Brain metastases 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.
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".
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
- 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.
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.
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.
Typically well-demarcated except for melanoma metastases. Their histological appearance will, of course, depend on the primary tumour.
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.
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 CT with contrast and 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.
- 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
- 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
- typically hyperintense
- haemorrhage may alter this
- typically hyperintense
- hyperintense peri-tumoural oedema of variable amounts
- intratumoural choline peak with no choline elevation in the peritumoural oedema
- any tumour necrosis results in a lipid peak
- NAA depleted
- oedema is out of proportion with tumour size and appears dark on DWI
- ADC demonstrates facilitated diffusion in oedema
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.
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 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.
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, leukemias 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 recent trial presented in the ASCO 2015 meeting has shown that whole brain radiation therapy did not improve the overall survival for those patients with a limited number of brain metastases, besides the fact it is related to a neurocognitive impairment.
General imaging differential considerations include:
- primary brain neoplasm especially gliobastoma
- NAA present to a degree
- epicentre on white matter
- extends to ependymal surface
- central restricted diffusion
- dual rim sign 5
- smooth complete low-intensity rim on SWI 5
- subacute stroke
- gyriform enhancement typical
- vascular territory
- usually obviously extraxaial
- homogeneous enhancement
- dural tail
- post-treatment effects (post-surgical or post-radiation) hypermetabolic acutely progressing to hypometabolic over time
- 1. Eichler AF, Loeffler JS. Multidisciplinary management of brain metastases. Oncologist. 2007;12 (7): 884-98. doi:10.1634/theoncologist.12-7-884 - Pubmed citation
- 2. Kumar V, Abbas AK, Fausto N et-al. Robbins and Cotran pathologic basis of disease. W B Saunders Co. (2005) ISBN:0721601871. Read it at Google Books - Find it at Amazon
- 3. Barnholtz-Sloan JS, Sloan AE, Davis FG et-al. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J. Clin. Oncol. 2004;22 (14): 2865-72. doi:10.1200/JCO.2004.12.149 - Pubmed citation
- 4. Greenberg MS. Handbook of Neurosurgery. Thieme Medical Pub. (2010) ISBN:1604063262. Read it at Google Books - Find it at Amazon
- 5. Toh CH, Wei KC, Chang CN et-al. Differentiation of pyogenic brain abscesses from necrotic glioblastomas with use of susceptibility-weighted imaging. AJNR Am J Neuroradiol. 2012;33 (8): 1534-8. AJNR Am J Neuroradiol (full text) - doi:10.3174/ajnr.A2986 - Pubmed citation
- 6. Purandare NC. Inclusion of brain in FDG PET/CT scanning techniques in cancer patients: Does it obviate the need for dedicated brain imaging?. Indian J Nucl Med. 2011;26 (2): 64-6. doi:10.4103/0972-3919.90253 - Free text at pubmed - Pubmed citation
- 7. Bochev P1 et al., Brain metastases detectability of routine whole body (18)F-FDG PET and low dose CT scanning in 2502 asymptomatic patients with solid extracranial tumors, Hell J Nucl Med. 2012 May-Aug;15(2):125-9. doi: 10.1967/s002449910030. Epub 2012 Jun 27.
- 8. Fink KR, Fink JR. Imaging of brain metastases. Surg Neurol Int. 2013;4 (Suppl 4): S209-19. Free text at pubmed - Pubmed citation
- 9. Soffietti R, Cornu P, Delattre JY et-al. EFNS Guidelines on diagnosis and treatment of brain metastases: report of an EFNS Task Force. Eur. J. Neurol. 2006;13 (7): 674-81. doi:10.1111/j.1468-1331.2006.01506.x - Pubmed citation
- 10. Kaal EC, Taphoorn MJ, Vecht CJ. Symptomatic management and imaging of brain metastases. J. Neurooncol. 2005;75 (1): 15-20. doi:10.1007/s11060-004-8094-5 - Pubmed citation