Common classification systems for brain tumors. Tumors of the brain and other parts of the central nervous system. Histological classification of tumors of the central nervous system.

Tumors of the central nervous system occupy the first place in frequency among solid malignant tumors in children, accounting for 20% of all cancer incidence in childhood. These tumors occur with a frequency of 2-2.8 per 100,000 children, ranking second among the causes of death in children with cancer. Children of preschool age get sick more often: the peak incidence occurs at 2-7 years. Although the mortality rate from these tumors still exceeds the mortality rate for many malignant processes in children, modern therapeutic approaches and the latest advances in diagnostic capabilities, allowing early diagnosis of the tumor and accurate treatment planning, make it possible to cure more children.

The etiology of this group of tumors is currently unknown, although there is evidence of the predisposition of patients, for example, with Recklinghausen's disease (neurofibromatosis), to the development of brain gliomas. There is a known connection between the occurrence of medulloblastomas in children and basal cell nevus syndrome (skin lesions, abnormalities of the skeleton, skin, hands, feet, and abnormalities of the central nervous system). An increased incidence of brain tumors is observed in children with congenital immunodeficiency and in children with ataxia-telangiectasia.

Often a brain tumor occurs as a second tumor in children suffering from acute leukemia, hepatocellular cancer, and adrenocortical tumors. All these data indicate the presence of a number of predisposing factors for the development of malignant brain tumors, which will need to be deciphered and their impact on prognosis determined in the future.

Classification

According to the WHO international classification (1990, second edition), the biological behavior of CNS tumors is determined (in addition to the presence of histological differentiation features) by the so-called degree of malignancy, or anaplasia: from I (benign) to IV (malignant). Tumors of a low degree of malignancy include tumors of I-II degrees (Low grade), and those of a high degree of malignancy - III-IV degrees (High grade).

The histological structure of brain tumors in children differs significantly from that in adults (Table 10-1). Meningiomas, schwannomas, pituitary tumors and metastases from other organs, which relatively often affect the brain of adult patients, are very rare in childhood. In children, 70% of tumors are gliomas. In adults, tumors are more often localized supratentorially, affecting mainly the cerebral hemispheres,

In children under 1 year of age, supratentorial tumors also dominate, and these are mainly low-grade gliomas, PNET (tumors from the primitive neuroectoderm), choroid plexus tumors, teratomas, and meningiomas.

The first classification of brain tumors was proposed in the 1920s by Bailey and Cushing. This classification is based on the histogenesis of brain tissues and all subsequent classifications are based on this principle.

Brain tumors diagnosed in children of the first years of life have a central location, i.e. most commonly affect the third ventricle, hypothalamus, optic chiasm, midbrain, pons, cerebellum, and fourth ventricle. Despite the fact that the volume of the substance of the brain of the posterior cranial fossa is only a tenth of the total volume of the brain, more than half of all malignant brain tumors in children older than 1 year are tumors of the posterior cranial fossa. These are mainly medulloblastomas, cerebellar astrocytomas, brainstem gliomas, and ependymomas of the fourth ventricle.

Supratentorial tumors in children are represented by astrocytomas arising in the frontal, temporal, and parietal areas of the brain, ependymomas of the lateral ventricles, and craniopharyngiomas. (Table 8-2)

Clinical picture.

Generally speaking, any brain tumor has a malignant behavior, regardless of its histological nature, since its growth occurs in a limited volume, and regardless of the histological nature of the tumor, the clinical picture of all brain tumors is determined mainly by the location of tumor growth, age and premorbid level of development of the patient. child.

Tumors of the CNS can cause neurological disorders by direct infiltration or compression of normal structures, or indirectly by causing obstruction of the CSF pathways.

The factor that determines the dominant symptoms in children with brain tumors is increased intracranial pressure, resulting in a classic triad - morning headache, vomiting and drowsiness. Severe, recurrent headache rarely occurs in children, but it is all the more important to pay attention to this complaint. Seizures are the second most common symptom after headache, especially in children with supratentorial tumors. In about a quarter of these patients, seizures are the first manifestation of the tumor. Sometimes these children tend to tilt their heads to one side. Involvement of the cerebellum can cause ataxia, nystagmus, and other cerebellar disorders. With damage to the brain stem, bulbar disorders (dysarthria, paresis and paralysis of the cranial nerves) are noted. Hemiparesis of the opposite side, resulting from compression of the corticospinal pathways, is one of the common symptoms. Violation of vision - a decrease in its sharpness, double vision and a number of other eye symptoms are the reason for a thorough examination of the child. In children under one year of age, rapid or slow development of macrocephaly with bulging of a large fontanelle is possible. If the tumor disseminates along the spinal canal, back pain and dysfunction of the pelvic organs may appear.

Currently, with the introduction of modern diagnostic methods into practice, it is possible to detect a tumor quite early, provided that a child with neurological symptoms is referred to CT and MRI in a timely manner.

Diagnostics.

In addition to routine clinical examinations, including an examination by an ophthalmologist, such children must undergo CT and MRI with contrast material of the brain and spinal cord. Especially when the tumor is localized in the posterior fossa, MRI is extremely informative, since this method has a high resolution. These studies have successfully replaced invasive procedures such as arterial angiography or air ventriculography.

Histological verification of the tumor is necessary, but sometimes difficult due to technical difficulties associated with the localization of the tumor, which involves vital structures in the process. Currently, with the gradual introduction into the practice of neurosurgeons of a new high-tech method of surgical intervention - stereotactic surgery, it becomes possible to perform tumor biopsies of almost any location. Sometimes, due to a significant increase in intracranial pressure, the first step is bypass surgery, which significantly improves the neurological status of the patient.

Examination of the cerebrospinal fluid will provide information about the possible extracranial spread of the malignant process. In rare cases of tumor spread beyond the central nervous system (for example, in the presence of medulloblastoma), additional diagnostic measures are necessary, such as OSG, chest X-ray, abdominal ultrasound, myelogram.

Treatment.

The prognosis of the disease depends to a very large extent on the completeness of tumor removal, which is especially true for high-grade tumors such as malignant astrocytomas, medulloblastomas and PNETs. However, very often radical surgery is associated with significant damage to the normal structure of the brain, which subsequently has an extremely negative impact on the neurological and mental status of surviving patients. Foreign studies in recent years have convincingly shown that the neurological status of patients treated for tumors of the posterior cranial fossa depends to a very large extent on the amount of destruction of brain tissue that arose not only as a result of the growth of the tumor itself but also as a result of surgical intervention. Therefore, ideally, such children should be operated on by a pediatric neurosurgeon who has sufficient experience in treating these patients.

In recent years, radiation therapy has become firmly established in the standard treatment of central nervous system tumors and plays a leading role among conservative methods of treating this pathology. The volume of radiation (craniospinal or local) and dose depend on the nature of the tumor and its location. (see section LT). In connection with the unsatisfactory results of the treatment of high-grade gliomas and inoperable medulloblastomas, attempts to use polychemotherapy in various brain tumors, sometimes with significant success, are of great interest recently.

Astrocytomas

Astrocytomas are divided into two large groups: low grade and high grade.

Low-grade gliomas. (Low grade). More than half of gliomas in children are histologically benign. Low grade (i.e., pilocytic and fibrillar) astrocytomas have a pleomorphic structure, sometimes containing stellate structures, giant cells and microcysts. They exhibit epithelial proliferation with low mitotic activity.

The prognosis for these children depends on the location of the tumor and its resectability. Most of these tumors can be radically removed. In these cases, treatment is limited to surgery. If radical surgery is not possible or there is a residual tumor after surgery, then the issue of further treatment should be decided taking into account factors such as the child’s age, morphological structure and volume of the residual tumor. Since these tumors have a low growth rate, most researchers adhere to the practice of "wait and see", i.e. dynamic monitoring with regular CT and MRI, and begin re-treatment of such children only in case of tumor progression. If surgical removal of the tumor is not possible, radiation therapy to the tumor area is indicated at a dose of 45-50 Gy. There is no consensus regarding chemotherapy for low-grade astrocytomas. Currently, a number of foreign clinics are conducting randomized studies on the use of chemotherapy in such patients.

The choice of treatment tactics in a number of patients is quite difficult, especially with tumors arising from the diencephalic region in children under 3 years of age, since the main method of treatment, radiation therapy, is not applicable at this age due to the severe neurological and endocrinological consequences of treatment in this age group .

Thalamic/hypothalamic/(diencephalic) gliomas. Most often these are benign tumors (the most common are pilocytic astrocytomas). By the time of diagnosis, these tumors typically involve the diencephalon, optic nerves, and optic tract throughout, causing progressive visual impairment and proptosis along with symptoms of increased intracranial pressure. Localization of the tumor in the hypothalamus causes behavioral problems in the child. Spread to the pituitary region may cause precocious puberty or secondary hypopituitarism. Obstruction of the foramen of Monroe leads to hydrocephalus. These tumors are most often found in children under 3 years of age.

Optic tract gliomas are most often low-grade pilocytic and sometimes fibrillary astrocytomas. They make up approximately 5% of all CNS neoplasms in children. More than 75% of tumors affecting the optic nerves occur during the first decade of life, while chiasmal lesions are more common in older children).

Approximately 20% of children with optic chiasma gliomas suffer from neurofibromatosis, and a number of researchers argue that the prognosis for such children is better than for patients without neurofibromatosis. The course of intracranial tumors is more aggressive than gliomas located intraorbitally. Surgical removal of intraorbital tumors can often be total and in these cases it is recommended to resect the optic nerve at the maximum possible distance (up to the chiasm) in order to reduce the risk of recurrence. It is almost impossible to radically remove chiasmal tumors, but surgery - a biopsy is necessary in such patients for the purpose of differential diagnosis and sometimes partial resection improves the neurological status of these patients.

With tumor progression in children over 5 years of age, local radiation therapy at a dose of 55 Gy is indicated. Radiation therapy helps to at least stabilize the process within 5 years, although late relapses of the disease often occur.

If relapse occurs, chemotherapy is an alternative to radiation therapy. In young children, the combination of vincristine and dactinomycin has worked well, achieving 90% survival of patients within 6 years after relapse (Packer, 1988). This is especially important since the use of chemotherapy makes it possible to postpone radiation in young children. A number of studies indicate the high effectiveness of carboplatin in this type of tumor, as well as in most low-grade gliomas.

Older children have a slightly better prognosis than younger children and overall survival is about 70%. Patient survival rates range from 40% for intracranial tumors to 100% for patients with intraorbital tumors.

High-grade astrocytomas, or anaplastic gliomas, account for 5-10% of brain tumors, and in children these tumors have a more favorable course compared to similar processes in adults. The most common malignant gliomas are anaplastic astrocytoma and glioblastoma multiforme. They are characterized by the presence of characteristic “malignant” features, such as high cellularity, cellular and nuclear atypia, high mitotic activity, the presence of necrosis, endothelial proliferation and other features of anaplasia. Clinically, these tumors are very aggressive and are capable not only of invasive intracranial growth and seeding of the spinal canal, but also of spreading beyond the central nervous system, metastasizing to the lungs, lymph nodes, liver, and bones, which, however, is much more common in adult patients. The prognosis in such patients depends on the completeness of tumor resection, although total removal is hardly possible due to infiltrating growth.

Radical removal is possible if the tumor is localized in the frontal or occipital lobes of the brain. Postoperative local irradiation of these tumors with a dose of 50 - 60 Gy is the standard approach in most clinics around the world. The use of radiation improves the survival rate of such patients by up to 30%.

The role of chemotherapy in the treatment of these tumors remains controversial. Encouraging results were obtained in the USA using adjuvant polychemotherapy using lomustine and vincristine (Packer, 1992). In older patients, good results were obtained using a combination of CCNU, procarbazine and vincristine in the treatment of grade III gliomas (Kyritsis, 1993). The overall 5-year survival rate for low grade astrocytomas is about 60%, for high grade it is only 25%.

Cerebellar astrocytomas are indolent tumors that occur in two histological subtypes: juvenile piloid tumor with elongated unipolar cells and fibrillar structures and diffuse low-grade tumor. The tumors may contain cysts and are usually resectable. Rarely, these tumors can spread beyond the skull with dissemination along the spinal canal. The possibility of late malignant transformation of these tumors has been described. If radical surgery is not possible after partial tumor resection, local radiation therapy at a dose of 55 Gy is justified.

Anaplastic gliomas of the posterior fossa are treated similarly to gliomas of cortical localization, however, due to their ability to seed the spinal canal, these children in the postoperative period should receive craniospinal irradiation with a local increase in dose, as is used in the treatment of medulloblastomas. Adjuvant chemotherapy similar to that used in the treatment of supratentorial gliomas is also used in the treatment of these patients. The overall 10-year survival rate after total tumor removal is about 90%; in the case of complete tumor removal, survival rates range from 67 to 80%.

Medulloblastoma or PNET.

Medulloblastoma is the most common infratentorial tumor, with a typical location in the midline of the cerebellum. Located supratentorially, this tumor is called PNET. The peak diagnosis of these tumors is observed at the age of 5 years.

These tumors belong to the family of small round cell tumors and have an identical morphological structure. Tumors contain neural structures of varying degrees of differentiation with the formation of rosettes and stellate structures. The desmoplastic subgroup contains areas of connective tissue with nests of malignant cells. This type is the most favorable prognostically, since these tumors are localized superficially and are most often easily removed. They are highly malignant and tend to seed the spinal canal early and quickly. Therefore, the range of mandatory initial examination of these patients should include NMR scanning of the entire central nervous system with a contrast agent (gadolinium) and examination of the cerebrospinal fluid. Among all malignant neoplasms of the central nervous system, medulloblastoma has the highest capacity, although rarely, to metastasize beyond the central nervous system, for example, to the bone marrow, skeletal bones, lungs, liver and lymph nodes. Even in the case of seemingly radical removal of the primary tumor, morphological examination often indicates a microscopically non-radical intervention. Therefore, in any case, the treatment of such patients is not limited to surgery. The treatment complex for such patients necessarily includes radiation and chemotherapy.

Medulloblastoma is the most sensitive tumor of the central nervous system to chemoradiotherapy. In the treatment of this tumor, it is standard to carry out craniospinal irradiation at a dose of 34-35 Gy and additionally to the posterior cranial fossa - 20 Gy up to a total focal dose of 55 Gy. (see chapter "Radiation therapy"). For young children, RT doses can be reduced (since high doses of radiation cause adverse long-term consequences), which, accordingly, significantly increases the risk of relapse. When performing craniospinal irradiation, the radiologist should avoid overlapping the irradiation fields of the skull and spine due to the risk of radiation myelitis. Radiation therapy is not indicated for children under 3 years of age due to the sharply negative consequences of cranial irradiation at this age. Therefore, in early childhood, only polychemotherapy is performed either in the postoperative period or if surgery is impossible - as the only method of antitumor therapy. Reports in recent years indicate the successful use of combinations of vincristine, CCNU and steroids in young patients. Medulloblastoma is the most sensitive tumor of the central nervous system to chemotherapy. Treatment protocols adopted in different countries include different combinations of chemotherapy drugs. The CCSG protocol (USA) involves the use of a combination of vincristine, lomustine and cis-platinum. The International Society of Pediatric Oncology (SIOP) protocol uses a combination of vincristine, carboplatin, etoposide, and cyclophosphamide.

As has been shown in recent years, the effective use of chemotherapy may reduce radiation exposure in children with medulloblastoma.

For medulloblastoma, negative prognosis factors are the child's age under 5 years, male gender, non-radical tumor removal, involvement of the trunk in the process, extracranial spread, non-desmoplastic type of histology. 5-year survival rate is 36 - 60% (Evans, 1990)

Ependymoma.

This tumor arises from the inner lining of the ventricles of the brain or the lining of the central canal and accounts for approximately 5-10% of tumors of the central nervous system. In children, 2/3 of these tumors are localized in the posterior cranial fossa. More than half of the patients are children under 5 years of age. About 10% of all ependymomas arise in the spinal cord, but in these cases the tumor rarely affects children under 12 years of age.

Like medulloblastoma, ependymoma can infiltrate the brain stem and seed the spinal canal, which significantly worsens the prognosis, but more often these tumors tend to differentiate and are more benign. Its radical removal is always very difficult, although this is the cornerstone in the treatment of these patients. Therapeutic approaches are similar to those for medulloblastoma, although if the tumor is supratentorial, if it is completely removed and the histology is favorable, spinal irradiation can be excluded. Among the chemotherapeutic agents used in the treatment of ependymomas, platinum drugs are the most active. The 5-year survival rate of these patients is 40%. The best prognosis is for children with spinal tumor localization, especially in the cauda equina.

Brain stem gliomas.

These tumors account for 10-20% of all central nervous system tumors in children. These tumors infiltrate and compress the brain stem, causing multiple cranial nerve palsies, i.e. Due to their anatomical location, these tumors manifest relatively early. Most often they are localized in the bridge. According to their histological structure, they can belong to both low and high degrees of malignancy. The type of growth (exophytic or infiltrative) significantly affects the prognosis. The prognosis for an exophytically growing tumor with a low degree of malignancy can be 20%, while infiltrative high-grade gliomas are practically incurable. These tumors are diagnosed using CT and MRI with a high degree of confidence, so the extremely dangerous procedure of biopsy of a tumor in this location may not be performed. The exception is exophytically growing tumors, when it is possible to remove them, which significantly improves the prognosis in such patients.

Treatment of such patients includes local irradiation at a dose of 55 Gy with a noticeable improvement in the neurological status of these patients, but in more than 30% of cases there is a relapse of the disease on average 6 months from the start of therapy. Currently, studies are being conducted in the USA and Great Britain on the effectiveness of hyperfractionated irradiation and the use of aggressive chemotherapy regimens due to extremely unsatisfactory long-term treatment results. Attempts to improve the situation using additional chemotherapy have not yet led to significant success, but encouraging results have been obtained in the United States using platinum drugs.

Pineal tumors.

Tumors of the pineal region combine tumors of different histogenesis, but are usually described together due to their location. The incidence of damage to this area is 0.4 - 2% of all central nervous system tumors in children. Three main groups of tumors are found in this area: pineal tumors proper (pinealoblastoma and pineocytoma), accounting for 17%, germ cell tumors, diagnosed in 40-65% of cases, and glial tumors, found in 15% of tumors of this localization. Parenchymal pineal tumors are more common in children in the first decade of life, germ cell tumors are more often diagnosed in adolescents, predominantly boys. Astrocytomas of this localization have two age peaks: 2 - 6 years and the period from 12 to 18 years.

Pinealoblastoma is an embryonal tumor of the epiphysis tissue. This is a highly malignant tumor. Its histological characteristics are similar to PNET and medulloblastoma. Its biological behavior is similar to medulloblastoma, i.e. it tends to seed the spinal canal early and spread beyond the central nervous system. Bone, lungs and lymph nodes are the most common sites of metastasis.

Germ cell tumors arise in the brain due to pathological migration of germ cells during embryonic development. Histologically, this heterogeneous group, including germinomas, endodermal sinus tumors, embryonal carcinomas, choriocarcinomas, mixed cell germ cell tumors, and teratocarcinomas, is virtually indistinguishable from “classical” germ cell tumors. If a germ cell tumor is suspected, it is necessary to determine the level of alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG) in the cerebrospinal fluid and blood serum. Elevated levels of AFP and HGT are detected in embryonal cell carcinomas or mixed cell germ cell tumors. An increased content of only hCG is characteristic of choriocarcinomas. Although germinomas are more often negative in relation to these markers, a number of studies emphasize that 1/3 of patients with germinomas have an increased level of hCG, although its level is significantly lower than in patients with choriocarcinoma. In all patients with non-germ tumors of the pineal region, these tumor markers are not detected. These tumors (especially choriocarcinomas and yolk sac tumors) have the appearance of large infiltrating formations that early disseminate along the spinal canal and in 10% of cases metastasize beyond the central nervous system (to bones, lungs, lymph nodes).

Since the histological type of pineal tumor has prognostic significance, verification of the diagnosis is necessary, if possible. Germinomas and astrocytomas (usually low grade) have a better response to therapy and a better prognosis. Teratomas and true pineal tumors have a less favorable outcome. The worst prognosis is for patients with non-germ cell tumors, which are characterized by rapid progression, leading to death within a year from the date of diagnosis.

Radiation therapy is the main method of treatment for pineal tumors. The standard approach for germ cell tumors and pineablastomas is craniospinal irradiation with local dose escalation, as used for medulloblastomas. This group of tumors has a high sensitivity to RT.

If it is impossible to histologically verify the tumor in this area and there are negative markers of germ cell tumors, ex juvantibus radiation therapy is used as the treatment of choice: local irradiation at a dose of 20 Gy and, if the dynamics are positive (which will indicate the malignant nature of the tumor), expanding the irradiation field to craniospinal irradiation. If there is no response to radiation therapy, only local radiation followed by an attempt at exploratory surgery is recommended.

The absence of a blood-brain barrier in the pineal region and the success achieved in the treatment of germ cell tumors outside the central nervous system have led to the fact that the use of classical chemotherapy regimens, including platinum drugs, vinblastine, VP-16 and bleomycin, makes it possible to achieve complete or partial remission. Pineal parenchymal tumors are sensitive to platinum and nitrosourea. Pineacytoma and gliomas of this localization are treated according to the regimens used for similar tumors of other localizations.

Craniopharyngiomas account for 6-9% of all central nervous system tumors in children, the average age at diagnosis is 8 years. They are most often localized in the suprasellar region, often involving the hypothalamus, but can also occur within the sella turcica.

These are rather slow-growing tumors, histologically of low malignancy, often containing cysts. Malignant behavior of craniopharyngiomas with infiltration of surrounding normal structures is rarely described. Examination often reveals calcifications in the tumor. In the clinical picture in 90% of patients, along with the typical symptoms of increased ICP, neuroendocrine deficiency dominates: most often there is a deficiency of growth hormone and antidiuretic hormone. In 50-90% of patients there is a violation of the visual fields.

The prognosis in such patients largely depends on the completeness of tumor resection. If radical removal is not possible, the method of choice may be aspiration of the contents of the cysts, but one must keep in mind that patients with a non-radically removed tumor in 75% of cases have a relapse of the disease within the first 2-5 years. RT may reduce the incidence of relapse in patients with incomplete tumor removal or after cyst drainage. Local irradiation is usually used at a dose of 50-55 Gy, which, according to Japanese scientists, can provide a cure rate of up to 80%. The role of chemotherapy in patients with craniopharyngiomas is unclear due to very limited published data.

Meningiomas.

These tumors are rare in young children and are more common in teenage boys. They are usually localized supratentorially, affecting the cerebral hemispheres and lateral ventricles. Multiple meningiomas can occur in patients with Recklinghausen disease. Due to their location, these tumors are usually resectable and therefore do not require further treatment.

Choroid plexus tumors account for 2-3% of all brain tumors in children. In children under 1 year of age, these tumors occur in 10 - 20% of cases. Up to 85% of these tumors are localized in the lateral ventricles, from 10 to 50% in the fourth ventricle, and only 5 to 10% in the third ventricle. Most often, these tumors arise as functioning intraventricular papillomas that secrete cerebrospinal fluid. These tumors grow rather slowly and, due to their intraventricular location, often reach a large size (weighing up to 70 grams) by the time they are detected. In 5% of cases, tumors can be bilateral.

Choroid plexus carcinoma is a more aggressive tumor, accounting for 10–20% of all choroid plexus tumors. This tumor is characterized by features characteristic of anaplastic tumors and has a tendency to diffuse aggressive extracranial spread. Although choroid plexus papillomas may extend beyond the skull, their deposits are benign and usually asymptomatic.

The main treatment for these tumors is surgery. Complete removal of the tumor is possible in 75-100% of patients with papillomas, which ensures their cure. Patients with vascular plexus papillomas are not shown other methods of treatment. In case of tumor recurrence, repeated surgery is possible.

Patients with choroid plexus carcinoma after surgical removal of the tumor should receive RT, although the main prognostic factor in such patients is the completeness of tumor resection.

In small series of patients, the positive effect of the use of preoperative chemotherapy, consisting of ifosfamide, carboplatin and VP-16, has been shown to reduce the size of tumor vascularization.

SPINAL CORD TUMORS

These tumors are much less common than brain tumors. The clinical manifestations of the disease depend on the level of the lesion and the rate of tumor growth. Movement disorders, lameness, other gait abnormalities, and back pain are symptoms characteristic of these tumors. Localization of the tumor in the sacral segments causes dysfunction of the bladder and intestines.

Lymphomas and neuroblastomas, sometimes arising in the spinal canal, are treated according to appropriate programs. Approximately 80-90% of primary spinal cord tumors are gliomas. Less common are ependymomas and PNET. Approximately half of gliomas are of low grade and the best treatment for them is currently unknown. Two approaches are being studied: wide resection or less aggressive surgical tactics followed by local irradiation. Local irradiation is indicated for children with rapid tumor progression and worsening neurological symptoms. Anaplastic gliomas of the spinal cord have a worse prognosis due to rapid dissemination along the spinal canal already at the onset of the disease. In the treatment of these patients, craniospinal irradiation and adjuvant polychemotherapy (vincristine, lomustine, platinum drugs) are used.

The prognosis for children with central nervous system tumors is determined primarily by the degree of radicality of tumor removal, its histological structure and the adequacy of postoperative treatment (volume and dose of radiation therapy, chemotherapy). Recently, megadose chemotherapy regimens followed by autologous transplantation of peripheral stem cells have been introduced into the treatment program for highly malignant brain tumors, such as medulloblastoma and PNET, high-grade gliomas, and pineoblastoma.

Careful monitoring of patients with tumors of the central nervous system should include, in addition to regular neurological examinations, a number of instrumental examinations. The frequency of necessary examinations (CT, nuclear MRI, cerebrospinal fluid examination, etc.) depends on the type of tumor and the degree of initial spread. Early detection of disease relapse by CT or nuclear MRI (before the development of clinical symptoms) makes it possible to timely resume specific therapy. Unfortunately, many children cured of brain tumors subsequently have intellectual, endocrine and neurological problems, both as a result of the tumor itself and the therapeutic effects that were used on the child. Therefore, in addition to the oncologist, these children should be observed by an endocrinologist, a neurologist and a psychologist or psychiatrist.

Tumors of the central nervous system- various neoplasms of the spinal cord and brain, their membranes, liquor ducts, and blood vessels. Symptoms of a central nervous system tumor are highly variable and are divided into focal (neurological deficit), cerebral, manifestations in the neighborhood and distant. In diagnosis, in addition to a neurological examination, X-ray, electrophysiological, ultrasound methods and cerebrospinal fluid puncture are used. However, more accurate verification of the diagnosis is achieved using MRI or CT data and histological analysis of the tumor. For CNS tumors, surgical treatment is most effective. It is possible to use chemotherapy and radiotherapy as an additional or palliative treatment.

General information

According to various data, CNS tumors occur with a frequency of 2-6 cases per 100 thousand people. Of these, approximately 88% are cerebral tumors and only 12% are spinal tumors. Young people are most susceptible to the disease. In the structure of pediatric oncology, CNS tumors occupy 20%, and 95% of them are brain tumors. In recent years, there has been a trend towards an increase in the incidence among older people.

Neoplasms of the central nervous system do not quite fit into the generally accepted interpretation of the concept of benign tumors. The limited space of the spinal canal and the cavity of the cranium determine the compressive effect of tumors of this localization, regardless of their degree of malignancy, on the spinal cord and brain. Thus, as they grow, even benign tumors lead to the development of severe neurological deficits and death of the patient.

Causes

To date, the factors that initiate tumor transformation of cells remain the subject of study. The oncogenic effect of radioactive radiation, some infectious agents (herpes virus, HPV, certain types of adenoviruses), and chemical compounds is known. The influence of dysontogenetic aspects of tumor occurrence is being studied. The presence of hereditary syndromes of tumor lesions of the central nervous system indicates a genetic determinant. For example, Recklinghausen neurofibromatosis, tuberous sclerosis, Hippel-Lindau disease, Gorlin-Goltz syndrome, Turcot syndrome.

Factors that provoke or accelerate tumor growth are considered to be traumatic brain injuries, spinal cord injuries, viral infections, occupational hazards, and hormonal changes. A number of studies have confirmed that ordinary electromagnetic waves, including those coming from computers and mobile phones, do not belong to the above triggers. An increased incidence of CNS tumors has been noted in children with congenital immunodeficiency, Louis-Bar syndrome.

Classification of CNS tumors

In accordance with histiogenesis, 7 groups of tumors are distinguished in neurology and neurooncology.

1. Neuroectodermal tumors: Gliomas (benign and deducted astrocytomas, oligodendrogliomes, ependimums, glioblastoma), medical -medical, pinealoma and pineoblastoma, chorioidpapalloma, neurinomas, ganglionoclet tumors (gangliocytomas, ganglioneurias, ganglionomers, ganglionomers, ganglionom Lastoma)
2. Mesenchymal tumors of the central nervous system: meningioma, meningeal sarcoma, intracerebral sarcoma, hemangioblastoma, neurofibroma, angioma, lipoma
3. Tumors from the rudiments of the pituitary tract- craniopharyngiomas
4. Heterotopic ectodermal neoplasms(cholesteatomas, dermoid cysts)
5. Teratomas of the central nervous system(extremely rare)
6. Metastatic tumors of the central nervous system.

Capable of metastasizing to the central nervous system

• malignant tumors of the adrenal glands, etc.

In accordance with the WHO classification, there are 4 degrees of malignancy of CNS tumors. Grade I corresponds to benign tumors. I-II degrees belong to the low class of malignancy (Low grade), III-IV degrees - to high grade (High grade).

Symptoms of a central nervous system tumor

It is generally accepted to divide the symptoms of a tumor process of the central nervous system into general cerebral, focal, distant symptoms and symptoms in the neighborhood.

General cerebral manifestations are characteristic of cerebral and craniospinal tumors. They are caused by impaired cerebrospinal fluid circulation and hydrocephalus, swelling of brain tissue, vascular disorders resulting from compression of arteries and veins, and a disorder of cortical-subcortical connections. The leading cerebral symptom is cephalgia (headache). It has a bursting, first periodic, then permanent, character. Often accompanied by nausea. At the peak of cephalalgia, vomiting often occurs. A disorder of higher nervous activity is manifested by absent-mindedness, lethargy, and forgetfulness. Irritation of the meninges can lead to symptoms typical of inflammation - meningitis. Possible occurrence of epileptic seizures.

Focal symptoms are associated with damage to the brain tissue at the site of the tumor. Based on them, one can presumably judge the location of the central nervous system tumor. Focal symptoms are a so-called “neurological deficit,” i.e., a decrease or absence of a certain motor or sensory function in a specific area of ​​the body. These include paresis and paralysis, pelvic disorders, hypoesthesia, disorders of muscle tone, disturbances in the statics and dynamics of the motor act, signs of dysfunction of the cranial nerves, dysarthria, visual and hearing impairments not associated with pathology of the peripheral analyzer.

Symptoms in the neighborhood appear when the tumor compresses nearby tissues. An example is radicular syndrome, which occurs with meningeal or intramedullary tumors of the spinal cord.

Long-term symptoms arise due to displacement of cerebral structures and compression of areas of the brain distant from the tumor site.

More detailed information about the symptoms of central nervous system tumors of various locations can be found in the articles:

Course of CNS tumors

The onset of clinical manifestations of CNS tumors and the development of symptoms over time can vary significantly. However, there are several main types of their course. Thus, with a gradual onset and development of focal symptoms, they speak of a tumorous course, and with the manifestation of a tumor from an epileptic attack, they speak of an epileptiform course. An acute onset similar to a cerebral or spinal stroke, refers to the vascular type of tumor progression, and occurs with hemorrhage in the tumor tissue. The inflammatory course is characterized by a gradual development of symptoms such as inflammatory myelopathy or meningoencephalitis. In some cases, isolated intracranial hypertension is observed.

The course of CNS tumors is divided into several phases:

1. Compensation phase accompanied only by asthenia and emotional disturbances (irritability, lability). Focal and general cerebral symptoms are practically not defined.
2. Subcompensation phase characterized by general cerebral manifestations, mainly in the form of moderate headaches, symptoms of irritation - epileptic seizures, hyperpathy, paresthesia, hallucinatory phenomena. The ability to work is partially impaired. Neurological deficits are mild and are often defined as some asymmetry of muscle strength, reflexes and sensitivity in comparison with the opposite side. Ophthalmoscopy can reveal initial signs of congestive optic discs. Diagnosis of a central nervous system tumor in this phase is considered timely.
3. Moderate decompensation phase is characterized by a moderately severe condition of the patient with severe disability and decreased adaptation to everyday life. There is an increase in symptoms and a predominance of neurological deficit over symptoms of irritation.
4. In the phase of severe decompensation patients do not leave their beds. There is a profound neurological deficit, disorders of consciousness, cardiac and respiratory activity, and long-term symptoms. Diagnosis in this phase is delayed. The terminal phase represents irreversible disturbances in the functioning of the main systems of the body. Disturbances of consciousness up to coma are observed. Possible cerebral edema, dislocation syndrome, hemorrhage into the tumor. Death may occur hours or days later.

Diagnosis of a central nervous system tumor

A thorough examination by a neurologist and anamnesis can suggest the presence of a space-occupying lesion in the central nervous system. If cerebral pathology is suspected, the patient is referred to an ophthalmologist, where he undergoes a comprehensive examination of visual function: ophthalmoscopy, perimetry, determination of visual acuity. General clinical laboratory tests are carried out; if a pituitary adenoma is suspected, the level of pituitary hormones is determined. Indirect evidence of the presence of a tumor of the brain or spinal cord can be obtained as a result of EEG, Echo-EG and radiography of the spine, respectively. Lumbar puncture allows one to judge the state of liquorodynamics. When examining cerebrospinal fluid, a tumor is indicated by pronounced hyperalbuminosis; tumor cells are not always detected.

Brain tumors account for 10% of all neoplasms and 4.2% of all diseases of the nervous system. Spinal cord tumors are 6 times less common than brain tumors.

Etiology. Among the causes of the development of brain tumors can be called dysembryogenesis. It plays a role in the development of vascular tumors, malformations, and ganglioneuromas. The genetic factor plays a role in the development of vascular tumors and neurofibromas. The etiology of gliomas remains poorly understood. The development of neuroma of the vestibular-auditory nerve is associated with viral damage.

Classification of brain tumors

1. Biological: benign and malignant.

2. Pathogenetic: primary tumors, secondary (metastatic) from the lungs, stomach, uterus, breast.

3. In relation to the brain: intracerebral (nodular or infiltrative) and extracerebral with expansive growth.

4. Working neurosurgical classification: supratentorial, subtentorial, tuberogypophyseal.

5. Pathomorphological classification:

1. Neuroepithelial tumors (astrocytomas, oligodendrogliomas, ependymal and choroid plexus tumors, pineal gland tumors, neuronal tumors, medulloblastomas).

2. Tumors from nerve sheaths (acoustic neuroma).

3. Tumors of the meninges and related tissues (meningiomas, meningeal sarcomas, xanthomatous tumors, primary melanomas).

4. Blood vessel tumors (capillary hemangioblastoma)

5. Germ cell tumors (germinomas, embryonal cancer, chorionic carcinoma, teratoma).

6. Dysontogenetic tumors (craniopharyngioma, Rathke's pouch cyst, epidermoid cyst).

7. Vascular malformations (arteriovenous malformation, cavernous angioma).

8. Tumors of the anterior pituitary gland (acidophilic, basophilic, chromophobic, mixed).

9. Adenocarcinomas.

10. Metastatic (6% of all brain tumors).

Glioma is a specific tumor of the nervous system, consisting of brain matter. Gliomas occur in adults and the elderly. The degree of malignancy of gliomas depends on the type of glioma cells. The less differentiated the tumor cells, the more malignant the course is observed. Among gliomas, glioblastomas, astrocytomas, and medulloblastomas are distinguished.

Glioblastoma has infiltrating growth. This is a malignant tumor. Glioblastomas range in size from a walnut to a large apple. Most often, glioblastomas are solitary, much less often - multiple. Sometimes cavities form in gliomatous nodes, sometimes calcium salts are deposited. Sometimes hemorrhage occurs inside the glioma, then the symptoms resemble a stroke. The average life expectancy after the first signs of the disease appear is about 12 months. With radical removal, tumor recurrences often occur.

Astrocytoma. They have benign growth. Growth continues slowly and for a long time. Large cysts form inside the tumor. Average life expectancy is about 6 years. Once the tumor is removed, the prognosis is favorable.

Medulloblastoma. A tumor consisting of undifferentiated cells that have no signs of either neurons or glial elements. These tumors are the most malignant. They are found almost exclusively in the cerebellum in children (usually boys) aged about 10 years.

Other gliomas include oligodendroglioma. This is a rare, slow-growing tumor. Has relatively benign growth. Found in the hemispheres of the brain. May be subject to calcification. Ependymoma develops from ventricular ependyma. It is located in the cavity of the fourth ventricle or, less commonly, in the lateral ventricle. Has benign growth.

Meningiomas make up 12-13% of all brain tumors and occupy the second place in frequency after gliomas. They develop from the cells of the arachnoid membrane. They have benign growth. They are located outside the brain tissue along the venous sinuses. They cause changes in the underlying bones of the skull: the formation of usuria, endostosis occurs, and the diploetic veins expand. Meningiomas are more common in women aged 30-55 years. Meningiomas are divided into convexital and basal. In some cases, meningiomas calcify and develop into psammomas.

Tumors of the pituitary region make up 7-18% of all brain tumors. The most common are craniopharyngiomas and pituitary adenomas.

Craniopharyngioma develops from embryonic remains of gill arches. Tumor growth is expansive. Located in the area of ​​the sella turcica. Forms cystic cavities. Occurs in the first two decades of life.

Pituitary adenomas develop from the glandular pituitary gland, i.e. front They develop in the cavity of the sella turcica. There are basophilic, eosinophilic and chromophobic depending on the type of cell. When malignant, the tumor is called adenocarcinoma. As the tumor grows, it destroys the back of the sella turcica, the diaphragm and grows into the cranial cavity. May put pressure on the chiasm, hypothalamus and cause related symptoms.

Metastatic formations account for 6% of all brain tumors. Sources of metastasis are bronchogenic lung cancer, breast, stomach, kidney, and thyroid cancer. The routes of metastasis are hematogenous, lymphogenous and cerebrospinal fluid. Most often, metastases are single, less often multiple. They are located in the brain parenchyma, less often in the bones of the skull.

Brain Tumor Clinic

The clinical picture of brain tumors consists of three groups of symptoms. These are general cerebral symptoms, focal and distant symptoms.

General cerebral symptoms occur due to increased intracranial pressure. A complex of cerebral symptoms forms the so-called hypertension syndrome. Hypertension syndrome includes headache, vomiting, congestion of the optic discs, changes in vision, mental disorders, epileptic seizures, dizziness, changes in pulse and respiration, and changes in the cerebrospinal fluid.

Headache - one of the most common symptoms of a brain tumor. It occurs as a result of increased intracranial pressure, impaired blood and liquor circulation. At the beginning, headaches are usually local, caused by irritation of the dura mater, intracerebral and meningeal vessels, as well as changes in the bones of the skull. Local pains are boring, pulsating, jerking, paroxysmal in nature. Identifying them is of some importance for topical diagnosis. During percussion and palpation of the skull and face, pain is noted, especially in cases of superficial location of the tumor. Expanding headaches often occur at night and early in the morning. The patient wakes up with a headache that lasts from several minutes to several hours and reappears the next day. Gradually, the headache becomes prolonged, diffuse, spreads throughout the head and may become permanent. It can increase with physical exertion, excitement, coughing, sneezing, vomiting, tilting the head forward and defecation, depending on the posture and position of the body.

Vomit appears when intracranial pressure increases. With tumors of the fourth ventricle, medulla oblongata, and cerebellar vermis, vomiting is an early and focal symptom. It is characterized by its occurrence at the height of a headache attack, the ease of occurrence, more often in the morning, when changing the position of the head, there is no connection with food intake.

Congested optic discs arise due to increased intracranial pressure and the toxic effect of the tumor. The frequency of their appearance depends on the location of the tumor. They are almost always observed with tumors of the cerebellum, fourth ventricle and temporal lobe. They may be absent in tumors of the subcortical formations; they appear late in tumors of the anterior part of the brain. Transient blurred vision and a progressive decrease in its acuity indicate stagnation and possible incipient atrophy of the optic discs. In addition to secondary atrophy of the optic nerves, primary atrophy can also be observed when the tumor exerts direct pressure on the optic nerves, chiasm or initial segments of the optic tracts in cases of its localization in the area of ​​the sella turcica or at the base of the brain.

General cerebral symptoms of a tumor also include epileptic seizures, mental changes, dizziness, and slow pulse.

Epileptic seizures can be caused by intracranial hypertension and the direct effect of the tumor on the brain tissue. Seizures can appear in all stages of the disease (up to 30%), often serve as the first clinical manifestations of the tumor and precede other symptoms for a long time. Seizures are more common with tumors of the cerebral hemispheres located in the cortex and close to it. Less commonly, seizures occur with deep tumors of the cerebral hemispheres, brain stem and posterior cranial fossa. Seizures are observed more often at the onset of the disease, with a slow growth of a malignant tumor than with its more rapid development.

Mental disorders more often occur in middle and old age, especially when the tumor is located in the anterior lobes of the brain and the corpus callosum. Patients are depressed, lethargic, drowsy, often yawn, get tired quickly, disoriented in time and space. There may be memory problems, slow mental processing, difficulty concentrating, irritability, mood changes, agitation, or depression. The patient may be stunned, as if separated from the outside world - “loaded”, although he can answer questions correctly. As intracranial pressure increases, mental activity ceases.

Dizziness often occurs (50%) due to congestion in the labyrinth and irritation of the vestibular stem centers and temporal lobes of the cerebral hemispheres. Systemic vertigo with rotation of surrounding objects or one’s own displacement of the body is relatively rare, even with acoustic neuroma and tumor of the temporal lobe of the brain. Dizziness that occurs when the patient changes position may be a manifestation of ependymoma or metastasis to the fourth ventricle.

Pulse with brain tumors it is often labile, sometimes bradycardia is detected. Blood pressure may increase with a rapidly growing tumor. In a patient with a slowly growing tumor, especially in the subtentorial localization, it is often reduced.

Frequency and character breathing also changeable. Breathing can be rapid or slow, sometimes with a transition to the pathological type (Cheyne-Stokes, etc.) in the late stage of the disease.

Cerebrospinal fluid flows out under high pressure, transparent, often colorless, sometimes xanthochromic. Contains an increased amount of protein with normal cellular composition.

The greatest severity of hypertension syndrome is observed with subtentorial tumors, extracerebral localization with expansive growth.

Focal symptoms associated with the direct effect of the tumor on the adjacent area of ​​the brain. They depend on the location of the tumor, its size and stage of development.

Tumors of the anterior central gyrus. In the initial stages of the disease, Jacksonian-type seizures are observed. Convulsions begin in a certain part of the body, then spread according to the topical projection of body parts to the anterior central gyrus. Generalization of a convulsive seizure is possible. As they grow, convulsive phenomena begin to be accompanied by central paresis of the corresponding limb. When the focus is localized in the paracentral lobule, lower spastic paraparesis develops.

Tumors of the posterior central gyrus. Irritation syndrome affects sensory Jacksonian epilepsy. There is a sensation of goose bumps in certain areas of the body or limbs. Paresthesia can spread to the entire half of the body, or to the entire body. Symptoms of loss may then follow. Hypesthesia or anesthesia occurs in areas corresponding to the cortical lesion.

Frontal lobe tumors. For a long time they can be asymptomatic. The following symptoms are most characteristic of a tumor of the frontal lobe. Mental disorders. They are expressed by decreased initiative, passivity, lack of spontaneity, indifference, lethargy, decreased activity and attention. Patients underestimate their condition. Sometimes there is a tendency towards flat jokes (moria) or euphoria. Patients become untidy and urinate in inappropriate places. Epileptic seizures can begin with turning the head and eyes to the side. Frontal ataxia is detected on the side opposite to the lesion. The patient staggers from side to side. There may be loss of the ability to walk (abasia) or stand (astasia). Smell disorders are usually unilateral. Central paresis of the facial nerve occurs due to tumor pressure on the anterior central gyrus. This is most often observed with tumors localized in the posterior part of the frontal lobe. When the frontal lobe is damaged, the phenomenon of obsessive grasping of objects (Janiszewski's symptom) may occur. When the tumor is localized in the posterior part of the dominant hemisphere, motor aphasia occurs. In the fundus, changes can either be absent, or there may be bilateral congestive nipples of the optic nerves, or a congestive nipple on one side and atrophic on the other (Foerster-Kennedy syndrome).

Tumors of the parietal lobe. Hemiparesis and hemihypesthesia develop most often. Among sensory disorders, the sense of localization suffers. Astereognosis occurs. When the left angular gyrus is involved, alexia is observed, and when the supramarginal gyrus is affected, bilateral apraxia is observed. When the angular gyrus suffers at the junction with the occipital lobe of the brain, visual agnosia, agraphia, and acalculia develop. When the lower parts of the parietal lobe are damaged, a violation of right-left orientation, depersonalization and derealization appears. Objects begin to appear large or, on the contrary, reduced, patients ignore their own limbs. When the right parietal lobe suffers, anosognosia (denial of one's illness) or autotopagnosia (disturbance in the body diagram) may occur.

Temporal lobe tumors. The most common aphasia is sensory, amnestic, and alexia and agraphia may occur. Epileptic seizures are accompanied by auditory, olfactory, and taste hallucinations. Visual disturbances in the form of quadrant hemianopia are possible. Sometimes there are attacks of systemic dizziness. Large tumors of the temporal lobe may cause herniation of the temporal lobe medulla into the notch of the tentorium cerebellum. This is manifested by oculomotor disorders, hemiparesis or parkinsonism. Memory disorders most often occur with damage to the temporal lobe. The patient forgets the names of relatives, loved ones, and the names of objects. General cerebral symptoms in tumors of the temporal lobes are significantly expressed.

Tumors of the occipital lobe. They are rare. The most common are visual disturbances. Optical agnosia develops.

Brain stem tumors. Causes alternating paralysis.

Tumors of the cerebellopontine angle. As a rule, these are acoustic neuromas. The first sign may be noise in the ear, then there is a decrease in hearing up to complete deafness (otiatric stage). Then signs of damage to other cranial nerves join. These are V and VII pairs. Trigeminal neuralgia and peripheral paresis of the facial nerve occur (neurological stage). In the third stage, the posterior cranial fossa is blocked with pronounced hypertensive phenomena.

Pituitary tumors. Cause bitemporal hemianopsia due to compression of the chiasm. There is a primary atrophy of the optic nerves. Endocrine symptoms, adipose-genital dystrophy, and polydipsia develop. On radiographs, the sella turcica is enlarged in size.

"Symptoms at a Distance" This is the third group of symptoms that can occur with brain tumors. They should be taken into account, as they can lead to errors in determining the location of the tumor. Most often this is due to unilateral or bilateral damage to the cranial nerves, especially the abducens, less often the oculomotor nerve, as well as pyramidal and cerebellar symptoms in the form of ataxia and nystagmus.

Diagnostics. It is carried out on the basis of the clinical picture of the disease. Additional methods include liquor diagnostics. Its value is now decreasing. The main diagnosis is carried out using CT and MRI.

Treatment

Dehydration therapy with glucocorticosteroids is carried out. By reducing the swelling of the underlying substance of the brain, some regression of symptoms may be observed. Osmodiuretics (mannitol) can be used as diuretics.

Surgical treatment is most effective for extracerebral tumors (meningiomas, neuromas). For gliomas, the effect of surgical treatment is lower and a neurological defect remains after surgery.

Types of surgical interventions:

 Craniotomy is performed on superficial and deep tumors.

 Stereotactic intervention is performed if the tumor is deep and produces minimal clinical manifestations.

 The tumor can be radically removed and part of it resected.

Other treatment methods include radiation therapy and chemotherapy.

In each case, an individual approach is taken.

Histological classification

The basis for most of the existing classifications of CNS tumors was the classification of Baily and Cushing (1926), built on the histogenetic principle; in the USSR, the most common modification was the modification of L. I. Smirnov (1951) and B. S. Khominsky (1962). It was assumed that the cellular composition of neuroectodermal tumors (brain tumors themselves) reflects one or another stage of development of various cells of mature nervous tissue; the name of the tumor is determined by the embryonic element that most closely resembles the bulk of the tumor cells; the degree of malignancy is determined by the severity of cell anaplasia, the nature of growth (invasive, non-invasive) and other biological characteristics of the tumor.

The existing terminological inconsistency between different classifications became one of the main motivating reasons for the development in 1976 of the International (WHO) histological classification of tumors of the central nervous system.

However, in 1993, WHO adopted a new histological classification of CNS tumors. The basis for the changes made were the results of many years of research by morphologists in the field of in-depth study of the histogenesis of tumors, cytoarchitectonics and biochemistry of tumor cells, factors and kinetics of their growth. To solve these problems, various modern techniques were used, among which immunohistochemical and ultrastructural immunocytochemical studies occupied a particularly important place.

Some of the tumors more accurately found their place in the classification, built, like the previous ones, on the histogenetic principle; a number of terminological inaccuracies were eliminated. The section with the list of vascular malformations has been excluded from the classification of central nervous system tumors.

Much attention was paid to studying the factors of “aggressive” growth of some tumors and their tendency to recur after surgical treatment.

As a result, the authors of the new classification considered it expedient to abandon the principle proposed in the WHO classification (1976) of determining the degree of malignancy of a tumor based on the life span of patients after “radical” surgery. It is proposed to evaluate in detail such signs as nuclear atypia, cellular polymorphism, mitotic activity, endothelial or vascular proliferation and the presence of necrosis - in direct dependence on the number of signs present, the degree of malignancy of each specific tumor is determined.

INTERNATIONAL (WHO) HISTOLOGICAL CLASSIFICATION OF TUMORS OF THE CENTRAL NERVOUS SYSTEM (1993)

Neuroepithelial tissue tumors

A. Astroscal tumors

1. Astrocytoma: fibrillar, protoplasmic, mixed

2. Anaplastic (malignant) astrocytoma

3. Glioblastoma: giant cell glioblastoma, gliosarcoma

4. Piloid astrocytoma

5. Pleomorphic xanthoastrocytoma

6. Subependymal giant cell astrocytoma (usually associated with tuberous sclerosis)

B. Oligodendroglial tumors

1. Oligodendroglioma

2. Anaplastic (malignant) oligodendroglioma

B. Ependymal tumors

1. Ependymoma: dense cell, papillary, epithelial, clear cell, mixed

2. Anaplastic (malignant) ependymoma

3. Myxopapillary ependymoma

4. Subependymoma

D. Mixed gliomas

1. Mixed oligoastrocytoma

2. Anaplastic (malignant) oligoastrocytoma

3. Other tumors

D. Tumors, choroid plexus

1. Choroid plexus papilloma

2. Choroid plexus carcinoma

E. Neuroepithelial tumors of uncertain origin

1. Astroblastoma

2. Polar spongioblastoma

3. Gliomatosis brain

G. Neuronal and mixed neuronal-glial tumors

1. Gangliocytoma

2. Dysplastic gangliocytoma of the cerebellum

3. Desmoplastic infantile ganglioglioma

4. Disembryoplastic neuroepithelial tumor

5. Ganglioglioma

6. Anaplastic (malignant) ganglioglioma

7. Central neurocytoma

8. Olfactory neuroblastoma - esthesioneuroblastoma (option: olfactory neuroepithelioma)

3. Pineal tumors

1. Pineocytoma

2. Pineoblastoma

3. Mixed pineocytoma-pineoblastoma

I. Embryonic tumors

1. Medulloepithelioma

2. Neuroblastoma (option: ganglioneuroblastoma)

3. Ependymoblastoma

4. Retinoblastoma

5. Primitive neuroectodermal tumors (PNETs) with polymorphism of cell differentiation: neuronal, astrocytic, ependymal, etc.

a) medulloblastoma (options: medullomyoblastoma, melanocellular medulloblastoma) b) cerebral or spinal PNETs

II. Tumors of the cranial and spinal nerves

1. Schwannoma (neurilemmoma, neurinoma): dense cell, plexiform, melanotic

2. Neurofibroma: nodular, plexiform

3. Malignant tumor of the peripheral nerve sheaths (neurogenic sarcoma, anaplastic neurofibroma, “malignant schwannoma”)

III. Tumors of the meninges

A. Tumors arising from meningothelial cells of the meninges

1. Meningioma: meningotheliomatous, mixed, fibrous, psammomatous, angiomatous, metaplastic (xanthomatous, ossified, cartilaginous, etc.), etc.

2. Atypical meningioma

3. Anaplastic (malignant) meningioma

a) with options

b) papillary

B. Nonmeningeal tumors of the meninges

1. Mesenchymal tumors

1) benign tumors

a) osteochondral tumors

b) lipoma

c) fibrous histiocytoma

2) malignant tumors

a) hemangiopericytoma

b) chondrosarcoma

c) mesenchymal chondrosarcoma

d) malignant fibrous histiocytoma

e) rhabdomyosarcoma

e) sarcomatosis of the membranes

3) primary melanocellular lesions

a) diffuse melanosis

b) melanocytoma

c) malignant melanoma (including meningeal melanomatosis)

2. Tumors of uncertain histogenesis

a) hemangioblastoma (capillary hemangioblastoma, angioreticuloma)

IV. Lymphomas and tumors of hematopoietic tissue

1. Primary malignant lymphomas

2. Plasmacytoma

3. Granulocytic sarcoma

V. Germ cell tumors

1. Germinoma

2. Embryonic carcinoma

3. Yolk sac tumor (epidermal sinus tumor)

4. Choriocarcinoma

5. Teratoma: mature, immature, malignant

6. Mixed tumors

VI. Cysts and tumor-like processes

1. Rathke's pouch cyst

2. Epidermoid cyst (cholesteatoma)

3. Dermoid cyst

4. Colloid cyst of the third ventricle

5. Enterogenous cyst

6. Neuroglial cyst

7. Granular cell tumor (choristoma, pituicytoma)

8. Neuronal hamartoma of the hypothalamus

9. Nasal glial heterotopia

10. Plasma cell granuloma

VII. Tumors of the sella turcica region

1. Pituitary adenoma

2. Pituitary carcinoma

3. Craniopharyngioma

VIII. Growth of tumors from nearby tissues

1. Paraganglioma (chemodectoma, jugular glomus tumor)

2. Chordoma

3 Chondroma (including chondrosarcoma)

4. Carcinoma (nasopharyngeal squamous cell carcinoma, adenoid cystic carcinoma)

The main innovation is the need to determine the molecular genetic subtype of the tumor when making a diagnosis. I see this as a big step towards personalization towards determining treatment tactics and prognosis in routine practice, although of course the problem rests more on the lack of technological capabilities (especially in our country, unfortunately).

Summary of major changes in the 2016 WHO classification of CNS tumors:

1. A concept has been formulated on how diagnoses of CNS tumors are structured in the molecular era

2. Basic reconstruction of diffuse gliomas, combining genetically defined forms

3. Basic reconstruction of medulloblastomas, with the unification of genetically determined forms

4. Major reconstruction of other embryonal tumors, combining genetically defined forms and removing the term "primitive neuroectodermal tumor"

5. Consolidation of genetically defined ependymoma variants

6. Innovative, distinctive approach in pediatrics, including identification of new, genetically defined forms

7. Adding newly selected forms and options, patterns

a. IDH-wild type and IDH-mutant variant of glioblastomas (forms)

b. Diffuse midline glioma, H3 K27M - mutation (form)

c. Embryonic tumor with multilayered rosettes, C19MC- alteration (form)

d. Ependymoma, RELA-positive (form)

e. Diffuse leptomeningeal glioneuronal tumor (form)

f. Anaplastic PXA (form)

g. Epithelial glioblastoma (variant)

h. Glioblastoma with a primitive neuronal component (pattern)

8. Abbreviation of old forms, variants and terms

a. gliomatosis cerebri

b. protoplasmic and fibrillar variants of astrocytoma

c. cellular variant of ependymoma

d. term: primitive neuroectodermal tumor

9. Addition of brain invasion as a criterion for atypical meningioma

10. Reconstruction of solitary fibrous tumors and hemangiopericytomas (SFT/HPC) as one form and adaptation of the staging system to order these changes

11. Enlargement and transformation of forms, including nerve sheath tumor with the addition of hybrid nerve sheath tumor and separation of melanocytic schwannoma and other schwannomas

12. Increase in forms, including hematopoietic/lymphoid tumors of the central nervous system (lymphomas and histiocytic tumors.

DIFFUSE GLIOMAS

Previously, all astrocytic tumors were combined into 1 group, now diffuse infiltrative gliomas (astrocytic or oligodendroglial) are combined together: based not only on the characteristics of their growth and development, but more on the basis of common driver mutations in the IDH1 and IDH2 genes. From a pathogenetic point of view, this provides a dynamic classification that is based on phenotype and genotype; from a prognostic point of view, these are groups of tumors with similar prognostic markers; in terms of treatment tactics, this is a guide to the use of therapy (conventional or targeted) for biologically and genetically similar forms.

In this classification, diffuse gliomas include stage 2 and 3 astrocytic tumors, stage 2 and 3 oligodendrogliomas, stage 4 glioblastomas, and related diffuse childhood gliomas. This approach allows us to distinguish astrocytomas that have more restricted growth patterns, rare inherited IDH mutations, and frequent BRAF mutations (pilocytic astrocytoma, pleomorphic xanthoastrocytoma) or TSC1/TSC2 mutations (subepindymal giant cell astrocytoma) from diffuse gliomas. In other words, diffuse astrocytoma and oligodendroblastomas are nosologically more similar than diffuse astrocytoma and pilocytic astrocytoma; The family tree has been redrawn.

Diffuse astrocytoma and anaplastic astrocytoma

Stage 2 diffuse astrocytoma and stage 3 anaplastic astrocytoma are now divided into IDH-mutant type, IDH-wild type, and NOS categories. In stage 2 and 3 tumors, the majority of cases will be of the IDH-mutant variant if detection of the mutation is available. If IHC mutation R132H of the IDH1 protein and sequencing mutations in codon 132 of the IDH1 gene and in codon 172 of the IDH gene are not identified, or only mutations in 132 of the IDH1 gene and in codon 172 of the IDH gene are not identified, then the sample can be classified as IDH-wild type. It must be remembered that diffuse IDH-wild type astrocytomas are extremely rare and misdiagnosis of gangliogliomas must be avoided; Moreover, IDH-wild-type anaplastic astrocytomas are also rare, and such tumors often have the genetic features of IDH-wild-type glioblastomas. If complete identification of IDH mutations is not possible, the diagnosis is diffuse NOS astrocytoma or anaplastic NOS astrocytoma. The prognosis for cases with an IDH mutation is more favorable.

2 variants of diffuse astrocytoma have been removed from the classification: protoplasmacytic astrocytoma and fibrillary astrocytoma. Thus, only gemistocytic astrocytoma, as a variant of diffuse astrocytoma, is an IDH mutation. Gliomatosis cerebri has also been removed from the classification.

GLIOBLASTOMA

Glioblastomas are divided into IDH-wild type glioblastomas (about 90% of cases), which correspond to the most commonly clinically defined primary or de novo glioblastomas and predominate in patients over 55 years of age; glioblastomas IDH-mutant type (about 10% of cases), which correspond to the so-called secondary glioblastomas with primary diffuse low-stage glioma and more often occur in young patients (Table 4); and glioblastoma NOS, a diagnosis for cases where complete identification of the IDH mutation is not possible.

One conditionally new variant of glioblastoma has been introduced into the classification: epithelioid glioblastoma. Thus, giant cell glioblastoma and gliosarcoma are combined under the term IDH-wild type glioblastoma. Epithelioid glioblastomas are characterized by large epithelioid cells with eosinophilic cytoplasm, vesicular chromatin (a characteristic of cell staining when there is little chromatin????), a prominent nucleus (similar to melanoma cells), sometimes with the presence of rhabdoid cells. More common in children and young adults, usually a superficial cerebral or diencephalic lesion, BRAF V600E mutation is common (can be determined by IHC).

Rhabdoid glioblastoma was differentiated from similar epithelioid glioblastomas based on loss of INI1 expression. Epithelioid glioblastomas, IDH-wild type, often have few of the other molecular characteristics of conventional adult IDH-wild type glioblastomas, such as EGFR amplification and loss of chromosome 10; on the other hand, hemizygous deletion of ODZ3 is common. Such cases may often be associated with a low-stage precursor, often demonstrating the characteristics of a pleomorphic astrocytoma