eMedicine Specialties > Neurology > Neuro-oncology

Brain Metastasis: Differential Diagnoses & Workup

Author: Victor Tse, MD, PhD, Associate Professor, Department of Neurosurgery, Stanford University Medical Center, Santa Clara Valley Medical Center
Contributor Information and Disclosures

Updated: Nov 10, 2009

Differential Diagnoses

Other Problems to Be Considered

Any subacute neurological disease: About 11% of mass lesions in patients with cancer are not metastases. Mass lesions that can masquerade as brain metastasis include abscess (20%) and granuloma (less common and mostly associated with mycobacterial or fungal infection).

Acute demyelinating diseases (mostly secondary to acute postinfective demyelination)

Progressive multifocal leukoencephalopathy (PML)

Radiation necrosis, if patient had prophylactic radiotherapy for previous metastases to the brain

Nonbacterial thrombotic endocarditis (NBTE) and intravascular thrombosis: This is frequently encountered in patients with disseminated disease of the lung, breast, or GI or genitourinary tract or with tumors of hematopoietic origin. NBTE is uncommon in patients whose disease is in remission.

Resolving hematoma due to coagulopathy secondary to NBTE or intravascular thrombosis from associated coagulation disorder

Coagulopathy: Coagulopathies have been associated with breast cancer and leukemia. In some cases, cardiolipin antibodies are present; in other cases, abnormalities in viper-venom coagulation results have been documented.

Workup

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.
• Recent advancement in proteomics and the use of serum markers may be useful in the future for target treatment and diagnosis.

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.
  • 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.⁵
  • 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.

Procedures

• Tissue diagnosis: 11% of patients with cancer with a solitary mass in the brain have lesions other than metastatic disease. Hence, tissue diagnosis is sometime necessary to resolve this diagnostic uncertainty, especially when the imaging study results in ambiguity.
  • 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.
• Brain biopsy
  • The morbidity rate for stereotactic brain biopsy is 3% overall; 1% is due to hemorrhage and 1% to deficits without bleed. The mortality rate is 3%.
  • The morbidity rate for tumor resection is 20%, and the mortality rate is 2%.
  • With recent advances in intraoperative navigation, the morbidity and mortality rates of excision biopsy have been reduced to 10% and 0.5-2%, respectively, which are slightly higher than the rates of stereotactic brain biopsy alone.

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