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To characterize atherogenesis functionally, we studied the functional heterogeneity of endotheliocytes in carotid vessels with atherosclerotic plaques and identified several distinct cell clusters. We measured the Ki-67 labeling index (Ki-67 LI), percentage of Bcl-2 cells (CP) and expression of CCL5, IL 6 and VCAM1 in each cell cluster. We also investigated how these indicators change when the plaque becomes unstable and how they affect the risk of adverse cerebrovascular events in patients. We evaluated the inter-cluster gradient of marker activity and its relation to patient prognosis. We identified five endothelial clusters: the under plaque cluster (UPC), peripheral cluster (PC), marginal cluster (MC), transient cluster (TC) and outside plaque cluster (OC). The UPC exhibited the greatest proliferative, proinflammatory and adhesive activity, but low anti-apoptotic activity. The PC exhibited the second greatest proliferative, adhesive and proinflammatory activity. Progression of atherosclerosis and transition of a stable atherosclerotic plaque to an unstable one was accompanied by increased expression of nearly all markers. The proliferative activity in the UPC, PC and OC, and the pro-inflammatory activity in UPC and anti-apoptotic activity in the PC, were correlated with prognosis. Also, two gradients of proliferative activity and a gradient of pro-inflammatory activity were associated with risk of adverse events. [ABSTRACT FROM AUTHOR]

Background: To date, 16 cases of en plaque hyperostotic meningioma of the convexity have been described. There are no clinical guidelines for the treatment of such patients., Objective: To study the factors influencing the results of surgical treatment of en plaque convexity hyperostotic meningioma, to formulate the appropriate decision-making algorithm., Material and Methods: A retrospective total group of 69 patients with en plaque convexity hyperostotic meningioma who underwent surgery at Burdenko Neurosurgical Center between 2014 and 2023. We analyzed clinical manifestations, tactics and results of surgery and radiotherapy using statistical methods., Results and Discussion: Total resection of small local non-infiltrative hyperostotic meningioma not involving the superior sagittal sinus did not cause neurological deterioration. In case of spread infiltrative hyperostotic meningiomas, the best results (including regression of intracranial hypertension in all cases) were obtained after non-radical surgeries (resection of hyperostosis without wide excision of the dura or even without dura opening). Extent of resection of involved dura and intracranial tumor did not affect relapse-free survival. Additional morbidity at discharge from the clinic was 35%, after ≥6 months - 16%. The most common (27.5%) complication was pseudomeningocele. Redo surgery rate for pseudomeningocele - 7%, hematomas - 7%, wound infection - 6%. There were no mortality in the series. Radiotherapy increased relapse-free survival without statistical confirmation., Conclusion: Total resection provides optimal results in patients with small convexity hyperostotic meningioma and no brain invasion. Resection of hyperostosis and expansive cranioplasty are preferable for large and giant convexity hyperostotic meningioma involving venous sinuses and / or the brain.

Despite slow growth of most pituitary tumors and high rates of total resection and/or effective therapy, pituitary neoplasms are characterized by aggressive behavior with high growth rate, frequent relapses and resistance to standard treatments in 10% of cases. In modern WHO classifications of tumors of the central nervous system, endocrine and neuroendocrine tumors, the authors propose the definition «pituitary neuroendocrine tumor» instead of previous «pituitary adenoma» and «metastasizing pituitary neuroendocrine tumor» instead of «pituitary carcinoma». Currently, there are no effective prognostic markers of aggressive tumors. This complicates early diagnosis. It is proposed to apply a five-stage prognostic classification based on proliferation rate (including mitotic count, Ki-67 index and p53 immunoexpression) and morphometric markers of invasiveness for all resected pituitary neoplasms. This approach would be valuable for earlier detection of aggressive tumors and pituitary carcinomas. Compression of visual pathways, third ventricle and brain stem due to rapid growth of aggressive tumors usually requires redo surgeries with subsequent radiotherapy. Hormonally active tumors require therapy with somatostatin analogues and dopamine agonists in maximum possible doses. Chemotherapy with temozolomide as first-line option is recommended if standard treatment is ineffective. Alternative treatment includes peptide receptor radionuclide therapy (PRRT), molecular targeted therapy (bevacizumab, tyrosine kinase inhibitors, everolimus and cyclin-dependent kinase inhibitors) and immunotherapy (checkpoint inhibitors). Considering the need for combined treatment, these cases should always be discussed by a multidisciplinary team (neurosurgeon, endocrinologist, radiotherapist, oncologist, pathologist) with necessary qualifications and experience in treating these patients. Treatment of aggressive tumors and pituitary carcinomas is becoming an active and rapidly developing direction in neurosurgery, endocrinology and oncology.

Background: Methylation analysis has become a powerful diagnostic tool in modern neurooncology. This technique is valuable to diagnose new brain tumor types., Objective: To describe the MRI and histological pattern of neuroepithelial tumor with PLAGL1 gene fusion., Material and Methods: We present a 6-year-old patient with small right frontal intraaxial tumor causing drug resistant epilepsy. Despite indolent preoperative clinical course and MRI features suggesting glioneuronal tumor, histological evaluation revealed characteristics of high-grade glioma, ependymoma and neuroblastoma., Results: Methylation analysis of tumor DNA confirmed a new type of a recently discovered neoplasm - neuroepithelial tumor with PLAGL1 fusion (NET PLAGL1). PCR confirmed fusion of PLAGL1 and EWSR1 genes. No seizures were observed throughout the follow-up period. There was no tumor relapse a year after surgery., Conclusion: Methylation analysis in neurooncology is essential for unclear tumor morphology or divergence between histological and clinical data. In our case, this technique confirmed benign nature of tumor, and we preferred follow-up without unnecessary adjuvant treatment.

Background: Chordoid glioma is a rare slow-growing tumor of the central nervous system. Available world experience includes no more than 200 cases (lesion of the third ventricle in absolute majority of cases). Recognition and treatment of chordoid glioma are currently difficult problems due to small incidence of this disease., Objective: To describe clinical manifestations and surgical treatment of chordoid glioma of the third ventricle considering literature data and own experience., Material and Methods: There were 12 patients (6 men and 6 women) with chordoid glioma between 2004 and 2023 (10 patients with lesion of the third ventricle, 1 - lateral ventricle, 1 - pineal region). Only patients with tumors of the third ventricle were analyzed., Results: Total and subtotal resection was performed in 1 and 3 cases, respectively. Five patients underwent partial resection, 1 patient underwent biopsy. The follow-up data were available in 7 out of 10 patients (mean 25 months). Radiotherapy was performed in 4 patients (continued tumor growth in 2 cases). One patient died., Conclusion: Chordoid glioma is a benign tumor predominantly localized in the third ventricle. Preoperative MRI and CT in some cases make it possible to suspect chordoid glioma and differentiate this tumor from craniopharyngioma, meningioma and pituitary adenoma by such signs as isointense signal in T1WI, hyper- or isointense signal in T2WI, homogeneous contrast enhancement and edema of basal ganglia in T2 FLAIR images. The only effective treatment for chordoid glioma is surgery. Total resection is often impossible or extremely dangerous due to location of tumor, large size and invasion of the third ventricle. Postoperative mental disorders and diabetes insipidus, including severe hypernatremia, are common that requires mandatory monitoring of water and electrolyte balance.

Methylation of the O-6-methylguanine-DNA methyltransferase ( MGMT ) gene promoter is currently the most important prognostic biomarker in therapy of IDH-wild-type glioblastoma. One can obtain information about this methylation from total DNA methylation profile., Objective: To analyze the DNA methylation signal intensity in the MGMT gene in samples of malignant gliomas and identify the most significant genomic positions for calculating the MGMT gene promoter status for further improvement of diagnostics and prediction of therapeutic options in patients with malignant gliomas., Material and Methods: The study is based on 43 samples (frozen tissue or paraffin blocks) from patients with malignant gliomas. Tumor DNA samples were prepared using the Illumina Infinium MethylationEPIC BeadChip Kit and the Illumina Next-Seq 550 Sequencing System platform. DNA methylation profiles were analyzed using computational algorithms in the R language, specialized libraries minfi and mgmtstp27, as well as basic statistical functions in the Rstudio environment., Results: We established the MGMT gene promoter status in 43 samples of malignant gliomas considering total DNA methylation profile. In 24 samples (55%), the MGMT gene promoter was methylated. We compared methylation signal in certain CpG islands in groups with methylated and unmethylated MGMT gene promoters and identified the most significant positions for further improvement of data analysis algorithm., Conclusion: These data demonstrate the possibilities and prospects for further improvement of algorithm for analysis of the MGMT gene promoter status based on total DNA methylation profile in patients with malignant gliomas as an alternative to methyl-specific PCR. Our results are consistent with data of other neuro-oncology researchers. Indeed, computational methods like MGMT-STP27 are quite powerful and can be used in scientific and clinical practice to assess prognosis and make decisions about chemotherapy with alkylating agents.

Background. Meningiomas may be accompanied by peritumoral edema. Incidence and pathogenesis of edema are nor clearly established. Prevalence and severity of edema vary significantly in patients with meningiomas similar in various parameters., Objective: To assess peritumoral edema in intracranial meningiomas and factors influencing incidence and severity of this process., Material and Methods: There were 126 patients (69% women) aged 19-76 years (median 53), who were diagnosed with 142 meningiomas. Patients underwent surgery ( n =111) and radiotherapy ( n =15) in 2016-2018. The MRI protocol included T1, T2, T2-FLAIR, DWI and post-contrast T1-weighted images in three projections, diffusion tensor MRI in 27 cases and MR spectroscopy in 21 patients., Results: Peritumoral edema was detected in 46% ( n =66) of cases including 21 (31%) patients with severe edema. The ALPS index was 1.510±0.1931 in meningiomas without edema and 1.308±0.19 in those with edema ( p =0.014). There was positive correlation between edema, dimensions and uneven contours of meningioma, as well as negative correlation with CSF cleft sign. Blood flow velocity was higher in atypical and anaplastic meningiomas with edema ( p =0.03). Other signs (localization, histological variant, malignancy grade, characteristics of MR signal, peaks of the main metabolites, diffusion and perfusion parameters of tumor) did not significantly affect peritumoral edema in patients with meningiomas ( p >0.05)., Conclusion: Diffusion tensor tomography with ALPS index revealed significant effect of glymphatic system dysfunction on peritumoral edema. Large meningioma with uneven contours increased the risk of peritumoral edema, while CSF cleft sign reduced this risk. Other factors did not affect cerebral edema in meningiomas.

Using the example of a recurrent tumor with a 10-year follow-up, the authors show that mutation of the IDH1/2 genes in astrocytomas is not always an early event in the pathogenesis of glioma, that in rare cases a 1p19q codeletion can be found in astrocytomas, and that IDH-mutant tumors can occur in childhood.

Background: Differential diagnosis of supratentorial ependymomas is of particular difficulty in neurooncology due to nonspecific clinical and radiographic findings, a rare seen «classic» morphological picture, and a nonspecific immunophenotype. Thanks to molecular genetic methods, in particular real-time PCR, it has become possible to verify supratentorial ependymomas and identify their molecular group, on which further prognosis depends., Objective: To develop a set of molecular genetic tests based on real-time PCR to verify supratentorial ependymomas., Material and Methods: 56 tissue samples were collected from patients with supratentorial ependymomas, WHO Grade II, and anaplastic ependymomas, WHO Grade III. We developed primers and fluorescent TaqMan probes for real-time PCR analysis to detect the ZFTA::RELA , ZFTA::MAML2 , ZFTA::NCOA2 , ZFTA::MAML3, YAP1::MAMLD1 , and YAP1::FAM118B gene fusions. For immunohistochemical analysis, monoclonal rabbit anti-NF-kb p65 antibodies (HUABIO, China) were used, the study was carried out on AutostainerLink 48 immunostainer (DAKO, Denmark)., Results: Real-time PCR was able to verify the diagnosis for 69.9% ( n =39) of samples and classify them into molecular groups of ZFTA- or YAP1-positive supratentorial ependymomas. Immunohistochemically it was possible to verify 58% ( n =29) ependymomas., Conclusion: Diagnosis by real-time PCR is a relatively fast, accessible and easily interpreted method that allows verification of the molecular group in 70% of cases of supratentorial ependymomas without the use of additional methods.

Introduction: Stereotactic radiosurgery is one of the main treatments for vestibular schwannomas (VS). Their feature is frequent post-radiation pseudoprogression. This may be due to hormonal status of patients., Objective: To analyze expression of progesterone and estrogen receptors in women and men with VS., Material and Methods: Immunohistochemical analysis of expression of progesterone (PR) and estrogen receptors (ER) after biopsy was performed in 240 patients with VS between 2018 and 2021. ER/PR expression was assessed in men ( n =120) and women ( n =120) in 3 age subgroups: young age (18-44 years), middle age (45-59 years) and old age (60-79 years). Each subgroup included 40 patients. Statistical analysis was performed using the Mann-Whitney test and MedCalc software., Results: ER expression is not typical for VS (men - 1 (0.01%), women - 3 (2.5%)). At the same time, PR expression was found in 29 (24.2%) men and 21 (17.5%) women. We found no significant difference in expression of ER and PR between men and women. However, variability in PR expression was revealed, i.e. predominance of this indicator in young women ( p =0.0463) and middle-aged men ( p =0.0110). Expression of PR was similar in elderly patients ( p =0.2382)., Conclusion: The established incidence of PR expression may be one of the probable causes affecting development and duration of VS pseudoprogression after radiosurgery without clear relationship between sex and age. Further prospective research is needed to predict the risks of pseudoprogression.

Background: Pathogenesis of peritumoral cerebral edema is unclear and potentially associated with glymphatic system dysfunction. Diffusion tensor MRI (DT-MRI) with analysis of ALPS (Analysis along the Perivascular Space) index may be valuable for assessment of edema. This approach visualizes fluid flow along perivascular spaces of deep cerebral veins., Objective: To assess glymphatic system function in supratentorial tumors and healthy volunteers using DT-MRI., Material and Methods: There were 52 patients (59% men) aged 43 (28-64) years with supratentorial tumors (meningioma - 20, grade 3-4 glioma - 15, metastases - 9, lymphoma - 8). Tumors and perifocal edema did not involve deep cerebral veins. The control group included 6 healthy volunteers aged 34-66 years. MRI protocol (Signa HDxt, 3 T) contained standard T1, T2, T2FLAIR, DWI and post-contrast T1 (3D BRAVO). DT-MRI had the following parameters: TR=10 000 ms, TE min =102 ms, FOV=240 mm, isotropic voxel size 3×3×3 mm 3 , 60 directions of diffusion gradients. Measurements were carried out at b-factor 0 and 1000 s/mm 2 . Analysis was carried out in the ReadyView software., Results: Right- and left-sided ALPS indices were similar in the control group ( p =0.917). Perifocal edema (regardless of histological type of tumor) in the ipsilateral hemisphere was accompanied by significantly lower ALPS index ( p <0.005), while these values in contralateral (intact) hemisphere were similar in both groups ( p =0.7)., Conclusion: We found significantly lower ALPS index in deep parts of the affected hemisphere in patients with perifocal edema. These data can indicate the role of glymphatic system dysfunction in pathogenesis of this pathology.

The review is focused on a relatively new research method in oncology - DNA methylation. Starting from the methylation of individual genes, the method is gradually expanding and becoming routine for studying the global structure of DNA methylation (methylome) in tumors of various localizations. For some tumors (carcinomas of the mammary and thyroid glands), the study of the global structure of DNA methylation is just beginning, while methylation classifiers have been proposed and successfully used in the Russian Federation for brain tumours and sarcomas. This article compares the fifth edition of the WHO Classification of tumours of the Central Neurvous System and the methylation brain classifier.

Diffuse midline gliomas are relatively rare in adults. Regardless of age, all diffuse midline gliomas are routinely examined in our Center for the presence of the H3F3A K27M gene mutation. However, we identified IDH -mutant brainstem glioma in a 42-year-old man for the first time.

The paper presents the experience of using DNA methylation status in patients with meningiomas of the craniovertebral junction area in a neurosurgical clinic. A clinical case of combined treatment of a patient with meningioma of the craniovertebral junction and the choice of tactics based on the result of DNA methylation analysis of meningioma are described.

Identification of specific alterations in tumors (as a rule, these are mutations or gene fusions) makes it possible to prescribe targeted drugs of the second line of therapy or, in some cases of inoperable tumors, to observe not only a gradual partial response of the tumor to treatment, but also the removal of these patients from the category of incurable ones. The article describes a new rare type of BRAF::EPB41L2 gene fusion detected in a piloid astrocytoma that developed in the posterior cranial fossa in an 11-year-old boy.

Over the past decade, next generation sequencing (NGS) has become the standard method in research of cancer genomics; currently NGS is entering a new stage - direct usage in clinical oncology to improve diagnostics and establish personalized tumor treatments. NGS allows to read the genome and it is successfully applied to detect mutations and other somatic changes (translocations, inversions, insertions and deletions, copy number variants) leading to the development of a tumor. With a focus on transcriptome sequencing allows to clearly identify differences in gene expression, improve the classification of tumors and detect somatic chimeras. All these possibilities are especially relevant for pediatric neurooncology filed in view of the existing limitations in treatment and the need for the most accurate identification of the key factors of tumor development. In this article, we describe sequencing technology basis, its application on brain tumor materials to improve diagnostics, and other relevant possibilities that can be considered for direct usage in medicine.

The authors present 2 patients. One of them had typical multifocal primary multiple synchronous wild-type IDH1/2 glioblastoma subtype RTK1, chromosome 7 duplication, homozygous CDKN2A deletion and chromosome 10 deletion. In another patient, the nature of tumors remains debatable. We can talk about either a rare atypical case of metachronous multicentric various glial tumors (oligodendroglioma, IDH1-mutant and 1p/19q-codeleted, WHO grade 2 and RTK2-glioblastoma) or secondary glioblastoma after previous oligodendroglioma arose a year after radiotherapy.

Here we report three patients with rare primary intracranial sarcomas, two of them were CIC-sarcomas and one was a DICER1 -sarcoma. Tumors were examined using DNA methylation. It is important to study of CIC fusions and DICER1 mutations in malignant brain tumors.

Complex management of patients with intracranial pilocytic astrocytoma (PA) consists of surgical treatment, drug therapy (mainly in young children) and radiotherapy. For many years, radiotherapy (RT) has been a standard for residual tumors, recurrence or continued growth of PA. Currently, stereotactic radiosurgery and radiotherapy are preferred for PA, because these procedures are characterized by high conformity and selectivity, precise irradiation of tumor with minimal damage to surrounding intact tissues. Stereotaxic approach is very important since PAs are localized near functionally significant and radiosensitive brain structures in most cases. There is significant experience of single-center studies devoted to radiotherapy of patients with PA at the Department of Neuroradiosurgery of the Burdenko Neurosurgery Center. In this research, the authors analyzed the results of stereotactic irradiation of 430 patients with PA for the period from 2005 to 2018.

Central neurocytoma is a rare benign brain tumor. These tumors may be giant and accompanied by compression of ventricular system and surrounding structures. Modern treatment of brain neurocytoma includes extended resection and restoration of normal CSF circulation. Surgical treatment does not often lead to total resection of these tumors. Redo resection was preferred in patients with tumor progression for a long time. In the last decade, various authors report stereotactic irradiation for continued tumor growth to ensure local growth control. This study was aimed at evaluation of postoperative outcomes in patients with brain neurocytomas, as well as treatment of tumor progression in long-term period., Objective: To analyze recurrence-free survival in patients with brain neurocytomas, risk factors of recurrence-free survival, effectiveness of various treatments for tumor progression and delayed complications., Material and Methods: Long-term postoperative follow-up data of patients with brain neurocytomas are reported in the manuscript. We analyzed recurrence-free survival and risk factors of recurrence-free survival, treatment outcomes in patients with progression of brain neurocytomas, long-term complications and their prevention., Results: Follow-up included 84 out of 115 patients with brain neurocytoma after surgical treatment in 2008-2017. Follow-up period ranged from 2 to 10 years (mean 6 years) after resection. Most patients had regression of neurological symptoms after surgery. Continued tumor growth within 12-96 months after surgery occurred in 26 (30.19%) out of 84 patients (19 cases after partial resection and 7 cases after total resection according to MRI data). Two-year recurrence-free survival was 94%, 5-year survival - 83%. Risk factors of continued tumor growth were resection quality and Ki-67 index. Redo resection was performed in 7 cases. Eleven patients underwent stereotactic irradiation for tumor progression. Indications for stereotactic irradiation of central neurocytoma are MR data on continued growth of lateral ventricle tumor without signs of ICH and CSF flow impairment. There were no cases of hemorrhage inside the residual tumor and CSF flow impairment in early postoperative period after redo resection. In all cases ( n =11), stereotactic irradiation (mean follow-up 2.5 years) ensured satisfactory control of tumor growth with reduction of the neoplasm in 4 cases and no tumor growth in 7 cases., Conclusion: Resection of central neurocytoma ensures long-term recurrence-free period. The main causes of tumor recurrence are partial resection and high proliferative activity (Ki-67 index over 5%). Redo resection is advisable for tumor progression followed by CSF flow impairment. In case of continued growth of neurocytoma without signs of intracranial hypertension, stereotactic irradiation with various fractionation modes ensures effective and safe control of tumor growth.

Glioma metastasis outside the central nervous system is a quite rare phenomenon. The disease in a young woman manifested itself as back pain and loss of vision in the left eye. Magnetic resonance imaging (MRI) revealed a tumor of the optic nerve; positron emission tomography showed multiple secondary bone changes. At the same time, MRI detected no signs of neoplasm in the midline brain structures (the brain stem and subcortical nuclei) and spinal cord. Two biopsies (superior iliac spine trephine biopsy and optic nerve tumor biopsy) were performed. There were similar histological tumors; the optic nerve tumor was found to have K27M mutation in the H3F3A gene, whereas the metastatic tumor lacked this mutation (possibly due to the quality and quantity of DNA isolated from the tumor cells). The interesting features of this case are the simultaneous detection of primary and metastatic tumors before receiving any treatment and the absence of the K27M mutation in the H3F3A gene in the metastasis.

Diffuse brainstem tumor is a fatal disease and the main cause of child mortality from neoplasms of central nervous system. So far, no effective therapy has been found for this disease. The authors discuss the modern aspects of clinical data, biology, diagnosis and treatment of patients with diffuse brainstem tumors.

The purpose of this study was to assess the influence of resection quality on overall survival and disease-free survival in children with atypical teratoid-rhabdoid tumors (ATRT). The study included children younger than 18 years old for the period from 2008 to 2019. There were 134 interventions in 105 patients with ATRT including 11 redo resections («second-look» surgery) and 18 procedures for tumor recurrence. Age of patients ranged from 2 to 168 months (median 21 months). Patients with supratentorial tumors prevailed (50.5%), infratentorial neoplasms were diagnosed in 45.7% of patients, spinal cord lesion - 3.8% of cases. At the first stage, all patients underwent surgical treatment. Total resection was achieved in 34 (32.4%) patients, subtotal - 37 (35.2%) patients, partial resection - 30 (28.6%) patients. Biopsy was performed in 4 (3.8%) patients. Quality of resection and age at surgery significantly influenced overall and disease-free survival. Extended resection of tumor followed by adjuvant chemo- and radiotherapy are required to improve survival although ATRTs are high-grade neoplasms with poor prognosis.

DnA methylation has recently been accepted as the most reliable and effective method of diagnosing central nervous system (CNS) tumors. Healthy organs and tumors of different localizations have their own unique methylation structure. Determination of total tumor DNA methylome is the detection of all methylated nucleotides in a tumor. The "gold standard" for analyzing the methylation state of individual cytosines is bisulfite conversion, in which unmethylated cytosines are converted to uracils and read as thymines, while methylated cytosines are protected from conversion.

Express MS identification of biological tissues has become a much more accessible research method due to the application of direct specimen ionization at atmospheric pressure. In contrast to traditional methods of analysis employing GC-MS methods for determining the molecular composition of the analyzed objects it eliminates the influence of mutual ion suppression. Despite significant progress in the field of direct MS of biological tissues, the question of mass spectrometric profile attribution to a certain type of tissue still remains open. The use of modern machine learning methods and protocols (e.g., "random forests") enables us to trace possible relationships between the components of the sample MS profile and the result of brain tumor tissue classification (astrocytoma or glioblastoma). It has been shown that the most pronounced differences in the mass spectrometric profiles of these tumors are due to their lipid composition. Detection of statistically significant differences in lipid profiles of astrocytoma and glioblastoma may be used to perform an express test during surgery and inform the neurosurgeon what type of malignant tissue he is working with. The ability to accurately determine the boundaries of the neoplastic growth significantly improves the quality of both surgical intervention and postoperative rehabilitation, as well as the duration and quality of life of patients.

Neuroblastoma is a malignancy developing from the embryonic neuroblasts of sympathetic nervous system. Primary sellar neuroblastomas are extremely rare (there are currently only 11 case reports in the literature). Possible development of neuroblastoma in sellar region expands differential diagnosis of local processes due to inclusion of neuroblastoma into the spectrum of suspected tumors. We report a literature review and description of a patient with primary sellar neuroblastoma.

Background: Development of meningiomas correlating with irradiation has been described in the last century. Different biological features of radiation-induced meningiomas depending on dose and type of irradiation have been observed in recent years., Material and Methods: There were 8848 patients (women - 74.3%) with intracranial meningiomas for the period from 2000 to 2014 who underwent surgery at the Burdenko Neurosurgical Center. Radiation-induced meningiomas were identified in 33 patients (13 (38%) men and 20 (62%) women) aged 16-76 years (median 56 years). Medical data were retrospectively analyzed. Follow-up period ranged from 5 to 22 years (median 12) after verification of histological diagnosis. Meningiomas were preceded by X-ray irradiation of the scalp for ringworm (microsporia or trichophytosis) in 26 cases (79%) (group A). Group B enrolled 7 (21%) patients after previous radiotherapy for other tumors (retinoblastoma, chiasmal glioma, pituitary adenoma, basalioma). Data were compared using Mann-Whitney and Fisher's exact tests., Results and Discussion: Incidence of radiation-induced meningiomas was 0.37% in our sample. Meningioma diagnosis dates after X-ray epilation (median 52 years) significantly differed from that after radiotherapy (median 22 years) (Mann-Whitney test, p =0.0003). Primary multiple meningiomas were diagnosed only in the 1 st group (Fisher's exact test, p =0.0005). Recurrent meningiomas after the first surgery were more common in the first group (58%) compared to the second one (14%) (Mann-Whitney test, p =0.0003)., Conclusions: The latency period is shorter after radiotherapy (median 22 years compared to 52 years after X-ray epilation). Incidence of atypical and malignant meningiomas directly correlates with irradiation dose. Approximately equal incidence of radiation-induced meningiomas after X-ray epilation in women and men can indicate other mechanisms of development of these tumors in comparison with spontaneous ones. Radiotherapy is followed by occurrence of meningiomas within the irradiated area. These tumors are usually single. In case of X-ray epilation, the tumors may be localized anywhere within the intracranial space (convexital and/or parasagittal localization in 77% of cases). Multiple neoplasms occur in 42% of cases. Refusal of head X-ray epilation for the treatment of a ringworm for the last 50 years may be followed by reduced incidence of radiation-induced meningiomas, especially multiple ones. However, extended indications for radiotherapy of various brain diseases can result an increase of the incidence of meningiomas within the irradiated area.

Medulloblastoma (MB) is the most common brain malignancy in children occurring in the posterior cranial fossa. This tumor is characterized by high risk of metastasis along the CSF pathways. Significant progress in research of this tumor and appropriate treatment is associated with determining the various molecular categories of primary medulloblastomas. This analysis includes certain factors of cytogenetic and transcriptional proliferation. Modern treatment approaches for patients older than 3 years include advanced resection, craniospinal irradiation with a boost on the postoperative bed followed by platinum-based chemotherapy. Conventional radiotherapy including craniospinal irradiation results a significant number of complications. Morbidity rate is increased throughout long-term follow-up. Secondary tumors including glioblastomas are under special attention since their occurrence is associated with a fatal outcome. This may partially explaine the fact that chemotherapy without repeated morphological verification doesn't always ensure tumor growth control in patients with recurrent medulloblastomas. The authors consider irradiation-induced glioblastomas secondary to primarily verified medulloblastomas in patients who had previously undergone craniospinal irradiation as a component of combined treatment after tumor resection. It was found that the incidence of this phenomenon is significant and made up about 10% among patients with recurrent medulloblastomas. This value is significantly higher compared to previous data. The authors analyzed patterns of occurrence of irradiation-induced glioblastomas depending on the molecular genetic group and clinical characteristics of patients after primary surgery. Treatment outcomes were estimated too. It was concluded that morphological verification is necessary if long-term recurrence is diagnosed after combined treatment of medulloblastoma.

Background: Immunohistochemistry is a basic diagnostic technique. Immunohistochemical examination results reflect mainly qualitative and less quantitative characteristics of proteomic status of cells. A combined approach with complex quantitative evaluation of marker expression using colorimetric analysis and computer technologies can expand the diagnostic capabilities of immunohistochemistry. We studied such an approach developed by using expression of the proliferative marker Ki-67 in pituitary adenomas., Methods: A retrospective, blind, randomized, comparative study was performed of Ki-67 expression activity in pituitary adenomas using the traditional Ki-67 labeling index and a simple immunohistochemical cytocolorimetric analysis developed by us with immunohistochemical cytocolorimetric index (ICI) estimation as predictors of relapse, assessing the relationships of these indicators with the time before relapse., Results: Mean Ki-67 labeling index was 3.87% ± 0.29% in the relapse-free group and 4.01% ± 0.29% in the relapse group; the difference was not statistically significant. The average Ki-67 ICI was 24.16% ± 0.51% in the relapse-free group and 30.68% ± 0.64% in the relapse group; the difference was statistically significant. The correlation coefficient of ICI values and time before relapse was -0.302, indicating the presence of a weak negative correlation., Conclusions: We successfully tested an ICI estimation method developed by us to assess Ki-67 expression in pituitary adenomas. The ICI technique can be used both as a prognostic factor for relapse and, in combination with other modern proteomic and genetic methods, as the basis for creation of new multimodal analyzing systems for functional state assessment of cells and tissues., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The paper describes a clinical case of atypical teratoid/rhabdoid tumor with preserved INI1 expression and SMARCA4 gene mutations in an 8-month-old girl. Genome-wide DNA methylation, hierarchical clustering, and next-generation sequencing were used to make a tumor diagnosis. However, BRG1 immunohistochemical examination may be recommended in the routine practice of diagnosis and study of childhood CNS malignant tumors.

In most cases, oncogene amplification are prognostic and predictive markers for various tumors, therefore DNA probes are unable to reveal changes in the copy numbers should not be used to diagnose malignant tumors., Objective: To comparatively analyze DNA probes from different manufacturers to detect MYC gene amplification in routine practice., Material and Methods: The study material was formalin-fixed paraffin-embedded medulloblastoma fragments from 4 patients, with discrepancies in the results in the detection of MYC gene amplification., Results: MYC gene amplification was determined using DNA probes: Kreatech MYC (8q24)/SE 8, Vysis LSI MYC SO, Vysis CEP 8 (D8Z2) SG, and Zytolight SPEC MYC/CEN 8 Dual Color Probe. The use of the probes Kreatech TERC (3q26)/MYC (8q24)/SE7 Triple-Color probe failed to detect MYC gene amplification; this probe showed a balanced profile of chromosome 8., Conclusion: In routine practice, fluorescence in situ hybridization with the DNA probes Kreatech MYC (8q24)/SE 8, Vysis LSI MYC SO, Vysis CEP 8 (D8Z2) SG and Zytolight SPEC MYC/CEN 8 Dual Color Probe can be the method of choice for studying the copy number of the MYC gene. However, the authors strongly recommend that the Kreatech TERC (3q26)/MYC (8q24)/SE7 Triple-Color should not be used for this purpose. In addition, probes for fluorescence in situ hybridization must be necessarily tested in large reference laboratories dealing with one or another area of oncopathology.

Objective: To comprehensively assess the functional molecular biological status of different tumor cell populations in glioblastoma samples., Material and Methods: The activity of Ki-67, Bcl-2, and BCL6 expression was determined in 20 tumor samples from patients with glioblastoma. After that, a spatial analysis of heterogeneity in the expression of these markers in different tumor cell populations was carried out using computer and software tools and calculating the percentage of cells (PC) expressing this marker (Ki-67 labeling index (LI)) and a modified histoscore in different cell clusters., Results: Analysis of heterogeneity in the distribution of Ki-67, Bcl-2, and BCL6 expression could identify five cell clusters differing in the expression level of the above-mentioned markers. The most active cluster was the perivascular one (the highest mean Ki-67 LI (22.23±1.4%) and histoscore (118.59±3.36%); BCL6 PC and histoscore (17.4±1.4 and 79.32±4.86%, respectively). The least proliferative activity was observed in the perinecrotic cluster (Ki-67 LI (6.83±0.5%) and histoscore (62.46±2.25%)), while the neighboring transient necrotic cluster displayed sufficiently active proliferative processes (Ki-67 LI (18.39±0.56%) and histoscore (112.65±2.76%)). In addition, the transient vascular cluster was noted for a low proliferative activity (Ki-67 LI (8.37±0.35%) and histoscore (75.48±2.04%)). Finally, the intermediate cluster was characterized by the mean values of all parameters (Ki-67 LI (10.68±0.39%) and histoscore (95.73±2.37%). It should be noted that the differences in the expression activity for markers in these clusters were statistically significant., Conclusion: The perivascular cluster carries the greatest potential for tumor progression and recurrence, which agrees with the data available in the literature: the perivascular zone is the most important niche for glioma stem cells that make a considerable contribution to the malignant potential of glioblastoma. Tumor pathogenesis and morphogenesis are a complex interweaving of interrelated factors, the realization of which within the framework of a multi-level heterochronic pathological process leads to the segregation of tumor cells and to the appearance of separate cell populations described in this paper.

5-ALA intraoperative fluorescence is widely used in surgery of brain tumors for intraoperative demarcation of boundaries and more total resection because 5-ALA metabolites are not accumulated in the intact brain and vascular tissues. Given this fact, it was hypothesized that fluorescence of vessels in the immediate vicinity of a brain tumor may indicate their infiltration by tumor cells as a potential pathway for their dissemination and as a factor for continued tumor growth after surgery and adjuvant therapy., Purpose: Identification of fluorescent vessels located near cerebral gliomas, with a histological description of their structure, relationships with the tumor, and potential invasion of the walls by tumor cells., Material and Methods: A prospective cohort study included 14 patients with malignant supratentorial gliomas, aged 20 to 78 years. Five patients were operated on due to continued tumor growth. Two hours before surgery, all patients received 5-ALA orally. During surgery, a microscope (Carl Zeiss OPMI Pentero, Germany) with a fluorescent module (BLUE-400) was used. In all cases, molecular-genetic and immunohistochemical examinations of the tumor material were performed. During surgery, fluorescent vessels, after evaluating their functional significance, were also resected for histological examination., Results: Glioblastoma and anaplastic astrocytoma were verified in 10 and 4 patients, respectively. In 4 out of 10 glioblastoma cases, vessels with homogeneous or fragmentary fluorescent walls were detected in the tumor bed after resection of most of the tumor; in patients with anaplastic astrocytomas, vascular fluorescence was not observed. In the four vascular samples with intraoperatively detected wall fluorescence, tumor invasion into the vascular layers was revealed in all cases. These patients underwent an immunohistochemical examination with monoclonal antibodies to the glial GFAP marker, which clearly identified areas of ingrowth of tumor cells into the vascular wall., Conclusion: 5-ALA intraoperative fluorescence is a fundamentally new approach in the rapid diagnosis of tumor-infiltrated blood vessels. Invasion of tumor cells to intact vessels may be a mechanism of tumor progression and dissemination. Additional resection of fluorescent vessels may affect the radicalness of surgical treatment, but requires a mandatory assessment of their functional significance.

Juvenile nasal angiofibroma (JNA) is a benign, fibro-vascular, locally aggressive tumor with invasive growth patterns and high probability of recurrence. JNA present exclusively in adolescent boys between 9 and 19 years of age, total about 0.05% of head and neck tumors. 143 patients with JNA had been treated surgically from 2002 to August 2018 at N.N. Burdenko National Medical Research Center for Neurosurgery. All patients (primary and recurrences) were males of the age 7-38 years (16.1 [11.3; 19] years). The age of patients with primary JNA was less than 18-year old, of the exception of presenting case. There are more and more publications about case reports and successful treatment series of JNA. However, after detailed review the literature we revealed some kind of confusion: there are case reports of JNA in women and elderly people, JNA in patients with some systemic diseases, JNA with different places of origin and different morphological structure. In this paper we present a very rare case of 38 year-old male with pure primary JNA, accidentally diagnosed on CT and pathologically proven after endoscopic removal. This case confirms the possibility of detecting the JNA in adult men and explains why proper diagnosis of angiofibromas is necessary. The unique case and the literature review are presented.

Background: Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines., Methods: In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MB WNT ), SHH (MB SHH ), group 3 (MB Group3 ), and group 4 (MB Group4 ). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma., Findings: We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MB SHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MB SHH subgroup). Patients with germline APC mutations developed MB WNT and accounted for most (five [71%] of seven) cases of MB WNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MB SHH . Germline TP53 mutations presented only in childhood patients in the MB SHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MB SHH , MB Group3 , and MB Group4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40-69) and 5-year overall survival was 65% (95% CI 52-81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes., Interpretation: Genetic counselling and testing should be used as a standard-of-care procedure in patients with MB WNT and MB SHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics., Funding: German Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The relationship between molecular genetic and metabolic disorders is one of the challenges of modern oncology. In this review, we consider lipid metabolism and its changes as one of the factors of oncogenesis of glial tumors. Also, we demonstrate that the genome and the metabolome are interconnected by a large number of links, and the metabolic pathways, during their reorganization, are able to drastically affect the genetic structure of the cell and, in particular, cause its tumor transformation. Our own observations and analysis of the literature data allow us to conclude that mass spectrometry is a highly accurate current method for assessing metabolic disorders at the cellular level. The use of mass spectrometry during surgery allows the neurosurgeon to obtain real-time data on the level of specific molecular markers in the resected tissue, thereby bringing intraoperative navigation techniques to the molecular level. The generation of molecular fingerprints for each tumor significantly complements the available neuroimaging, molecular genetic, and immunohistochemical data.

Introduction: Radiation therapy of small vestibular schwannomas is quite often used as an effective alternative to surgical treatment. At the same time, 2-10% of patients are detected with radioresistant tumors progressing to varying degrees, which is associated with continued tumor growth. In these cases, a decision on surgical resection or re-irradiation of the tumor is made depending on the neurological symptoms, patient's somatic status, and neuroimaging data. Surgical outcomes and intraoperative findings in pre-irradiated patients have been poorly represented in the literature, for which reason we decided to conduct this study. The paper presents a series of patients with vestibular schwannomas who underwent surgical removal of the tumor after radiotherapy., Material and Methods: A total of 39 patients with vestibular schwannomas after radiotherapy underwent surgery at the Burdenko Neurosurgical Institute in 2007-2017. Of these, 22 patients had a tumor removed after a previously performed combined surgical and radiotherapy treatment (group I), and 17 patients underwent tumor resection after previous radiological treatment (group II). The surgical outcomes were studied depending on various factors, and an analysis of the morphological changes in vestibular schwannomas after radiological treatment was carried out., Results: In group I, the tumor was resected totally in 18% of patients, almost totally in 5% of patients, subtotally in 68% of patients, and partially in 9% of patients. In group II, the tumor was resected totally in 6% of patients, almost totally in 12% of patients, subtotally in 76% of patients, and partially in 6% of patients. We found that post-radiation changes in patients undergoing surgery led to an increase in the response of neurovascular structures to surgical intervention, development of pronounced fibrosis around tumors, and changes in the structure of tumors that became more solid. As a result, surgical morbidity increased, and the patient's quality of life after surgery deteriorated.

The median overall survival of glioblastoma patients is about 15 months. Only a small number of patients survive 3 years. The factors of a favorable prognosis for the 'longevity phenomenon' in glioblastoma patients are not fully understood., Objective: to determine the occurrence rate of long-living patients with glioblastomas, identify clinical predictors of a favorable prognosis, and identify the presence and prognostic significance of an IDH1 mutation., Material and Methods: Among 1494 patients operated on for glioblastoma at the Burdenko Neurosurgical Institute from 2007 to 2012, there were 84 (5.6%) patients who lived more than 3 years after primary surgery. In all the cases, histological specimens were reviewed, and immunohistochemical detection of a mutant IDH1 protein was performed. Overall survival was calculated from the time of first surgery to the date of the last consultation or death, and the recurrence-free period was calculated from the time of first surgery to MRI-verified tumor progression., Results: The median age of long-living patients with glioblastoma was 45 years (19-65 years). All tumors were located supratentorially. The median Karnofsky performance status score at the time of surgery was 80 (range, 70-100). All patients underwent microsurgical resection of the tumor, followed by chemoradiotherapy. The median recurrence-free period was 36 months (5-98 months). Overall survival of 48, 60, and 84 months was achieved in 23, 15 and 6% of patients, respectively. Among 49 specimens available for the IDH1 analysis, 14 (28.6%) specimens had a mutant protein. There was no significant difference in survival rates in patients with positive and negative results for IDH1 (44.1 vs. 40.8 months; p>0.05)., Conclusion: The significance of various factors that may be predictors of a favorable course of the disease is discussed in the literature. This work is the first part of analysis of prognostically significant factors positively affecting overall survival of glioblastoma patients. In our series, the predictors of a favorable prognosis for long-living patients with the verified diagnosis of glioblastoma were as follows: young age, the supratentorial location of the tumor, a high Karnofsky score before surgery, and tumor resection. In our series, we used immunohistochemical tests and found no prognostic significance of the IDH1 gene mutation; further analysis will require application of direct sequencing. We plan to study other morphological and molecular genetic features of tumors, which explain prolonged survival of glioblastoma patients, as well as the role of various types of combined chemoradiation treatment.

Aim: To identify mutations in cerebral cavernous malformation (CCM) genes in patients with hereditary and sporadic CCMs in the Russian population., Material and Methods: Blood samples from 73 randomly selected patients, including 29 MRI-confirmed familial cases, 8 clinically confirmed familial cases and 38 so-called sporadic cases, were examined. A search for large deletions/duplications was performed using multiplex ligation-dependent probe amplification (MPLA). For MLPA-negative samples, the whole genome sequencing was performed to search for single nucleotide polymorphisms (SNP)., Results: Deletions in three genes (ССМ1, ССМ2, ССМ3) were identified in 14 patients, including 5 without definitely established familial type, in whom the familial character of disease was not confirmed by clinical and neuroimaging results. SNP mutations were found in 13 patients, CCM gene mutations in 27. Mutations were detected in 91.7% of familial cases. In two patients, new CCM3 deletions were identified. Gene distribution was as follows: 60.7 for CCM1, 32.2 for CCM2 and 7.1% for CCM3. In two members of a family with hereditary CCMs, no high effect mutations in the known CCM genes were found. Patients with mutations had greater severity of disease. Two patients with CCM3 mutations demonstrated the most aggressive clinical course. De novo formation and growth of CCM were observed only in patients with mutations., Conclusion: The distribution of pathogenic mutations in known CCM genes is consistent with other large-scale studies. Familial CCMs are associated with more severe disease course and may be caused by mutations beyond the known CCM genes.

We present a rare clinical case of a patient with a malignant peripheral nerve sheath tumor developed from the auditory nerve as well as a literature review, including 30 reported cases of this disease.

The work explores the molecular genetic features of anaplastic astrocytomas and oligodendrogliomas in a series of 43 cases. The mutational status was studied using domestic chemicals and reagent kits. We revealed clear genetic differences between astrocytic and oligodendroglial tumors and proposed an algorithm to study diagnostic and prognostic markers.

Unlabelled: Glioblastoma is the most common primary malignant glial tumor of the brain in adult patients., Aim: to define the prognostic value of isocitrate dehydrogenase-1 (IDH-1) mutation and methylguanine-DNA methyltransferase (MGMT) methylation status in patients with glioblastoma (GB) and to analyze the impact of clinical data (gender, age, and tumor site), histological variants of the tumor structure, and time to development of recurrences on the course of the disease., Subjects and Methods: The investigation enrolled 63 GB patients aged 18 to 71 years who had received combined treatment (surgery, chemo- and radiotherapy) at the N.I. Burdenko Research Institute of Neurosurgery, Ministry of Health of the Russian Federation, in the period 2008 to 2011. The investigators performed a morphological examination of all tumor tissue samples and an immunohistochemical examination using anti-IDH-1 R-132 antibody clone («Dianova», Germany) and defined MGMT methylation status by a polymerase chain reaction using the CpGenome DNA Modification Kit («Chemicon International», USA). The data were statistically processed using a package of Statistica 6.0 programs., Results: Patient age, time to development of recurrent glioblastoma, mutations in the IDH-1 gene and MGMT were found to be prognostic factors for overall survival among adult patients in this category., Conclusion: Analysis of clinical findings and identification of molecular genetic aberrations in the tumor cells will be able to elaborate an individual approach to treating patients with glioblastoma in order to increase their survival rates and to improve quality of life.

Unlabelled: Basal ganglia germinomas are a specific group of intracranial germinomas. Their early diagnosis is complicated due to their atypical localization and diversity of neuroimaging and clinical signs., Material and Methods: We describe 4 cases of basal ganglia germinoma in boys of 13, 14, 15, and 16 years of age. The medical history data, clinical features, neuroimaging and histological characteristics of basal ganglia germonomas, and preliminary results of the treatment are presented., Conclusion: Basal ganglia germinomas are usually verified at the late stage of the disease when patients are detected with extended lesions of the basal ganglia and severe neurological and neuroendocrine deficits. This situation is due to clinical and imaging signs that are untypical of common germinomas.

Objective: To describe a procedure and outcomes of comprehensive first-line treatment in glioblastoma patients., Material and Methods: We analyzed 107 glioblastoma patients operated on in 2010-2011. Seventy five patients underwent combined chemoradiotherapy (CRT) with simultaneous administration of 75 mg/m2 temozolomide (TMZ), followed by chemotherapy with 200 mg/m2 TMZ for 5 days, every 28 days. Separately, we examined 32 patients with large tumors who received alternative treatments., Results: The median time to progression was 11.7 months in the study group and 7.2 and 8.1 months in groups of alternative therapy. The one-year progression-free survival rate was 37%. Overall survival was 29.2 months., Conclusion: The chemoradiotherapy regimen involving TMZ followed by one-year TMZ monotherapy is the appropriate treatment for patients with resected glioblastoma. With this approach, no tumor progression occurs in one third of patients during the first year. A careful study of the clinical and radiological findings in the course of treatment makes it possible to achieve the maximum efficacy, avoid unreasonably early switch to second-line therapy, and timely detect tumor recurrence signs. The Response Assessment in Neuro-Oncology (RANO) criteria should be used for assessment of MRI detected changes in the tumor size. The rates of overall and recurrence-free survival were significantly lower in patients with inoperable or partially resected tumors. The applied approaches provide only a slight advantage in control of tumor growth, which necessitates searching for more efficient treatment options for these patients. One of the approaches may be addition of bevacizumab to the first-line therapy regimen.

The paper describes a rare clinical case of intramedullary melanocytoma, provides a detailed description of a pathomorphological study, and addresses the issues of differential diagnosis and surgical treatment.

A six-year-old patient with non-germinomatous germ cell tumor of the chiasmatic-sellar area developed polyuria and polydipsia as the first symptoms of the disease. Then there were signs of precocious puberty and vision impairment. MRI examination revealed a shiasmatic sellar tumor and occlusive hydrocephalus. Tumor marker levels in blood serum were elevated. The alpha-fetoprotein level was increased 5-fold; human chorionic gonadotropin 20-fold. These levels increased over time. The patient received 2 cycles of PEI multiagent chemotherapy (Ifosfamide 1.5 g/m(2), Cisplatin 20 mg/m(2), Etoposide 100 mg/m(2)) during 5 days and 1 cycle of second-line multiagent chemotherapy (Cisplatin 100 mg/m(2) for 1 day and Endoxan 1500 mg/m(2) for 2 days). Despite the decrease in tumor marker levels to normal values, the patient's vision still deteriorated. MRI examination revealed that tumor size increased and its structure changed. Total tumor resection led to vision improvement and regression of intracranial hypertension. Histological analysis of tumor tissue only revealed a mature teratoma. This phenomenon, known as growing teratoma syndrome, is very rare among patients with intracranial non-germinomatous germ cell tumors.

The histological diagnosis of malignant brain tumors in children is a complex process. In some cases, glioblastoma, primitive neuroectodermal tumor of the central nervous system, and atypical teratoid/rhabdoid tumor have a histological type similar to that of small blue round cell malignant tumor. Despite the similar histology, biological properties and approaches to treatment, these neoplasms are completely different and require their own treatment protocols. We retrospectively reviewed the most malignant types of childhood tumors and analyzed our own experience to propose a diagnostic algorithm for intracerebral small blue round cell malignant tumors in children based on the use of immunohistochemistry and fluorescence in situ hybridization.

Unlabelled: Complete removal is the treatment standard for most brain tumors. Outcomes of subsequent comprehensive treatment depend on biological features, the histological structure of the tumor, and radicality of surgery. The aim of this work was to study the morphological features of brain tumors in infants and to analyze long-term outcomes of surgical and comprehensive treatment., Material and Methods: The study included 80 infants with brain tumors aged from 1 to 12 months who had been operated on at the Burdenko Neurosurgical Institute during the period from 2000 to 2010., Results: Maximal radicality was achieved in the group of tumors of the lateral and third ventricles (85%), in the group of tumors of hemispheric localization (82%), and in the group of tumors of the posterior fossa (83%). The lowest percentage of radical tumor removal (15%) accrued to tumors of the chiasmosellar area, most of which were large visual pathway gliomas. The overall five-year survival rate associated with the treatment in the studied series of patients was 92 and 48% for Grade I-II and Grade III-IV tumors, respectively., Conclusion: The features of biology of brain tumors in infants include the increased proliferative activity (high Ki-67 index of 10% and higher) revealed at the diagnosis of choroid papillomas, a series of pilocytic astrocytomas of the chiasm and Grade III astrocytomas, which do not affect the clinical course. The best long-term results of the treatment were obtained in infants with complete resection of Grade I and III astrocytomas and in infants with choroid papillomas. Radical removal of such histological forms as anaplastic astrocytoma, choroidal carcinoma, and anaplastic ependymoma improves the prognosis, provides favorable conditions for adjuvant therapy, and increases the period of progression-free survival in infants.