M Pfister^{8

9

31

32}, Wolfgang Wick^{8

33}, Christel Herold-Mende³⁴, Andreas von Deimling^{1

2

8}

Affiliations

¹ Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.
² Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
³ Institute of Pathology, Kantonsspital Winterthur, Winterthur, Switzerland.
⁴ Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
⁵ German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁶ Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁷ Department of Neuropathology, University of Bonn, Bonn, Germany.
⁸ German Cancer Consortium (DKTK), Core Center Heidelberg, Heidelberg, Germany.
⁹ Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
¹⁰ Institute of Neuropathology, Heinrich Heine University, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany.
¹¹ German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹² Institute of Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.
¹³ Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, Freiburg, Germany.
¹⁴ Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.
¹⁵ Department of Neuropathology, Hannover Medical School, Hanover, Germany.
¹⁶ Institute of Pathology and Neuropathology, Comprehensive Cancer Center Tübingen, University Tübingen, Tübingen, Germany.
¹⁷ Department of Neurology, University Hospital and University Zürich, Zürich, Switzerland.
¹⁸ NOMIX Laboratories, Denver, Colorado, USA.
¹⁹ Institute of Neuropathology, University Hospital Zürich (USZ), Zürich, Switzerland.
²⁰ Institute of Neuropathology, Center for Pathology, Klinikum Bremen Mitte, Bremen, Germany.
²¹ Department of Neuropathology, Beaumont Hospital, Dublin, Ireland.
²² Department of Neuropathology, University Hospital Erlangen, Member of EpiCARE ERN, Erlangen, Germany.
²³ Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
²⁴ Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea.
²⁵ Department of Pathology, University of Campinas (UNICAMP), Campinas, Brazil.
²⁶ Epilepsy Surgery Center, Department of Neurosurgery, St. Ivan Rilski University Hospital, Sofia, Bulgaria.
²⁷ Section of Neuropathology, Department of Pathology, Oslo University Hospital, Oslo, Norway.
²⁸ Clinic for Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany.
²⁹ Department of Neurology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
³⁰ Clinical Cooperation Unit Neuroimmunology and Brain Tumour Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
³¹ Division of Paediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
³² Department of Paediatric Oncology and Hematology, University Hospital Heidelberg, Heidelberg, Germany.
³³ Neurology Clinic, University Hospital Heidelberg, Heidelberg, Germany.
³⁴ Division of Experimental Neurosurgery, Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany.

PMID: 35977725
DOI: 10.1111/nan.12847

Abstract

Aims: Anaplastic ganglioglioma is a rare tumour, and diagnosis has been based on histological criteria. The 5th edition of the World Health Organization Classification of Tumours of the Central Nervous System (CNS WHO) does not list anaplastic ganglioglioma as a distinct diagnosis due to lack of molecular data in previous publications. We retrospectively compiled a cohort of 54 histologically diagnosed anaplastic gangliogliomas to explore whether the molecular profiles of these tumours represent a separate type or resolve into other entities.

Methods: Samples were subjected to histological review, desoxyribonucleic acid (DNA) methylation profiling and next-generation sequencing. Morphological and molecular data were summarised to an integrated diagnosis.

Results: The majority of tumours designated as anaplastic gangliogliomas resolved into other CNS WHO diagnoses, most commonly pleomorphic xanthoastrocytoma (16/54), glioblastoma, isocitrate dehydrogenase protein (IDH) wild type and diffuse paediatric-type high-grade glioma, H3 wild type and IDH wild type (11 and 2/54), followed by low-grade glial or glioneuronal tumours including pilocytic astrocytoma, dysembryoplastic neuroepithelial tumour and diffuse leptomeningeal glioneuronal tumour (5/54), IDH mutant astrocytoma (4/54) and others (6/54). A subset of tumours (10/54) was not assignable to a CNS WHO diagnosis, and common molecular profiles pointing to a separate entity were not evident.

Conclusions: In summary, we show that tumours histologically diagnosed as anaplastic ganglioglioma comprise a wide spectrum of CNS WHO tumour types with different prognostic and therapeutic implications. We therefore suggest assigning this designation with caution and recommend comprehensive molecular workup.

Keywords: DNA methylation analysis; anaplastic ganglioglioma; ganglioglioma; methylation class; molecular glioma entities; molecular neuropathology.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Astrocytoma* / pathology
Brain Neoplasms* / genetics
Central Nervous System Neoplasms* / pathology
Child
Ganglioglioma* / pathology
Glioma* / pathology
Humans
Isocitrate Dehydrogenase
Retrospective Studies

Substances

Isocitrate Dehydrogenase