The etiology of brain tumors remain largely unknown, except for the hereditary form of retinoblastomas, genetically determined neurocutaneous syndromes and rare examples of tumors resulting from radiation or trauma.

However, the following factors appear to have a role:

Racial factors: Though brain tumors are found throughout the world,  certain varieties appear to be less frequently seen in certain races. Germinomas are more common in Japan than elsewhere in the world. Acoustic schwannomas have been reported to be rare in African Blacks.

Familial and genetic factors: An inborn, hereditary or inherited factor plays a role in the origin of gliomas. Oncogenes, a class of structural genes, play a decisive role in the development of neoplasms. Studies on malignant and low grade gliomas and on glioma cell lines have led to some speculative hypotheses about genetic pathways that may determine the transformation of normal glial cells to glioblastoma cells. < 5% of glioma patients have a family history of brain tumor. Several inherited diseases, such as tuberous sclerosis, neurofibromatosis type I, Turcot’s syndrome, and Li-Fraumeni syndrome, predispose 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, which appear in later years. Neurogenetic aspects are discussed elsewhere.

Transformation of ectopic tissue and vestigeal rests: Neoplasms, most often benign in nature, are seen to arise from vestigeal tissues. These include the teratomas and teratoid neoplasms, dermoid and epidermoid cysts, craniopharyngiomas and chordomas. These are clearly of malformative origin.

Age and Sex: While medulloblastomas and cerebellar astrocytomas are tumors almost entirely restricted to childhood, glioblastomas are generally seen in the adult. Primary parenchymal tumors are twice as common in males as in females, thus implicating obvious hormonal factors in the etiopathogenesis. Meningiomas are commoner in females, though some Indian and African neurosurgeons found a slight male preponderance.

Trauma: While head injury has been invoked in the pathogenesis of meningiomas, there is no evidence that such an injury plays any significant role in the development of a subsequent glioma. There are rare case reports of a glioblastoma occurring in the tract of a leucotomy or at the site of a gunshot wound.

Environmental factors: Prior cranial irradiation clearly increases the risk of subsequent intracranial neoplasms. Certain environmental factors have been tentatively linked to the development of gliomas, but they apply to few patients. Severe head trauma, chronic exposure to petrochemicals, or employment in the aerospace industry may be predisposing factors. Some reports suggest that with long term use of cell phones, there appears to be an increased risk for cases with tumors in the temporal, temporoparietal, or occipital lobe. No increased risk for brain tumors was found for medical diagnostic x-ray investigations. Brain tumors are not associated with lifestyle characteristics, such as cigarette smoking or alcohol use.

Irradiation: While gliomas do not appear to have resulted from previous therapeutic radiation to the head, this procedure might be an inciting factor in the production of an intracranial sarcoma. The hazard appears particularly associated with radiotherapy for pituitary adenomas and the resultant tumor is more frequently a fibrosarcoma of the dura, developing anywhere from 20 years later.

Chemical factors: Carcinogenic chemicals have long been employed to induce intracranial tumors in experimental animals. The most important of those are the nitrosamines-both methyl and ethyl nitrosourea. The exact mechanism of action is not clear, but may involve the binding of polycyclic hydrocarbon metabolites to guanine in DNA. It must be noted that to date no chemical carcinogen has been implicated in the production of a human cerebral neoplasm. There is no specific evidence linking human CNS tumors to chemical carcinogens.

Infective agents:  Experimentally a large number of viruses have been used for this purpose in animals. In man the only known virologic disorder of the brain associated with the production of bizarre astrocytes consistent with cytologic features of malignant cells, is the rare condition of progressive multifocal leucoencephalopathy. Here virions belonging to the papova group of viruses have been detected. Some patients with JC virus induced demyelination have developed multifocal astrocytomas

There is a wide histopathological variability (click for WHO classification) in brain tumors. Most brain tumors are named after the cells from which they develop. They may be intrinsic and arise from both the glial cells (mature and immature neuroepithelial cells), or extrinisic from the meninges, schwann cells of the nerve sheaths, and the pituitary.

Local extension from tumors of the skull or paranasal sinuses, metastasis from a distant organ, and occasionally, primary CNS lymphoma, form most of the rest. Hematological disorders, such as, leukemia, and rarely, myeloma are the other possibilities.

Hamartomas from the vestigeal remnants, and cysts are also traditionally included in brain tumor category. Other rare tumors have also been reported.

In fetal life and the first two years, supratentorial tumors are more common. Between 3 and 15 years infratentorial growth is much more frequent. In adults, supratentorial compartment is more commonly involved.

Intrinsic tumors produce regional parenchymal effects include, compression, invasion and destruction of surrounding brain leading to hypoxia, competition for nutrients and spread of necrosis. Diffuse Intracranial effects include elevated intracranial pressure due to tumor induced increases  in the volumes of brain, blood and CSF, vasogenic edema, infarction due to venous or arterial occlusion, and alteration in the balance of CSF production and absorption.

Extrinsic lesions, such as meningiomas, displace the brain, thereby compromising the brain function. In late stages, there may be degeneration, hemorrhage or necrosis. Peritumoral cysts arise from adhesions and accumulation of protein containing CSF, reactive gliosis, fibroblastic proliferation in the final stage of peritumoral edema or rarely as an exudate from the tumor surface, and behave like an intrinisic tumor.

There may be associated hydrocephalus which may be due to obstruction to CSF pathways, or change in CSF dynamics. It is more frequent in infratentorial lesions.

While the brain is a favorite site for metastases from tumors from the rest of the body, it is well known that central nervous system tumors do not metastasize outside the nervous system, except on rare occasions, when surgery has resulted in contact of the tumor with extracranial tissues.  

Malignant cells have been found in the veins in the neighborhood of a malignant glioma. Similarly such cells are also released into the CSF. There may be an immunological defence of the body tissue to the circulating malignant glial cells. On the contrary, the brain itself seems to be incapable of any significant degree of defence response. Though there are no lymphatic channels in the brain, mononuclear cells expressing T lymphocytes and macrophage cell surface markers have been identified in the perivascular spaces of the brain. It has also been observed that a third of all human gliomas show lymphocytic and mononuclear infiltration mostly around the blood vessels. Gliomas containing such infiltrates had a longer survival.   

There are a few reports of the presence of sensitized lymphocytes as well as humoral antibodies in patients with gliomas.  Considerable evidence indicates that tumors in man and animals can provoke an immune response in the host, thus providing the basis for employing immunotherapy in the treatment of human tumors.  In the perivascular lymphocytic collections, cytotoxic and suppressor T lymphocytes are predominant. Monocytes, macrophages with cell surface expression of major histocompatability antigens, are also present. Abnormalities in cell mediated and humoral immunity occur in patients with gliomas.  Abnormalities in cell mediated immunity are more severe in patients with higher grade gliomas.