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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]

(1) Purpose: To determine the borders of malignant gliomas with diffusion kurtosis and perfusion MRI biomarkers. (2) Methods: In 50 high-grade glioma patients, diffusion kurtosis and pseudo-continuous arterial spin labeling (pCASL) cerebral blood flow (CBF) values were determined in contrast-enhancing area, in perifocal infiltrative edema zone, in the normal-appearing peritumoral white matter of the affected cerebral hemisphere, and in the unaffected contralateral hemisphere. Neuronavigation-guided biopsy was performed from all affected hemisphere regions. (3) Results: We showed significant differences between the DKI values in normal-appearing peritumoral white matter and unaffected contralateral hemisphere white matter. We also established significant ( p < 0.05) correlations of DKI with Ki-67 labeling index and Bcl-2 expression activity in highly perfused enhancing tumor core and in perifocal infiltrative edema zone. CBF correlated with Ki-67 LI in highly perfused enhancing tumor core. One hundred percent of perifocal infiltrative edema tissue samples contained tumor cells. All glioblastoma samples expressed CD133. In the glioblastoma group, several normal-appearing white matter specimens were infiltrated by tumor cells and expressed CD133. (4) Conclusions: DKI parameters reveal changes in brain microstructure invisible on conventional MRI, e.g., possible infiltration of normal-appearing peritumoral white matter by glioma cells. Our results may be useful for plotting individual tumor invasion maps for brain glioma surgery or radiotherapy planning.

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: 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.

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: Meningiomas are rather uncommon tumors in the pediatric population, differing significantly from those found in adults by their atypical location, higher rate of more malignant types, consequently higher risk of recurrence and a less favorable outcome. Even in children, suprasellar meningiomas without dural matrix are rare findings mimicking more common suprasellar lesions., Case Presentation: Here we describe a case of a 12-year-old girl who presented with a rapidly progressing chiasmal syndrome and was diagnosed by MRI with an unusual suprasellar tumor that could not fit the diagnoses expected in a case of a parasellar mass in a child, similar to a craniopharyngioma or optic pathway glioma. After multiple clinical investigations, the tumor etiology was still unclear, so the preferred option of treatment was surgical resection. An endoscope-assisted gross total resection through a supraorbital keyhole approach was performed uneventfully, with total vision recovery in a short time. Benign meningiomas located in the skull base without dural attachment appear to be rare, even in pediatric patients., Conclusion: Differential diagnoses of suprasellar and para sellar tumor lesions in pediatric patients can be confusing. There are peculiar features of pediatric tumor diseases that should be considered while working out the management strategy. The main principle of meningioma treatment is the highest possible extent of resection minimally affecting the quality of life., (© 2022. The Author(s).)

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.

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.

The authors report a patient with spinomedullary tumor who underwent resection with subsequent histological examination. However, the authors encountered difficulties in determining the exact histological type of neoplasm. Microscopic and immunohistochemical examination of spinomedullary neoplasm revealed two types of tumor: ependymoma and hemangioblastoma. However, analysis of literature data indicated that the identified tumor could be attributed to a certain cellular type of hemangioblastoma.

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.

Histiocytosis is a group of idiopathic diseases accompanied by metabolic disorders and accumulation of metabolic products in histiocytes. Isolated Rosai-Dorfman histiocytosis of central nervous system is observed in less than 5% of cases. The authors report treatment and follow-up of a patient with intracranial Rosai-Dorfman disease. There were symptoms of lesion of the left cerebellopontine angle and epileptic seizures. Preoperative MRI identified two tumors (posterior cranial fossa on the left and right-sided parasagittal neoplasm). The authors carried out total resection of supratentorial tumor, after 3 weeks - subtotal resection of tumor in posterior cranial fossa. No recurrence after total resection was observed. Irradiation of infratentorial tumor with a total focal dose of 50 Gy after 6 months resulted tumor shrinkage throughout 12 months. Radiotherapy with the same dose was repeated throughout subsequent 12-month follow-up period due to progression of this focus. This treatment had a positive effect, but new skull base foci occurred. The authors emphasize the effectiveness of total resection and lower efficiency of subtotal excision combined with radiotherapy.

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.

Embryonal tumor with multilayered rosettes (ETMR) is a rare and highly malignant brain tumor that develops in children younger 4 years old. This neoplasm is characterized by extremely aggressive course, low sensitivity to chemotherapy and radiotherapy. Thanks to the progress of pathologists, diagnosis of ETMR is now available using immunohistochemical examination with LIN28A and SALL4 antibodies. Moreover, detection of microRNA amplification in the 19q13.42 locus by fluorescent hybridization in situ allows an unmistakable diagnosis., The authors describe clinical course and treatment outcome in a 2-year-old patient with a giant tumor of the right parietotemporal region. Postoperative histological examination verified ETMR. Despite adjuvant treatment, we observed fast progression of disease and unfavorable outcome after 5 months. Case report is supplemented by literature review., Conclusion: ETMR is very rare and poorly understood neoplasm. The authors present a giant hemispheric ETMR in a 2-year-old boy with an extremely aggressive course of disease. Despite the advances in diagnosis and treatment of CNS tumors in children, there are currently more questions than answers regarding ETMR. Pooled analysis of all available data with large-scale studies is needed. It is necessary to emphasize an exceptional role of each clinical case for global study of this tumor. Timely adjuvant/neoadjuvant therapy in highly specialized centers is also essential.

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.

There are no literature data on brainstem arachnoid cysts in humans., Objective: To describe the clinical case of brainstem (pontomesencephalic) arachnoid cyst and to analyze classification, pathogenesis, differential diagnosis and treatment of this pathology considering literature data and own experience., Material and Methods: A 29-year-old patient with pontomesencephalic arachnoid cyst is reported. The disease manifested in childhood with a headache aggravated by bending and pushing. Later, syncope, vegetative-visceral paroxysms, mild oculomotor disturbances, transient paresthesia and numbness of the left half of the face occurred. Headaches became significantly more severe and resulted nausea and vomiting. Magnetic resonance imaging (MRI) revealed a two-chambered arachnoid cyst. A smaller chamber was localized in interpeduncular cistern, a larger one - in brainstem., Results and Discussion: Differential diagnosis included cystic glioma and Virchow-Robin space enlargement. Fenestration of the cyst wall within interpeduncular cistern was performed via right-sided pterional approach. The diagnosis was verified by histological examination. The follow-up period was 14 months. We observed postoperative cyst reduction confirmed by MR data and regression of all symptoms except for minimal signs of medial longitudinal fasciculus dysfunction., Conclusion: Correct surgical approach for brainstem arachnoid cyst complicated by progressive neurological deterioration is confirmed by postoperative regression of cyst and symptoms.

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.