Disclosure
Background: Metastasis to the brain is the most feared complication of systemic cancer and the most common intracranial tumor in adults. Incidence is rising with improved 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. Brain metastases are an increasingly important cause of morbidity and mortality in cancer patients. Thus, brain metastases present a therapeutic challenge for the treating physician and an emotionally and physically debilitating event for the patient. Early diagnosis and aggressive treatment of brain metastases 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 is (1) mostly via arterial circulation and (2) less often via Batson venous plexus (pelvic and GI tumors). Most metastases are round well-demarcated lesions located at the junction of gray and white matter. Leaky tumor vessels result in an extensive zone of edema surrounding the tumor. Since arterial blood must pass through the lungs before entering the brain, and larger aggregates of tumor cells are filtered out in the capillaries, 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 also may pass from the venous 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, multiple as opposed to solitary metastases occur, but this varies with the type of primary tumor. Melanoma, lung, and breast primaries are more likely to produce multiple metastases. Intracranial metastases can 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, malignant melanoma, and, less commonly, with lymphoma, leukemia, and other tumors. Patients usually present with headache, vague neurologic complaints, and one or more cranial nerve palsies. Frequency:
Mortality/Morbidity: Prognosis typically is poor. Therapeutic considerations must be individualized and depend on many factors, which include the patient's neurologic status, extent of systemic tumor, number and location of brain metastases, and 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, patients with a solitary brain metastasis treated by surgical resection show an approximately doubled rate of survival after 1 year. Most available treatment is palliative; however, consider prolonging the patient's quality of life through specific therapy to the brain. Sex: Predilection for gender follows that of the primary tumor. Lung cancer is the most common source of metastases in male patients, while 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: Incidence of brain metastases based on age parallels that of primary systemic tumors. Most brain metastases occur in patients aged 35-70 years. Clinical Details: 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 have a gradual onset. However, if seizures are excluded, 5-10% of patients may 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 and most likely is seen in metastases from melanoma, choriocarcinoma, renal, thyroid, lung, breast, and germ-cell tumors. However, bronchogenic metastases are the most common source of hemorrhagic lesions because of their 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 diagnosis of brain metastases varies from 6-9 months for lung cancer and 2-3 years for melanoma, breast, and colon cancer. In 20% of patients, metastases are detected during diagnosis of the primary tumor, and in 50% of patients, they are detected within 1 year following diagnosis. In 5-10% of cancer patients, brain metastasis is the first clinical manifestation of systemic cancer. The primary site can be located in 45% of patients, and in those in whom the primary site is discovered, lung carcinoma is the primary tumor in 45%. Surgical resection is the preferred treatment in patients with one apparent metastasis detected on enhanced CT or MRI. Radiosurgery provides a simple, effective, noninvasive, cost-effective method to treat surgically inaccessible lesions and is a therapeutic option for 2-6 metastases. When 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 in 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. Perform imaging on patients with other cancers based on their clinical evaluation. In the presence of multiple cerebral metastases from an unknown primary source, a limited search for the primary tumor is of value and 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 in patients presenting with a solitary intracranial tumor or to search for a possible primary tumor. Patients treated with dexamethasone show reduced evidence on MRI of peritumoral edema and, occasionally, the extent of contrast enhancement. If a lesion is found and a definitive diagnosis cannot be established, perform a biopsy. Surgical removal of the lesion is indicated for single or solitary brain metastasis in patients with good systemic performance status, since 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. Preferred Examination: Most patients with a known primary tumor receive imaging studies when neurologic signs and symptoms develop. MRI with contrast enhancement currently is the procedure of choice, since MRI is more sensitive and specific than other imaging techniques in determining the presence, location, and number of metastases. Contrast-enhanced CT is used widely because of its easy accessibility and low cost. Limitations of Techniques: Approximately one third of patients operated on for a “single” cerebral metastasis diagnosed by 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 possible surgical management. Standard-dose or high-dose gadolinium-enhanced MRI can demonstrate the additional lesions that support suggested 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.
Brain, Abscess
History of systemic cancer and a single supratentorial lesion (nearly 90% of patients receive diagnosis of brain metastases)
Findings: Skull radiograms may detect multiple lytic or sclerotic deposits when the metastatic process involves the cranium. Lung and breast tumors are the most common primary malignancies to affect the skull. Multiple lytic lesions secondary to multiple myeloma tend to be uniformly small. Blastic metastases are seen in primary prostate cancer or treated breast cancer. Calcifications are uncommon in metastases but do occur in primary adenocarcinoma, osteogenic sarcoma, and lung and breast carcinoma. Plain radiographs are noncontributory in detecting metastatic disease of the brain. Degree of Confidence: Multiple lytic or blastic lesions are highly suggestive of a metastatic process. Solitary lesions must be differentiated from other pathologic processes affecting the skull vault. False Positives/Negatives: Normal anatomic variants, such as emissary vein, arachnoid granulation, and bone island, may mimic a metastatic lesion in a known cancer patient. Using CT with bone windows can eliminate false diagnoses. |
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Findings: Metastases frequently are multiple and seen at the junction of gray and white matter, usually with significant surrounding edema (see Images 2-3). CT findings are as follows:
Contrast-enhanced CT is effective in detecting major leptomeningeal spread (see Image 8). Contrast-enhancing subdural or epidural metastases may be seen, usually secondary to calvarial lesions (see Image 10). Of breast, lung, prostate, and renal-cell neoplasms, 5% metastasize to the calvarium, and 15% of these extend into the subdural space. Degree of Confidence: Multiple, enhancing solid lesions at the gray-white matter junction and prominent surrounding edema can be diagnosed confidently as metastases in a patient with known primary cancer. Approximately 90% of patients with a history of cancer who present with a single supratentorial lesion have brain metastases. Patients with multiple lesions are even more likely to have metastatic disease. Prior to definitive therapy, patients with a single metastasis by contrast-enhanced CT should undergo a contrasted MRI examination, if available. False Positives/Negatives: Routine cranial CT is useful in staging cancer in the patient with non–small-cell lung cancer and has 92% sensitivity, 99% specificity, and 98% accuracy in detecting brain metastases. Contrast-enhanced CT is useful and perhaps the best method to identify calvarial metastases. Studies comparing contrast-enhanced CT with contrast-enhanced MRI indicate that approximately 20% of patients who demonstrate a single lesion on CT may demonstrate multiple lesions on MRI. Mostly, the lesions missed on contrast-enhanced CT were smaller (<2 cm in diameter), located next to the bone, and in a frontotemporal location. Dural-based metastases may mimic meningioma.
Findings: Multiple lesions (see Image 5) with marked vasogenic edema (see Image 1) and mass effect are typically seen in patients with brain metastases. MRI findings are as follows:
The usefulness of diffusion-weighted and perfusion-weighted imaging and proton-MR spectroscopy in the initial diagnosis of brain metastases has not been established. Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. As of late December 2006, the FDA had received reports of 90 such cases. Worldwide, over 200 cases have been reported, according to the FDA. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape. Degree of Confidence: Gadolinium-enhanced MRI is superior to contrast-enhanced CT in the diagnosis of brain metastases. Gadolinium-enhanced MRI can accomplish the following:
High-dose gadoteridol (ProHance) detects additional smaller lesions when compared to routine-dose gadopentetate dimeglumine (Magnevist). Detection of additional lesions is important when considering surgical treatment of a solitary lesion. Magnetization transfer used with routine-dose gadolinium contrast is closely comparable to the high-dose technique. False Positives/Negatives: The imaging appearance of dural-based metastases (see Image 6) may mimic meningioma. Leptomeningeal carcinomatosis (see Image 7) may resemble chronic meningitis; however, an appropriate history or detection of primary cancer can establish the diagnosis. Leptomeningeal enhancement also can occur following irradiation, prior extra-axial hemorrhage, or below a craniotomy site. Single or multiple ring-enhancing lesions with edema may need to be differentiated from infectious processes. Solitary lesions resemble primary brain tumors.
Findings: US does not contribute to the diagnosis of brain metastases. Intraoperative US may help in surgical removal of brain metastases.
Findings: Currently, routine nuclear medicine studies are not employed as primary imaging techniques for detecting intracranial metastatic disease. Typical findings are multiple intracerebral areas of increased activity. The standard isotope used is technetium Tc 99m. The isotope whole-body bone scan can detect calvarial metastases as multiple focal areas of increased activity. Whole-body 18-fluorodeoxyglucose (FDG) positron emission tomography (PET) for cancer staging can detect intracerebral metastases as areas of increased metabolism. Degree of Confidence: Radionuclide studies are sensitive but highly nonspecific. FDG-PET studies in a small number of patients have been associated with low sensitivity and specificity rates. Currently, FDG-PET is not considered superior to CT or MRI in the initial evaluation of suspected brain metastases. False Positives/Negatives: Older reports indicate that radionuclide studies can detect intracerebral metastases in approximately 90% of patients but the findings are nonspecific. Neoplasm, inflammation, vascularity, or trauma may cause the abnormal uptake. FDG-PET has been reported to detect approximately two thirds of brain metastases resulting from systemic cancer.
Findings: Angiography currently is not used as a primary diagnostic procedure for metastatic disease. Rarely, preoperative angiography and embolization of large hypervascular metastases from renal and thyroid cancer may be useful. Degree of Confidence: Angiography is useful in evaluating tumor vascularity in selected metastatic lesions prior to biopsy. False Positives/Negatives: Angiography is nonspecific for the diagnosis of metastases.
Intervention: Endovascular procedures using particles or surgical gelatin (Gelfoam) can be used for presurgical or palliative embolization of hypervascular tumors.
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