Low-grade gliomas are solid tumors and arise from altered cells in the brain or spinal cord. They originate directly in the central nervous system (CNS), which is why low-grade gliomas are also referred to as primary CNS tumors.
In principle, such low-grade gliomas can develop anywhere in the CNS. However, they develop more frequently in certain areas:
- in children, mainly in the cerebellum or in the central parts of the cerebrum,
- in adults mainly in the cerebrum.
What causes low-grade gliomas is still largely unknown.
The starting point for tumor development is the supporting cells of the CNS, the so-called glial cells. The most common glial cells in the CNS are called astrocytes and oligodendrocytes. If the glioma is caused by their cell changes, it is therefore also referred to as an astrocytoma, oligodendroglioma or oligonedrocytoma.
Only around 5% of cases of cell changes in adults that ultimately lead to a tumor are due to hereditary genetic changes.
In addition, certain congenital malformations appear to increase the risk of low-grade gliomas. These include, for example
For example, one in five children with congenital neurofibromatosis type 1 will develop low-grade gliomas early in life.
Previous cancer can also be a risk factor for low-grade glioma. For example, radiation treatment of leukemia patients in childhood increases their risk of developing this type of brain tumor later in life.
The World Health Organization (WHO) divides gliomas into four risk classes (grades I-IV). Low-grade gliomas are found in risk classes I and II. Grades III and IV, on the other hand, are reserved for higher-grade gliomas.
Grade I gliomas are benign CNS tumors that grow slowly and usually remain confined. Although grade I gliomas can grow in a displacing manner, they do not destroy tissue layers or spread into deeper tissue.
In contrast, grade II gliomas grow diffusely and also into the surrounding tissue.
The transition from grade II to grade III glioma (= dedifferentiation) is smooth in adults - in children, however, this rarely occurs.
The symptoms of a low-grade glioma mainly depend on the location of the tumor in the CNS and how far it has spread. A distinction is made between general and specific symptoms.
The general symptoms of low-grade glioma are non-specific and therefore not very characteristic. This means that they can also be found in other diseases. These general symptoms include
The low-grade glioma often develops gradually. It often grows over several years. Typically, symptoms can occur during this time, which then manifest themselves as follows , depending on the area of the CNS affected:
- If the glioma is located in the cerebellum- as is more common in children - balance, gait and movement disorders occur.
- A low-grade glioma in the cerebrum, on the other hand, often leads to seizures, paralysis or speech disorders.
- If the tumor is located in the spinal cord, various paralysis, sensory disorders and pain can occur.
The diagnosis of low-grade glioma is often an incidental finding. The first indications of a potentially malignant tumor in the CNS can be found in
- the case history (medical history) and
- physical and neurological examination.
As a rule, deficits, paralysis or gait disorders are also noticed. Various imaging procedures are available for further clarification of the suspected tumor, e.g.
Using these methods, the doctor can detect a low-grade glioma and at the same time determine its size and location in the CNS. Particularly active tumor centers, the so-called "hot spots", can be spatially depicted in PET.
In contrast to higher-grade gliomas, low-grade gliomasdo not absorb contrast medium. As a result, they tend to appear as a diffuse cloud on MRI. This is because the blood-brain barrier is usually intact and the contrast agent cannot yet penetrate the tumor. In principle, this is a positive predictor for the prognosis.
A tissue sample of the low-grade glioma is used for the final pathological description of the tumor. The tumour is characterized histologically and molecularly. An important role is played in particular by
- the IDH mutation status,
- the MGMT promoter status and
- the 1p/19q codeletion.
In the case of low-grade gliomas, particular attention is paid to the IDH mutation status. This involves isocitrate dehydrogenase, whose gene mutates relatively frequently in this type of tumor. On the one hand, this increases the probability that the glioma will dedifferentiate into a higher-grade tumor over time. On the other hand, this group of tumors responds better to chemotherapy so that it can be used in a more targeted manner
The 1p/19q codeletion provides information about the nature of the chromosomes in the mutated tumor cells. The human DNA is wound up in the so-called chromosomes. In oligodendrogliomas in particular, there is a segment loss at chromosomes 1 and 19. If this deletion is present, the tumors respond well to drug-based chemotherapy. This would be followed by surgical removal of the tumor.
X and Y chromosomes contain the actual DNA strands © SciePro | AdobeStockIn healthy cells, the MGMT promoter is responsible for repairing damaged sections of DNA. Every day, various DNA sections of the chromosomes are read and duplicated, whereby miscoding can occur. The MGMT promoter searches for this damage and repairs it.
In gliomas, especially glioblastomas, this promoter is often methylated. This means that carbon and hydrogen atoms are incorrectly attached. This renders the enzyme inactive and DNA damage can no longer be repaired. This is why tumors with a methylated MGMT promoter respond better to the combined therapy of chemotherapy and radiation.
First and foremost, low-grade gliomas are treated surgically. The aim is to completely remove the tumor surgically.
In some cases, the tumor cannot be completely removed, for example
- due to its location,
- multiple tumor foci or
- due to its occasional extensive infiltrating growth.
Further surgery would risk neurological damage to the brain.
In such cases, the functionally still active mixed tissue of brain and tumor tissue is left in place. Also depending on the histological and molecular biological analysis (see above), the patient is then
- follow-up observation or
- treatment with radiotherapy and/or chemotherapy.
Awake craniotomy: specialized surgical procedure for adult glioma patients
Awake craniotomy is a specialized form of surgery for tumor resection in the CNS. It is used for
- circumscribed low-grade gliomas with infiltrating growth and multiple tumor foci and
- higher-grade tumors
tumors.
Its great advantage is that the patient is briefly responsive during the operation. This makes it possible to operate very close to healthy brain tissue.
Patients are fully anesthetized at the beginning of the operation. The surgeon then opens the skull and creates an access route to the tumor. As soon as the target area is reached, the patient is gently awakened. Dissecting the brain does not cause any pain as the brain tissue has no pain receptors.
Neuropsychologists and neurologists accompany the awake operation. They carry out various tests with the patients before the operation, which they repeat during the operation.
At the same time, the brain functions are visualized in the surgical area using so-called "brain mapping" by means of brief microelectrical stimulation. This provides the doctors with a functional map of the brain. With the help of this map, the doctors decide in which areas tumor tissue can be safely removed without causing any loss of
- motor function,
- speech or
- other sensory perceptions
occur. If there are indications of deficits during various fine electrical stimulations, the patient feels them immediately during the intraoperative awake state. The surgeons then adjust the tumor resection accordingly and make it more precise.
The awake operation is often accompanied by
- intraoperative MRI,
- high-resolution ultrasound,
- tumor fluorescence and
- 3D navigation
are used.
Low-grade glioma has a good prognosis if the tumor is completely resected. Almost 90 % of patients survive in the long term.
Studies have shown that the extent of tumor resection is one of the most important parameters for the best possible prognosis. Therefore, all available technical means should be used. This allows surgeons to maintain a balance between maximum tumor resection and the risk of a neurological deficit caused by the operation.
The prognosis can also be positively influenced if there is a residual tumor. To do this, the oncologists must determine the correct and customized radio and/or chemotherapy.
This is always done by an interdisciplinary team of specialists from the fields of
