Brain metastases are estimated to account for approximately 25-50% of intracranial tumors in hospitalized patients. Due to great variation in imaging appearances, these metastases present a common diagnostic challenge that 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.
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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 estimates are as high as 200,000 cases per year in the United States alone 1.
Five primary tumors account for 80% of brain metastases 2:
gastrointestinal tract adenocarcinomas (the majority are colorectal carcinoma)
A population-based study of 169,444 cancer patients from 1973-2001 in Detroit revealed that overall, 10% of patients diagnosed with one of these five primaries went on to develop brain metastases. Specifically, 20% of lung cancers, 7% of melanomas, 7% of renal cancers, 5% of breast cancers and 2% of colorectal cancers metastasized to the brain 3.
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 regimens can have poor permeability through the blood-brain barrier. This can lead to presentation with cerebral metastases, even with quiescent systemic disease.
Pathology
Location
Often these tumors can be found at the grey/white matter junction. Parenchymal blood flow is an important determinant of the distribution of metastases 8:
80% localize to the cerebral hemispheres
15% localize to the cerebellum
3% localize to the basal ganglia
Macroscopic appearance
Typically metastases are relatively well-demarcated from the surrounding parenchyma, and there is usually a zone of peritumoural edema out of proportion with the tumor size.
Microscopic appearance
Typically well-demarcated except for melanoma metastases. Their histological appearance will depend on the primary tumor.
Radiographic features
The appearance of brain metastases is variable depending on their size, location and histology, and they can mimic other pathologies such as high-grade gliomas and infections.
Although they most often occur at the grey-white matter junction or in the arterial watershed areas, they can occur essentially anywhere in the neuraxis. Similarly, 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 even after examination of the body with other modalities 4,13,14.
Hemorrhage
Certain malignancies are more susceptible to hemorrhage which can aid in suggesting a primary malignancy. Metastases that classically hemorrhage include melanoma, renal cell carcinoma, choriocarcinoma and thyroid cancer. Both lung and breast cancers can also occasionally hemorrhage, and as they are far more common primaries than the classically hemorrhagic tumors, they should also be considered.
Vasogenic edema
Most larger metastases are surrounded by vasogenic edema due to poorly formed new blood vessels that mimic the microcirculation of the primary tumor and in some instances, the degree of edema can be striking. It is important to note, however, that when metastases are small they often do not have any surrounding edema. The size threshold at which metastases develop edema varies depending on histology (from 4 to >30 mm) with those from the gastrointestinal tract developing edema at the smallest diameter 15.
CT
Often the first line of imaging, contrast-enhanced CT was previously thought to be equivalent to MRI for the detection of metastases. However, 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 pre-contrast imaging, the mass may be isodense, hypodense or hyperdense (classically melanoma) compared to normal brain parenchyma with variable amounts of surrounding vasogenic edema. Following administration of contrast, enhancement is also variable and can be intense, punctate, nodular or ring-enhancing if the tumor has outgrown its blood supply.
MRI
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T1
typically iso- to hypointense
if hemorrhagic may have intrinsic high signal
non-hemorrhagic melanoma metastases can also have intrinsic high signal due to the paramagnetic properties of melanin
-
T1 C+ (Gd)
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 standard for small metastases detection
-
T2
typically hyperintense
hemorrhage/melanin may alter this
mucinous metastases are typically profoundly low 12
-
FLAIR
typically hyperintense
hyperintense peri-tumoral edema of variable amounts
-
DWI/ADC
edema is out of proportion with tumor size and appears dark on DWI
ADC demonstrates facilitated diffusion in edema
-
MR spectroscopy
intratumoral choline peak with no choline elevation in the peritumoural edema
any tumor 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 >1.5 cm in size, therefore contrast MRI remains the gold standard to rule out small metastases.
-
hypermetabolic metastases
lung
breast
colorectal
head and neck
melanoma
thyroid
-
hypometabolic metastases
mucinous adenocarcinoma
renal cell carcinoma
-
variable FDG uptake
gliomas
lymphomas
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
Corticosteroids are given for symptomatic treatment to limit the effects of peritumoural edema. Hyperosmolar agents (e.g. mannitol) can be given to decrease ICP and antiseizure medications are given to prevent seizures. Medications such as methylphenidate and donepezil may have benefits in regards to cognition, mood, and quality of life 16,17.
Therapeutic treatment includes 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 tumors, leukaemias and lymphomas, palliation is the rule and curative therapy is the subject of case reports.
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 glioblastoma
NAA present to a degree
epicenter on white matter
extends to ependymal surface
-
central restricted diffusion
smooth complete low-intensity rim on SWI 5
-
subacute stroke
gyriform enhancement typical
vascular territory
-
usually obviously extra-axial
homogeneous enhancement
post-treatment effects (post-surgical or post-radiation) hypermetabolic acutely progressing to hypometabolic over time
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