[Sarcomas of the central nervous systems. Clinical observations]. / Sarkomy tsentral'noi nervnoi sistemy. Klinicheskie nablyudeniya.

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.

[Multimodal method of tissue differentiation in neurooncology using Raman spectroscopy, fluorescence and diffuse reflectance spectroscopy]. / Mul'timodal'nyi metod differentsiatsii tkanei v neiroonkologii s ispol'zovaniem spektroskopii kombinatsionnogo rasseyaniya, fluorestsentsii i diffuznogo otrazheniya.

BACKGROUND: There is a need to expand the possibilities of urgent analysis of intracranial tumor type during resection. These measures are necessary to improve resection quality with preservation of intact tissues and avoiding recurrence and neurological impairment in postoperative period. OBJECTIVE: To create optical-spectral method for differentiating the intracranial tumor types. MATERIAL AND METHODS: We used a combination of certain methods such as fluorescence spectroscopy to analyze the content of endogenous and exogenous fluorophores in samples, diffuse reflectance spectroscopy to analyze structural integrity of tissues according to light scattering and blood filling according to hemoglobin spectrum absorption, as well as spontaneous Raman spectroscopy detecting individual molecular components of tissues. The study was conducted at the Laboratory of Neurosurgical Anatomy and Conservation of Biological Materials of the Burdenko Neurosurgical Center and included 93 tissue samples from 60 patients diagnosed with glioblastoma (n=28), meningioma (n=12), astrocytoma (n=9), oligodendroglioma (n=5), and metastasis (n=6). RESULTS: Different types of intracranial tumors that cannot be differentiated using one of the considered spectroscopy modes can be distinguished in another one. Thus, we can conclude possible advantages of combined optical-spectral approach.

[Heterogeneity of tumor cells in glioblastomas]. / Geterogennost' opukholevykh kletok v glioblastomakh.

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.

[Central nervous system atypical teratoid/rhabdoid tumor without loss of nuclear expression of INI1]. / Atipicheskaia teratoidno-rabdoidnaia opukhol' TsNS bez poteri iadernoi ékspressii INI1.

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.

[Li-Fraumeni syndrome in a patient with multiple anaplastic oligodendrogliomas of the brain (a case report and literature review)]. / Sindrom Li-Fraumeni u patsienta so mnozhestvennymi anaplasticheskimi oligodendrogliomami golovnogo mozga (klinicheskoe nabliudenie i obzor literatury).

Li-Fraumeni syndrome (LFS) is a clinically and genetically heterogeneous hereditary syndrome with predominantly oncological manifestations, which is associated with mutations in the TP53, MDM2, and CHEK2 genes. The most common variant is a TP53 mutation. OBJECTIVE: To analyze the literature and present a clinical case of a patient with Li-Fraumeni syndrome and multiple anaplastic oligodendrogliomas of the brain. CLINICAL CASE: A 42-year-old male patient presented with complaints of headaches, word finding difficulty, memory loss, right hemianopsia, and generalized convulsive attacks. For 10 years, he underwent multiple interventions and chemotherapy courses for colon adenocarcinoma and recurrent B-cell lymphoma. MRI revealed multiple space-occupying lesions of the cerebraln hemispheres, which were located in the left temporo-occipital and right frontal regions. RESULTS: The patient underwent resection of multiple space-occupying lesions of the left temporo-occipital and right frontal regions. The postoperative period proceeded without complications. The histological diagnosis was WHO grade III anaplastic oligodendroglioma. The patient and one of his sons were detected with a R248W missense mutation in the TP53 gene. The patient underwent six courses of temozolomide chemotherapy. At a follow-up examination 20 months after surgery and chemotherapy, the patient's condition was satisfactory; he returned to work. Control MRI of the brain revealed no signs of continued tumor growth. CONCLUSION: An analysis of the literature and the clinical case indicate the success of multiple surgical interventions and chemotherapy courses performed for a long time in the patient with Li-Fraumeni syndrome manifested by colon adenocarcinoma, recurrent B-cell lymphoma, and multiple anaplastic oligodendroglioma of the brain. The patient had a good quality of life and returned to professional activity.

[The spectrum of genetic alterations in anaplastic gliomas: and anaplastic oligodendrogliomas]. / Spektr geneticheskikh narushenii v anaplasticheskikh astrotsitomakh i anaplasticheskikh oligodendrogliomakh.

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.

[NMDA receptors expression activity in anaplastic astrocytomas]. / Aktivnost' ekspressii NMDA-retseptorov glutamata v anaplasticheskikh astrotsitomakh.

OBJECTIVE: To study the relationship of NMDA receptors expression activity with proliferative activity and genetic properties of anaplastic astrocytomas, as well as the survival of patients with this disease. MATERIAL AND METHODS: To solve this problem, we compared the expression activity of the least studied NMDA receptors in the context under consideration, detected using immunofluorescent studies and polymerase chain reaction, with the results of histological and molecular studies, the proliferative activity of neoplasms, and the survival of patients. RESULTS: The expression activity of NMDA receptors is higher in astrocytomas, grade 3, which do not carry mutations in IDH1 and IDH2 genes. In addition, the activity of NMDA receptors expression directly correlates with proliferative activity in the tumors. The activity of NMDA receptor expression has a significant impact on the prognosis of disease-free survival. CONCLUSION: We have shown for the first time the significant role of NMDA receptors in the progression of diffuse astrocytomas, which can become the basis for creating new therapeutic and diagnostic tools.

Radiomics in Determining Tumor-to-Normal Brain SUV Ratio Based on 11C-Methionine PET/CT in Glioblastoma.

Modern methodology of PET/CT quantitative analysis in patients with glioblastomas is not strictly standardized in clinic settings and does not exclude the influence of the human factor. Methods of radiomics may facilitate unification, and improve objectivity and efficiency of the medical image analysis. The aim of the study is to evaluate the potential of radiomics in the analysis of PET/CT glioblastoma images identifying the relationship between the radiomic features and the 11С-methionine tumor-to-normal brain uptake ratio (TNR) determined by an expert in routine. Materials and Methods: PET/CT data (2018-2020) from 40 patients (average age was 55±12 years; 77.5% were males) with a histologically confirmed diagnosis of "glioblastoma" were included in the analysis. TNR was calculated as a ratio of the standardized uptake value of 11C-methionine measured in the tumor and intact tissue. Calculation of radiomic features for each PET was performed in the specified volumetric region of interest, capturing the tumor with the surrounding tissues. The relationship between TNR and the radiomic features was determined using the linear regression model. Predictors were included in the model following correlation analysis and LASSO regularization. The experiment with machine learning was repeated 300 times, splitting the training (70%) and test (30%) subsets randomly. The model quality metrics and predictor significance obtained in 300 tests were summarized. Results: Of 412 PET/CT radiomic parameters significantly correlated with TNR (p<0.05), the regularization procedure left no more than 30 in each model (the median number of predictors was 9 [7; 13]). The experiment has demonstrated a non-random linear correlation (the Spearman correlation coefficient was 0.58 [0.43; 0.74]) between TNR and separate radiomic features, primarily fractal dimensions, characterizing the geometrical properties of the image. Conclusion: Radiomics enabled an objective determination of PET/CT image texture features reflecting the biological activity of glioblastomas. Despite the existing limitations in the application, the first results provide a good perspective of these methods in neurooncology.

Identification of different cell clusters in the endothelium of atherosclerotic vessels and determination of inter-cluster gradient of proliferative and inflammatory activity as new diagnostic markers.

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.