Glioblastoma is a malignant glial neoplasm of the brain that develops mainly in its white matter. Clinical signs include increased intracranial pressure, convulsive syndrome, variable focal symptoms in the form of paresis, visual and cognitive disorders, speech disorders. Diagnosis is carried out on the basis of neurological examination data, neuroimaging results and histological examination of the tissues of the formation. Radical surgical removal, chemotherapy, drug anticonvulsant and decongestant treatment are performed.
C71 Malignant neoplasm of the brain
Glioblastoma is the most common primary malignant brain tumor, accounting for 16% of all primary neoplasms of the central nervous system. The average incidence rate ranges from 2.9-4.5 per 100,000 population. The formation is localized almost exclusively in the white matter of the brain, can appear in the brain stem, cerebellum and spinal cord. The average age of patients with primary glioblastoma is 62-64 years, secondary formations develop in younger patients. There are cases of occurrence at any age, including children. The incidence is slightly higher in men than in women, as well as in representatives of the Caucasian race compared to other ethnic groups.
The exact mechanism of neoplasm development is not well understood. The results of a number of studies indicate in favor of the viral theory of the occurrence of the disease. Gene mutations leading to the disease have been found. The trigger effect of electromagnetic fields, formaldehyde, and cell phone radiation has not been proven. Among the main etiological factors are considered:
- Cytomegalovirus infection. Cytomegalovirus was detected in a large percentage of malignant glioma cells, but was absent in neighboring normal brain tissues.
- Spontaneous genetic mutations. Changes in the IDH1 gene, provoking oxidative stress, contribute to genetic rearrangements and may cause the development of glial formations. Glioblastoma is also characterized by mutations of the TERT, ATRX genes.
- Ionizing radiation. It is one of the few known risk factors. Radiation-induced glioblastoma is observed years after therapeutic irradiation.
- Genetic diseases. An increased risk of glioblastoma is observed in neurofibromatosis, tuberous sclerosis, Li-Fraumeni syndrome, retinoblastoma.
Initially, it was believed that glioblastoma originates exclusively from glial elements. However, according to recent data, it originates from several types of cells with properties similar to neural stem cells. Cellular elements are at various stages of differentiation: from stem cells to neurons and glia. In 10% of cases, the neoplasm develops as a result of the transformation of a less malignant cerebral tumor.
Macroscopically, the tumor has a mottled appearance with areas of necrosis and hemorrhages. Histologically, small rounded fusiform, protoplasmic, giant cellular species are determined. Pronounced neovascularization, the presence of pseudopolysads formed by necrotic masses surrounded by malignized cells are typical.
Glioblastomas are classified as primary (de novo), arising without a known precursor, and secondary, developing from a tumor of low malignancy. Histological classification distinguishes 3 types of tumor depending on the morphology of the predominant cells:
- Multiform — characterized by variability of its constituent cellular elements. Small rounded, oval or elongated cells predominate, single large ones.
- Gigantocellular — the cell mass is dominated by multinucleated giant cells.
- Gliosarcoma — contains a sarcomatous component in the form of stained reticular fibers. Previously it was considered a separate nosological unit.
The clinic varies greatly depending on the size and location of the tumor, as well as the affected anatomical structures of the brain. Patients often come with symptoms of increased intracranial pressure, including headache, feeling of pressure on the eyes, nausea not associated with eating.
Seizures are an early symptom in 25% of patients and can occur in the later stages of the disease in 50% of cases. When glioblastoma germinates into the cerebrospinal fluid pathways, there is a violation of the circulation of cerebrospinal fluid, which leads to hydrocephalus with an aggravation of the symptoms of intracranial hypertension.
In the future, a combination of general cerebral symptoms with a progressive focal neurological deficit corresponding to the localization of the process is typical. Speech disorders in the form of dysarthria or aphasia, disorders of visual function with loss of part of the visual field, mono- and hemiparesis, cognitive changes are possible. There is weakness, in some cases — confusion.
The resulting neurological deficit is persistent and disabling for the patient. The progression of paresis leads to paralysis of the affected limbs, the patient needs outside care. A vital complication of the disease is severe hydrocephalus, which, without medical assistance, leads to compression and dislocation of the brain. Complications include a recurrence of the neoplasm. Since glioblastoma has no clear boundaries and is aggressively growing, it is extremely difficult to completely remove it during neurosurgical intervention.
With an early initial visit to a neurologist, only signs of intracranial hypertension are determined in the neurological status. Further, focal loss of nervous functions is revealed. The rapidly progressive nature of the symptoms (within 3 months) makes it possible to suspect a neoplasm, which becomes obvious with careful collection of the anamnesis of the disease. Initial diagnostic imaging is carried out by the following methods:
- Computed tomography. Reveals isodense cerebral formation with hypodense site of central necrosis, perifocal edema, hemorrhagic component. The mass effect is characteristic. CT with contrast shows annular uneven staining. Microscopic infiltration usually extends beyond the visualized focus.
- Magnetic resonance imaging. MRI with gadolinium contrast shows the formation of an irregular shape with a dense gain ring, necrotic center. Necrosis is considered a hallmark of glioblastoma. Vasogenic edema surrounding the formation, hemorrhages, cystic component, curvature or displacement of the ventricles can also be visualized. In about 13% of cases, there is a multi-focal lesion.
- MR-perfusion. It demonstrates an increase in the maximum relative cerebral blood flow and permeability, which is typical for neoplasms of a high degree of malignancy.
- Positron emission tomography. It determines glucose hypermetabolism characteristic of highly malignant formations and active accumulation of fluorodeoxyglucose.
In clinical neurology, glioblastoma is differentiated with intracerebral hematoma, abscess, CNS lymphoma, astrocytoma, arteriovenous malformation. Differentiation is carried out according to the results of neuroimaging. A distinctive feature of glioblastoma is the presence of a necrotic site. However, lymphoma in AIDS patients also has a necrotic component. In this case, the differential diagnosis is carried out during the histological examination of the biopsy material.
The current standard of treatment for patients with epiprimes includes the use of antiepileptic drugs, but routine use of anticonvulsant treatment in patients without seizures is not recommended. Many patients are prescribed corticosteroids to control vasogenic edema and relieve concomitant symptoms.
A radical method of treatment is neurosurgical removal. Extensive resection of the tumor is often difficult due to its location in functionally significant cerebral areas responsible for speech, motor function, sensitivity. The invasiveness of glioblastoma causes a high frequency of postoperative relapses. However, the use of fluorescent identification of cancer cells to differentiate pathological tissues from healthy parts of the brain makes it possible to achieve a more extensive resection with preservation of function and quality of life, to delay the occurrence of relapse. In the postoperative period, chemotherapy is recommended, in some cases combined with radiotherapy.
The researchers found that the hyoblastoma grows rapidly and recurs as it produces micro-RNA-138. A theory is being developed that the neutralization of this molecular marker will slow down the progression of the disease, as well as increase the survival rate of patients.
Glioblastoma immunotherapy is in the stage of clinical research. Passive immunotherapy consists in stimulating antitumor immunity, active — in the introduction of vaccines that potentiate the immune response to tumor antigens. The possibility of using oncolytic viruses capable of selectively attacking tumor cells is being considered. The latest technology is limited by the emergence of an immune response to the introduction of the virus.
Prognosis and prevention
Glioblastoma refers to steadily progressive, recurrent malignant brain tumors. The average survival rate of patients is 15 months. The prognosis depends on the age of the patient, the localization of education, the stage of the process at the time of its detection. Secondary neoplasms have a better prognosis than primary ones. Comprehensive treatment, including radical surgery and chemotherapy, allows to achieve remission of the disease and prolong the life of patients. Prevention of glioblastoma is reduced to the prevention of infection with viruses, the exclusion of the effects of mutagenic factors.