Medulloblastoma

introduction

The Medulloblastoma is a malignant, embryonic Brain tumor of Cerebellum, which according to the WHO classification of tumors des Central nervous system is classified as the most severe grade, i.e. grade IV. Despite his grade, he has a pretty good prognosis. At 30%, the medulloblastoma is the most common brain tumor in children and adolescents.

Epidemiology

The incidence of brain tumors in general is said to be around 50 per 100,000 inhabitants per year; among the primary brain tumors, medulloblastoma is a rather rare type of tumor with 5%. Nevertheless, at 30%, it is the most common brain tumor in children and adolescents, with the number of new cases being 0.5 per 100,000 children under 15 years of age.

The mean age of onset is 7 years, with boys being affected 2 to 3 times as often as girls. About a quarter of medulloblastomas occur in young adulthood, 70% of those affected are younger than 16 and very few are over 50 years old.

localization

The medulloblastoma is mainly located in the cerebellar worm, the center of the cerebellum. Growing downwards, it fills the fourth ventricle, a cavity in the brain filled with cerebrospinal fluid (liquor cerebrospinalis), and presses on the rearmost part of the brain, the medulla oblongata. It pushes the cerebellar worm upwards and presses its front part against a part of the hard meninges (tentorium).

Metastases

Cells easily detach from the medulloblastoma and spread through the liquor. The spread of tumor cells creates new tumors in other places in the body. The medulloblastoma can spread along the central nervous system via the nerve fluid (liquor). In this way, so-called daughter tumors (metastases) can develop on the meninges or in the spinal canal and cause further problems. In a third of the patients, such daughter tumors (metastases) are found at the initial diagnosis. Metastases in the CSF occur in 15-40% of cases, metastases outside the nervous system (extraneural) are rather rare in medulloblastoma, but 4% occur primarily in bones and lymph nodes, but also in the liver and lungs.

Appearance

The medulloblastoma is usually an indistinct, soft tumor with a gray-white cut surface, but can occasionally also be sharply delineated and coarse. Larger tumors have central areas in which actually active cells die (necrosis).

Microscopically, the classic medulloblastoma consists of densely packed cells with round to oval, strongly stainable (hyperchromatic) nuclei, surrounded by little cytoplasm. Sometimes round cells with less stainable cell nuclei are also mixed in. In less than a third of the cases one finds the typical pseudo rosettes, called Homer-Wright rosettes. These consist of tumor cells arranged in a ring around a center of cytoplasm, in which the cell nuclei are at the edge (peripheral). Many of the cells are also in the process of cell nucleus division (mitosis) or are just dying off (apoptosis).

Classification

The World Health Organization (WHO) has developed a classification that classifies brain tumors. A distinction is made between grades 1 to 4.The basis for the classification is mainly the growth behavior of the tumor:

• Grade 1 tumors grow slowly and are mostly benign.
• Grade 2 tumors are predominantly benign, but some of them already consist of malignant cells and can also spread further, so grade 2 tumors are still benign tumors with a tendency to degenerate.
• According to the World Health Organization (WHO) tumor classification, grade 3 tumors are malignant brain tumors. While grade 3 tumors are already malignant, they grow a little slower than grade 4 tumors.
• Grade 4 tumors are characterized by extremely rapid growth

By definition, medulloblastoma is always a grade 4 tumor, as it is malignant, spreads quickly and, if left untreated, quickly leads to death.

causes

The medulloblastoma is one of the embryonic tumors (primitive neuroectodermal tumors), so it develops from embryonic, immature cells. The causes for the degeneration of the cells are still largely unexplained. In most cases, the tumor develops spontaneously.

The role of genetic factors in the development of brain tumors has become increasingly important in recent years, even if they are not relevant for the majority of brain tumors. In medulloblastomas, changes on the long arm (q arm) of chromosome 17 are often described. The p53 tumor suppressor gene, which codes for the p53 protein, is located on this chromosome. p53 controls the cell cycle and changes in the protein (mutations) lead to the growth (progression) of malignant tumors. But other genes also influence the complex process of tumor development.

Brain tumors also increasingly develop growth factors and growth factor receptors, which leads to the exceptionally rapid growth of the tumors.

Symptoms

The most common initial symptoms are headache, and nausea Vomitcaused by the increased pressure in the skull (intracranial) and the disruption of the cerebral water flow (cerebrospinal fluid circulation). In addition, the obstruction of the liquor flow leads to swelling on both sides (edema) the exit point of the optic nerve (Congestive papilla) and thus a significant deterioration in vision up to 6 or 7 Diopters Since the child's skull can still expand at this age, the symptoms of general skull pressure appear relatively late. When persistent headaches set in, the tumor has usually already reached a large extent. The initial symptoms also include gait disorders (Ataxia), which the children try to balance by supporting them with their hands and carefully standing and walking with their legs apart. They often hold their heads in a constrained position that is slightly inclined forward. Other typical symptoms are dizziness, double vision, signs of paralysis, numbness in the face and paralysis of the facial muscles (facial paresis) due to a functional disorder of the facial nerve (facial nerve).

At the time the symptoms appear (clinical manifestation), metastases are already present in 50% of patients.

You can find further information under our topic: Brain tumor signs.

diagnosis

When diagnosing a medulloblastoma, as with all brain tumors, in addition to the medical examination, the imaging procedures are particularly important.

In the Computed tomography (CT) Medulloblastomas appear as masses with an increased optical density (hyperdense) that bulge into the fourth ventricle. The optical density can be increased even further by administering a contrast agent, a substance that increases the image contrast, so that the tumor can be recognized even better. The medulloblastomas consist of solid tumor tissue with occasional necrosis.

In the Magnetic resonance imaging (MRI) the medulloblastoma can be shown even better: In the longitudinal view (T1 image) the medulloblastoma has a reduced optical density (hypotensive), in the transverse view an increased optical density (hypodense). It is easy to distinguish from the cerebellum. The clear contrast medium uptake is typical of medulloblastomas and shows the extent of the tumor in the brain stem better than on CT. The MRI can also be used to detect metastases in the liquor or in the ventricles. To display metastases in the spinal canal (spinal metastases), high-resolution, high-contrast MRI images are required.

In addition, the patient's CSF is examined for tumor cells (CSF cytology). The liquor is obtained by a liquor puncture, in which liquor is removed from a liquor space. The most common form of CSF extraction is Lumbar puncturewhich is taken from the lower spinal canal. The detection of tumor cells is associated with an unfavorable prognosis, but does not say anything about the extent of the metastasis of the spinal canal. CSF cytology is important in the differential diagnosis of embryonic tumors, such as medulloblastomas, ependymomas or pinealomas, if the type of tumor cannot be reliably diagnosed using imaging techniques.

Differential diagnosis

Medulloblastomas must be differentiated from similar small-cell embryonic tumors such as neuroblastomas, ependymoblastomas, pinealomas and tumors of the lymphoid tissue (lymphomas).

therapy

The therapy consists in the most radical surgical removal of the tumor and the subsequent high-dose irradiation with 40 Gray with direct irradiation of the posterior fossa and the entire liquor space (neuro-axis). Not every tumor responds well to radiation. Medulloblastomas, however, are radiation-sensitive tumors. This means that the tumor cells are effectively killed by radiation. Since brain tumors often infiltrate into the surrounding nerve tissue, they can usually not be completely removed during an operation. Remaining tumor cells are only killed by the irradiation. Therefore, the prognosis for the patient improves significantly through the radiation. Since the medulloblastoma often forms daughter bulges in the entire central nervous system, it is usually decided to irradiate the brain and spinal cord over a large area. Since medulloblastomas are very sensitive to radiation, a cure can be achieved in over 50% of cases.

The combination of postoperative radiation with chemotherapy produced positive results in terms of recurrence rate and survival rates, and can even be curative. In chemotherapy, agents that inhibit cell division (cytostatics) from the group of nitrous ureas such as CCNU, but also vincristine and cisplatin are administered. In children under 3 years of age, chemotherapy can delay the time of radiation and in some cases even replace radiation

prophylaxis

Since the risk factors and triggers for the development of glioblastomas are largely unknown, there are no recommendations for prevention. In general, it is advisable to avoid unnecessary radiation (especially in children) and contact with cancer-causing chemicals and pollutants, even if environmental factors only play a subordinate role in the development of Brain tumors play.

forecast

Patients with a complete resection of the tumor, no evidence of CSF metastases and no evidence of tumor cells in the CSF (negative CSF cytology) who have received combined radiation and chemotherapy postoperatively have a relatively good prognosis despite the high malignancy of medulloblastomas. However, recurrence or growth (relapse) of the tumor is common.

Medulloblastomas that only manifest in adulthood have a better prognosis and metastasize less often.

If left untreated, survival time is short.

What is the recurrence rate?

A relapse is the recurrence of a tumor after an originally successful treatment. Although the tumor was completely destroyed by surgery, radiation and chemotherapy, individual tumor cells can survive and grow again. If the tumor occurs again in the same place, it is called a local recurrence. About a third of the children suffer this fate. Small children in particular, whose tumors had already formed daughter tumors when the diagnosis was made, have a very high rate of recurrence. Older children (over 4 years) without metastases have a low recurrence rate and therefore a better prognosis.

A relapse usually occurs within the first two years after initial therapy. The two-year survival rate is on average 70%, the five-year survival rate around 50-70%, the ten-year survival rate around 50% and even after 10 years around a third of the patients are still free of recurrences.

Summary

Medulloblastomas are rapidly growing, malignant tumors in childhood and adolescence that originate from the cerebellar worm and can metastasize into the liquor space. Symptoms are vomiting, ataxia with a tendency to fall, and congestive papillae with loss of vision. A CT and an MRI are used for diagnosis. The therapy consists of the most complete surgical removal of the tumor (total resection), radiotherapy and chemotherapy. Operation and subsequent irradiation of the entire central nervous system lead to a relatively favorable prognosis.