Oxford Textbook of Fundamentals of Surgery

William E. G. Thomas (ed.) et al.

https://doi.org/10.1093/med/9780199665549.001.0001
Published: 2016 Online ISBN: 9780191810817 Print ISBN: 9780199665549

CHAPTER

2.13.2 Neuro-oncology 

Downloaded from https://academic.oup.com/book/31816/chapter/266641814 by University of Sydney user on 25 September 2022

Ian Sabin

https://doi.org/10.1093/med/9780199665549.003.0062 Pages 460–464

Published: July 2016

Abstract
This chapter summarizes the modes of presentation of intracranial and spinal lesions with reference to
some of the less rare tumours. The principles of oncology surgery, en-bloc resection of tumour with
clearance of the margins, does not apply to the central nervous system where attempts are made to
reduce signi cant de cits from damage to neural tissue by central debulking of tumours, and if
appropriate, by subtotal resection. Histologically benign tumours do not necessarily behave in a
clinically benign fashion, and their location within the brain and spine is crucial. A di usely in ltrating
lesion in the optic nerve or brainstem may be slowly growing but can have devastating e ects in terms
of progressive neurological de cits Advances in adjuvant radiotherapy and chemotherapy have, in
some cases, reduced the need for radical surgical resection, whereas radiosurgery ( ve or less fractions
of stereotactic radiotherapy) has replaced surgical resection for some benign skull base tumours.

Keywords: neuro-oncology, radiosurgery, glioma, cerebral secondary, vestibular schwannoma, pituitary

adenoma, meningioma
Subject: Surgery, Neurosurgery, Urology, Paediatric Surgery, Cardiothoracic Surgery, Peri-operative Care,
Trauma and Orthopaedic Surgery, Upper Gastrointestinal Surgery, Colorectal Surgery, Surgical Oncology,
Breast Surgery, Transplant Surgery, Vascular Surgery, Surgical Skills
Series: Oxford Textbooks in Surgery

Incidence

In 2010, 9156 new central nervous system tumours were registered in the UK (O ce for National Statistics).
This gure does not include metastases, which are much more common than primary tumours.

Their incidence has increased over the past three decades, which may be a genuine rise but may also be due
to the increasing availability and quality of scanning and possibly also to changes in coding.

Of the tumours diagnosed in 2010, 54% were malignant and 46% benign. The de nition of benign relates to
histological appearances, but the behaviour of a ‘benign’ tumour may still lead to death. In the UK in 2011
there were 311 deaths from ‘benign neoplasms of the meninges’.
For the Membership of the Royal College of Surgeons examination, a detailed knowledge of neuro-oncology
is not required. The principles behind the mechanisms leading to presenting symptoms, basic patient
examination, and appropriate investigations should, however, be understood.

Presentation

The presence of a growing mass within the cranium or spine may present in a limited number of ways:

◆ Generalized intracranial mass e ect: headache, problems with memory/concentration, altered level

Downloaded from https://academic.oup.com/book/31816/chapter/266641814 by University of Sydney user on 25 September 2022

of consciousness.

◆ Cerebral irritation: epileptic seizures.

◆ Hydrocephalus secondary to ventricular obstruction (non-communicating) or to di use

carcinomatous meningitis (communicating): failure of memory/concentration, ataxia, visual
obscurations, headache, incontinence and a depressed level of consciousness.

◆ Neurological de cit dependent on the location of the mass: hemiparesis, cranial nerve de cits,
dysphasia, visual eld de cits, personality change, quadriparesis, paraparesis, cauda equina
syndrome.

Diagnosis

The history and examination will direct subsequent investigations, but these will normally include magnetic
resonance imaging (MRI) and/or computed tomography (CT) scans. The appearances of lesions on scan may
strongly suggest a diagnosis and in some cases (vestibular schwannoma/meningioma) are characteristic
enough to allow treatment without a histological diagnosis, while others (lymphoma/low-grade glioma)
may require a biopsy for con rmation.

Additional investigations may also be useful before planning any therapy, including functional MRI to
delineate eloquent areas of cortex that may be at risk during treatment, tractography to determine the
relationship of important bre bundles to the mass, MR spectroscopy to determine the chemical
composition, and positron emission tomography/CT in an attempt to di erentiate areas of active tumour
from radionecrosis in previously irradiated brain.

Management

There are essentially three options:

Observation
A watch-and-wait policy is often adopted for small, benign lesions with minimal or no referable symptoms.
Surgery
Surgical resection may be radical and complete, or subtotal depending on the biology of the tumour
(encapsulated or di usely in ltrating) and the location of nearby critical structures. Surgery remains a good
treatment for relief of mass e ect, con rmation of diagnosis, and, potentially, cure of suitably located
benign tumours. The operating microscope signi cantly improved outcomes when introduced in the 1960s
but the addition to the surgical armamentarium of ultrasonic aspirators, image guidance, high-speed drills,
haemostatic agents, and, more recently, endoscopes have all helped to transform surgical techniques, aided
by the impressive advances in neuro-imaging.

Downloaded from https://academic.oup.com/book/31816/chapter/266641814 by University of Sydney user on 25 September 2022

Radiotherapy/radiosurgery
Fractionated, conformal, external beam radiotherapy has been used for decades to treat malignant brain
tumours. There have been technical advances in the planning software and linear accelerators delivering
this mode of radiotherapy but the greatest change in practice in the treatment of benign tumours has been
the emergence of ‘stereotactic radiosurgery’. The term radiosurgery is used to imply surgical precision in
the administration of radiation, giving a high dose to the target with a rapid fall o of dose to the
surrounding structures. This accuracy requires high-resolution imaging to de ne the target and complex
hardware to deliver multiple beams of radiation, which converge on that target. Radiosurgery is now
internationally de ned as treatment given in ve fractions or less, with the gamma knife normally
delivering single-fraction treatments and the CyberKnife often using three to ve fractions.

Central nervous system tumours: intrinsic

Gliomas are the commonest primary intrinsic central nervous system (CNS) tumours, occurring in the
brain, brainstem, and spinal cord. As the name implies, they arise from glial cells (usually astrocytes,
oligodendrocytes or ependymal cells). Although grouped together as gliomas, there are signi cant
di erences in behaviour and response to treatment for the di erent subtypes shown in Box 2.13.2.1.
 Box 2.13.2.1 The World Health Organization 2007 classification of central nervous
system tumours

The subclassi cation of CNS tumours above is complex, but the following subdivision is often used:

Brain

Intrinsic (gliomas, metastatic deposits)

Downloaded from https://academic.oup.com/book/31816/chapter/266641814 by University of Sydney user on 25 September 2022

Extrinsic (meningiomas, vestibular schwannomas)

Spine

Intramedullary (ependymomas, gliomas)

Extramedullary intradural (meningiomas, schwannomas)

Extramedullary extradural (secondary deposits in the vertebral bodies)

Adapted with permission from David N Louis et al., The 2007 WHO Classification of Tumours of the Central Nervous
System, Acta Neuropathologica, Volume 114, Issue 2, pp. 97–109, Copyright © Springer-Verlag 2007, reproduced under a
Creative Commons license CC-BY.

Astrocytomas
The World Health Organization (WHO) classi cation recognizes four grades (I–II low grade, III–IV high
grade). Grade IV astrocytomas are also referred to as glioblastoma multiforme.

Although grade II lesions are considered low grade, they are not benign and will usually grow slowly over
years before ‘transforming’ into grade III or IV with subsequent rapid growth.

True grade I tumours are uncommon and may be either di usely in ltrating or discrete and encapsulated.
These tumours are often histologically ‘pilocytic’ (formed of cells with long hair-like processes). A
cystic/solid enhancing tumour in the cerebellum of a child is likely to be a juvenile pilocytic astrocytoma,
which surgical resection alone may cure.

Grade II astrocytomas occur throughout the neuraxis and are di usely in ltrating, slowly growing tumours.

In the spinal cord, they normally present by causing damage to the neural pathways leading to motor
weakness, sensory disturbance, and proprioceptive loss in varying degrees. The level in the cord determines
the pattern of weakness produced; quadriparesis or paraparesis.

In the brain, their presentation depends on location. Epilepsy is the most common initial symptom, but if
they arise in an eloquent area, they may cause dysphasia, limb weakness, or hemianopia. In non-eloquent
brain, particularly the frontal lobe, headache or other features of raised intracranial pressure such as
disturbance of memory and concentration or changes in personality and behaviour may be the initial signs.
A signi cant number are also now being discovered incidentally on scans for minor head injury or unrelated
headache.

The management of grade II tumours remains controversial and has included biopsy followed by external
beam radiotherapy, biopsy followed by simple observation, and more recently resection where possible,
often during an ‘awake craniotomy’ in the hope of reducing the risk of iatrogenic de cits. Surgical
debulking may have an e ect in delaying malignant transformation, improving overall survival. This
potential bene t has to be balanced against the surgical risk of neurological de cit and the knowledge that
their di use nature makes complete resection unlikely.

Management of grade III (anaplastic) and grade IV (glioblastoma multiforme) tumours generally comprises
surgical debulking where location allows, chemotherapy, and fractionated conformal external beam
radiotherapy to a total dose of 55–60 Gy. Currently temozolomide is the chemotherapeutic agent of rst
choice for grade IV tumours. Methylguanine-DNA methyltransferase is an enzyme involved in DNA repair
that may reduce the e cacy of temozolomide chemotherapy and consequently positivity for this in the

Downloaded from https://academic.oup.com/book/31816/chapter/266641814 by University of Sydney user on 25 September 2022

histological specimen is considered an indicator of a poor response to the drug.

Oligodendrogliomas
Oligodendrogliomas are generally less aggressive than astrocytomas (median survival for low-grade
oligodendroglioma 13 years versus 7.5 years for low-grade astrocytoma). They are more sensitive to
systemic chemotherapy than astrocytomas of similar grade and have characteristic genetic markers, with
most having deletions of the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q).
This co-deletion appears to predict sensitivity to chemotherapy.

Medulloblastoma
The most common malignant brain tumour of childhood, these normally present with signs and symptoms
of raised intracranial pressure, including headache, nausea, vomiting, and altered level of consciousness.
These symptoms are similar to meningitis and lumbar punctures have resulted in death from cerebellar
tonsillar herniation. The nding of an enhancing midline cerebellar tumour on MRI scan is very suggestive
and treatment generally comprises surgical resection, radiotherapy and chemotherapy. These tumours may
disseminate throughout the subarachnoid space, with enhancing nodules visible over the brain surface,
within the ventricles or in the spinal canal. Radiotherapy is usually given to the whole craniospinal axis to
deal with this risk of dissemination. In children under the age of 3, however, radiotherapy is delayed in view
of the very great risk of cognitive impairment when the growing brain is irradiated. Chemotherapy (often
using four- or ve-drug regimens) is given to infants under 3 years of age, but the result of treatment in
terms of disease-free survival is not as good as in the older age groups, when radiotherapy is also given
(60% versus 80%).

Metastases
It is estimated that between 10% and 30% of patients with disseminated malignancy will develop CNS
secondary deposits, and this percentage may be increasing due in part to better imaging but possibly also to
better systemic treatment of extracerebral disease. These lesions may be intracerebral or intraspinal, with
intramedullary or subarachnoid spread around the spinal cord being commoner than previously thought.

In adults the most common primary tumours producing cerebral secondaries are breast, lung, melanoma,
renal, and colon, occurring in:

◆ cerebrum (80%)

◆ cerebellum (15%)

◆ brainstem (5%).
This distribution is in keeping with the comparative size and blood ow of each of these regions and these
deposits are characteristically at the junction of the grey and white matter.

Mass e ect, intratumoural haemorrhage, or epilepsy are frequent presentations, but di use seeding
throughout the cerebrospinal uid spaces may lead to ‘carcinomatous meningitis’ causing hydrocephalus
and multiple cranial nerve palsies.

MRI scans normally show multiple enhancing lesions, which may be solid or show ‘ring’ enhancement
secondary to central necrosis or cyst formation.

Where the diagnosis is clear due to the presence of a known primary tumour, biopsy is not often indicated.

Downloaded from https://academic.oup.com/book/31816/chapter/266641814 by University of Sydney user on 25 September 2022

Treatment may be surgery, with resection of suitable single lesions, or radiotherapy, either fractionated
whole brain or stereotactic radiosurgery. Prognosis and decision making depends on:

◆ Karnofsky performance status/performance status (Box 2.13.2.2)

◆ type and extent of primary cancer

◆ volume load of CNS tumour

◆ age.
Box 2.13.2.2 Karnofsky performance status/performance status

The performance status and Karnofsky status are both now commonly used in referrals of patients
with cancer.

Performance status

The World Health Organization (WHO) designed the scale that doctors use most often. It has categories
from 0 to 4.

Downloaded from https://academic.oup.com/book/31816/chapter/266641814 by University of Sydney user on 25 September 2022

0: You are fully active and more or less as you were before your illness.

1: You cannot carry out heavy physical work, but can do anything else.

2: You are up and about more than half the day and can look after yourself, but are not well enough
to work.

3: You are in bed or sitting in a chair for more than half the day and you need some help in looking
after yourself.

4: You are in bed or a chair all the time and need a lot of looking after.

Adapted from Oken MM et al., Toxicity and response criteria of the Eastern Cooperative Oncology
Group, American Journal of Clinical Oncology, Volume 5, Issue 6, pp. 649–55, Copyright © 1982
Lippincott-Raven Publishers, with permission from Wolters Kluwer Health, Inc. All rights reserved.

Karnofsky performance status

Similar to the WHO scale, but goes to up 100.

100: You don’t have any evidence of disease and feel well.

90: You only have minor signs or symptoms but are able to carry on as normal.

80: You have some signs or symptoms and it takes a bit of e ort to carry on as normal.

70: You are able to care for yourself but not able to carry on with all your normal activities or do
active work.

60: You need help from time to time but can mostly care for yourself.

50: You need quite a lot of help to care for yourself.

40: You always need help to care for yourself.

30: You are disabled and may need to stay in hospital.

20: You are ill, in hospital and need a lot of treatment.

10: You are very ill and unlikely to recover.

Reproduced from Karnofsky DA and Burchenal JH, ʻThe Clinical Evaluation of Chemotherapeutic Agents in Cancerʼ, p. 146,
in MacLeod CM (Ed.), Evaluation of Chemotherapeutic Agents, Columbia University Press, New York, USA, Copyright ©
1949, with permission from Columbia University Press.
The best outcomes are seen in those patients with Karnofsky scores of >70, controlled or controllable
systemic disease, and a small volume load of metastatic lesions. Without therapy the median survival is
measured in months.

Treatment for multiple brain metastases in the UK has traditionally involved whole brain radiotherapy
(WBRT), frequently given to a dose of 30 Gy in ten fractions. This has the advantage of being relatively cheap
and relatively easy to administer. By irradiating the whole brain, there is a chance that microscopic deposits
will be ‘nipped in the bud’. The disadvantage, however, is the potential for damage to cognition, particularly
where there is a reasonable expectation of long term survival, such as systemically controlled breast cancer.

Downloaded from https://academic.oup.com/book/31816/chapter/266641814 by University of Sydney user on 25 September 2022

More recently, stereotactic radiosurgery has been promoted as an alternative to WBRT and there is
increasing evidence of e cacy in selected cases. The treatment is usually single fraction and day case, and
some early data suggest less e ect on cognition than with WBRT. The disadvantages are the possible
development of new lesions outside the treatment eld and the greater cost.

Central nervous system tumours: extrinsic

Meningioma
These account for approximately 30% of all primary brain and CNS tumours, with an estimated annual
incidence of 2 per 100 000.

They are classi ed according to location (frontal convexity, cerebello-pontine angle, etc.) and histological
grade (WHO I–III). Grade I tumours comprise more than 90% of the total, are histologically benign,
normally very slowly growing, and if resected along with their dural origin have a low risk of recurrence.
Grade II tumours account for approximately 5%, are more rapidly growing, and more prone to recurrence.
Grade III lesions (around 3%) are frankly malignant, and usually rapidly fatal although some series show a
5-year survival of approximately 30%.

Many small tumours may be observed with serial scanning but where treatment is indicated, surgical
resection including the dural origin is considered the gold standard. Sometimes their location precludes this
due to the risk of damage to cerebral arteries or cranial nerves. In these cases, subtotal removal followed by
radiotherapy (increasingly radiosurgery) gives excellent control, with radiosurgery leading to growth arrest
in more than 90% of residual grade I tumours.

Vestibular schwannoma
With an annual incidence of approximately 2 per 100 000, vestibular schwannomas account for 80% of
tumours within the cerebello-pontine angle. They arise, as their name suggests, from the vestibular nerves
and generally present with hearing loss, tinnitus and disturbance of balance.

The current investigation of choice for unexplained, asymmetric sensorineural hearing loss is an MRI scan
of the internal auditory meati. Most of these scans will be normal but a signi cant number will show
classical schwannomas, growing both into the internal auditory meatus and the cerebello-pontine angle.
These often demonstrate inhomogeneous enhancement, due to the presence of intratumoural cysts.

Schwannomas are normally slowly growing (1–2 mm per annum) with no need for urgent treatment. They
may rarely present acutely, with haemorrhage or hydrocephalus, requiring rapid decompression or
shunting, but most patients have time to make an informed decision about management.
With small tumours, a watch-and-wait policy is often adopted, with annual scanning to detect those that
are uncommonly rapid in their growth. If treatment is recommended, it has to be emphasized that any
hearing loss on the a ected side will not be restored (and instead is likely to be sacri ced), that tinnitus is
unlikely to be reduced, and that a good result is one which leaves them neurologically no worse.

Radiosurgery has become the treatment of choice over the past 15 years, except for tumours considered too
large. Many surgeons will now debulk these tumours, attempting to preserve the facial nerve, and then treat
the residual with radiosurgery. The control of growth with gamma knife treatment is approximately 95%,
with few tumours escaping and requiring surgical resection. There is a small risk of malignant change, but
this is estimated to be 1:5000 at most, and is much less than the risk of death from surgery.

Downloaded from https://academic.oup.com/book/31816/chapter/266641814 by University of Sydney user on 25 September 2022

Pituitary tumours
Intrasellar tumours include pituitary adenoma (the most common), meningioma, and craniopharyngioma.
Their presentation may be with visual failure due to mass e ect, or endocrine e ects such as
hypopituitarism, Cushing’s disease, hyperprolactinaemia, or acromegaly. The typical visual eld loss is a
bitemporal hemianopia due to optic chiasm compression, usually with red elds being disproportionately
impaired.

Patients may be managed conservatively if they harbour relatively small, non-functioning adenomas. Once
the tumour reaches the optic chiasm, however, surgery is normally recommended unless the tumour is a
prolactinoma as these respond very well to dopamine agonists such as cabergoline and shrink in response to
medication alone. Other endocrine-active tumours are resected regardless of size, although there is
currently a trend to pre-treat growth hormone secreting tumours with somatostatin analogues such as
lanreotide or octreotide as these drugs will often shrink the tumour and may facilitate complete surgical
resection.

Surgery now is almost exclusively trans-nasal, transphenoidal, and in many centres is entirely endoscopic
as this gives an excellent view of the tumour cavity, the cavernous sinuses and the suprasellar extension.
Occasionally craniotomy is still recommended if the con guration of the tumour precludes adequate
transphenoidal resection.

Spinal tumours

Benign tumours are usually slowly growing and will normally cause progressive limb weakness and sensory
loss, which may be profound before diagnosis and treatment. Once decompressed in these circumstances,
neurological recovery may be gratifying, often with excellent recovery of function. This is in marked
contrast to metastatic disease, where severe de cits rarely recover despite decompression, possibly due to
vascular compromise. Prompt diagnosis and, where indicated, treatment of spinal secondaries is required
before there is signi cant neurological damage, in an attempt to preserve quality of life.

Spinal secondary deposits causing vertebral collapse are common and if treated surgically will often require
decompression of the spinal cord followed by reconstruction and stabilization with adjuvant radiotherapy
and chemotherapy.

Intradural tumours are generally managed in the UK by neurosurgeons and are usually resected using
microsurgical techniques. The most common intradural tumours are meningiomas and schwannomas, with
astrocytomas and ependymomas being found within the spinal cord and posing particular surgical
challenges in the attempt to resect them without causing additional signi cant neural injury.
Further reading
Patten J. Neurological Di erential Diagnosis. London, Springer, 1998.
Google Scholar Google Preview WorldCat COPAC

Love S, Perry A, Ironside J, et al. (eds). Greenfieldʼs Neuropathology (9th ed). London: Hodder Arnold 2015.
Google Scholar Google Preview WorldCat COPAC

© Oxford University Press

Downloaded from https://academic.oup.com/book/31816/chapter/266641814 by University of Sydney user on 25 September 2022