Brain Metastasis Workup

Updated: Nov 21, 2022
  • Author: Victor Tse, MD, PhD; Chief Editor: Nicholas Lorenzo, MD, CPE, MHCM, FAAPL  more...
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Laboratory Studies

Laboratory investigations include blood work, such as CBC, electrolyte panel, coagulation screen, and liver function panel.

Specific markers, such as anti-Hu antibody in limbic encephalopathy, anti-Yo antibody in cerebellar degeneration, and anti-Ri antibody in opsoclonus and ataxia are of some value, especially in patients with small-cell lung cancer, ovarian cancer, and breast or lung cancers.

Chronic anemia is common in systemic disease.

Electrolyte imbalance, such as in hyponatremia (hypothyroidism or syndrome of inappropriate secretion of antidiuretic hormone [SIADH]), can be found in patients with metastasis to the pituitary gland and meninges.

Abnormal coagulopathy can be observed in patients with breast cancer or leukemia.

Abnormal liver function is common in patients with advanced systemic diseases or in those receiving chemotherapy.

Specific markers, such as anti-Hu antibody in limbic encephalopathy, anti-Yo antibody in cerebellar degeneration, and anti-Ri antibody in opsoclonus and ataxia, are of some diagnostic value, especially in patients with small-cell lung cancer, ovarian cancer, breast cancer, or lung cancers.

The recent advancement in genomic and proteomic medicine allows the use of a molecular signature to gauge the risk of developing brain metastasis. For example, in young breast cancer patients, an ER-positive, PR-positive, and HER2 -negative profile incurs a higher brain metastasis risk compared with a triple-negative or HER2 -positive profile. [12] It is especially true if the patient has a short interval between initial diagnosis and systemic metastasis; this risk is noted to be even higher if there are multiple sites of systemic metastasis. In current practice, this is beginning to be used as a method to guide personalized therapy.


Imaging Studies

Imaging study for metastatic disease to the brain can be divided into systemic imaging and imaging of the neuraxis. Images provide information on tumor burden in the brain and associated structures, in addition to the rest of the body, and are integral part in formulating the optimal treatment plan.

Systemic imaging studies

Chest radiography should be included in the workup of any mass lesion in the brain, specifically in patients without a history of systemic cancer.

Chest radiographs may reveal the primary cancer and suggest an alternative site for obtaining tissue for histologic diagnosis.

Additional imaging modalities such as CT, positron emission tomography (PET), and bone scanning are used to stage the systemic disease.

Imaging of the neuraxis (brain and spinal cord)

Head CT imaging of the brain is not as reliable as MRI in determining the extent of brain metastases.

Head CT can cause underestimation of the number of brain lesions. In 20% of cases and even when contrast medium is used, head CT shows a solitary lesion but subsequent MRI shows multiple lesions.

High-resolution MRI can be used to detect additional brain metastases in patients undergoing Gamma Knife surgery. [13]

Contrast medium enhances visualization of mass lesions in the brain and should be used in both CT and MRI.

Newer imaging modalities, such as magnetization transfer imaging and perfusion imaging, are not particularly useful.

Diffusion-perfusion MRI

Diffusion-perfusion MRI has been used to differentiate poorly enhancing lesions.

Tien et al reported that peritumoral edema and nonenhancing tumor have distinguishable features. [14]

The utility of this imaging technique in metastatic diseases is not established, though peritumoral edema is prominent in most cases.

Magnetic resonance (MR) spectrometry and PET scan (positron emission tomography).

MR spectroscopy uses the chemical signature of rapid membrane turnover of proliferative cells to reveal the presence of cancer cells.

Multiple voxel analysis is more commonly used because it has an advantage over signal voxel study to yield more information about the region of interest and to differentiate edema and possible necrosis.

CT-PET and bone scans are used to stage the extent of the systemic disease. This helps to formulate the extensiveness of future treatments (see Treatment) and their justification. Patients with multiple systemic metastasis do not do well in intensive therapy.

Other experimental imaging studies such as receptor-targeted and ligands-based molecular imaging are on the horizon. These imaging modalities are cancer specific.

Both MRI spectrometry and PET studies are useful to differentiate radiation necrosis from tumor.

Thallium-201 chloride PET seems to have high specificity (91%) in this regard.

Neither of these methods is useful for differentiating metastasis from primary brain tumors, but they are helpful whenever the possibility of an abscess is being considered.



Tissue diagnosis

Eleven percent of cancer patients with a solitary mass in the brain have lesions other than metastatic disease. Hence, tissue diagnosis is sometimes necessary to resolve this diagnostic uncertainty, especially when there is ambiguity in the imaging study.

Brain biopsy

Tissue diagnosis should be performed in cases of uncertain etiology. Of note, most surgeons advocate excision biopsy for a solitary lesion in an accessible area of the brain.

For stereotactic brain biopsy, the morbidity rate is 3% with a 1% rate of hemorrhage and a 1% rate of deficit without hemorrhage. The mortality rate is 3%.

In the past, the morbidity rate associated with tumor resection was 20%, and mortality rate was 2%. With recent advances in intraoperative navigation, the morbidity and mortality rates of excisional biopsy have been reduced to 10% and 0.5-2%, respectively, which are still higher than the rates with biopsy alone.