Pediatric high-grade gliomas and the WHO CNS Tumor Classification-Perspectives of pediatric neuro-oncologists and neuropathologists in light of recent updates

Gerrit H Gielen; Joshua N Baugh; Dannis G van Vuurden; Sophie E M Veldhuijzen van Zanten; Darren Hargrave; Maura Massimino; Veronica Biassoni; Andres Morales la Madrid; Michael Karremann; Maria Wiese; Ulrich Thomale; Geert O Janssens; André O von Bueren; Thomas Perwein; Gunther Nussbaumer; Eelco W Hoving; Pitt Niehusmann; Marco Gessi; Robert Kwiecien; Simon Bailey; Torsten Pietsch; Felipe Andreiuolo; Christof M Kramm

doi:10.1093/noajnl/vdac077

Pediatric high-grade gliomas and the WHO CNS Tumor Classification-Perspectives of pediatric neuro-oncologists and neuropathologists in light of recent updates

Neurooncol Adv. 2022 May 20;4(1):vdac077. doi: 10.1093/noajnl/vdac077. eCollection 2022 Jan-Dec.

Authors

Gerrit H Gielen¹, Joshua N Baugh², Dannis G van Vuurden², Sophie E M Veldhuijzen van Zanten², Darren Hargrave³, Maura Massimino⁴, Veronica Biassoni⁴, Andres Morales la Madrid⁵, Michael Karremann⁶, Maria Wiese⁷, Ulrich Thomale⁸, Geert O Janssens², André O von Bueren⁹, Thomas Perwein¹⁰, Gunther Nussbaumer¹⁰, Eelco W Hoving², Pitt Niehusmann¹¹, Marco Gessi¹², Robert Kwiecien¹³, Simon Bailey¹⁴, Torsten Pietsch¹, Felipe Andreiuolo¹, Christof M Kramm⁷

Affiliations

¹ Institute of Neuropathology, Medical Center Bonn, Bonn, Germany.
² Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
³ Great Ormond Street Hospital for Children, NHS Trust, London, UK.
⁴ Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan, Italy.
⁵ Pediatric Neuro-Oncology, Department of Pediatric Oncology, Hospital Sant Joan de Deu, Passeig Sant Joan de Déu 2, Barcelona, Spain.
⁶ Department of Pediatric and Adolescent Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁷ Division of Pediatric Hematology and Oncology , University Medical Center Goettingen, Goettingen, Germany.
⁸ Pediatric Neurosurgery, Charité Universitätsmedizin Berlin, Berlin, Germany.
⁹ Division of Pediatric Oncology and Hematology, Department of Women, Child and Adolescent, University Hospital of Geneva, Geneva, Switzerland.
¹⁰ Division of Pediatric Hemato-Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
¹¹ Department of Neuropathology, Oslo University Hospital, Oslo, Norway.
¹² Department of Pathology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
¹³ Institute of Biostatistics and Clinical Research, Faculty of Medicine, University of Münster, Münster, Germany.
¹⁴ Sir James Spence Institute of Child Health, Royal Victoria Infirmary, Newcastle upon Tyne, UK.

Abstract

Background: The WHO Classification of Tumors of the Central Nervous System has undergone major restructuring. Molecularly defined diagnostic criteria were introduced in 2016 (revised 4th edition) and expanded in 2021 (5th edition) to incorporate further essential diagnostic molecular parameters. We investigated potential differences between specialists in perception of these molecularly defined subtypes for pediatric high-grade gliomas (pedHGG).

Methods: We designed a 22-question survey studying the impact of the revised 4th edition of the WHO classification on pedHGG. Data were collected and statistically analyzed to examine the spectrum of viewpoints and possible differences between neuro-oncologists and neuropathologists.

Results: 465 participants from 53 countries were included; 187 pediatric neuro-oncologists (40%), 160 neuropathologists (34%), and 118 additional experts (26%). Neuro-oncologists reported issues with the introduction of molecularly defined tumor types, as well as the abolishment or renaming of established tumor entities, while neuropathologists did not to the same extent. Both groups indicated less relevant or insufficient diagnostic definitions were available in 2016. Reported issues were classified and assessed in the 2021 WHO classification and a substantial improvement was perceived. However, issues of high clinical relevance remain to be addressed, including the definition of clinical phenotypes for diffuse intrinsic pontine glioma and gliomatosis cerebri.

Conclusions: Within the WHO classification of pediatric brain tumors, such as pedHGG, rapid changes in molecular characterization have been introduced. This study highlights the ongoing need for cross talk between pathologist and oncologist to advance the classification of pedHGG subtypes and ensure biological relevance and clinical impact.

Keywords: DIPG; World Health Organization; diffuse midline glioma; pediatric high-grade glioma.