are estimated to account for approximately 25-50% of intracranial tumours in

hospitalised patients. Due to great variation in imaging appearances, these

metastases present a common diagnostic challenge which can importantly affect the
management approach for individual patients.

This article will discuss metastatic lesions affecting both the cerebrum, the
cerebellum and the brainstem parenchyma. For other intracranial metastatic
locations, please refer to the main article on intracranial metastases.

Terminology
The term brain technically includes the cerebrum, the cerebellum and the brainstem.
As the cerebrum corresponds to the majority of the brain volume and thus receives
most of its blood supply, it is more common for metastatic lesions to appear in the
cerebral parenchyma. Consequently, the term "cerebral metastases" is a synonym for
"brain metastases".

Epidemiology
The true incidence of brain metastases is unknown, but recent estimates are as high
as 200,000 cases per year in the United States alone 1.

Five primary tumours account for 80% of brain metastases 2:

lung cancer
renal cell carcinoma
breast cancer
melanoma
gastrointestinal tract adenocarcinomas (the majority colorectal carcinoma)
A population-based study of 169,444 cancer patients from 1973 to 2001 in Detroit
revealed that overall, 10% of patients diagnosed with one of these five primaries
went on to develop brain metastases. Specifically, 19.9% of lung cancers, 6.9% of
melanomas, 6.5% of renal cancers, 5.1% of breast cancers and 1.8% of colorectal
cancers metastasized to the brain 3.

Parenchymal blood flow is an important determinant of the distribution of

metastases: 80% of metastases localise to the cerebral hemispheres, 15% localise to
the cerebellum, and 3% localise to the basal ganglia 8. Often these tumours can be
found at the grey/white matter junction.

Clinical presentation
These patients can commonly present with headaches, seizures, mental status
alterations, ataxia, nausea and vomiting, and visual disturbances. However, up to
60-75% of patients can be asymptomatic at the time of imaging 9.

In patients with known malignancies, the brain can sometimes act as a reservoir for
metastatic disease as traditional chemotherapy regimes can have poor permeability
through the blood-brain barrier. This can lead to presentation with cerebral
metastases even with quiescent systemic disease.

Pathology
Macroscopic appearance
Typically metastases are relatively well demarcated from the surrounding
parenchyma, and usually, there is a zone of peritumoural oedema out of proportion
with the tumour size.

Histology
Typically well-demarcated except for melanoma metastases. Their histological
appearance will, of course, depend on the primary tumour.

Radiographic features
There is a variability in the appearance of these tumours, which can make it
challenging to evaluate these lesions on cross-sectional imaging.

Although cerebral metastases are often thought of as being multiple, ~50% are
seemingly solitary at diagnosis and in a minority of cases, no known or
identifiable malignancy is present 4. They often occur at the grey-white matter
junction or in the arterial watershed areas.

It is known that certain malignancies are more susceptible to haemorrhage and it is

important to remember this characteristic when suggesting the diagnosis. Metastases
that haemorrhage include melanoma, renal cell carcinoma, choriocarcinoma, thyroid
cancer, lung and breast cancers.

CT
Often the first line of imaging, contrast enhanced CT was previously thought to be
equivalent to MRI for the detection of metastases. However, current MRI technology
has been shown to be more sensitive than CT and is the preferred imaging of choice.
In any case, there is no evidence that MRI-based screening improves outcomes when
compared to contrast enhanced CT yet so many institutions continue to employ CT as
the initial test of choice.

On precontrast imaging, the mass may be isodense, hypodense or hyperdense

(classically melanoma) compared to normal brain parenchyma with variable amounts of
surrounding vasogenic oedema. Following administration of contrast, enhancement is
also variable and can be intense, punctate, nodular or ring-enhancing if the tumour
has out grown its blood supply.

MRI
T1
typically iso- to hypointense
if haemorrhagic may have intrinsic high signal
non-haemorrhagic melanoma metastases can also have intrinsic high signal due to the
paramagnetic properties of melanin
T1C+
enhancement pattern can be uniform, punctate, or ring-enhancing, but it is usually
intense
delayed sequences may show additional lesions, therefore contrast-enhanced MR is
the current standard for small metastases detection
T2
typically hyperintense
haemorrhage may alter this
FLAIR
typically hyperintense
hyperintense peri-tumoural oedema of variable amounts
DWI/ADC
oedema is out of proportion with tumour size and appears dark on DWI
ADC demonstrates facilitated diffusion in oedema
MR spectroscopy
intratumoural choline peak with no choline elevation in the peritumoural oedema
any tumour necrosis results in a lipid peak
NAA depleted
Nuclear medicine
FDG PET
Generally considered the best imaging tool for metastases. However it can only
detect metastases up to 1.5 cm in size, therefore contrast MRI remains the gold
standard to rule out small metastases. Lung, breast, colorectal, head and neck,
melanoma and thyroid metastases are usually hypermetabolic. Mucinous adenocarcinoma
and renal cell carcinoma are typically hypometabolic, and gliomas and lymphomas are
variable. Any central hypometabolism indicates necrosis.
PET/CT
May overcome some of the shortcomings and has been shown to possess higher
sensitivity in detecting metastases, partly due to hybrid imaging part CT. It may
even demonstrate asymptomatic metastases in patients examined for extracranial
disease. However, MRI remains gold-standard 6,7.

Treatment and prognosis

Symptomatic treatment
Corticosteroids are given to limit the effects of peritumoural oedema.
Hyperosmolar agents (e.g. mannitol) can be given to decrease ICP and
anticonvulsants are given to prevent seizures. Recently, methylphenidate and
donepezil have been used to improve cognition, mood, and quality of life.

Therapeutic treatment
Radiation (whole brain external beam or stereotactic for smaller masses),
chemotherapy and surgical resection are done to prolong survival and palliate
symptoms. Other than germ cell tumours, leukaemias and lymphomas, palliation is the
rule and curative therapy is the subject of case reports.

Prognosis
Overall patients with brain metastases typically have a mean survival of one month
without treatment. With treatment, survival improves, but it is still dismal. The
mean age of survival is still less than one year, although in some patients with
solitary metastases longer survival is encountered.

A 2016 trial showed that whole brain radiation therapy did not improve the overall
survival for those patients with a limited number of brain metastases, and was
associated with more cognitive impairment 11.

Differential diagnosis
General imaging differential considerations include:

primary brain neoplasm especially gliobastoma

NAA present to a degree
epicentre on white matter
extends to ependymal surface
cerebral abscess
central restricted diffusion
dual rim sign 5
smooth complete low-intensity rim on SWI 5
subacute stroke
gyriform enhancement typical
vascular territory
meningioma
usually obviously extraxaial
homogeneous enhancement
dural tail
post-treatment effects (post-surgical or post-radiation) hypermetabolic acutely
progressing to hypometabolic over time