What Are the Signs of Medulloblastoma in Children?

Myeloblastoma is the most malignant glioma in the skull. Its highly malignant manifestations are in three aspects: extremely rapid growth; surgery is not easy to completely remove; tumor cells tend to produce disseminated implantation along the cerebrospinal fluid. It mainly occurs in children under the age of 14, and a few are seen in people over the age of 20. Both Toronto and Philadelphia Children's Hospital have reported the incidence of medulloblastoma, second only to cerebellar astrocytoma, and the second most common tumor in children's posterior cranial fossa. It accounts for 10.7% of gliomas and 7.6% of intracranial tumors in children. It accounts for 6.5% to 10% of gliomas in the literature. The average age was 14 years, and children under 12 accounted for 69% of all patients with this tumor, with a male to female ratio of 2: 1. Almost all children are located in the cerebellar vermicompost, protruding into the fourth ventricle, and even filling the cerebellar bulbar cistern. Occasionally seen in the cerebellar hemisphere. It is also common in the cerebellum and occasionally in the cerebral hemisphere in adults, but some scholars believe that the diagnosis of medullary tumor of the brain is actually neuroblastoma.

Du Jianxin	(Chief physician)	Department of Neurosurgery, Xuanwu Hospital, Capital Medical University
Wu Yanfei	(Attending physician)	Department of Neurosurgery, Xuanwu Hospital, Capital Medical University

Medulloblastoma is a childhood posterior fossa malignant glioma named by Bailey and Cushing. The cell morphology of medulloblastoma resembles embryonic medulloblastoma, hence the name. Myeloblast is a very primitive, non-polar cell. It is found only in the posterior medulla in human embryos, which is consistent with the occurrence of medulloblastoma in the cerebellar vermis. Myeloblastoma is the most malignant glioma in the skull.

Western Medicine Name: Medulloblastoma
English name: medulloblastoma

Affiliated Department: Surgery-Neurosurgery
Disease site: Brain
Contagious: Non-contagious

Introduction to medulloblastoma disease

Medulloblastoma pathology

Myeloblastoma is a soft, friable, parenchymal tumor with recognizable boundaries. The cut surface is purple-red or gray-red. Necrosis can occur in the center of larger tumor masses, and cystic changes and calcification are rare. The tumor is mainly located in the cerebellar vermicompost, which penetrates into the fourth ventricle and often invades the bottom of the fourth ventricle. From the fourth ventricle, the tumor can block the aqueduct upward, block the median hole downward, and grow into the cerebellar medulla cistern. The cerebellum can be violated. Literature and data show that there are significantly more cerebellar hemispheres in older groups than in younger cases. Some people believe that the reason for this difference is that younger children's medulloblastoma originates from embryonic residual cells in the myelin appreciation center, while older children Or in adults, the tumor may originate from the outer granular cell layer of the cerebellum embryo. This layer of cells is located on the surface of the subchondral cerebellar molecular layer, which usually disappears within 1.5 years after birth. Myeloblastoma has a tendency to diffuse and spread along the subarachnoid space. The pia mater near the tumor is often infiltrated, forming a layer of milky white gel-like tissue on the surface of the brain. Spreading along the subarachnoid space, the oncology metastases into the spinal canal and the surface of the brain; or spreading along the ventricle to the third ventricle. The latter case is rare. Individual extracranial metastases to lungs, bones and lymph glands.

Microscopic examination showed that the western cells were extremely abundant, small in size, and the cell membrane was unclear. Tumor cells are round, oval, oblong and carrot-shaped, densely arranged. There is very little cytoplasm. Most cells can barely see the cytoplasm and show naked nucleus shape. The nucleus is round or oval, ranging in size, with deep staining. There are many divisions. Most tumors do not have a special arrangement of cells, and the tumor cells are irregularly clustered into a pile; a small part of them form a pseudo-chrysanthemum-like shape, with cross-sections such as acinar and longitudinal sections such as glandular ducts, but no glandular cavity. This phenomenon indicates that the tumor The cells differentiate into neuroblasts. There are few stroma and small blood vessels. Intertwined bipolar nucleus glial fibers are seen in a few tumors, suggesting differentiation into glial cells. In the tissue image, adult medulloblastoma is no different from children, but the prognosis is better.

Clinical manifestations of medulloblastoma

The tumor is highly malignant, grows fast, and has a short course of disease. The average time from onset to consultation is about 4 months, with the shortest 10 days and the longest 1 year. The main symptoms are increased intracranial pressure and cerebellar symptoms.

Symptoms of increased intracranial pressure in medulloblastoma

Because the tumor is likely to block the fourth ventricle, hydrocephalus and increased intracranial pressure can cause headaches (79%), vomiting (82%), and papillary edema (75%). In young children, the skull can be enlarged, and the sound of cracking cans. Ankylosing episodes and foramen magnum hernia may occur at a late stage. Vomiting occurs most frequently and early rise can be the only symptom. In addition to increased intracranial pressure, vomiting can also be caused by tumors directly stimulating the vagus nucleus at the base of the fourth ventricle. Vomiting often occurs in the morning and is often accompanied by excessive ventilation. After vomiting, children often feel that their symptoms are significantly reduced, and they can still eat and go to school. As a result, it often fails to get parents' attention or even delay treatment within weeks or months. Multiple headaches and forehead. Children often wake up at night due to headaches, which are mainly caused by increased intracranial pressure. Like vomiting, it is often accompanied by excessive ventilation. Excessive ventilation and vomiting can alleviate headaches because excessive ventilation can reduce intracranial blood volume and reduce intracranial pressure.

Cerebellar symptoms and cranial nerve symptoms of medulloblastoma

The tumor mainly destroys the cerebellar vermicompost, manifested as physical balance disorder, unstable walking and standing. When the tumor is located in the lower earthworm, it tends to dump backward. This is because the tumor destroys the structure of the earthworm and damages the connection between the cerebellar earthworm and the spinal cord and vestibule, so it is difficult for the body to maintain balance. It is more common for tumors to invade the lower earthworm, so most children manifest backward. If the tumor occurs in the cerebellar vermicompost, or if it develops to one side, it will also cause different degrees of cerebellar hemisphere damage, showing limb ataxia. Patients with primary tumors in the cerebellar hemisphere may have instability. Finger-nose test and knee-tib test are positive. Some patients also have poor articulation (cerebellar speech). Muscle tone and tendon reflexes are mostly underneath. Nystagmus is also a sign of the cerebellum and is a manifestation of ataxia of the eye muscles. Nystagmus was mostly horizontal, according to statistics, 68.3% were positive, and Cuneo and other statistics were 63.6%. Signs of ataxia such as nystagmus, decreased muscle tone, and weakened tendon reflexes were also common (56%). Involved brainstem may have posterior cranial nerve symptoms and long conduction tract signs. Some have diplopia (34%), vision loss (27%), abducent nerve palsy (47%), facial paralysis, etc., and may also have forced head and neck resistance.

Symptoms of medulloblastoma metastasis

Symptoms of tumor metastasis are an important feature of this disease. Tumor cells of medulloblastoma can shed, and disseminated implants can be produced along the subarachnoid space through the cerebrospinal fluid circulation. The common site is the spinal cord, especially the pony tail. A few can be transferred to various parts of the brain; a very small number can be transferred to other parts of the body through the bloodstream (distant septum). Although metastases can occur before surgery, most occur after surgery. Park counted 144 cases of medulloblastoma, of which 14.6% had metastasis, 12.5% had spinal cord metastases, and 9% had metastases outside the central nervous system. Berry counts 46% of neurological metastases and 35% of central nervous system metastases. Cuneo reported that 18.1% of patients with spinal cord metastases from this disease occurred after surgery (some appeared after radiotherapy). Metastatic symptoms can occur from 8 months to 6 years after surgery, but most occur within 1 year after surgery. Rubinstein noted that metastases can be seen in about 1/2 of autopsy patients. Quest has performed autopsy on 30 cases of myeloblastoma, and 23 cases found metastases. The vast majority of patients with metastases are implanted in the soft membrane of the spinal cord, and about half of them involve the brain and ventricle. Cases where extracranial metastases occur in the wound have been reported. The extracranial distant metastases are mostly hematogenous dissemination, and the common parts are the lungs and bones. Makevev et al. Reported a pulmonary metastasis in a patient after ventricular-jugular shunt. In addition to metastasis, it is worth mentioning that myeloblastoma is prone to relapse. The recurrence is mostly within 6 to 9 months after operation, up to 10 years. The recurrence is mostly in the original lesion, which can be single or multiple. Jereb counted 15% of 40 recurrent cases at the sieve plate at the base of the anterior cranial fossa, so he emphasized that radiotherapy should include this area.

Auxiliary examination of medulloblastoma

Cerebrospinal fluid examination of medulloblastoma

In addition to increased pressure, the amount of protein and white blood cells can increase. Easy to see tumor cells. However, the detection of tumor cells may not necessarily cause metastasis, but it only indicates the necessity of radiotherapy.

X Plain X-ray film of myeloblastoma

Most of the signs of intracranial pressure increase in children may have bone suture separation, enlarged skull, thin bones and so on. Calcification of tumors and rare.

Medulloblastoma brain angiography

Vertebral angiography shows irregular arteries adjacent to the tumor, showing fine tumor blood vessels, and early vein filling.

Ventricular myeloma

It shows that the uniformity of the ventricle system above the aqueduct is enlarged. It can be seen that the lower part of the aqueduct and the fourth ventricle are shifted forward, but rarely laterally. The fourth ventricle may have filling defects or even not filling. The filling condition of the aqueduct and the fourth ventricle is of great value for preoperative assessment of the size and location of the tumor. The main manifestations are as follows: If the tumor protrudes from the aqueduct and does not develop, it appears as aqueduct obstruction. Only by clinical manifestations and CT examination can be identified. Tumors on the upper earthworm can shorten the aqueduct and bend it downward at right angles. There is no left-right displacement of the upper aqueduct in the Tang's position. When the tumor is located in the lower earthworm, the aqueduct is dilated and there is no lateral displacement of the fourth ventricle.

CT CT scan of medulloblastoma

A typical medullary tumor is larger than 3.5 cm in diameter and is located in the cerebellar vermicompost of the midline of the posterior cranial fossa. Tumors involving the upper vermicompost extend above the cerebellar notch. CT plain scan tumors are usually uniform high-density lesions with clear borders. The enhancement examination was uniform and intensified. When there are small necrotic lesions in the lesion, the plain scan can also show uneven mixed density, which is enhanced after injection. Tumor calcification is common, and sometimes a thin, low-density edema band surrounds the lesion. The fourth ventricle is often pushed forward and may be accompanied by obstructive hydrocephalus. It is distinguished from ependymal tumor mainly by calcification of medulloblastoma and cystic changes, and the lesion density is uniform. When the ventricular membrane is down, a full or incomplete slightly high-density image may appear around the ventricle, which is band-shaped and significantly enhanced.

MRI MRI of myeloblastoma

The substantial part of medulloblastoma is long T1 and long T2, and the characteristics of signal intensity are not outstanding. The median sagittal scan is particularly important for diagnosis. Generally, the signal intensity of medulloblastoma is uniform. When necrosis or cystic change occurs, the internal Lesions with longer T1 and longer T2 than the tumor can be seen. Gd-DTPA enhanced scan, the substantial part of the tumor was significantly enhanced. For the examination of disseminated implantation of medulloblastoma along the cerebrospinal fluid, MRI sagittal or coronary scans are more valuable. At the same time, the implanted lesions can also be marked by Gd-DTPA Enhanced.

Differential diagnosis of medulloblastoma

Myeleoblastoma should be distinguished from the following diseases:

Medulloblastoma fourth ventriculoventricular tumor

The disease originates from the ventricular membrane of the fourth ventricle. Early vomiting is caused by the stimulation of the bottom of the fourth ventricle. The course of disease is longer than that of medulloblastoma, and the substantial damage to the cerebellum is not as severe as that of medulloblastoma. In some cases, there are no obvious cerebellar signs.

Medulloblastoma cerebellar astrocytoma

Occurred in children's cerebellar hemisphere, benign. The course can be very long, mainly manifested by increased intracranial pressure and ataxia of one side of the limb. Skull X-ray plain radiographs have a higher calcification rate than medullary tumors, and in some cases (especially younger children), occipital squamous bulges on the tumor side and bone thinning can be seen. Ventricular radiography showed that the aqueduct was flexed forward, and the fourth ventricle was laterally displaced in the Tang position. CT and MRI can confirm the location and even the nature of the tumor.

Intracranial inflammation of medulloblastoma

Shedding tumor cells are sometimes widely implanted on the surface of the brain and spinal cord. Meningeal irritation and cerebrospinal fluid leukocytes appear, which is easily misdiagnosed as "meningitis". However, meningitis often has more white blood cells, often accompanied by fever, often lowering sugar and chloride in the cerebrospinal fluid. Cerebellar tuberculosis can also occur in children, but it is mostly located in the cerebellar hemisphere. It often has a history of tuberculosis or tuberculosis and has symptoms of nodular poisoning. ^[1]

Medulloblastoma treatment

Surgical treatment of medulloblastoma

For patients with a significant increase in intracranial pressure, the increase in intracranial pressure should be lifted first. Tumor resection or cerebrospinal fluid shunt surgery can be performed to remove the tumor as much as possible. Some people think that extensive resection of the tumor is likely to cause tumor play. The fourth ventricle is sufficient. Surgery can be performed with a occipital midline incision. After biting the posterior cranial fossa bone, the cerebellar vermiform swelling and widening can be seen, or a tumor can be seen in the large occipital pond. Tunnel suction can be used. Once the upper pole is absorbed, a large amount of cerebrospinal fluid can be seen, and the opening of the aqueduct that is expanded is clearly visible. At this time, the boundary between the tumor and the bottom of the fourth ventricle can be seen. Tumors can avoid manipulation affecting the brainstem. If the tumor is of the hard fiber type, it can be peeled off to both sides to block its blood supply source. The tumor can often be removed completely. In addition, the hemostasis should be thorough during operation, and the blood vessels on the tumor surface should be treated with bipolar electrocoagulation, and the cold saline should be washed in time to cool down. After the tumor is removed, bleeding from the tumor bed on the brainstem side can be stopped with cotton pads. At the end of the operation, the cerebrospinal fluid circulation obstructed by the tumor should be restored. Generally, the dura mater is not sutured, and the wound is sutured layer by layer.

Radiotherapy of medulloblastoma

Postoperative radiotherapy can prolong the survival of patients. Bruce noted that all myeloblastomas that have not undergone postoperative radiotherapy have relapsed, and most have died within 1 year of relapse. Postoperative radiotherapy, the 5-year survival rate is currently calculated to be 40% to 60%, and the 10-year survival rate is also 30% to 40%. Earlier, some people suggested that patients with medulloblastoma can be given radiation therapy alone, but there are two disadvantages: The tumor swells during the radiation therapy, which increases the pressure on the brainstem, and the patient may suffer from increased intracranial pressure and brainstem pressure fatal. Blind radiotherapy is not effective for more benign tumors (such as astrocytomas) and may delay the disease. Most authors now advocate that radiation therapy should be performed after surgical removal of the tumor to relieve cerebrospinal fluid circulation obstruction and at the same time make a precise pathological diagnosis.

Generally, early postoperative radiotherapy is emphasized, and it is usually started within 1 to 2 weeks after surgery. Based on the susceptibility to metastasis of myeloblastoma, radiotherapy should be performed for the entire central nervous system, and the radiation dose should be locally increased on the basis of this. The American Children's Oncology Group Coordinating Committee for the Treatment of Myeloblastoma (MPCPOG) is divided into three parts: whole brain, spinal cord, and posterior cranial fossa. Whole brain radiotherapy should include the sieve plate, the cervical spinal cord and the spinal cord radiotherapy to the level of 2. The dose is 40Gy (4000rad) for the whole brain, 15Gy (1500rad) for the posterior cranial fossa, and 35Gy (3500rad) for the spinal cord. The dose should not exceed 2Gy (200rad) each time, preferably 150rad ~ 180rad. For children under 3 years of age, the spinal cord is 24 Gy (2400rad), the whole brain is 35.2Gy (3520rad), and the total amount of the posterior cranial fossa is 48Gy (4800rad). The amount of radiotherapy used in this method is much higher than the dose used before the 1960s, which is now accepted by most people and is considered to be the limit of radiation tolerance in the cerebrospinal cord.

Medulloblastoma chemotherapy

There is no clear effect of chemotherapy alone for myeloblastoma after surgery. The results of chemotherapy even after surgery and radiotherapy are controversial. Mazza counted the 5-year survival rate of 47 patients, which was 60% in the surgery + radiotherapy + chemotherapy group, which was significantly higher than that in the non-chemotherapy group (37%). Thomas used BCNU, dexamethasone, and intrathecal methotrexate in combination with chemotherapy in 8 patients with recurrence. Of these, 5 patients received local low-dose radiotherapy at the same time. As a result, all patients had varying degrees of efficacy, of which 6 Obviously effective, 2 cases with insignificant curative effect were second recurrence tumors. However, it was found that chemotherapy had no significant effect on survival.

Regarding chemotherapy guidelines, Bloom believes that chemotherapy is not effective for patients with total tumor resection, so it is mainly used in patients with partial resection or only biopsy, or children under 2 years of age. Most authors believe that chemotherapy can be added to relapsed patients.

Grafts experiments found that when nitrosourea drugs were used in combination with methylbenzylhydrazine, the cellular activity of methylbenzylhydrazine could be obtained at a relatively low dose; It can greatly reduce the bone marrow suppression effect of the drug without reducing the effect of the drug. Therefore, in the combined application of chemotherapeutic drugs, special attention should be paid to their drug interactions to avoid increasing drug toxicity. In addition, peripheral blood changes should be monitored at all times during chemotherapy. Once the whole blood cell reduction is found, it should be treated in time or even chemotherapy should be suspended. ^[2]

Prognosis of medulloblastoma

The average survival after surgery was 0.9 years, and the prognosis for adults was better than that for children. With the continuous development of clinical medicine and basic research in recent years, the prognosis of patients with blastoma has been continuously improved. At present, the 5-year survival rate of most statistics is above 30%, and the highest statistics is 80%. Individuals can survive for more than ten years. Quest believes that the improvement in efficacy is inseparable from the postoperative emphasis on radiation treatment of the entire brain and spinal axis. Bruce believes that the treatment and outcome of pediatric medulloblastoma have improved significantly in recent years. Only one of his newly reported 15 cases died, and CT scans confirmed no signs of tumor recurrence. The prognosis of patients with medulloblastoma is related to many factors. It is currently believed that the degree of surgical removal of the tumor is closely related to the prognosis. Total resection can significantly improve the prognosis. Raimondi believes that there is no significant difference in survival between partial resection and biopsy alone.

Postoperative radiotherapy is an important means to prolong survival, and adjuvant chemotherapy also plays a role. In addition, the patient's age is also closely related to the prognosis. Most literature indicates that the prognosis of older children and adult patients with myeloblastoma is better. It should be noted that the recurrence and metastasis cases have a significantly lower prognosis than the first treatment, and even with radiotherapy and chemotherapy, satisfactory results will not be obtained.

To sum up, the factors affecting prognosis are various. Undoubtedly, complete resection of the lesion, supplemented with a sufficient dose of radiation therapy after surgery, and conditionally combined with comprehensive treatment measures such as chemotherapy, may greatly extend the survival time of patients with myeloblastoma and improve the quality of life of patients.