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KEY CONCEPTS

  • Brain tumors are a heterogeneous group of lesions divided into two main categories: (1) primary brain and spinal tumors arising from the cells of the central nervous system (CNS) and (2) brain metastases from systemic cancer, which are significantly more common. Neurologic deficits are determined by the location and extent of CNS involvement, as opposed to histology. Brain tumors of all kinds can predispose to seizure and high intracranial pressure.

  • The most common systemic malignancy that gives arise to brain metastases is lung cancer followed by breast cancer, melanoma, renal cancer, and colorectal cancer. Of these solid tumors, melanoma is known to have the highest tropism to colonize the brain. Tumors classically associated with hemorrhagic brain metastases include melanoma, renal cell carcinoma, thyroid carcinoma, and choriocarcinoma.

  • Gliomas are the most frequently occurring primary brain tumors and include astrocytomas (including glioblastoma), oligodendrogliomas, and ependymomas. Primary brain glial tumors are graded according to the most malignant portion of the tumor. Grade is inversely correlated with prognosis. Increasingly, molecular features are being used to define and classify glial tumors because these features yield additional insight about the anticipated behavior of the tumor and response to therapy.

  • Mutation of isocitrate dehydrogenase (IDH) is thought to represent an early step in gliomagenesis and is nearly ubiquitous in low-grade gliomas. It therefore distinguishes secondary glioblastoma that has evolved from a low-grade tumor from primary glioblastoma that arises de novo. IDH mutation has been established as a positive prognostic factor in glioblastoma (GBM). The most common IDH mutation is R132H, which can be detected by immunohistochemistry, though other noncanonical mutations in IDH1 and IDH2 can be identified through next-generation sequencing. IDH inhibition is under investigation as a possible therapeutic strategy.

  • Hypermethylation of the promotor region of the O6-methylguanine-DNA methyltransferase (MGMT) gene is another prognostic alteration in glioblastoma. Promotor methylation decreases MGMT transcription, thereby also decreasing production of a DNA repair enzyme that reverses damage induced by alkylating chemotherapy.

  • The development of brain metastases and leptomeningeal carcinomatosis is predicated on complex interactions between tumor cells and the adjacent microenvironment, sometimes referred to as the “seed and soil” hypothesis. Emerging therapeutic options for brain metastases include molecularly targeted therapies and immunotherapy used either in addition to or in lieu of conventional treatment depending on the clinical scenario.

  • Patients with brain tumors experience unique physical and cognitive symptoms that can have a significant impact on functional status and quality of life such as weakness, aphasia, memory impairment, hemispatial neglect, vision changes, dysphagia, mood dysregulation, and personality change. Care should be taken to identify and manage such symptoms in addition to treating the underlying disease process.

OVERVIEW

Brain tumors are a heterogeneous group of lesions that range from benign, slow-growing tumors found only incidentally on autopsy to malignant, rapidly growing tumors that cause death within months. The most common intracranial tumors are brain metastases from systemic cancer, estimated at 200,000 new cases per year in the United States, ...

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