Anaplastic astrocytoma of the brain

Astrocytoma is a tumor focus in the brain, which develops from specific cells of the nervous tissue - astrocytes. Such cells have a star-shaped shape, which determined their name. Such tumors are different, including the degree of malignancy. Anaplastic astrocytoma of the brain belongs to the third, rather dangerous degree: such a tumor is prone to rapid infiltration, does not have a clear configuration, which greatly complicates its treatment and, in particular, removal. [1]

Epidemiology

Anaplastic astrocytoma of the brain is more often diagnosed in adult patients. The average age of patients is 45 years.

The predominant localization of detected foci is the large cerebral hemispheres. In the process of neoplasm enlargement, focal symptoms dominate - in particular, increased arterial and intracranial pressure.

Anaplastic astrocytoma accounts for about 25% of all astrocytomas in the brain. Men are almost twice as often affected (1.8:1). The pathology is of astroglial nature.

Overall, the incidence of astrocytomas is about 6 cases per hundred thousand population in developed regions.

Causes Anaplastic astrocytoma of the brain

To date, the mechanisms of the development of anaplastic astrocytoma of the brain are still being investigated, so the exact causes of the pathology have not yet been determined. Presumably, some influence is exerted by such factors:

• hereditary genetic predisposition; [2]
• radiation, chemical poisoning, other intoxications;
• the impact of oncogenic viruses;
• head injuries.

Most experts believe that certain mutations and gene defects (both inherited and acquired) increase the risk of anaplastic astrocytoma. At the same time, some external influences can cause spontaneous mutation, such as ultraviolet or X-ray radiation, chemical reagents or infectious agents, and so on. To date, there is no evidence that lifestyle is directly related to the formation of tumorigenesis. However, this factor cannot be completely ruled out.

Risk factors

Risk factors for developing anaplastic astrocytoma of the brain include the following:

• Genetic predisposition in general to cancer, and to brain tumors in particular (if among close relatives there were cases of oncopathologies of the brain, then a person belongs to the risk group of developing astrocytoma).
• High radiation (radiation exposure causes clumping of healthy astrocytes with its transformation into malignancy).
• Malicious smoking, abuse of alcoholic products, drug addiction, substance abuse.
• Severe infectious-inflammatory pathologies in the history (especially meningitis, encephalitis).
• Harmful occupational conditions, work in chemical, metalworking, oil refining industries, etc.

If a person is included in the risk group for the development of tumor processes such as astrocytoma, it is recommended to regularly visit doctors for preventive examinations. This will make it possible to detect the disease at an early stage and start its treatment in time.

Pathogenesis

Anaplastic astrocytoma is formed in the brain and belongs to the third degree of malignancy. It develops in the smallest brain structures - astrocytes. These are the cells of the nervous system, the main function of which is to provide limiting and supporting functions of the body.

The cerebrum is represented by two types of cells:

• protoplasmic, present in the cerebral gray matter;
• fibrous, localized in the white matter of the brain and carrying out communication between blood supplying vessels and neurons.

To date, the pathology is still being studied. Meanwhile, there is a dominant opinion that anaplastic astrocytoma of the brain is the result of malignant degeneration of diffuse astrocytoma. The main pathomorphologic characteristics are signs of diffuse infiltrative astrocytoma with intense anaplasia and pronounced proliferative potential. Anaplastic process does not have typical tomographic characteristics and often has the appearance of diffuse astrocytoma or glioblastoma.

Symptoms Anaplastic astrocytoma of the brain

All symptoms of anaplastic astrocytoma are divided into general and local manifestations. General manifestations include those that occur during the development of the neoplasm, with attachment to a specific part of the brain. Symptoms reveal themselves, depending on the localization of the lesion and the degree of damage to neighboring tissues.

General symptomatology may include:

• constant pain in the head;
• A constant or frequent feeling of nausea, up to and including vomiting;
• loss of appetite;
• a feeling of blurred consciousness, foggy eyes;
• impaired concentration;
• vestibular disorders;
• memory impairment;
• general weakness, unmotivated fatigue, muscle aches;
• less often, seizures, convulsions.

Local signs include:

• when the frontal part is affected - disorders of consciousness, paralysis;
• in parietal lesions - fine motor disorders;
• when localization of astrocytoma in the zygomatic region - speech disorders;
• if there is a focus in the cerebellum - vestibular disorders;
• when the occipital region is affected - deterioration of visual function up to its complete loss.

Depending on the location of the anaplastic astrocytoma, a particular clinical symptomatology predominates. In some people, there is a deterioration of coordination and balance, memory and cognitive reactions, while in other patients, vision or hearing is reduced, speech and tactile sensitivity are affected, fine motor skills are impaired, and hallucinations occur.

The first signs of the disease are often mild, becoming more apparent as the tumor grows. These signs may include:

• severe and persistent headaches, dizziness;
• nausea unrelated to meals;
• constant feeling of fatigue, severe unmotivated fatigue, asthenia, deterioration of appetite;
• foggy eyes, double vision;
• sudden mood swings, bouts of irritability;
• seizures, epileptic seizures.

Stages

Nodular and diffuse astrocytomas are distinguished according to the type of growth. Nodular neoplasms are predominantly benign, may have numerous cysts. Typical representatives of nodular astrocytomas:

• piloid astrocytoma;
• pleomorphic xanthoastrocytoma.

Diffuse astrocytomas are primarily anaplastic astrocytomas and glioblastomas. These tumors are not clearly defined and often reach enormous sizes, as they grow rapidly and uncontrollably.

Four types of astrocytomas are distinguished by degrees of malignancy:

• Piloid (pilocytic), anaplastic astrocytoma of grade 1 malignancy grows relatively slowly. Such neoplasms as subependymoma and subependymal giant cell astrocytoma also correspond to this grade.
• Diffuse, fibrillary, anaplastic astrocytomas of grade 2 malignancy are often accompanied by the formation of cysts. This grade also includes pleomorphic xanthoastrocytoma, sometimes found in patients with temporal lobe epilepsy.
• Directly anaplastic astrocytoma grade 3 malignancy grows relatively quickly, rapidly sprouting into other brain tissues.
• Glioblastoma is a particularly dangerous neoplasm with aggressive growth.

Depending on the location, anaplastic astrocytomas of the frontal lobe, cerebellum, ventricles, and brain shell are distinguished.

In addition, the malignant process proceeds by stages:

1. A neoplasm appears in one part of the brain without infiltrating nearby tissues or compressing surrounding brain areas.
2. The tumor grows slowly, but is already beginning to infiltrate neighboring tissues.
3. Cell division is accelerated, sprouting into nearby parts of the brain is noted.
4. Astrocytoma reaches large size, spreads to neighboring brain structures; distant metastasis is possible.

Complications and consequences

Anaplastic astrocytoma often causes severe head pain, vomiting, seizures, and damage to the cranial nerves as a result of increased intracranial pressure. If the optic nerve is affected, complete loss of vision is possible. Astrocytoma of the spinal cord can cause pain, severe weakness or paresthesias in the extremities.

In the postoperative period, the development of complications such as bleeding (hemorrhages into the brain tissue), the formation of cysts, infectious processes and tissue edema, which, in turn, leads to the appearance of motor and cognitive disorders, is not excluded:

• paresis;
• apraxia;
• agnosias (visual, tactile disorders, auditory and spatial perception disorders);
• speech disorders (aphasia, dysarthria);
• impairment of memory, thinking and attention.

There is an increased likelihood of a primary disorder of visual and auditory realization due to compression of the brain structures responsible for the corresponding function.

Recurrence of anaplastic astrocytoma

Anaplastic astrocytoma of the brain often leads to severe disability and even death. The consequences in each specific case may be different, depending on the location and size of the tumor, as well as on the timeliness and completeness of treatment.

Recurrences are particularly common in cases where the astrocytoma is hard to reach and difficult to radically remove. On average, recurrence of the neoplasm is noted within the first year of treatment. If a recurrence is detected, the doctor may prescribe radiotherapy or repeated surgery to remove the neoplasm.

Recurrence of anaplastic astrocytoma several years after treatment is not excluded. If the recurrent tumor is operable, repeated surgery is performed, while radiosurgery is more often used for inoperable tumors. In both the first and second cases, chemotherapy and radiation therapy are additionally prescribed.

Diagnostics Anaplastic astrocytoma of the brain

In the early stages of development, anaplastic astrocytoma does not reveal itself by any symptomatology, but in most cases the tumor can be detected diagnostically. In particular, this is facilitated by the following methods:

• MRI - magnetic resonance imaging helps visualize brain structures and characterize pathology.
• CT - computed tomography - can be an alternative to MRI in some situations. However, it is impossible to see tumor metastasis in this case.
• Positron emission tomography - involves the injection of a radioactive substance with further tomographic scanning. As a result, the specialist receives a color image of brain structures, the study of which helps to find out the localization of the neoplasm and determine the appropriate treatment.
• Biopsy - a study involving the removal of a piece of biological material with subsequent histological analysis, which allows to establish the nature of the tumor.

In the vast majority of cases, instrumental diagnostics, namely MRI, helps to establish the correct diagnosis. MRI with contrast is indicated for anaplastic astrocytoma. The procedure provides an opportunity to obtain accurate information about the boundaries of the neoplasm, which by other means are not determined. The patient is injected in the ulnar vein with a special substance that reaches and accumulates in tumor tissues, which clearly distinguishes them against the background of healthy brain structures. High-contrast images help the doctor to clarify the nature, size, outlines of the tumor process, to determine its interaction with nearby tissues.

Laboratory tests are nonspecific. General and biochemical blood tests, urinalysis, blood for hormone levels and oncomarkers are prescribed.

Differential diagnosis

Differential diagnosis of anaplastic astrocytoma is performed with such pathologies:

• primary lymphoma of the central nervous system;
• inflammatory diseases;
• degenerative diseases;
• metastatic lesions of the central nervous system, etc.

Stereotactic biopsy (STB) is recommended as a differentiating technique.

In order to avoid diagnostic errors and to determine the degree of malignancy of the neoplasm, during surgical intervention or biopsy, a tissue particle most typical for astrocytoma is used as a biomaterial. Most often it is a tissue that intensively accumulates contrast agent (according to information obtained during preoperative MRI or CT with contrast, or positron emission tomography with amino acids).

Treatment Anaplastic astrocytoma of the brain

Treatments for anaplastic astrocytoma include:

• Neurosurgical removal of the astrocytoma (complete or partial);
• radiation treatment using high-energy rays to kill tumor cells (usually in combination with surgery and chemotherapy);
• chemotherapy (use of special chemopreparations in the form of tablets or intravenous injections as part of complex treatment).

In addition, palliative (supportive) treatment is provided to help patients feel better. Palliative support includes the use of painkillers, anti-edema, anticonvulsants, tranquilizers and other medications, both before and after surgery, chemotherapy, radiation therapy.

Drugs that are used as part of antitumor therapy:

• Temozolomide;
• Etoposide;
• Vincristine;
• Procarbazine;
• platinum derivatives - Carboplatin, Cisplatin;
• Bevacizumab (alone or in combination with Irinotecan).

In recurrent anaplastic astrocytoma, Temozolomide is prescribed alone or in combination with repeated radiation therapy. Bevacizumab may be used (alone or in combination with Irinotecan). [3]

In patients with anaplastic astrocytoma, it is recommended that as part of the initial treatment after resection or biopsy, a treatment regimen combining radiation and chemotherapy with Temozolomide should be performed. Temozolomide is administered daily for the duration of radiation therapy, followed by maintenance similar Idh1 mutant chemotherapy.

For astrocytoma recurrence after concomitant chemoradiation, Bevacizumab-based treatment in combination with Irinotecan or alone or in combination based on nitro derivatives and platinum-based agents is prioritized.

The doses of drugs and the duration of the course of treatment are calculated individually in each case. The most significant clinical side effect of chemopreventive drugs is hematologic toxicity with a drop in leukocyte and platelet levels, neutrophils and hemoglobin.

Before prescribing chemotherapy drugs, the doctor must take into account possible hematotoxicity and other side effects, depending on the specific chemotherapeutic regimen. During treatment, blood counts and blood counts must be monitored regularly.

Basic anti-edema agents for patients with anaplastic astrocytoma are often corticosteroids (Prednisolone, Dexamethasone), diuretics (Furosemide, Mannitol). The dosage and intensity of the treatment course is determined strictly individually, based on clinical manifestations and neuroimaging information. Administration of corticosteroids is accompanied by the use of _H2-histamine blockers (Ranitidine, etc.).

In seizures, as well as for their prevention, anticonvulsants are prescribed: preferable are Kepra, sodium valproate, Lamotrigil.

Symptomatic analgesic therapy is usually represented by non-steroidal anti-inflammatory drugs.

Surgical treatment

The feasibility of surgery for anaplastic astrocytoma depends on the patient's age, general health, expected histologic characteristics, anatomic localization of the neoplasm itself, and its surgical accessibility. The neurosurgeon will always try to maximize the removal of malignant tissue, with minimal risk of exacerbation of neurological manifestations and the possibility of preserving the quality of life. Tactics of surgical intervention is chosen based on the following factors:

• the location and accessibility of the tumor to the surgeon;
• functional status of the patient, his/her age, present somatic diseases;
• mass-effect reduction opportunities;
• term after previous intervention in patients with recurrent anaplastic astrocytoma.

The most common operations involved are:

• stereotactic biopsy;
• open biopsy;
• partial resection;
• complete (total) removal of the neoplasm.

The surgery is performed following the plan of maximum possible elimination of tumor structures, normalization of intracranial pressure, reduction of neurological insufficiency and removal of a sufficient volume of biomaterial. Surgical access is performed by bone-plastic trepanation. Astrocytoma is removed using microsurgical technique and intraoperative visualization. If necessary, neuronavigation, intraoperative metabolic navigation, and electrophysiologic mapping may be used. The dura mater is hermetically sealed as standard, and scalp aponeurosis and other tissues (including artificial tissues) are used as indicated.

Stereotactic biopsy is used when there are difficulties in determining the diagnosis, when it is impossible or inexpedient to surgically remove the tumor.

Prevention

The exact causes of anaplastic astrocytoma formation are currently unknown, and there is no specific prophylaxis. In general, oncology specialists give the following preventive recommendations:

• lead as healthy a lifestyle as possible;
• Practice adequate physical activity, avoiding excessive activity and avoiding hypodynamia;
• to get a good night's rest;
• completely give up bad habits (smokers, alcoholics and drug addicts are more than a quarter more likely to develop anaplastic astrocytoma);
• Adhere to a diet rich in plant-based foods;
• Limit negative stressors, avoid conflicts, fears, excessive anxiety;
• timely treat any infectious and inflammatory diseases, regularly visit a doctor for routine preventive examinations.

Sporting activities

It is a common belief that people with or after anaplastic astrocytoma should take every possible precaution, including avoiding physical activity. However, experts are confident that physical activity is not only safe during treatment and rehabilitation, but also can accelerate recovery and improve the quality of life. However, we are talking about well-considered exercises, without excessive loads.

Patients who have had an astrocytoma, or who have astrocytoma, are indicated:

• light calisthenics;
• hiking in the fresh air;
• swimming;
• breathing exercises;
• stretching exercises.

It is undesirable to engage in boxing, soccer and basketball, martial arts, weightlifting, high jumping, skiing, equestrian, skating.

Before starting sports activities, you should consult with your doctor beforehand.

Forecast

The average life expectancy after surgical and complex treatment is approximately 3 years. The clinical outcome of the disease depends on the course of the pathologic process, its transformation into glioblastoma, which occurs approximately a couple of years after diagnosis. Among the clinically favorable prognostic factors especially can be distinguished:

• young age;
• complete successful removal of the neoplasm;
• satisfactory preoperative clinical status of the patient.

Anaplastic astrocytoma of the brain with the presence of an oligodendroglial component has a high risk of survival up to seven years or more.