Causes and pathogenesis of brain astrocytoma

When studying the mechanism of the development of the disease, doctors pay special attention to the causes that can cause the pathological process. In this case, there is no general theory regarding the causes of brain astrocytomas. Scientists can not clearly name those factors that cause the rapid growth of glial cells, but do not exclude the influence of such endogenous (internal) and exogenous (external) factors, which usually provoke cancer.

Cause

The risk factors for the development of tumor processes include:

• High radioactive background (the more a person is under its influence, the higher the risk of the formation of malignant tumors) [1].
• Prolonged exposure to the body of chemicals, which, presumably, also can change the property and behavior of cells.
• Viral diseases. We are not talking about any virus carrier, but about the presence of oncogenic viruses in the body of virions.[2], [3], [4]
• Genetic predisposition. It is believed that the risk of developing cancer is higher for those in whose family already had cancer patients. Geneticists have found that in patients with brain astrocytoma, not everything is “clean” with one of the genes. In their opinion, violations in the TP53 gene are one of the most likely causes of the disease.[5]

Sometimes this list also includes bad habits: alcohol abuse, smoking, although there is no clear correlation between them and the development of the disease.

Scientists cannot clearly say why a tumor appears and what provokes uncontrolled cell division, but they justifiably believe that the tendency to degenerate a tumor is genetically incorporated. Therefore, different types of tumors are found in different people, differing not only in shape and localization, but also in their behavior, i.e. The ability to transform from a generally safe tumor into cancer.

Pathogenesis

Astrocytoma, by its nature, refers to tumor processes that develop from brain cells. But not all cells are involved in the formation of a tumor, but only those that perform an auxiliary function. To understand what an astrocytoma consists of, let's delve a little into the physiology of the nervous system.

It is known that nerve tissue consists of 2 main types of cells:

• Neurons are the main cells that are responsible for the perception of stimuli, the processing of information coming from outside, the generation of nerve impulses and their conduction to other cells. Neurons can have different shapes and number of processes (axon and dendrites).
• Neuroglia are auxiliary cells. The name "glia" means "glue." This explains the functions of the neuroglia: they form a grid (skeleton) around the neurons and the blood-brain barrier between the blood and the neurons of the brain, feed the neurons and metabolism in the brain, control blood flow. If it were not for the neuroglia, any brain shake, not to mention serious injuries, would end badly for a person (the death of neurons, and hence the extinction of mental functions). Glial cells soften the blow, protecting our brain as well as the skull.

It is worth mentioning that neuroglia are a more numerous type of brain cells (about 70-80%) compared with neurons. They may have different sizes and vary in shape. Small neuroglia (microglia) perform phagocytosis, i.e. Absorb the obsolete cells (such a cleaning company in the nervous system). Larger neuroglia (macroglia) perform the functions of nutrition, protection and support for neurons.

Astrocytes (astroglia) - one of the varieties of macroglial glial cells. They have multiple processes in the form of rays, for which they are called radiant neuroglia. These rays form the skeleton for neurons, thanks to which the nervous tissue of the brain has a certain structure and density.

Despite the fact that the transmission of nerve impulses, due to which the nervous activity is carried out, is answered by neurons, there is an assumption that it is the amount of astrogly that predetermines the characteristics of memory and even intelligence.

It would seem that the tumor is formed from the rapidly multiplying cells, which means that the number of astrogly increases, which should lead to an improvement in mental abilities. In fact, the local accumulation of cells in the brain does not bode well, because the tumor begins to put pressure on the surrounding tissues and disrupt their functioning.

The human brain consists of different parts: the medulla, middle and diencephalon, cerebellum, pons, and the terminal brain, which consists of both hemispheres and the cerebral cortex. All these structures consist of neurons and the neuroglia surrounding them, i.e. A tumor can form in any of these areas.

There are astrocytes in both white and gray matter of the brain tissue (they differ only in the length of the processes, but perform the same functions). White matter of the brain is called pathways through which nerve impulses are transmitted from the center (CNS) to the periphery and back. The gray matter contains the central parts of the analyzers, the nuclei of the cranial nerves, the cerebral cortex. In whatever area a tumor is formed, it will press on the brain from the inside, disrupting the functionality of the nerve fibers passing nearby, disrupting the functioning of the nerve centers.

When we found out that an astrocytoma of the brain is nothing but a tumor formation, a clear interest may arise among readers: is astrocytoma a cancer or a benign tumor? I would not like to upset our readers, because the disease is not as rare as one would expect, but this tumor is prone to degeneration into cancer, although the degree of malignancy largely depends on its type. Some neoplasms are characterized by slow growth and are quite amenable to surgical treatment, others are characterized by rapid growth and not always a good prognosis.

Astrocytomas can vary in shape and size, some do not have clear outlines, can sprout into other brain tissues. Within the nodal tumors (tumors with clear contours and localization), single and multiple cysts (cavities with semi-liquid contents) can be found. The growth of such tumors occurs mainly due to an increase in cysts, which causes squeezing of nearby brain structures.

Nodular tumors, although they can reach large sizes, are usually not prone to rebirth. They can be attributed to the category of benign tumors that can develop into a purely theoretical cancer. 

Another thing astrocytomas prone to diffuse growth, i.e. Those that capture nearby tissue, metastasize to other brain structures and neighboring tissues. They usually have a fairly high degree of malignancy (3-4 degrees), over time acquire enormous size, since they are initially prone to growth, like any cancer tumor. Such tumors tend to turn from benign to malignant quickly, so they should be removed as early as possible, not focusing on the severity of the symptoms.

Scientists already know quite a lot about glial tumors consisting of astrocytes: their types, possible localizations and consequences, behavior, the ability to develop into cancer, treatment options, a tendency to relapse, etc. The main question remains a mystery, astrocytes begin to behave inadequately, which causes them to multiply vigorously, i.e. Mechanism of formation and development of the tumor process. The pathogenesis of  astrocytoma of the brain remains unclear, and this is an obstacle to the development of methods for the prevention of the disease, the treatment of which requires a neurosurgical operation. The molecular pathogenesis of astrocytic tumors in children is being actively studied. [6], [7]  And we know that surgery on the brain is always a risk, even if the surgeon is highly competent.

Various pathways of genetic changes were found during the progression of primary glioblastomas, characterized by increased / overexpression of EGFR and PTEN mutations, while, on the contrary, secondary glioblastomas developing in younger patients show frequent mutations of p53. [8], [9]

Recent studies have shown that primary glioblastomas appear to be characterized by a loss of heterozygosity (LOH) 3 across chromosome 10, while secondary glioblastomas predominantly show LOH on chromosomes 10q, 19q and 22q [10], [11]

Genomic association studies have identified hereditary risk alleles in 7 genes that are associated with an increased risk of glioma. [12]

Epidemiology

Tumor diseases of the brain, fortunately, are far from the most common variant of oncology. But this statement is more typical for the adult population. But cancer does not spare anyone, does not look at age, gender and position in society. Alas, more often than I would hope, it is diagnosed in young patients.

Brain and central nervous system (CNS) tumors are the most common tumors and the second leading cause of cancer death in people aged 0–19 years in the United States and Canada. [13], [14], [15]

The incidence of brain cancer among children under the age of 15 years is in different countries from 1.7 to 4.1 per 100,000 children. The most common brain tumors were astrocytomas (41.7%), medulloblastomas (18.1%), ependymomas (10.4%), supratentorial primary neuroectodermal tumors (PNET; 6.7%), and craniopharyngiomas (4.4%) ). They were located mainly in the cerebellum (27.9%) and brain (21.2%). The 5-year survival rate for all brain tumors was 64%, with the worst prognosis for children with PNET. [16]Thus, in the category of risk factors of oncology of such localization can be considered as children and adolescents. And this statistic does not change in the direction of decrease.

Studies have shown that brain tumors often develop in people with immunodeficiency and, conversely, diseases in which the immune system is in a state of increased activity, are an obstacle to cell regeneration. Patients with certain systemic diseases are also at risk: neurofibromatosis, Tukot and Turner syndromes. The influence of such factors as high-voltage lines, mobile communications, radiation and chemotherapy for cancer of other localization is also being considered.

The biggest problem for oncology of the brain is the difficulty of considering the etiology of the disease, the lack of accurate information about the causes of pathology. Doctors have learned how to diagnose many other types of tumors at an early stage, and effective treatment regimens have been developed that will significantly prolong the life of the patient and reduce his suffering. But the brain is a difficult structure to study, the study of which in humans is very difficult. Animal experiments do not provide a clear picture of what can happen in the brain of a human being.

Tumors of glial cells (astrocytes and oligodendroglia) are only a particular variant of oncology of the brain. Cancer cells can also be found in other structures of the brain: neurons, secretory cells that produce hormones, brain membranes, and even blood vessels. But glial cell tumors remain the most common variant of brain cancer, diagnosed in 45-60% of cases of this terrible disease. In this case, about 35-40% falls on astrocytoma of the brain.

Astrocytomas are referred to as primary tumors, therefore, it is possible to determine the exact localization of the source of cancer cells without much difficulty. In secondary cancer, a brain tumor in most cases is formed by metastases, i.e. Migrating cancer cells, and its source can be located in any part of the body. But the difficulty usually lies not in determining the location of the astrocytoma, but in the fact that the tumor may have a different behavior.

Focal (nodal) tumors that have a clear localization, often found in children. These are mostly benign neoplasms, clearly defined in the pictures and relatively easy to remove quickly. Astrocytomas that affect the cerebellum, brain stem (medulla and midbrain, pons) are more commonly diagnosed in childhood, less often the optic chiasm or optic nerve. For example,  about 70% of children and only 30% of adults come with  astrocytoma  of the  brain stem. Among brain stem tumors, the most common is the tumor of the pons, where the nuclei of 4 pairs of cranial nerves (facial, block, trigeminal, abducent) are located.[17]

In adults, the glial tumor is more often located in the nerve fibers of the cerebral hemispheres and has no clear boundaries. Such tumors grow quite quickly, diffusely spreading to the nervous tissue, and can reach gigantic sizes. At the same time, the risk of such a transformation into a cancer is extremely high. Some researchers believe that brain astrocytoma is more often diagnosed in men of young and middle age (60%).[18]