Intracranial neoplasms can arise from any of the structures or cell types present in the cranial vault, including the brain, meninges, pituitary gland, skull, and even residual embryonic tissue. The overall annual incidence of primary brain tumors in the United States is approximately 20 cases per 100,000 person-years. In 2015, it is estimated that cancer of the brain and central nervous system (CNS) will be diagnosed in 22,850 men and women. The 5-year relative survival rate following this diagnosis is 33.8%.
The most common primary brain tumors are meningiomas, representing 34.7% of all primary intracranial tumors. Gliomas are the second most common primary brain tumor, at 30%, and account for 80% of malignant primary intracranial tumors. In children, primary brain tumors are the most common of the solid tumors and the second most frequent cause of cancer death after leukemia.
Brain metastases (secondary brain tumors) occur in approximately 15% of cancer patients as a result of hematogenous dissemination of systemic cancer, and the incidence may be rising because of better control of systemic disease. Lung and breast cancers are the most common solid tumors that metastasize to the CNS. Proportionate to their incidence, melanoma and testicular and renal carcinomas have the greatest propensity to metastasize to the brain, but their relative rarity explains the low incidence of these neoplasms in large series of patients with brain metastases. Patients with brain metastases from nonpulmonary primaries have a 70% incidence of lung metastases. Although many physicians presume that all brain metastases are multiple, in fact, half are single and many are potentially amenable to focal therapies.
There is a slight predominance of malignant primary brain tumors in men, although meningiomas are more likely to develop in women.
Primary brain tumors have a bimodal distribution, with a small peak in the pediatric population and a steady increase in incidence with age, beginning at age 20 years and reaching a maximum of 20 cases per 100,000 person-years between the ages of 75 and 84 years.
The cause of primary brain tumors is unknown, although genetic and environmental factors may contribute to their development.
Clear heritable factors play a minor role in the genesis of primary brain tumors; less than 5% of patients with glioma have a family history of brain tumor. Several inherited diseases, such as tuberous sclerosis, neurofibromatosis type I, Turcot syndrome, and Li-Fraumeni cancer syndrome, predispose patients to the development of gliomas. However, these tumors tend to occur in children or young adults and do not account for the majority of gliomas that appear in later life. A large genome-wide association study identified five risk loci for glioma susceptibility: 5p15.33 (TERT), 8q24.21 (CCDC26), 9p21.3 (CDKN2A-CDKN2B), 20q13.33 (RTEL1), and 11q23.3 (PHLDB1).
One historical prognostic marker, the epigenetic silencing of the MGMT (O6-methylguanine-DNA methyltransferase) DNA-repair gene by promoter methylation, is an independent prognostic factor in patients with glioblastoma and has been associated with longer survival in patients who received the alkylating agent temozolomide. Epidermal growth factor receptor (EGFR) amplification and overexpression are present in about 60% of glioblastomas. Mutations of the isocitrate dehydrogenase genes (IDH1 and IDH2) predict prolonged progression-free and overall survival, probably as a consequence of identifying a separate class of lesions. Shown to be early glioma-initiating events, IDH gene mutations are present in the majority of World Health Organization (WHO) grade II and III gliomas as well as secondary glioblastoma, but they are rare in primary glioblastoma. Molecular markers of brain tumors can predict survival and will become increasingly important in the diagnosis and treatment of glioma.
Prior cranial irradiation is the only well-established environmental risk factor for intracranial neoplasms.
Brain tumors are not associated with lifestyle characteristics such as cigarette smoking, alcohol intake, and cellular phone use.
Brain tumors produce both nonspecific and specific signs and symptoms.
Nonspecific symptoms include headaches, which occur in about half of patients but are rarely an isolated finding of intracranial tumors, and nausea and vomiting, which are caused by an increase in intracranial pressure. Because of the widespread availability of CT and magnetic resonance imaging (MRI), papilledema is now seen in less than 10% of patients, even when symptoms of raised intracranial pressure are present.
Specific Signs and Symptoms
Specific signs and symptoms are usually referable to the particular intracranial location of the tumor and are similar to the signs and symptoms of other intracranial space-occupying masses.
Lateralizing signs, including hemiparesis, aphasia, and visual-field deficits, are present in approximately 50% of patients with primary and metastatic brain tumors.
Seizures are a common presenting symptom, occurring in approximately 25% of patients with high-grade gliomas, at least 50% of patients with low-grade tumors, and 50% of patients with metastases from melanoma, perhaps because of their hemorrhagic nature. Otherwise, seizures are the presenting symptom in 15% to 20% of patients with brain metastases. Seizures may be generalized, partial, or focal.
Hemorrhage into a tumor may present like a stroke, although the accompanying headache and alteration of consciousness usually suggest an intracranial hemorrhage rather than an infarct. Hemorrhage is usually associated with high-grade gliomas, occurring in 5% to 8% of patients with glioblastoma. However, oligodendrogliomas have a propensity to bleed, and hemorrhage occurs in 7% to 14% of these low-grade neoplasms. Sudden visual loss and fatigue may be seen with bleeding into or infarction of pituitary tumors, termed pituitary apoplexy.
Altered mental status
Approximately 75% of patients with brain metastases and as many as half of patients with malignant gliomas have impairment of consciousness or cognitive function. Some patients with multiple bilateral brain metastases may present with an altered sensorium as the only manifestation of metastatic disease; this finding can be easily confused with metabolic encephalopathy.