Ebook Oxford textbook of neuro-oncology: Part 1

Oxford Textbook of

Neuro-Oncology

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Oxford Textbook of

Neuro-Oncology
Edited by

Tracy T. Batchelor
Count Giovanni Auletta Armenise-Harvard Professor of
Neurology, Harvard Medical School, Executive Director,
Stephen E. and Catherine Pappas Center for NeuroOncology, Massachusetts General Hospital; Associate
Clinical Director, Massachusetts General Hospital
Cancer Center; Co-Leader, Neuro-Oncology Program,
Dana-Farber/Harvard Cancer Center, Boston, MA, USA

Ryo Nishikawa
Professor and Chair, Department of Neurosurgery, Head,
Department of Neuro-Oncology, Comprehensive Cancer
Center, International Medical Center, Saitama Medical
University, Saitama, Japan

Nancy J. Tarbell
CC Wang Professor of Radiation Oncology, Dean for
Academic and Clinical Affairs, Harvard Medical School,
Boston, MA, USA

Michael Weller
Professor and Chairman, Department of Neurology,
University Hospital and University of Zurich, Zurich,
Switzerland

Series Editor

Christopher Kennard
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7


Foreword

During my 50 years of laboratory research and caring for patients with
central nervous system (CNS) tumours, I have witnessed and participated
in many developments that at first seemed promising, but dead-ended in
disappointing blind alleys; fortunately, others resulted in greater
knowledge and clarity about CNS diseases as well as improved outcomes.
Over the years, books published on CNS cancer and its treatment were
met with mixed reviews by small audiences, but, nonetheless, helped
educate multiple generations of physicians and scientists. When I began
my career, I was one of very few in the world willing to focus on CNS
cancer research and treatment. Learning from books and experts in other
fields helped in that process. Book chapters, being less constrained than
articles, can provide more contextual information for the reader than a
single article can provide. In my view, a book is frequently the best vehicle

for educating others. After moving to Houston, Texas, United States, to
become Chair of the Department of Neuro-Oncology at The University of
Texas MD Anderson Cancer Center, I wanted to write a textbook, which
became Cancer in the Nervous System (1996, 2002, Oxford University
Press), to educate a new generation of neuro-oncologists and address
problems in treatment as well as concerns about symptom management for
tumour- and treatment-related effects.
We are now at another crossroads in information because of the
explosion of molecular and genetic studies that affect the way we classify
tumours and, in turn, how we treat the considerable number of rare benign
and malignant tumours of the CNS. I believe this novel paradigm was why
so many senior international authors from the multiple specialties essential
to our field took the time to create this well-structured and highly
informative book. This book brings together the changing neuropathology
landscape, important molecular–genetic drivers of these tumours, and
provides thoughtful discussions by experts on how best to treat and
manage patients afflicted with these rare tumours. Each generation must
strive to educate the next generation of clinicians and scientists if we are to
make progress in the care of our patients. This requires a book, such as the
Oxford Textbook of Neuro-Oncology, to bring together the relevance of
8


pathology, molecular–genetic associations, prospective clinical trials, and
the experiential insights gained by experts who have treated the very rare
tumours absent from formal clinical trials. This panoply of knowledge is
well conveyed in this textbook. Taken together, it informs and affects how
these tumours are understood today and how best to approach their diverse
treatments.
This 21-chapter book, modeled after the World Health Organization

classification of central nervous system tumors, takes a ‘meet the
professor’ approach. It provides a framework to assist the reader prepare to
understand how we treat and inform patients with respect to treatment
options and prognosis when new molecular–genetic knowledge is
revealed. Is this textbook the last word? Certainly not, but it is the current
word and, as such, deserves a special place in the library of those who care
for individuals with CNS tumours and those who research possibilities for
improving their survival.
Victor A. Levin, M.D.
Emeritus Professor, Department of Neuro-Oncology,
The University of Texas,
MD Anderson Cancer Center, Houston, TX, USA
Clinical Professor, Department of Neurosurgery, University of
California San Francisco, San Francisco, CA, USA

9


Preface

The practice of neuro-oncology entails the management of many different
types of tumours of the nervous system by a multidisciplinary team of
healthcare providers. These tumours represent a diverse spectrum of
underlying molecular biological subtypes, prognostic categories, age
distributions, and treatment recommendations. The World Health
Organization (WHO) classification of central nervous system tumours is
the foundation for the categorization and, by extension, clinical
management and treatment of patients with all types of nervous system
tumours. The WHO classification has traditionally been based on light
microscopic description of the cellular elements of tumours in the brain,

spinal cord, nerves, and meninges. The 2016 WHO classification of central
nervous system tumours for the first time incorporates molecular markers
into the categorization of some types of nervous system tumours,
particularly gliomas. This revised classification will serve as the basis for
future clinical trials and, ultimately, management recommendations for
these newly recognized pathological-molecular subsets of central nervous
system tumours. Current management guidelines are derived, however,
from clinical trials and studies utilizing earlier versions of the WHO
classification system. This book is intended for clinicians as a complement
to the WHO classification system with a focus on clinical management of
nervous system tumours in adults and children. Each chapter is coauthored by a multidisciplinary, international group of leading authorities
in adult and paediatric neuro-oncology. The book is organized according
to the 2007 WHO classification of central nervous system tumours and
each chapter follows a similar framework. The introductory chapter
reviews the 2016 revision of the WHO classification of central nervous
system tumours and how these changes may influence future clinical trials,
clinical practice, and subsequent editions of this book.
Tracy T. Batchelor
Ryo Nishikawa
Nancy J. Tarbell
Michael Weller
10


Contents

Abbreviations
Contributors
1 The 2016 revision of the WHO classification of tumours of the
central nervous system

Paul Kleihues, Elisabeth Rushing, and Hiroko Ohgaki
2 Astrocytic tumours: pilocytic astrocytoma, pleomorphic
xanthoastrocytoma, and subependymal giant cell astrocytoma
Brian P. O’Neill, Jeffrey Allen, Mitchell S. Berger, and Rolf–Dieter
Kortmann
3 Astrocytic tumours: diffuse astrocytoma, anaplastic astrocytoma,
glioblastoma, and gliomatosis cerebri
Michael Weller, Michael Brada, Tai–Tong Wong, and Michael A.
Vogelbaum
4 Oligodendroglial tumours
Wolfgang Wick, Colin Watts, and Minesh P. Mehta
5 Ependymal tumours
Mark R. Gilbert and Roberta Rudà
6 Choroid plexus tumours
Maria Santos, Eric Bouffet, Carolyn Freeman, and Mark M.
Souweidane
7 Other neuroepithelial tumours: astroblastoma, angiocentric
glioma, and chordoid glioma
Martin J. van den Bent, Frederic Dhermain, and Walter Stummer
8 Neuronal and mixed neuronal–glial tumours
Riccardo Soffietti, Hugues Duffau, Glenn Bauman, and David Walker
9 Embryonal and pineal tumours
Roger E. Taylor, Barry L. Pizer, Nancy J. Tarbell, Alba A. Brandes,
and Stephen Lowis
11


10 Tumours of the cranial nerves
Joerg–Christian Tonn and Douglas Kondziolka
11 Meningiomas

Rakesh Jalali, Patrick Y. Wen, and Takamitsu Fujimaki
12 Other tumours of the meninges
M. Yashar S. Kalani, Sith Sathornsumetee, and Charles Teo
13 Tumours of the haematopoietic system
Tracy T. Batchelor, Oussama Abla, Zhong–ping Chen, Dennis C.
Shrieve, and Samar Issa
14 Germ cell tumours
Claire Alapetite, Takaaki Yanagisawa, and Ryo Nishikawa
15 Familial tumour syndromes: neurofibromatosis, schwannomatosis,
rhabdoid tumour predisposition, Li–Fraumeni syndrome, Turcot
syndrome, Gorlin syndrome, and Cowden syndrome
Scott R. Plotkin, Jaclyn A. Biegel, David Malkin, Robert L. Martuza,
and D. Gareth Evans
16 Familial tumour syndromes: von Hippel–Lindau disease
Hiroshi Kanno and Joachim P. Steinbach
17 Familial tumour syndromes: tuberous sclerosis complex
Howard Weiner and Peter B. Crino
18 Pituitary tumours
Edward R. Laws, Jr, Whitney W. Woodmansee, and Jay S. Loeffler
19 Metastatic brain tumours
Matthias Preusser, Gabriele Schackert, and Brigitta G. Baumert
20 Metastatic tumours: spinal cord, plexus, and peripheral nerve
David Schiff, Jonathan Sherman, and Paul D. Brown
21 Neoplastic meningitis: metastases to the leptomeninges and
cerebrospinal fluid
Marc C. Chamberlain, Stephanie E. Combs, and Soichiro Shibui
Index

12

Abbreviations

5-ALA
AED
ASCT
CBTRUS
CBV
CCG
CHOP
CI
CNS
COG
CPC
CPP
CPT
CR
CSF
CSI
CSRT
CT
DI
DIA
DIG
DIPG
DLBCL
DNET
EANO
EBRT
ED

EFS
EGFR
EMA

5-aminolevulinic acid
antiepileptic drug
autologous stem cell transplantation
Central Brain Tumor Registry of the United States
cerebral blood volume
Children’s Cancer Group
cyclophosphamide, doxorubicin, vincristine, and prednisone
confidence interval
central nervous system
Children’s Oncology Group
choroid plexus carcinoma
choroid plexus papilloma
choroid plexus tumour
complete response
cerebrospinal fluid
craniospinal irradiation
craniospinal radiotherapy
computed tomography
diabetes insipidus
desmoplastic infantile astrocytoma
desmoplastic infantile ganglioglioma
diffuse intrinsic pontine glioma
diffuse large B-cell lymphoma
dysembryoplastic neuroepithelial tumour
European Association for Neuro-Oncology
external beam radiotherapy

Erdheim–Chester disease
event-free survival
epidermal growth factor receptor
epithelial membrane antigen
13


EOR
EORTC
ESCC
ETMR
FAP
FLAIR
GC
GFAP
GG
GH
GTR
HAART
HAR
HDT
HFRT
HIV
HL
HNPCC
IARC
IDH
IELSG
iGCT
IPCG

ISCM
JXG
KPS
LDD
LEAT
MB
MGMT
MPNST
MRI
MRS
mTOR
NCCN
NF
NGGCT

extent of resection
European Organization for Research and Treatment of Cancer
epidural spinal cord compression
embryonal tumour with multilayer rosettes
familial adenomatous polyposis
fluid-attenuated inversion recovery
gangliocytoma
glial fibrillary acidic protein
ganglioglioma
growth hormone
gross total resection
highly active antiretroviral therapy
hyperfractionated accelerated radiotherapy
high-dose therapy
hyperfractionated radiotherapy

human immunodeficiency virus
Hodgkin’s lymphoma
hereditary nonpolyposis colorectal cancer
International Agency for Research on Cancer
isocitrate dehydrogenase
International Extranodal Lymphoma Study Group
intracranial germ cell tumour
International PCNSL Collaborative Group
intramedullary spinal cord metastasis
juvenile xanthogranuloma
Karnofsky performance score
Lhermitte–Duclos disease
long-term epilepsy-associated tumour
medulloblastoma
O6-methylguanine-DNA methyltransferase
malignant peripheral nerve sheath tumour
magnetic resonance imaging
magnetic resonance spectroscopy
mammalian target of rapamycin
National Comprehensive Cancer Network
neurofibromatosis
non-germinomatous germ cell tumour
14


NHL
NIH
NK
NM
NOA

non-Hodgkin’s lymphoma
National Institutes of Health
natural killer
neoplastic meningitis
Neuro-Onkologische Arbeitsgemeinschaft/German NeuroOncology Group
NSCLC non-small cell lung cancer
NSE
neuron-specific enolase
ONG
optic nerve glioma
ONSM optic nerve sheath meningioma
OS
overall survival
PA
pilocytic astrocytoma
PCNSL primary central nervous system lymphoma
PCV
procarbazine, CCNU (lomustine), and vincristine
PET
positron emission tomography
PFS
progression-free survival
PNET
primitive neuroectodermal tumour
PPT
primary parenchymal tumour
PTEN
phosphatase and tensin homologue
PXA

pleomorphic xanthoastrocytoma
RDD
Rosai–Dorfman disease
RGNT rosette-forming glioneuronal tumour
RTOG Radiation Therapy Oncology Group
SBRT
stereotactic body radiotherapy
SEER
Surveillance, Epidemiology and End Results
SEGA
subependymal giant cell astrocytoma
SFOP
Société Française d’Oncologie Pédiatrique/French Pediatric
Oncology Society
SFT
solitary fibrous tumour
SIOP
International Society of Paediatric Oncology
SRS
stereotactic radiosurgery
SRT
stereotactic radiotherapy
TSC
tuberous sclerosis complex
UKCCSG United Kingdom Children’s Cancer Study Group
VAD
ventricular access device
VPS
ventriculoperitoneal shunt
WBRT whole-brain radiotherapy

15


WHO

World Health Organization

16


Contributors

Oussama Abla, Staff Oncologist, Division of Haematology/Oncology,
Department of Paediatrics, The Hospital for Sick Children, Toronto, ON,
Canada; Associate Professor of Paediatrics, University of Toronto, ON,
Canada
Claire Alapetite, Institut Curie, Radiation Oncology Department, Paris &
Proton Therapy Center, Orsay, France
Jeffrey Allen, Otto and Marguerite Manley and Making Headway
Foundation Professor of Pediatric Neuro-Oncology, Department of
Pediatrics; Professor, Department of Neurology, NYU Langone Medical
Center, New York, USA
Tracy T. Batchelor, Count Giovanni Auletta Armenise-Harvard Professor
of Neurology, Harvard Medical School, Executive Director, Stephen E.
and Catherine Pappas Center for Neuro-Oncology, Massachusetts General
Hospital, Associate Clinical Director (Academic Affairs), Massachusetts
General Hospital Cancer Center, Co-Leader, Neuro-Oncology Program,
Dana-Farber/Harvard Cancer Center, Boston, MA, USA
Glenn Bauman, Department of Oncology, Western University and
London Regional Cancer Program, London, ON, Canada

Brigitta G. Baumert, Department of Radiation Oncology and Clinical
Cooperation Unit Neurooncology, MediClin Robert Janker Clinic &
University of Bonn Medical Center, Bonn, Germany
Martin J. van den Bent, Neuro-oncology Unit, The Brain Tumor Center
at Erasmus MC Cancer Institute, Rotterdam, The Netherlands
Mitchell S. Berger, Professor and Chairman, Department of Neurological
Surgery, Bethold and Belle N. Guggenheim Endowed Chair, Director,
Brain Tumor Research Center, University of California, San Francisco,
CA, USA
Jaclyn A. Biegel, Chief, Division of Genomic Medicine, Director, Center
for Personalized Medicine, Department of Pathology and Laboratory
17


Medicine, Children’s Hospital Los Angeles, Professor of Clinical
Pathology (Clinical Scholar), USC Keck School of Medicine, Los
Angeles, CA, USA
Eric Bouffet, Professor of Paediatrics, Director, Brain Tumour Program,
The Hospital for Sick Children, Toronto, ON, Canada
Michael Brada, University of Liverpool, Department of Molecular &
Clinical Cancer Medicine and Department of Radiation Oncology,
Clatterbridge Cancer Centre, Wirral, UK
Alba A. Brandes, Chair, Medical Oncology Department, AUSL-IRCCS
Institute of Neurological Sciences, Bologna, Italy
Paul D. Brown, Department of Radiation Oncology, Mayo Clinic,
Rochester, MN, USA
Marc C. Chamberlain, University of Washington, Department of
Neurology and Neurological Surgery, Division of Neuro-Oncology, Fred
Hutchinson Research Cancer Center, Seattle Cancer Care Alliance, Seattle,
WA, USA

Zhong–ping Chen, Professor and Chairman, Department of Neurosurgery
and Neuro-oncology, Sun Yat-Sen University Cancer Center, Guangzhou,
China
Stephanie E. Combs, Institute of Innovative Radiotherapy (IRT),
Department of Radiation Sciences (GAS), Helmholtz Zentrum München,
Oberschleißheim, Germany
Peter B. Crino, Professor and Chairman, Department of Neurology,
University of Maryland School of Medicine, Baltimore, MD, USA
Frederic Dhermain, Department of Radiation Oncology, Gustave Roussy
University Hospital, Cancer Campus Grand Paris, France
Hugues Duffau, Department of Neurosurgery, Gui de Chauliac Hospital,
Montpellier, Montpellier, France
D. Gareth Evans, Department of Genomic Medicine, MAHSC,
University of Manchester, Division of Evolution and Genomic Medicine,
St Mary’s Hospital, Manchester, UK
Carolyn Freeman, Professor of Oncology and Pediatrics and Mike
Rosenbloom Chair of Radiation Oncology, Department of Radiation
Oncology, McGill University Health Centre, Montreal, QC, Canada

18


Takamitsu Fujimaki, Professor, Department of Neurosurgery Saitama
Medical University, Japan
Mark R. Gilbert, Director, Neuro-Oncology Branch, National Cancer
Institute and National Institute of Neurologic Disorders and Stroke,
National Institutes of Health, Bethesda, MD, USA
Samar Issa, Consultant Haematologist, Clinical Head, Lymphoma
Services, Founding Chair, Lymphoma Network of New Zealand, Member,
Scientific Advisory Committee, Auckland Regional Tissue Bank,

Honorary Academic, Department of Molecular Medicine & Pathology,
University of Auckland School of Medicine, Middlemore Hospital,
Auckland, New Zealand
Rakesh Jalali, Professor of Radiation Oncology, Tata Memorial Hospital,
Mumbai, India
M. Yashar S. Kalani, Department of Neurosurgery, University of Utah
School of Medicine, Salt Lake City, UT, USA
Hiroshi Kanno, Department of Neurosurgery, International University of
Health and Welfare Atami Hospital, Atami, Japan
Paul Kleihues, Medical Faculty, University of Zurich, Zurich, Switzerland
Douglas Kondziolka, NYU Langone Medical Center, NYU Neurosurgery
Associates, New York, USA
Rolf–Dieter Kortmann, Department of Radiation Oncology, Leipzig,
Germany
Edward R. Laws, Jr, Department of Neurosurgery, Brigham and
Women’s Hospital and Harvard Medical School, Boston, MA, USA
Jay S. Loeffler, Joan and Herman Suit Professor of Radiation Oncology,
Departments of Neurosurgery and Radiation Oncology, Chair, Department
of Radiation Oncology, Massachusetts General Hospital and Harvard
Medical School, Boston, MA, USA
Stephen Lowis, MacMillan Consultant in Paediatric and Adolescent
Oncology, Department of Paediatric Haematology, Oncology and BMT,
Bristol Royal Hospital for Children, Bristol, UK
David Malkin, Professor, Department of Paediatrics, University of
Toronto, Senior Oncologist, Division of Haematology/Oncology, Senior
Scientist, Genetics and Genome Biology Program, The Hospital for Sick
Children, Toronto, ON, Canada
19

Robert L. Martuza, William and Elizabeth Sweet Professor in
Neuroscience, Harvard Medical School, Department of Neurosurgery,
Massachusetts General Hospital, Boston, MA, USA
Minesh P. Mehta, Deputy Director and Chief of Radiation Oncology,
Miami Cancer Institute, Miami, FL, USA
Ryo Nishikawa, Professor and Chair, Department of Neurosurgery; Head,
Department of Neuro-Oncology, Comprehensive Cancer Center,
International Medical Center, Saitama Medical University, Saitama, Japan
Brian P. O’Neill, Professor of Neurology, Department of Neurology,
Mayo Clinic, Rochester, MN, USA
Hiroko Ohgaki, Molecular Pathology Section, International Agency for
Research on Cancer (IARC), Lyon, France
Barry L. Pizer, Consultant Paediatric Oncologist, Alder Hey Children’s
Hospital; Honorary Professor, Institute of Translational Medicine,
University of Liverpool, UK
Scott R. Plotkin, Professor of Neurology, Associate Director, Stephen E.
and Catherine Pappas Center for Neuro-Oncology, Massachusetts General
Hospital and Harvard Medical School, Boston, MA, USA
Matthias Preusser, Department of Medicine I and Comprehensive Cancer
Center, Medical University of Vienna, Vienna, Austria
Roberta Rudà, Division of Neuro-Oncology, Departments of
Neuroscience and Oncology, University and San Giovanni Battista
Hospital, Turin, Italy
Elisabeth Rushing, Institute of Neuropathology, University Hospital
Zurich, Zurich, Switzerland
Maria Santos, Neurosurgery Department, University Hospital of Santa
Maria, Lisbon, Portugal
Sith Sathornsumetee, Associate Professor and Director of NeuroOncology Program, Department of Medicine (Neurology), Faculty of
Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Gabriele Schackert, Department of Neurosurgery, University of Dresden,

Germany
David Schiff, Departments of Neurology, Neurological Surgery, and
Medicine (Hematology-Oncology), University of Virginia, Charlottesville,
20


VA, USA
Jonathan Sherman, Department of Neurological Surgery, George
Washington University, Washington, DC, USA
Soichiro Shibui, Department of Neurosurgery, Teikyo University
Hospital, Tokyo, Japan
Dennis C. Shrieve, Huntsman Cancer Institute Chair in Cancer Research,
Professor and Chair, Department of Radiation Oncology, University of
Utah School of Medicine, The Huntsman Cancer Hospital, Salt Lake City,
UT, USA
Riccardo Soffietti, Department of Neuro-Oncology, University and City
of Health and Science Hospital, Turin, Italy
Mark M. Souweidane, Professor of Neurological Surgery, Weill Cornell
Medical College, New York, NY, USA
Joachim P. Steinbach, Dr. Senckenberg Institute of Neuro-Oncology,
Department of Neurology, Frankfurt University Hospital, Frankfurt,
Germany
Walter Stummer, Department of Neurosurgery, University of Münster,
Albert-Schweitzer Campus, Münster, Germany
Nancy J. Tarbell, CC Wang Professor of Radiation Oncology, Dean for
Academic and Clinical Affairs, Harvard Medical School, Boston, MA,
USA
Roger E. Taylor, Professor of Clinical Oncology, College of Medicine,
Swansea University, Swansea, UK; Honorary Consultant Clinical
Oncologist, South West Wales Cancer Centre, Singleton Hospital,

Swansea, UK
Charles Teo, Centre for Minimally Invasive Neurosurgery, Sydney, NSW,
Australia
Joerg–Christian Tonn, Department of Neurosurgery, Ludwig Maximilian
University Muenchen, Munich, Germany
Michael A. Vogelbaum, Professor of Surgery (Neurosurgery), The Robert
W. and Kathryn B. Lamborn Chair for Neuro-Oncology, Cleveland Clinic
Lerner College of Medicine of Case Western Reserve University,
Associate Director, Rose Ella Burkhardt Brain Tumor and NeuroOncology Center, Cleveland Clinic, Cleveland, OH, USA

21


David Walker, Department of Paediatric Oncology, Nottingham, UK
Colin Watts, Reader in Neurosurgical Oncology, University of
Cambridge, Department of Clinical Neurosciences, Division of
Neurosurgery, Addenbrooke’s Hospital, Cambridge, UK
Howard Weiner, Chief of Neurosurgery, Texas Children’s Hospital,
Houston, TX, USA
Michael Weller, Professor and Chair, Department of Neurology,
University Hospital and University of Zurich, Zurich, Switzerland
Patrick Y. Wen, Professor of Neurology, Harvard Medical School,
Director, Center For Neuro-Oncology, Dana-Farber Cancer Institute,
Boston, MA, USA
Wolfgang Wick, Chairman and Professor, Neurology Clinic, Heidelberg
University Medical Center, Clinical Cooperation Unit Neurooncology,
German Cancer Research Center, Heidelberg, Germany
Tai–Tong Wong, Division of Pediatric Neurosurgery, Taipei Veterans
General Hospital, National Yang Ming University School of Medicine,
Taipei, Taiwan, China

Whitney W. Woodmansee, Division of Endocrinology and Metabolism,
Brigham and Women’s Hospital, Harvard Medical School, Boston, MA,
USA
Takaaki Yanagisawa, Professor, Division of Paediatric Neuro-oncology,
Department of Neurosurgery, Jikei University School of Medicine, Tokyo,
Japan

22


CHAPTER 1

The 2016 revision of the WHO
classification of tumours of the
central nervous system
Paul Kleihues, Elisabeth Rushing, and Hiroko
Ohgaki

Introduction
Uniform classification and nomenclature of human cancers are a
prerequisite for epidemiological studies of cancer causation, comparison of
clinical trials, and the validation of novel cancer therapies. In 1957, the
World Health Organization (WHO) established a worldwide network of
collaborating centres to establish uniform histological criteria for the
diagnosis of human neoplasms. The first edition of the Histological Typing
of Tumours of the Central Nervous System was edited by K.J. Zülch and
published in 1979 (1). Considering the highly divergent views held in the
Americas, Asia, and Europe, this classification and grading scheme was a
remarkable achievement, although some misclassifications were soon
recognized. These were eliminated in the second edition published in

1993, mainly due to the introduction of more sophisticated diagnostic
methods, in particular immunohistochemistry (2, 3). A further refinement
in the typing of brain cancers was achieved with the addition of genetic
profiling, reflected in the title of the third edition: Pathology and Genetics
of Tumours of the Nervous System (4, 5). A revision of the 2007 fourth
edition (6, 7) has been published in 2016 and comprises several newly
recognized tumour entities (8). Some of these are histologically
recognized, but an ever increasing fraction of CNS neoplasms are now
defined by their genetic profile (Table 1.1).
The WHO Classification of Tumours of the Central Nervous System has
become the internationally accepted nomenclature for brain neoplasms.
Cancer registries worldwide now routinely assign the morphology code of
23


the International Classification of Diseases for Oncology (ICD-O) to each
tumour entity (9), which facilitates the generation of population-based,
epidemiological data on brain tumour incidence and mortality. The WHO
grading system assigns a malignancy grade to each neoplasm that is
widely used in clinical practice, particularly for gliomas.
Table 1.1 2016 WHO classification of tumours of the central nervous
system
Diffuse astrocytic and oligodendroglial tumours
Diffuse astrocytoma, IDH-mutant

9400/3

Gemistocytic astrocytoma, IDH-mutant

9411/3

Diffuse astrocytoma, IDH-wildtype

9400/3

Diffuse astrocytoma, NOS

9400/3

Anaplastic astrocytoma, IDH-mutant

9401/3

Anaplastic astrocytoma, IDH-wildtype

9401/3

Anaplastic astrocytoma, NOS

9401/3

Glioblastoma, IDH-wildtype

9440/3

Giant cell glioblastoma

9441/3

Gliosarcoma

9442/3

Epithelioid glioblastoma

9440/3

Glioblastoma, IDH-mutant

9445/3*

Glioblastoma, NOS

9440/3

Diffuse midline glioma, H3 K27M–mutant

9385/3*

Oligodendroglioma, IDH-mutant and 1p / 19q-codeleted

9450/3

Oligodendroglioma, NOS

9450/3

Anaplastic oligodendroglioma, IDH-mutant and 1p/19q-codeleted

9451/3

Anaplastic oligodendroglioma, NOS

9451/3

Oligoastrocytoma, NOS

9382/3

Anaplastic oligoastrocytoma, NOS

9382/3

Other astrocytic tumours
Pilocytic astrocytoma

9421/1

Pilomyxoid astrocytoma

9425/3

Subependymal giant cell astrocytoma

9384/1

Pleomorphic xanthoastrocytoma

9424/3

24


Anaplastic pleomorphic xanthoastrocytoma

9424/3

Ependymal tumours
Subependymoma

9383/1

Myxopapillary ependymoma

9394/1

Ependymoma

9391/3

Papillary ependymoma

9393/3

Clear cell ependymoma

9391/3

Tanycytic ependymoma

9391/3

Ependymoma, RELA fusion–positive

9396/3*

Anaplastic ependymoma

9392/3

Other gliomas
Chordoid glioma of the third ventricle

9444/1

Angiocentric glioma

9431/1

Astroblastoma

9430/3

Choroid plexus tumours
Choroid plexus papilloma

9390/0

Atypical choroid plexus papilloma

9390/1

Choroid plexus carcinoma

9390/3

Melanotic schwannoma

9560/1

Neurofibroma

9540/0

Atypical neurofibroma

9540/0

Plexiform neurofibroma

9550/0

Neuronal and mixed neuronal-glial tumours
Dysembryoplastic neuroepithelial tumour

9413/0

Gangliocytoma

9492/0

Ganglioglioma

9505/1

Anaplastic ganglioglioma

9505/3

Dysplastic cerebellar gangliocytoma (Lhermitte–Duclos disease)

9493/0

Desmoplastic infantile astrocytoma and ganglioglioma

9412/1

Papillary glioneuronal tumour

9509/1

Rosette-forming glioneuronal tumour

9509/1

Diffuse leptomeningeal glioneuronal tumour
Central neurocytoma

9506/1

25