Generality
Glioblastoma is probably the most malignant and aggressive brain tumor known. Unfortunately, those who suffer from it generally die within a few months, even if they have been subjected to all the necessary care.
From unknown causes - like most brain tumors - glioblastoma manifests as headache, nausea, amnesia, behavioral changes, fatigue, etc.
Diagnosis requires numerous examinations, including a tumor biopsy.
The most effective therapy for prolonging patients' lives involves surgical removal and radiotherapy.
Brief reference to brain tumors
When we talk about brain tumors, or brain tumors or brain neoplasms, we refer to benign or malignant masses of tumor cells that affect the brain (ie an area between the telencephalon, diencephalon, cerebellum and brainstem) or the spinal cord . Together, encephalon and spinal cord form the central nervous system ( CNS ).
Fruit of genetic mutations, of which however the precise cause is not known very often, brain tumors can:
- originate directly from a cell of the central nervous system (in this case we also speak of primary brain tumors );
- derive from a malignant tumor present in other sites of the body, such as the lungs (in this second case they are also called secondary brain tumors ).
Given the extreme complexity of the central nervous system and the large number of different cells that compose it, there are many different types of brain tumors: according to the latest estimates, between 120 and 130.
Regardless of their malignant power or not, brain tumors are almost always removed and / or treated with radiotherapy and / or chemotherapy, as they often cause neurological problems incompatible with a normal life.
What is glioblastoma?
Glioblastoma, or glioblastoma multiforme ( GBM ), is a highly malignant brain tumor belonging to the class of astrocytomas.
An astrocytoma originates from an aberrant astrocyte that grows and divides abnormally.
Astrocytes are glia cells; therefore astrocytomas in general and glioblastomas in particular are gliomas, or cerebral neoplasms with principle in a glia cell.
Difference between a benign tumor and a malignant tumor
A benign tumor is a mass of abnormal cells that grows slowly, has little infiltrative power and an equally poor (if not zero) metastasizing power.
Conversely, a malignant tumor is an abnormal cell mass that grows quickly, has high infiltrative power and almost always a high metastasizing power.
NB: due to infiltrative power, this refers to the ability to affect adjacent anatomical regions. With metastasizing power, on the other hand, reference is made to the ability of cancer cells to spread, through blood or lymphatic circulation, to other organs and tissues of the body (metastasis).
GLIA AND CELLS OF THE GLIA
With its cells, the glia provides support, stability and nourishment to the intricate network of neurons, present within the human body and having the task of transmitting nerve signals.
In the central nervous system, the cellular elements of the glia are astrocytes, oligodendrocytes, ependymal cells and microglia cells.
In the peripheral nervous system ( SNP ), the cellular elements of the glia are Schwann cells and satellite cells.
TYPICAL LOCATION OF GLIOBLASTOMA
Glioblastomas can arise in any region of the brain or spinal cord.
However, it has been observed that in adults they tend to develop more frequently in one of the two cerebral hemispheres (ie in the telencephalon or brain proper), while in young people they have an equal tendency to form in the brainstem, in the cerebellum and in the proper brain. .
Most glioblastomas involve the white substance, which is surrounded by the gray substance in the brain and surrounds the latter in the spinal cord.
DEGREE OF A GLIOBLASTOMA
Brain tumors are divided into 4 degrees - identified with the first four Roman numerals - depending on their growth power.
Grade I and II brain tumors grow very slowly and involve a restricted brain area; generally they are benign.
In contrast, grade III and IV brain tumors expand with speed and invade the surrounding tissue regions; they are generally malignant.
A grade I or II brain tumor can, over time, turn into a grade III or IV tumor.
Glioblastoma is a grade IV astrocytoma, characterized by high mortality (the highest among astrocytomas and perhaps even among all brain tumors) and very difficult to cure.
| Table. Degree of other astrocytomas. | ||
| Type of astrocytoma | degree | Features |
Pilocytic astrocytoma | THE | They are focal tumor masses, quite distinct from the remaining healthy brain mass. From a histological point of view, they resemble cysts filled with liquid. |
Low-grade diffuse astrocytoma | II | They are widespread tumor masses, or dispersed in the remaining healthy brain mass. Precisely because they merge with healthy tissue, they are more difficult to cure than pilocytic astrocytomas. |
Anaplastic astrocytoma | III | They are tumor masses with a high malignant power (but lower than that of glioblastomas). They are called anaplastic because their constituent cells have lost their classical form and have taken on the appearance of undifferentiated cellular elements (anaplasia). |
GLIOBLASTOMA SUBTIPES
Glioblastomas are divided into primary and secondary .
Glioblastomas are primary, since they are Grade IV from the beginning; the glioblastomas, which at an earlier stage were grade I, II or III astrocytomas, are secondary.
As can be seen, in this context the meaning of the terms primary and secondary is very different from that of the same terms when they refer to brain tumors in general.
It is good to specify this, so that the reader does not get confused.
Epidemiology
Recalling that gliomas constitute (with astrocytomas in particular) at least 30% of brain and spinal cord neoplasms, glioblastomas represent:
- 15-17% of all primary brain tumors
- 54% of all gliomas
- Between 60-75% of all astrocytomas
- The most common malignant brain tumors
Anyone can get glioblastoma, however the statistics say that the most affected individuals are male adults over the age of 50.
The few juvenile cases of glioblastoma usually affect 9-10 year-olds.
Causes
Glioblastomas, as well as almost all astrocytomas and brain tumors in general, arise for reasons that are not yet known.
RISK FACTORS
After years of studies and analysis of numerous clinical cases, doctors and researchers have concluded that there are situations capable of predisposing to glioblastoma.
In detail, these favoring conditions are:
- Being male .
- Be over 50 years old . Glioblastoma is considered a brain tumor typical of old age.
- Belong to the Caucasian, Hispanic or Asian races .
- Suffering from an inferior-IV grade astrocytoma, therefore having a low-grade or anaplastic diffuse astrocytoma of the pilocytic type. As already mentioned, in fact, these tumors can evolve and become grade IV (secondary glioblastoma).
- Suffer from one of the following genetic-hereditary diseases : neurofibromatosis, tuberous sclerosis, Von Hippel-Lindau syndrome, Li-Fraumeni syndrome or Turcot syndrome.
Many brain tumors (for example also medulloblastoma) are associated with these rare diseases.
- Having had previous contact with the SV40, HHV-6 (or human herpes virus 6 ) and cytomegalovirus viruses . Some researchers believe that these infectious agents, once they reach the brain cells, interfere with the latter's replication cycle and start the neoplastic process typical of a glioblastoma.
This is an interesting hypothesis, but it must be further investigated.
Figure: old age is a risk factor for glioblastoma. Carry out a job during which you handle PVC (polyvinyl chloride) materials daily. There are few studies on the subject, therefore the association found could be the result of chance and nothing else.
- Having contracted malaria . The same applies to the three previous viruses: there are data that suggest a relationship, but the question needs to be investigated further.
- Having been exposed to ionizing radiation in the past. In this regard, researchers have conflicting opinions. Indeed, some believe that there is no consequential relationship.
Symptoms and Complications
The symptoms and signs of a glioblastoma depend on the size and location of the tumor mass.
In general they are established very quickly and as soon as the tumor rises; however, in some cases, they appear when the disease has reached a very advanced stage.
Among the possible manifestations, we recall:
- Headache
- Nausea and vomiting, especially in the morning
- Seizures
- Memory problems (amnesia etc). They usually occur when the glioblastoma resides in the temporal lobe.
- Hemiparesis, or partial paralysis of only part of the body. It is a typical symptom of when brain tumors form at the level of the frontal lobe.
- Behavioral changes. They occur when the tumor mass is located on the frontal lobe.
- Changes in the faculties of thought
- Sense of vertigo
- Fatigue and weakness in one part of the body. They can be consequent to an involvement of the frontal and temporal lobes.
- Abnormalities of the neuro-endocrine system. They occur in children, when the glioblastoma has been formed near the hypothalamus, pituitary or epiphyseal endocrine glands.
HEADACHE, NAUSEA AND VOMITING
Headache, nausea and vomiting arise from an increase in intracranial (or intracranial) pressure ; increase that can take place for two reasons:
- Because the growing tumor mass prevents the cerebrospinal fluid (or liquor) from flowing normally.
- Because edema forms around the tumor mass.
If severe and affects the cerebral ventricles, the alteration of the liquor flow can determine the appearance of hydrocephalus .
COMPLICATIONS
Glioblastoma has a high infiltrative power. In fact, with extreme ease it invades the neighboring areas, reaches the meninges and / or diffuses its own cells in the cerebrospinal fluid.
It has a very rapid growth and its effects are devastating: without treatment, death occurs on average within 4 and a half months, due to cerebral edema and or increase beyond all limits of intracranial pressure .
Despite their very high malignancy, glioblastomas rarely spread to other parts of the body: generally, they act exclusively at the level of the central nervous system.
Diagnosis
Faced with a suspected case of glioblastoma, doctors begin their diagnostic investigations by careful physical examination and analysis of tendon reflexes .
Then they perform an ocular test and ask the patient some questions aimed at assessing mental status and cognitive abilities (reasoning, memory, etc.).
Finally, to dispel any doubts and to know the exact position and precise size of the tumor, they resort to specific tests such as:
- Nuclear magnetic resonance
- CT scan (or computerized axial tomography)
- Tumor biopsy
- Lumbar puncture
EXAMINATION OBJECTIVE AND TENDONS TRIMS, EYE TEST AND MENTAL-COGNITIVE EVALUATION
- The physical examination consists in the analysis of the symptoms and signs, reported or manifested by the patient. Although it does not provide any certain data, it can be very useful for understanding the type of pathology in place.
- The examination of tendon reflexes is a test that serves to assess the presence or absence of neuromuscular and coordinative disorders.
- Through an ocular test, the doctor observes the optic nerve and analyzes its involvement.
- The assessment of mental status and cognitive abilities is carried out with the intent to understand which area of the central nervous system may have developed a neoplasm. For example, finding memory disorders would tend to suggest a neurological problem located in the temporal lobes, rather than in the parietal lobes and so on.
NUCLEAR MAGNETIC RESONANCE (RMN) AND TAC
Nuclear magnetic resonance ( NMR ) is a painless diagnostic test that allows the visualization of the internal structures of the human body without the use of ionizing radiation (X-rays).
Its operating principle is quite complex and is based on the creation of magnetic fields, which emit signals capable of being transformed into images by a detector.
The magnetic resonance of the encephalon and the medulla provide a satisfactory view of these two compartments. However, in some cases, to improve the quality of the visualization, it could be necessary to inject a contrast liquid to venous level. In such situations, the test becomes minimally invasive, because the contrast liquid (or medium) could have side effects.
A classical nuclear magnetic resonance lasts about 30-40 minutes.
CT scan is a diagnostic procedure that uses ionizing radiation to create a highly detailed three-dimensional image of the internal organs of the body.
Although it is painless, it is considered invasive due to exposure to X-rays (NB: whose doses are by no means negligible compared to a normal radiograph). Furthermore, like MRI, it may require the use of a contrast agent - not without possible side effects - in order to improve the quality of the display.
A classic CT scan takes about 30-40 minutes.
With RMN and CT, a glioblastoma can appear as an area characterized by hemorrhagic lesions and surrounded by edema.
Both situations (especially the first one) can also occur during a heart attack or a brain abscess ; therefore it is always advisable to investigate the situation with other diagnostic tests.
BIOPSY
A tumor biopsy consists of the collection and histological analysis, in the laboratory, of a sample of cells from the neoplastic mass. It is the most suitable test if you want to go back to the type of tumor, its exact nature (benign or malignant) and to its precise degree.
In the case of glioblastoma, sampling generally takes place during a CT scan - this allows a highly precise collection - and requires a small but delicate head surgery.
What does the tumor look like?
At histological laboratory examination, a glioblastoma contains cysts filled with minerals, calcium deposits, blood vessels and different types of abnormal cells.
In particular, the vascular apparatus is highly developed, this because it must support a very consistent tumor mass composed of numerous cells.
LUMBAR PUNCTURE
The lumbar puncture consists in the collection of the cerebrospinal fluid and in its analysis in the laboratory.
To remove the liquor, a needle is used that the doctor inserts between the lumbar vertebrae L3-L4 or L4-L5. At the insertion point, an injection of local anesthetic is obviously practiced.
The execution of the lumbar puncture can be very significant, because in the liquor there may be some neoplastic cells and / or evident signs of pleocytosis (ie an unusual increase in leukocytes in the cerebrospinal fluid).
Treatment
The considerable aggressiveness and high malignancy of the glioblastoma make it a tumor that is difficult to cure .
The most widely adopted therapy consists of surgery to remove the tumor mass, followed by radiotherapy and, sometimes, also by chemotherapy .
Moreover, in addition to these treatments, doctors also set up a symptomatic cure, that is aimed at reducing certain symptoms (such as epilepsy and headache).
Surgery
Surgically removing a glioblastoma is a very complex and dangerous operation, for at least two reasons:
- For the high number of cells that make up glioblastomas . Since it is impossible to remove all the neoplastic cells, the surgeon can do nothing but eliminate most of the tumor and then rely on other treatments.
The total non-removal of the tumor is the reason why, within a short time, the glioblastoma reappears again.
- For the infiltration power of tumor masses . With their cells, glioblastomas wedge into healthy surrounding tissues, which makes their efficient removal impossible. In fact, to eliminate a group of cancer cells dispersed in a healthy area, this same healthy area must be removed. This is, however, impossible, as each region of the central nervous system has its own function, which cannot be ignored. For example, eliminating healthy brain tissue could lead to the loss of some fundamental cognitive functions in the patient.
Furthermore, the inaccessible position of the tumor mass can further complicate the operation. In fact, if the glioblastoma is in an uncomfortable position, difficult to reach by the surgeon, its removal is complicated (if not impossible).
It is statistically proven that patients whose glioblastoma has been almost completely removed live longer than patients whose tumor mass has only been partially removed.
Therefore, when surgery is possible, it is good to do it.
RADIOTHERAPY
Tumor radiotherapy is the treatment method based on the use of high-energy ionizing radiation, with the aim of destroying the neoplastic cells.
In the case of glioblastoma, it is adopted in two different situations:
- After and completing the surgery . The aim is to eliminate the neoplastic cells that the surgeon was unable to remove.
- When the tumor is not surgically removable . In these situations, radiotherapy becomes the first and most important therapeutic treatment.
CHEMOTHERAPY
Chemotherapy consists of the administration of drugs capable of killing all rapidly growing cells, including cancer ones.
The efficacy of chemotherapy in the case of glioblastoma has been the subject of numerous scientific discussions and still raises several doubts. In fact, most doctors and researchers believe that the use of chemotherapy drugs, in combination with radiotherapy, does not significantly improve patient survival. Moreover, the studies that prove the opposite are few and concern only one drug in particular: temozolomide .
| Side effects of radiotherapy and chemotherapy. | |
Main side effects of radiotherapy | Main side effects of chemotherapy |
Fatigue itch Hair loss | Nausea He retched Hair loss Sense of fatigue Vulnerability to infections |
SYMPTOMATIC TREATMENTS
To remedy the problem of epilepsy, doctors generally resort to anticonvulsants . An anticonvulsant is a drug capable of inhibiting (or limiting) convulsions caused by an epileptic seizure.
Corticosteroids are helpful because of the headache and edema that the tumor creates around itself; these drugs are powerful anti-inflammatories, which, if used for a long time and / or in wrong doses, can cause serious side effects (osteoporosis, obesity, indigestion, hypertension, agitation, sleep disorders, etc.).
Prognosis
Unfortunately, glioblastoma is a tumor that, even if treated in the best way, almost always leads inevitably to death.
The speed with which it acts is impressive and, to realize it, it is sufficient to analyze the following numbers:
- In the absence of any type of treatment, the average life expectancy is around 17 weeks, or 4 and a half months previously discussed.
- With radiotherapy alone, life expectancy is extended from 17 weeks to 30 weeks (NB: it is always an average value).
- If the tumor has been surgically removed and radiotherapy has been practiced, life expectancy ranges from just under a year to 14-15 months.
Only 6 cases out of 100 survive incredibly for another 5 years.
A late diagnosis and the very advanced age of the patients contribute to further impair the prognosis of a glioblastoma.
