eMedicine Specialties > Radiology > Brain/Spine

Brain, Metastases

Author: Anil Khosla, MBBS, Assistant Professor, Department of Radiology, Section of Neuroradiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, Veterans Affairs Medical Center of St Louis
Contributor Information and Disclosures

Updated: Sep 8, 2008

Introduction

Background

Metastasis to the brain is the most feared complication of systemic cancer and the most common intracranial tumor in adults. The incidence of brain metastasis is rising with the increase in survival of cancer patients. Currently, cancer patients live longer as a result of important advances in cancer diagnosis and management, and in particular, the widespread use of MRI to detect small metastases. Approximately 40% of intracranial neoplasms are metastatic. Multiple, large autopsy series suggest that, in order of decreasing frequency, lung, breast, melanoma, renal, and colon cancers are the most common primary tumors to metastasize to the brain.^1,2

Brain metastases are an increasingly important cause of morbidity and mortality in cancer patients. Thus, brain metastasis presents a therapeutic challenge for the treating physician and is an emotionally and physically debilitating event for the patient. Early diagnosis and aggressive treatment of brain metastasis may result in remission of brain symptoms and may enhance the quality of the patient's life and prolong survival. The radiologist plays a primary role in the management of cancer patients by helping detect, localize, and diagnose the lesion.

For excellent patient education resources, visit eMedicine's Cancer and Tumors Center. Also, see eMedicine's patient education article Brain Cancer.

Pathophysiology

Metastatic spread to the brain through blood circulation occurs mostly via arterial circulation; (2) less often, it occurs via the Batson venous plexus (pelvic and GI tumors). Most metastases are round, well-demarcated lesions located at the junction of gray and white matter.³ Leakage from tumor vessels results in an extensive zone of edema surrounding the tumor.

Before entering the brain, arterial blood must pass through the lungs, where larger aggregates of tumor cells are filtered out in the capillaries; as a result, many emboli traveling to the brain via the arterial route originate either from a primary lung tumor or a metastatic site in the lung. However, single tumor cells may pass through the capillaries of the lung, and larger tumor emboli may pass from the venous circulation to the arterial circulation through a persistently patent foramen ovale between the right and left atrium of the heart.

Metastatic tumor growth in the brain depends on complex organotropic factors, as well as passive vascular delivery of tumor cells. Lesions are located in the cerebrum (80-85%), in the cerebellum (10-15%), and in the brain stem (3-5%). Slightly more than 50% of the time, metastases are multiple, not solitary; primary melanoma, as well as primary lung and breast tumors, are more likely to produce multiple metastases.

Intracranial metastases may be categorized by location as skull, dura, leptomeninges, and parenchymal brain metastases. Lesions of the brain and leptomeninges account for 80% of intracranial metastases. Meningeal carcinomatosis most commonly occurs in patients with breast carcinoma and malignant melanoma; less commonly, it occurs in patients with lymphoma, leukemia, and other tumors. Patients usually present with headache, vague neurologic complaints, and one or more cranial nerve palsies.

Frequency

United States

Approximately 170,000 cancer patients develop brain metastases annually. Intracranial metastases are seen in approximately 24% of patients who die from cancer (as reported in different series, the rate varies from 11-35%).

• Brain metastases represent the most common neurologic manifestation of cancer, occurring in 15% of cancer patients. Intracranial metastases eventually develop in approximately one third of patients with lung carcinoma; 50% of brain metastases result from this type of cancer.
• Brain metastases are less frequent in children; the incidence is approximately 6%.
• Brain metastases from unknown primary neoplasms are most likely to be from a primary lung cancer (72%), followed in frequency by breast cancer, colon carcinoma, and melanoma.

Mortality/Morbidity

The prognosis for patients with brain metastases typically is poor. Therapeutic considerations must be individualized; there are many relevant factors, including the patient's neurologic status, the extent of systemic tumor, the number and location of brain metastases, and the sensitivity of the tumor to radiation and chemotherapy. Patients with the best prognostic indicators often die within 18-24 months. Of particular relevance to imaging is the fact that for patients with a solitary brain metastasis who undergo treatment by surgical resection, the survival rate after 1 year is approximately doubled. Most available treatment is palliative; however, consideration should be given to prolonging the patient's quality of life through specific therapy to the brain.

Sex

Brain metastases demonstrate the same predilection for gender that the primary tumors do. Lung cancer is the most common source of metastases in male patients, whereas breast cancer is the most common source in female patients. As the frequency of lung cancer in women increases, it may become the most common primary tumor to metastasize to the brain in women as well.

Age

The incidence of brain metastases as determined on the basis of age parallels that of primary systemic tumors. Most brain metastases occur in patients 35-70 years of age.

Presentation

Approximately two thirds of brain metastases are symptomatic at some point. Symptoms primarily are caused by (1) increased intracranial pressure resulting in headache, nausea, vomiting, confusion, and lethargy and (2) focal irritation or destruction of neurons resulting in hemiparesis, visual field defects, aphasia, focal seizures, ataxia, and other focal neurologic signs or deficits.

The most common symptoms, in order of decreasing frequency, are headache, focal weakness, and mental status changes. Symptoms typically are of gradual onset. However, if seizures are excluded, 5-10% of patients develop other acute symptoms. An acute strokelike presentation may occur and often is precipitated by hemorrhage into the tumor.

Hemorrhage is present in 3-14% of metastases; it is most often seen in metastases from melanoma, choriocarcinoma, and renal, thyroid, lung, breast, and germ-cell tumors. Bronchogenic metastases are the most common hemorrhagic lesions because they occur in much greater numbers. Generalized or focal seizures may occur in 20% of patients with brain metastases.

Different primary tumors spread to the brain at different points in the disease course. The median latent interval between the initial diagnosis of a primary tumor and the diagnosis of brain metastases varies from 6-9 months for lung cancer and from 2-3 years for melanoma, breast, and colon cancer. In 20% of patients, metastases are detected during diagnosis of the primary tumor; in 50% of patients, they are detected within 1 year of the diagnosis.

In 5-10% of cancer patients, brain metastasis is the first clinical manifestation of systemic cancer. Lung carcinoma is the primary tumor in 45% of those in whom the primary site is discovered.

Surgical resection is the preferred treatment for patients with one apparent metastasis detected on enhanced CT or MRI. Radiosurgery is a simple, effective, noninvasive, cost-effective method of treating surgically inaccessible lesions; it is a therapeutic option in 2-6 of cases of brain metastases.

With regard to screening for intracranial metastases, no consensus has been reached concerning when to use CT or MRI for initial staging evaluation of a patient with cancer. However, brain MRI for patients with primary cancers that frequently metastasize to the brain (eg, bronchogenic carcinoma) is probably cost effective. Numerous studies have shown that contrast-enhanced MRI detects 2-3 times as many lesions as contrast-enhanced CT, especially lesions less than 5 mm in diameter. In addition, approximately 20% of patients with solitary metastatic lesions on CT show multiple lesions on MRI. The decision to perform imaging for patients with other cancers is made on the basis of the clinical evaluation.

In the presence of multiple cerebral metastases from an unknown primary source, a limited search for the primary tumor is of value; such a search includes a chest radiograph, breast examination and mammography, and abdominal ultrasound (US). An extensive search for an occult malignancy is unrewarding. Surgery may be required for patients presenting with a solitary intracranial tumor or to search for a possible primary tumor.

It has been shown that treatment with dexamethasone leads to a reduction in evidence on MRI of peritumoral edema and, occasionally, a lessening in the extent of contrast enhancement. If a lesion is found and a definitive diagnosis cannot be established, biopsy should be performed.
 
Surgical removal of the lesion is indicated for single or solitary brain metastasis in patients with good systemic performance status, because surgery is both diagnostic and therapeutic.
 
Patients with multiple brain metastases or poor systemic performance status are possible candidates for whole-brain radiation therapy or radiosurgery.^4,5

Preferred Examination

Most patients with a known primary tumor undergo imaging studies when neurologic signs and symptoms develop. MRI with contrast enhancement currently is the procedure of choice, because MRI is more sensitive and specific than other imaging modalities in determining the presence, location, and number of metastases. Contrast-enhanced CT is used widely because of its accessibility and low cost.⁶

Limitations of Techniques

Approximately one third of patients operated on for a single cerebral metastasis diagnosed with contrast-enhanced CT probably have more than one lesion. Contrast-enhanced MRI is more sensitive than CT in detecting the number of cerebral metastases.

Medical care is influenced significantly by the additional information gained from gadolinium-enhanced MR studies. If a solitary metastasis is found, definitively ruling out the presence or absence of additional lesions is important for diagnosis and for deciding upon possible surgical management. Standard-dose or high-dose gadolinium-enhanced MRI may demonstrate additional lesions that suggest metastatic disease. Use of magnetization transfer with single-dose gadolinium administration is roughly equivalent to triple-dose, postcontrast, spin-echo imaging in detecting lesions and lesion conspicuity.

Differential Diagnoses

Brain, Abscess
Brain, Hypertensive Hemorrhage
Brain, Lymphoma
Brain, Stroke
Meningioma, Brain

Other Problems to Be Considered

Other problems or factors to consider include the following:

• History of systemic cancer and a single supratentorial lesion (nearly 90% of such patients are diagnosed with brain metastases)
• Single brain lesions and no history of cancer (15% of such patients receive a histologic diagnosis of brain metastases)
• Multiple intracranial lesions without history of cancer (in older patients, metastases should be considered)
• Solitary or multiple brain masses (40% of all intracranial tumors are metastatic)
• The differential diagnosis for a solitary mass includes inflammatory disease, cerebrovascular disease, degenerative disease, and primary neoplasm
• The differential diagnosis for multiple lesions (more likely to be metastases) includes multicentric glioma, multifocal abscesses, toxoplasmosis, lymphoma, and multiple enhancing infarcts
• Brain vasculitis

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