[Intraosseous metastasis of K27-mutant glioma]. / Vnutrikostnoe metastazirovanie K27-mutantnoi gliomy.

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.

[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.

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.