Medulloblastoma
Introduction
Introduction to medulloblastoma Medulloblastoma occurs in children, second only to astrocytoma, which accounts for 25% of children's intracranial tumors. The age of onset is 75% below 15 years old. Occasionally Adults, more men than women (2 ~ 3:1). The first symptoms were headache (68.75%), vomiting (53.75%), and unstable walking (36.25%). In the future, there may be diplopia, ataxia, and loss of vision. basic knowledge The proportion of illness: 0.005% Susceptible people: no special people Mode of infection: non-infectious Complications: cerebellar tonsil, hydrocephalus, edema
Cause
Medulloblastoma etiology
Recent studies suggest that medulloblastoma is derived from primitive neural stem cells, which have the potential to differentiate into a variety of cells, such as neurons and glial cells, and belong to primitive neuroectodermal tumors (PNETs). Neuroblastoma, which is located in the posterior fossa, is also known as medulloblastoma. The medulloblastoma at the midline of the posterior fossa is derived from the primordial cells of the ependymal proliferation center that differentiates into the outer granular layer in the posterior medullary sail. These cells may still exist several years after birth, while medulloblastomas that grow on one side occur in the embryonic granule layer of the cerebellar cortex. This layer of cells is located on the surface of the subdural cerebellar layer, which is normal. In the case of disappearing within 1 year after birth, this may be one of the reasons why medulloblastoma is more common in children. Some people think that the tumors in older children and adults are mainly from the former, while the medulloblastoma in young children is derived from the latter. .
Genetic factors (30%):
In the field of neurosurgery, some tumors have obvious family predispositions, such as retinoblastoma, vascular reticuloma, multiple neurofibromas, etc., which are generally considered to be autosomal dominant hereditary tumors. The rate is very high. Cell and molecular biology studies have shown that 26% to 45% of medulloblastomas have a short arm of the chromosome 17 (17p). However, despite the tumor suppressor gene p53 at 17p, further studies have shown that the medulla There is no significant correlation between blastoma cell mutation and loss of p53 gene, and the alteration of oncogene and tumor suppressor gene associated with medulloblastoma remains unclear.
Physical and chemical factors (25%):
Among the physical factors that have been confirmed to be tumor-causing, there are many reports of intracranial tumors caused by cranial radiotherapy. Among chemical factors, polycyclic aromatic hydrocarbons and nitric acid compounds such as methylcholanthrene and benzene Compared with methylnitrosourea and nitrosopiperidine, brain tumors can be induced in some animal experiments.
Virus (20%):
Experimental studies have shown that some viruses, including DNA viruses and RNA viruses, can induce brain tumors if inoculated into the brain of animals.
Immunosuppression (10%):
The use of organ transplant immunosuppressive agents increases the risk of intracranial or peripheral tumorigenesis.
Tissue differentiation (5%):
Craniopharyngioma, epithelioid and dermoid cysts, teratomas, and chordomas occur in embryonic tissues that remain in the brain. These residual tissues have the potential to proliferate and differentiate, and can develop into tumors under certain conditions.
pathology
Most of the medulloblastoma are grayish purple or pink, the texture is brittle and soft, invasive growth, most of them have pseudo-envelop, sometimes necrosis and hemorrhage in the tumor, calcification or cystic change is rare, older Group tumors occur in the cerebellar hemisphere more than in the younger group. Medulloblastoma can grow in one side of the cerebellar hemisphere. Most of the tumor occurs in the cerebellar vermis and fills the fourth ventricle. Most of them form oppression on the fourth ventricle. Only a small number of tumors invade the bottom of the fourth ventricle. The upward development of the tumor can obstruct the aqueduct. In very few cases, the catheter can protrude into the aqueduct and reach the posterior part of the third ventricle. The tumor can be filled down to the occipital pool, and a few of the occipital macropores extend into the spinal canal. .
Observed under the microscope, the cells are densely arranged, often round, elliptical, oblong or nearly pyramidal. There are nerve fibers between the cells. The tumor cells have very few cytoplasm, most of them become naked nuclei, and the cell size is the same. It has a chrysanthemum-like structure, but most cells are not arranged in a special arrangement. The nucleus is round or oval, the chromatin is extremely rich, the stain is densely stained, and the mitotic figures are more common. The tumor contains only capillaries scattered between the tumor cells, and the fiber component. Very few, you can see the necrosis of a single tumor cell, but rarely see the fire necrosis and hemorrhagic lesions, the pseudo-rosette nodules are formed to varying degrees in the tumor, and the tumor cells forming the pseudo-rosette nodules are elongated, nodules There is no blood vessel or true lumen, surrounded by eosinophilic fiber synapses, which are markers of neuroblast differentiation. Tumor vascular stroma is composed of thin blood vessels, sometimes with endothelial cell proliferation, medullary cells. Tumors occur in the cerebellar hemisphere. The cells contain a large amount of reticular fibers. They are relatively tough and have a clear boundary. They are called "proficient fibroproliferative medulloblastoma", also known as " Medulloblastoma fiber type ", such slightly better prognosis than usual medulloblastoma.
Medulloblastoma can differentiate into neurons, astrocytes, and oligodendrocytes. A few can be multi-directionally differentiated, and some become multi-fibrous. About 20% of medulloblastomas are connective tissue variants. Common in older children or adults, it has been reported that medulloblastoma differentiates into mature astrocytoma and ependymoma after treatment. Due to the pluripotent differentiation of medulloblastoma, there are even myeloid myocytes in the literature. Report of tumor differentiation.
Under the electron microscope, there are staggered cell protrusions arranged in the tumor cells, which are called "neuromatine-like oasis arrangement". The tumor cells are round and polygonal, and the adjacent cells are tightly pressed and twisted, showing a characteristic die-casting pattern. Small and small, electron-poor, lack of cell gas, but the longitudinal 20mm microtubules are common, sometimes the cell bodies are arranged in an outer ring, the center is solid, filled with staggered protrusions, microvilli and cilia are lacking, cells are rare The structure of the connection, part of the cytoplasm is dense and thick, the nucleus is large, there may be deep gully, the nucleus is a special multi-leaf, chromatin is fine particles, occasionally peripheral nucleoli, medullary cells Tumors can express ganglion cell differentiation and glial differentiation. The former has axon formation under electron microscope, microtubule structure is obvious, occasionally hollow or solid vesicles, individual synaptic vesicles can be formed; the latter is in the nucleus There are bundles of short-strand gels in the surrounding and protuberances. Neuronal and glial cell differentiation is seen as a manifestation of the two-way differentiation potential of tumor cells to maintain normal medulla cells.
classification
There are many methods for classification of central nervous system intracranial tumors. The most representative ones are the following. The classification of Bailey and Cushing can reflect the source and malignancy of tumor tissues. It has been used by neurosurgery and pathology in most parts of the world for a long time. On this basis, some new classification methods have been derived, such as Kernohan's I-IV classification, Russell's glioma classification, and more influential is that Kernohan proposed to treat gliomas, including astrocytoma, less acne. Astrocytoma, ependymoma and neurogenic tumors are classified into I-IV according to their degree of differentiation. According to this classification, it seems that the development of tumors and the prognosis of patients can be easily judged, so they are welcomed by clinicians at home and abroad. It has been used for many years, but this classification method is also flawed. For example, the same tumor can be differentiated in different parts of the tumor. Some mixed tumors cannot be graded, and some tumors have little meaning. On this basis, the World Health Organization has developed a new classification. The method is characterized by careful classification, including various types of tumors that occur in the brain, and absorbs the characteristics of various classifications in the past. At both reflect tumor morphology, but also indicate the source of the tumor, and the use of change between this concept can be considered as the best classification.
Tumor cells can be disseminated to the subarachnoid space with the cerebrospinal fluid or transferred to the extracranial cavity, up to 11% to 43%. The tumor tissue is grayish red or purple red, soft and fragile, the boundary is unclear, and the tumor cells are dense under the microscope. The nucleus is round or elliptical, deeply stained, with many mitotic divisions, less cytoplasm and interstitial, and some are arranged in the form of fake daisy.
Prevention
Medulloblastoma prevention
Refer to the general tumor prevention methods, understand the risk factors of tumors, and formulate corresponding prevention and treatment strategies to reduce the risk of tumors. There are two basic clues to prevent tumors. Even if tumors have begun to form in the body, they can help the body to improve resistance. These strategies are as follows:
1. Avoid harmful substances (promoting factors)
It is able to help us avoid or minimize exposure to harmful substances.
2. Improve the body's immunity against tumors
Can help to strengthen and strengthen the body's immune system and cancer.
(1) Avoid harmful substances: Some related factors of tumorigenesis are prevented before the onset of the disease. Many cancers can be prevented before they are formed. A report in the United States in 1988 compared the international situation of malignant tumors in detail, and proposed many The external factors of known malignant tumors are in principle preventable, that is, about 80% of malignant tumors can be prevented by simple lifestyle changes, and the last 10 years will continue to be traced back. In 1969, Dr. Higginson's research concluded that 90 % of malignant tumors are caused by environmental factors. "Environmental factors", "lifestyle" refers to the air we breathe, the water we drink, the food we choose to make, the habits of activities, and social relationships.
The focus of our current cancer prevention efforts should first focus on and improve those factors that are closely related to our lives, such as quitting smoking, eating properly, exercising regularly, and losing weight. Anyone who follows these simple and reasonable lifestyles can Reduce the chance of cancer.
(2) Promote the body to improve immunity against cancer: The most important thing to improve the function of the immune system is: diet, exercise and control troubles. Healthy lifestyle choices can help us stay away from cancer, maintain good emotional state and appropriate physical exercise. It can make the body's immune system in the best condition, and it is also good for preventing tumors and preventing other diseases. In addition, studies have shown that appropriate activities not only enhance the body's immune system, but also reduce the incidence of colon cancer by increasing the peristalsis of the human intestinal system. Rate, here we mainly understand some of the problems of diet in preventing tumors.
Human epidemiology and animal studies have shown that vitamin A plays an important role in reducing the risk of cancer. Vitamin A supports normal mucosa and vision. It directly or indirectly participates in most of the body's tissue functions. Vitamin A is present in animal tissues. In the liver, whole eggs and whole milk, the plant is in the form of -carotene and carotenoids, which can be converted into vitamin A in the human body. Excessive intake of vitamin A can cause adverse reactions in the body and -carrot This is not the case with carotenoids, and the low vitamin A content in the blood increases the risk of malignant tumors. Studies have shown that those with low levels of vitamin A intake in the blood increase the likelihood of lung cancer, while those with low blood levels in smokers Levels of vitamin A ingestors have the potential to double lung cancer. Vitamin A and its mixture can help remove free radicals in the body (free radicals can cause damage to genetic material), and secondly stimulate the immune system and help differentiate cells in the body. Ordered tissue (while the tumor is characterized by disorder), some theories suggest that vitamin A can help early carcinogens Invasion mutated cells become reversed the occurrence of the normal growth of cells.
In addition, some studies suggest that supplementation with -carotene alone does not reduce the risk of cancer, but rather increases the incidence of lung cancer. However, when -carotene binds to vitamin C, E and other antitoxin substances, his protective effect. It is shown, because the free radicals in the body can be increased when he consumes himself. In addition, there are interactions between different vitamins. Both human and mouse studies have shown that the use of -carotene can reduce 40% of vitamins in the body. At E-level, a safer strategy is to eat different foods to maintain a balanced vitamin to protect against cancer, as some protective factors have not been discovered so far.
Vitamin C, E is another anti-tumor substance that prevents the harm of carcinogens such as nitrosamines in food. Vitamin C protects sperm from genetic damage and reduces the risk of leukemia, kidney cancer and brain tumors in their offspring. Vitamin E can reduce the risk of skin cancer. Vitamin E has the same anti-tumor effect as vitamin C. It is a scavenger that protects against toxins and scavenges free radicals. The combination of vitamins A, C and E protects the body against toxins. Better than applying it alone.
At present, research on phytochemistry has attracted widespread attention. Phytochemistry is a chemical found in plants, including vitamins and other substances found in plants. Thousands of plant chemicals have been found, many of which have anticancer properties. The protective mechanism of these chemicals not only reduces the activity of carcinogens but also enhances the body's immunity against carcinogens. Most plants provide antioxidant activity that exceeds the protective effects of vitamins A, C, and E, such as a cup of cabbage juice. Contains 50mg of vitamin C and 13U of vitamin E, but its antioxidant activity is equivalent to the antioxidant activity of 800mg of vitamin C and 1100u of vitamin E. It can be inferred that the antioxidant effect in fruits and vegetables is far better than what we know. The effect of vitamins is strong, and no doubt natural plant products will help prevent cancer in the future.
Complication
Medulloblastoma complications Complications cerebellar tonsil hydrocephalus edema
Combined with chronic cerebellar tonsil, it can cause neck resistance or forcing the head position by stimulating the upper cervical nerve root. When the tumor invades the facial mound, it can spread and facial nerve paralysis. The spinal cord metastasis can cause paraplegia.
If surgery is performed, the following complications may occur:
Bleeding
Hemorrhage after surgery in the fourth ventricle and cerebellar sacral tumor is easy to cause acute obstructive hydrocephalus or direct compression of the medullary respiratory center to cause respiratory arrest. For example, there is lateral drainage outside the brain before surgery, which can help identify whether there is postoperative bleeding, and a small amount of oozing can be It is relieved by drainage outside the brain; if the amount of bleeding is large, secondary surgery is necessary to stop bleeding.
2. Breathing stops
Traction or direct injury to the medullary respiratory center during surgery, or postoperative bleeding, edema compression medulla, can cause respiratory arrest, anterior or posterior inferior cranial artery injury, causing retrograde embolism caused by brain stem infarction, can also cause respiratory arrest .
3. Intracranial gas
Excessive loss of cerebrospinal fluid, high head position during surgery, severe strain can form a tension gas cranium, gas can be located under the dura mater, longitudinal fissure, brain pool or lateral cerebral ventricle, light can absorb it by itself, and severe Need to puncture and deflate.
4. Hydrocephalus
Due to incomplete tumor resection, postoperative aqueduct adhesion, surgical area adhesions, effusion, postoperative infection, brain tissue edema and other factors, can take measures to relieve the cause of hydrocephalus, remove the obstruction or the lateral ventricle - Abdominal shunt.
Symptom
Symptoms of medulloblastoma common symptoms ataxia loss of consciousness gait instability eyeball tremor neck tonic trauma double vision abdominal cavity implantation
The course of medulloblastoma is relatively short, which is determined by the biological characteristics of the tumor. Nearly half of the patients have a disease course within 1 month, and a few can reach several years. The literature reports that the general course of disease is 4 to 5 months, with the patient. The age of the disease increases, the medulloblastoma grows concealed, and the early symptoms are lacking. It is often ignored by patients, relatives and doctors. The first symptoms are headache (68.75%), vomiting (53.75%), gait instability. (36.25%), after the double vision, ataxia, vision loss, mainly manifested as cranial symptoms such as increased intracranial pressure and ataxia, invasive brainstem often have diplopia and a variety of cranial nerve disorders, cerebellum The tonsil tendon often has a stiff neck and a torticollis, and the intracranial pressure is increased due to the majority of the tumor obstructing the fourth ventricle.
1. Increased intracranial pressure
As the tumor of the cerebellum continues to grow, the fourth ventricle and/or the midbrain aqueduct is compressed, resulting in obstructive hydrocephalus, resulting in increased intracranial pressure, clinical manifestations of headache, vomiting and fundus optic edema, etc. Group headache accounted for 76.6%, vomiting accounted for 95%, optic disc edema accounted for 72.1%, smaller children may have cranial sutures, of which vomiting is the most common, which can be the only clinical manifestation in the early stage, except for increased intracranial pressure, tumor Direct stimulation of the vagus nucleus at the base of the fourth ventricle is also one of the important causes of vomiting. Vomiting is more common in the morning, and often accompanied by hyperventilation. Children with optic disc edema are less than adults, which may be due to childhood intracranial The increase in pressure can be partially compensated by cranial suture separation, and almost all optic edema in adults.
2. Cerebellar damage sign
Mainly for the tonic ataxia caused by cerebellar sacral damage, the patient's gait is different in weight and weight, the distance between the walking feet is widened, and even standing and standing and shaking, Romberg sign is positive, because the tumor invasion site is different. The performance is different. When the tumor invades the upper cerebellum, the patient dumps forward. The tumor located in the lower cerebellum of the cerebellum is more backwards. Because the tumor invades the lower jaw, it is more common, and the backward tilting is correspondingly more. One side development can cause different degrees of cerebellar hemisphere symptoms, mainly manifested as immature dyskinesia of the affected limb. The primary cerebellar hemisphere can show cerebellar language. About half of the patients show ocular muscle ataxia, mostly horizontal. Ocular stimuli, tumor compression medulla may have swallowing cyanosis and pyramidal tract signs, 2 / 3 of the children showed muscle tension and tendon reflexes, this group had cerebellar signs accounted for 88.3%.
3. Other performance
(1) double vision: due to increased intracranial pressure, bilateral bilateral nerve palsy, manifested as bilateral strabismus, limited abduction, unilateral nerve palsy with ipsilateral peripheral facial paralysis, often suggesting that the tumor has invaded The facial nerve hill at the bottom of the fourth ventricle.
(2) facial paralysis: the tumor directly invades the nerve floor of the fourth ventricle, which is relatively rare.
(3) Forced head position: When the tumor or cerebral cerebellar tonsil penetrates into the spinal canal, it stimulates and compresses the cervical nerve root, causing the patient's protective positional response.
(4) Head enlargement and McCuewen sign: more common in younger children, due to increased intracranial pressure, cranial suture separation.
(5) Cone beam sign: Due to the increase of tumor volume, it is caused by forward compression and brain stem, and pathological reflexes in both lower extremities are more common.
(6) Cough: The tumor compresses the brainstem and/or IX, X appears on the cranial nerve, and the clinical examination shows that the pharyngeal reflex is weakened or disappeared.
(7) Cerebellar crisis: due to cerebrospinal fluid circulation disorder, cerebellar tonsil sputum or tumor directly aggravates the brain stem compression, resulting in loss of consciousness, slow breathing and elevated blood pressure, accompanied by bilateral pathological reflexes, even to the brain Wait, you can quickly stop breathing and die in a short time.
(8) Subarachnoid hemorrhage: Tumor hemorrhage of medulloblastoma is one of the main sources of bleeding in children with non-traumatic posterior cranial fossa subarachnoid hemorrhage.
4. Brain tumor metastasis symptoms
Tumor metastasis is the main feature of medulloblastoma. After tumor cells have shed, they can be disseminated through the cerebrospinal fluid circulation along the subarachnoid space. The spinal cord, especially the cauda equina, is a common site of involvement. The anterior cranial fossa is also a common planting metastasis. A few parts of the brain are transferred to various parts of the brain. A very small number can be metastasized due to hematogenous spread. It can also be implanted with the shunt. The metastasis can occur before and after surgery, but the latter increases significantly. Common sites are the lungs and bones, and there are also reports of metastatic lesions that occur locally in the wound.
Examine
Examination of medulloblastoma
Lumbar puncture: Because the tumor cells can fall off and spread, it is very important to check the cerebrospinal fluid tumor cells.
Because most patients with medulloblastoma have increased intracranial pressure, preoperative lumbar puncture should be used with caution to avoid cerebral palsy. Cerebrospinal fluid can be used to find exfoliated cells in addition to routine tests. Usually, lumbar puncture suggests increased intracranial pressure, while cerebrospinal fluid biochemical findings are seen. Protein and leukocyte increase accounted for only 1/5. Postoperative lumbar puncture for tumor cell examination has important significance, suggesting the need for whole brain and spinal cord radiotherapy after surgery.
1. Skull X-ray film
Cranial X-rays such as cranial suture widening can be seen on the skull X-ray, and tumor calcification is extremely rare.
2.CT
It can be seen that the cerebellar vermis or the four chambers are uniform in uniform density or slightly high density, and there is a boundary between the brain and the fourth ventricle. The brain stem is moved forward, and the tumor is surrounded by a thin low-density edema zone, which is obviously uniform and strengthens. Calcified vesicles are rare.
A typical medulloblastoma is more than 3.5 cm in diameter, located in the cerebellar vermis of the posterior cranial fossa, and the tumor involving the upper palate extends over the cerebellar incision. 87% of the head CT presents a uniform high-density shadow. 10% is an equal-density lesion. When there is small necrosis in the lesion, the plain scan can also show uneven density. A few have calcification, even a low-density cystic change, and the lesion boundary is clear, mostly located in the cerebellum Adult patients can be more common in the cerebellar hemisphere. The enhanced examination is uniform and uniform. Sometimes there is a thin low-density edema around the lesion. The fourth ventricle is often moved forward, which may be accompanied by obstructive hydrocephalus. In the presence of ventricular subependymal metastasis, a complete or incompletely high-density image appears in the periphery of the ventricle, which is banded and can be significantly enhanced. The identification of ependymoma is mainly calcification and cystic of medulloblastoma. It is rare and the lesion density is relatively uniform.
3.MRI
The parenchymal part of the tumor is characterized by a long T1 long T2 signal. The sagittal position can better show the relationship between the tumor originating from the cerebellum and the tumor and the fourth ventricle. This can be regarded as the identification point with ependymoma, in MRI. On the T1 image, the general signal intensity of the tumor was uniform. When necrosis or cystic change occurred, the tumor showed a longer T1 and a longer T2 lesion area. In the T2 image, 67% of the tumors showed high signal, and another 33% showed The signal, 97% of the tumor has obvious edema, because the signal intensity of the parenchymal part of medulloblastoma is not very prominent, so the location of the tumor and the resulting indirect signs are more important, can understand the brain stem The relationship between the median and sagittal scans is particularly critical. Coronal scans can be used as a reference for 3D images. 74% of the MRI sagittal images have a very thin, low-signal separation zone between the tumor and the fourth ventricle. Different membranous tumors, medulloblastoma rarely extends to the fourth ventricle crypt and cerebral cerebral horn. A small number of patients with MRI can see the tumor metastasis along the subarachnoid space, showing blurred borders of the cerebellum, MRI sagittal or coronal scan More Value, simultaneous implantation of lesions can also be significantly enhanced by Gd-DTPA, 97.5% with moderate to severe hydrocephalus, enhanced medulloblastoma Gd-DTPA scan, a substantial increase in the parenchymal part of the tumor, and cystic or necrotic areas In the non-delayed scan state, there is no enhancement. The medulloblastoma has few cystic changes. The tumor is located in the upper temporal part and can extend into the pineal region through the cerebellar incision.
Tumors located in the cranial region of the cerebellum often press the midbrain aqueduct, advance or narrow, the tumor located at the top of the fourth ventricle, the quadrilateral plate, and the anterior pith sail from the normal upright position to the near horizontal position. The aqueduct is expanded and moved upwards. The medulloblastoma can have a crescent-shaped cerebrospinal fluid residual in front of and/or above the tumor in the T1 image, and is the remaining part of the fourth ventricle that is not completely occupied by the tumor.
Diagnosis
Diagnosis and diagnosis of medulloblastoma
diagnosis
Preschool or school-age children, especially boys, have unexplained headaches, vomiting, gait instability, nystagmus, and diplopia. First, the possibility of medulloblastoma should be considered. Further neurological examination should be performed to confirm the diagnosis. Some children can be diagnosed by finding detached tumor cells in the cerebrospinal fluid. The medulloblastoma is easy to spread and metastasize. If the posterior cranial tumor has intraventricular dissemination, the disease can be diagnosed before operation.
Differential diagnosis
Medulloblastoma should be differentiated from increased intracranial pressure and ataxia, and can be diagnosed by clinical manifestations and laboratory tests.
Medulloblastoma is mainly distinguished from the following diseases:
Fourth ventricle ependymoma
Ependymoma originates from the ependymal cells at the bottom or side wall of the fourth ventricle. The boundary between the tumor and the fourth chamber is unclear. It can grow along the ventricle side hole to the cerebellopontine angle of the cerebral ventricle, and extends into the spinal canal through the occipital foramen. The course of disease is longer than that of medulloblastoma. The substantial damage of the cerebellum is not as serious as that of medulloblastoma. In some cases, there is no obvious cerebellar sign.
2. Cerebellar astrocytoma
More common in the cerebellar hemisphere, the course of disease can be very long, mainly manifested as increased intracranial pressure and limbs dyskinesia, cranial X-ray calcification is more common, in smaller children may have tumor occipital scaly bulge and The bone is thin; the tumor is mostly cystic, there are tumor nodules on the wall, and the fourth ventricle is displaced laterally.
3. Vein from papilloma
Occurs in the fourth ventricle and lateral ventricle, the age is generally below 50 years old, children under 10 years old account for about 1/3, the length of the disease varies, the main symptoms of increased intracranial pressure, the emergence of joint movement disorders, Eyeball tremor and forced head position, CT showed high-density irregular lumps of the edge, more common calcification, enhanced significantly.
