Brain Cancer (tumor)- symptoms, types, diagnosis and treatment.

 Adult brain tumors are masses of abnormal cells that generally occur in adults, and result from the uncontrolled growth of those cells within the brain. OK - let’s start with some basic brain anatomy. First off, there’s the cerebral cortex which is the part of the brain that’s supratentorial or above the tentorium, and the cerebellum,which is infra tentorial or below the tentorium.

 And the brain has four interconnected cavities called ventricles, which are filled with cerebrospinal fluid - a fluid that helps provide buoyancy and protection, as well as metabolic fuel for the brain. Highest up, are two C-shaped lateral ventricles that lie deep in each cerebral hemisphere.

 The two lateral ventricles drain their cerebrospinal fluid into the third ventricle, which is a narrow, funnel-shaped, cavity at the center of the brain.

 The third ventricle makes a bit more cerebrospinal fluid and then sends all of the cerebrospinal fluid to the fourth ventricle via the cerebral aqueduct.

The fourth ventricle is a tent-shaped cavity located between the brain stem and the cerebellum. After the fourth ventricle, the cerebrospinal fluid enters the subarachnoid space, which is the space between the arachnoid and piamater, two of the inner linings of the meninges which cover and protect both the brain and spine. So this makes it possible for cerebrospinal fluid to also flow through the central canal of the spine.

 Now, focusing in on cells within the brain- there are many different types with specialized functions

For example, neurons communicate neurologic information through neurotransmitter regulated electrical impulses. Then there are cells that secrete hormones into circulation and regulate the functions of other cells throughout the body. These cells are found in glands, like the supratentorial pineal gland which is located just behind the third ventricle. Or the infratentorial pituitary gland located near the front of the third ventricle. There is also a category of cells called neuroglial cells that help support brain homeostasis, and neuronal functions. These include astrocytes which have cellular processes coming off their cell body, giving them a star-shaped appearance.

Astrocytes are found throughout the brain and spinal cord, and their main roles include maintaining the blood-brain barrier, providing nourishment to neurons, and recycling neurotransmitters. Another type of glial cell is the oligodendrocyte,which has a few cellular processes that look like branches. They are found mostly in the brain though they are in the spinal cord too. These branches wrap themselves around neurons,and produce a fatty substance made of lipo proteins called myelin, which helps transmit electrical impulses along the axons. Some brain cells have a limited ability to be replaced, especially during injury, and they do it by having undifferentiated - called embryonic stem cells - in the brain activate and mature into a specialized cell.

Now, a stem cells tumor develops if there’s a DNA mutation in any of these cell types that leads to uncontrolled cell division. Typically these are mutations in proto-oncogenes which results in a promotion of cell division, or mutations in tumor suppressor genes which results in a loss of inhibition of cell division. You can think of proto-oncogenes as the accelerator or gas pedal and tumor suppressor genes as the brakes. Too much acceleration or an inability to brake can lead to runaway cell division

As a result, the mutated cells can start piling up on each other and can become a tumor mass. Some of these tumors are benign and stay well contained or localized. But some become malignant tumors or cancers,and these are the ones that break through their basement membrane and invade near by tissues. Malignant tumor cells can get into near by blood or lymph vessels, and travel from the primary site to establish a secondary site of tumor growth somewhere else in the body - and that’s called metastasis.

Brain tumors can be categorized by their primary site location as either supratentorial, or infratentorial tumors – though some tumor scan form in either. They are typically named by the cell type involved, so an astrocytoma is a tumor formed by mutated astrocytes. But their severity is classified, or graded by the World Health Organization’s (WHO) scale. The scale goes from I to IV based on the morphologic and functional features of the tumor cells; a grade IV tumor being the most abnormal looking cells that also tend to be the most aggressive.

 But not all tumors have all four grades because some tumors are basically always more benign, whereas others are more aggressive. So let’s start with tumor types that are generally supratentorial tumors, because they make up the majority of adult brain tumors.

A common one is a type of astrocytoma calleda glioblastoma. Because astrocytes are found through the brain and spinal cord, astrocytomas can form in all of these locations, but glioblastomas are mostly in the cerebral hemispheres. And while astrocytomas can be graded I throughIV, glioblastomas are only grade IV because they are highly malignant tumors. Because of their quick growth and invasionof nearby tissues, glioblastomas tend to rapidly cross the corpus callosum. The corpus callosum is the midline structure that separates the two cerebral hemispheres, that looks like a characteristic “butterfly”on a cross-section of the brain. 

Cancer cells typically recruit blood vessels to provide them nourishment in a process called angiogenesis, but glioblastomas proliferateso fast that even with angiogenesis their nutrient demand outpaces the blood supply. As a result, because the blood supply serves the peripheral tumor cells first, the tumor cells at the center of the tumor die first because they’re the furthest from the blood cell network. Meanwhile the remaining viable tumor cells collect along the edges of the necrotic regions. Histologically, it appears like the viable cells are lining up like fence posts against the necrosis in the middle, producing a characteristic pseudo-palisading pattern.

Another common supratentorial tumor is a meningioma. Meningiomas come from cells found in the arachnoidmater of the meninges, called arachnoid cap cells. They typically form in parasagittal regions and on the surface of the brain just under the outermost layer of the meninges, the duramater. They are graded I through III and tend to be relatively slow growing. Histologically, they form nests of cells or a multinuclear syncytium of fused cells, which have an appearance like a wave in the ocean. These tumors may also cause the formation of calcifications called psammoma bodies.

 Another common supratentorial tumor in adults is the pituitary adenoma, which is formed in the pituitary gland by hormone secreting cells of the anterior pituitary. There are several cell types in the anterior pituitary that each secrete a tightly regulated level of a particular hormone; for example,lactotroph cells secrete the hormone prolactin. Pituitary adenomas are typically benign sothey’re classified by the hormone that’s released as the tumor forms, and by the sizeof the tumor; rather than using the standard WHO classifications. Histologically, the particular hormone secretingcell that’s causing the pituitary adenoma will increase in number.

Now, a relatively rare supratentorial tumor is an oligodendroglioma. Because oligodendrocytes are found through the brain and spinal cord, oligodendrogliomas can form in any of these locations, but adult oligodendrogliomas typically form in the frontal lobes of the cerebral cortex because those neurons are the most heavily myelinated. These tumors are categorized as grade II or III, with an overall tendency to be relatively slow-growing tumors, though they still have the ability to become malignant.

Histologically, prominent features can vary from fairly small, round nuclei, surrounded by well-defined “halos” or thick white borders of cytoplasm giving them a “fried egg” appearance in grade II tumors; to having a “chicken wired” pattern of nearby blood vessels with areas of calcifications in grade III tumors. Ok, so, now let’s focus on an infratentorial adult tumors, a hemangioblastoma. These tumors derive from cells with blood vessel origins, so while they can develop anywhere in the brain they are most often found in the cerebellum, especially in a middle-aged person.They are slow-growing tumors and are typically grade I. Histologically, there are often thin-walled capillaries that are arranged close to one another. Now, the most common symptoms of brain tumors include headaches, nausea, vomiting, and seizures - and they are a result of the compression and destruction of healthy brain tissue.

 In addition, it’s important to consider the cell type that’s involved. So, for example, a pituitary adenoma causing an increase in prolactin secretions may lead to amenorrhea in women and infertility in men. In addition, as the tumor grows in size, it can compress nearby cells and structures, interrupting their normal functions. For example, as meningiomas enlarge - the mass of the tumor can compress nearby ventricles blocking the flow of cerebrospinal fluid,causing swelling which results in hydrocephalus.

Diagnosis

Generally, the diagnosis of central nervous system tumors includes medical imaging, like CT scans but more commonly MRIs. But definitive diagnosis needs to be made based  on the histologic and molecular characteristics of a tissue biopsy.

Treatment

Treatments depend on the tumor type, grade,and symptoms. And can include surgical removal, radiotherapy,or chemotherapy - frequently in a combination. But specific courses of treatment are guided by the molecular characteristics of the tumor based on the biopsy. Finally, the chance of recurrence gets higher in high grade tumors and in tumors that have not been fully removed or destroyed.

Ok ,quick recap:

Adult brain tumors can beinfratentorial and supratentorial and form from a variety of cells. Tumor types are classified using WHO grading based on morphologic and functional features. Tumor symptoms depend on tumor cell type,size and location. Diagnosis includes medical imagining, with a definitive diagnosis being made with a tissue biopsy. Treatments are largely dependent on the molecular characteristics and tumor grade, and can incorporate surgical removal and a combination of radiotherapy and chemotherapy.