Intracerebral metastases overview

# Overview
Intracerebral metastases are cancers that have metastasized to the brain from another location in the body. Intracerebral metastases are different from the cancer that starts in the brain (called primary brain cancer). Primary brain tumors occur much less often than intracerebral metastases. It is estimated that 2040% of intracerebral tumors are metastatic. Cancers that start in the brain usually remain in one place (solitary mass). If there is more than one tumor in the brain, they are most probably intracerebral metastases. The ability of cancer cells to sever their link to the primary tumor site and commence the metastatic process, once specific functions have been acquired by an appropriate subset of cancer cells. The multistep cascade can be grouped into two stages: migration (intravasation, dissemination, and extravasation) and colonization. Genes involved in the pathogenesis of intracerebral metastases include RHoC, LOX, VEGF, and CSF1. On gross pathology, intracerebral metastases are characterized by single-to-multiple masses typically found in the watershed areas of the brain, that are sharply demarcated from the surrounding parenchyma and usually have a zone of peritumoral edema that is out of proportion with the tumor size. On microscopic histopathological analysis, intracerebral metastases are characterized by tubule formation, well-circumscribed and sharply demarcated from surrounding tissues, with mitoses and nuclear atypia. Intracerebral metastases are demonstrated by positivity to tumor markers such as pankeratin, TTF-1, CK7, and CK20. Common causes of intracerebral metastases include lung cancer, breast cancer, melanoma, and colorectal cancer. Occasionally, cancer spreads to the brain but the original location of the cancer in the body (primary site) is not known. This is called cancer of unknown primary (CUP). Intracranial metastases must be differentiated from glioblastoma multiforme, meningioma, primary CNS lymphoma, stroke, and epilepsy. Intracerebral metastases are the most common intracranial tumors in adults, occurring in up to 30% of adult cancer patients. They are estimated to account for approximately 25-50% of intracranial tumors in hospitalised patients. The incidence of intracerebral metastases is estimated to be 200,000 cases annually in the United States. The incidence of intracerebral metastases increases with age. The peak incidence occurs in patients over 65 years of age. Intracerebral metastases affect men and women equally. If left untreated, patients with intracerebral metastases may progress to develop seizures, altered mental status, hemiplegia, focal neurological deficits, hemorrhage, brain herniation, coma, and death. Common complications of intracerebral metastases include brain herniation, hemorrhage, coma, and stroke. Depending on the type of the primary cancer, the age of the patient, absence or presence of extracranial metastases, and the number of metastatic sites in the brain at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as poor. The median survival time of all patients with intracerebral metastases is 2.3 months. Symptoms of intracerebral metastases include headache, seizures, visual disturbances, cognitive dysfunction, paresthesia, and muscle weakness. Common physical examination findings of intracerebral metastases include bradycardia, high systolic blood pressure with widened pulse pressure, papilledema, altered mental status, ataxia, and focal neurological deficits. Head CT scan and brain MRI may be helpful in the diagnosis of intracerebral metastases. On CT scan, intracerebral metastases are characterized by iso- to hypodense mass with zero to marked peritumoral edema. On contrast administration, variable enhancement (intense, punctuate, nodular, or ring-enhanced) may be present. On MRI, intracerebral metastases are characterized by iso- to hypointensity on T1-weighted imaging and hyperintense portion on T2-weighted imaging. On contrast administration, intense enhancement is observed (uniform, punctate, or ring-enhancing). Peritumoral edema which is out of proportion with tumor size is observed on diffusion weighted imaging. Other imaging tests for intracerebral metastases include MR spectroscopy (intratumoural choline and lipid peak with depleted N-acetylaspartate), MR perfusion (reduced cerebral blood volume and cerebral blood flow in the region of metastasis), and positron emission tomography (hypermetabolic, hypometabolic, or variable metabolism depending on the primary). Brain biopsy is done to confirm the diagnosis of intracerebral metastases, if the type of primary tumor is unknown or the etiology of the brain abnormality is unknown. Histopathological findings on biopsy of intracerebral metastases can be found here. The optimal therapy for intracerebral metastases depends on the number, size, and location of the metastatic lesions. The various treatment options for intracerebral metastases include symptomatic treatment (corticosteroids and anticonvulsants), whole brain radiotherapy, chemotherapy, stereotactic radiosurgery, and surgery.

# Historical Perspective
Intracerebral metastases was first described by Posner and Chernik, following the largest and most comprehensive autopsy series at the Memorial Sloan-Kettering Cancer Center from 1970 to 1976.

# Classification
There is no classification system established for intracerebral metastases.

# Pathophysiology
Intracerebral metastases are different from the cancer that starts in the brain (called primary brain cancer). Primary brain tumors occur much less often than intracerebral metastases. It is estimated that 2040% of intracerebral tumors are metastatic. Cancers that start in the brain usually remain in one place (solitary mass). If there is more than one tumor in the brain, they are most probably intracerebral metastases. The ability of cancer cells to sever their link to the primary tumor site and commence the metastatic process, once specific functions have been acquired by an appropriate subset of cancer cells. The multistep cascade can be grouped into two stages: migration (intravasation, dissemination, and extravasation) and colonization. Genes involved in the pathogenesis of intracerebral metastases include RHoC, LOX, VEGF, and CSF1. On gross pathology, intracerebral metastases are characterized by single-to-multiple masses typically found in the watershed areas of the brain, that are sharply demarcated from the surrounding parenchyma and usually have a zone of peritumoral edema that is out of proportion with the tumor size. On microscopic histopathological analysis, intracerebral metastases are characterized by tubule formation, well-circumscribed and sharply demarcated from surrounding tissues, with mitoses and nuclear atypia. Intracerebral metastases are demonstrated by positivity to tumor markers such as pankeratin, TTF-1, CK7, and CK20.

# Causes
Common causes of intracerebral metastases include lung cancer, breast cancer, melanoma, and colorectal cancer. Occasionally, cancer spreads to the brain but the original location of the cancer in the body (primary site) is not known. This is called cancer of unknown primary (CUP).

# Differentiating Subependymal Giant Cell Astrocytoma from other Diseases
Intracranial metastases must be differentiated from glioblastoma multiforme, meningioma, primary CNS lymphoma, stroke, and epilepsy.

# Epidemiology and Demographics
Intracerebral metastases are the most common intracranial tumors in adults, occurring in up to 30% of adult cancer patients. They are estimated to account for approximately 25-50% of intracranial tumors in hospitalised patients. The incidence of intracerebral metastases is estimated to be 200,000 cases annually in the United States. The incidence of intracerebral metastases increases with age. The peak incidence occurs in patients over 65 years of age. Intracerebral metastases affect men and women equally.

# Risk factors
The risk of developing intracerebral metastases depends on the type and location of the primary tumor. Primary tumors that are commonly associated with the development of brain metastasis include lung cancer, breast cancer, melanoma, and colorectal carcinoma.

# Screening
There is insufficient evidence to recommend routine screening for intracerebral metastases.

# Natural History, Complications and Prognosis
If left untreated, patients with intracerebral metastases may progress to develop seizures, altered mental status, hemiplegia, focal neurological deficits, hemorrhage, brain herniation, coma, and death. Common complications of intracerebral metastases include brain herniation, hemorrhage, coma, and stroke. Depending on the type of the primary cancer, the age of the patient, absence or presence of extracranial metastases, and the number of metastatic sites in the brain at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as poor. The median survival time of all patients with intracerebral metastases is 2.3 months.

# Diagnosis

## Staging
There is no established system for the staging of Intracerebral metastases.

## History and Symptoms
When evaluating a patient for intracerebral metastases, you should take a detailed history of the presenting symptom (onset, duration, and progression), other associated symptoms, and a thorough family and past medical history review. Other specific areas of focus when obtaining the history include review of the primary tumor (lung, brain, melanoma, colorectal cancer). 60-75% of patients with intracerebral metastases may be asymptomatic. Symptoms of intracerebral metastases include headache, seizures, visual disturbances, cognitive dysfunction, paresthesia, and muscle weakness.

## Physical examination
Common physical examination findings of intracerebral metastases include bradycardia, high systolic blood pressure with widened pulse pressure, papilledema, altered mental status, ataxia, and focal neurological deficits.

## Laboratory Findings
There are no diagnostic lab findings associated with intracerebral metastases.

## Chest X Ray
There are no chest x-ray findings associated with intracerebral metastases. However, a large mass may be observed on chest x-ray, which may be suggestive of the primary lung tumor.

## CT
Head CT scan may be helpful in the diagnosis of intracerebral metastases. On CT scan, intracerebral metastases are characterized by iso- to hypodense mass with zero to marked peritumoral edema. On contrast administration, variable enhancement (intense, punctuate, nodular, or ring-enhanced) may be present.

## MRI
Brain MRI is helpful in the diagnosis of intracerebral metastases. On MRI, intracerebral metastases are characterized by iso- to hypointensity on T1-weighted imaging and hyperintense portion on T2-weighted imaging. On contrast administration, intense enhancement is observed (uniform, punctate, or ring-enhancing). Peritumoral edema which is out of proportion with tumor size is observed on diffusion weighted imaging.

## Ultrasound
There are no ultrasound findings associated with intracerebral metastases.

## Other Imaging Findings
Other imaging tests for intracerebral metastases include MR spectroscopy (intratumoural choline and lipid peak with depleted N-acetylaspartate), MR perfusion (reduced cerebral blood volume and cerebral blood flow in the region of metastasis), and positron emission tomography (hypermetabolic, hypometabolic, or variable metabolism depending on the primary).

## Other Diagnostic Studies
Brain biopsy is done to confirm the diagnosis of intracerebral metastases, if the type of primary tumor is unknown or the etiology of the brain abnormality is unknown. Histopathological findings on biopsy of intracerebral metastases can be found here.

# Treatment

## Medical Therapy
The optimal therapy for intracerebral metastases depends on the number, size, and location of the metastatic lesions. The various treatment options for intracerebral metastases include symptomatic treatment (corticosteroids and anticonvulsants), whole brain radiotherapy, chemotherapy, stereotactic radiosurgery, and surgery.

## Surgery
Surgery is not the first-line treatment option for patients with intracerebral metastases. Surgical resection is usually reserved for patients with either a solitary brain metastasis or no extracranial spread of the primary tumor. Stereotactic radiosurgery is indicated if there are multiple (< 3) but small metastatic tumor masses.

## Primary Prevention
There are no primary preventive measures available for intracerebral metastases.

## Secondary Prevention
There are no secondary preventive measures available for intracerebral metastases.