Daria Sitovskaya

Lhermitte-Duclos disease (LDD) is a rare pathological entity, histologically defined as dysplastic cerebellar gangliocytoma ‒ a benign cerebellar neoplasm (CNS WHO grade 1). Although its etiology remains unclear, cerebellar involvement may present either sporadically, predominantly in children, or as a component of Cowden syndrome, an autosomal dominant condition characterized by multiple hamartomas arising from all three germ layers. The prognosis of this slow-growing benign lesion is generally favorable, with surgical resection recommended only in symptomatic cases. We report a clinical case of successful neurosurgical management in a 3-year-old patient presenting with hypertensive-hydrocephalic syndrome. Magnetic resonance imaging revealed the characteristic “tigroid” striation pattern on T2-weighted images, while histopathological examination of the cerebellar cortex confirmed the presence of large dysplastic ganglionic cells. This case highlights the importance of an individualized therapeutic approach in neuro-oncology and underscores the key clinical and morphological features of Lhermitte-Duclos disease.

Although meningiomas are predominantly benign tumors, a subset of lesions morphologically classified as Grade 1-2 demonstrates clinically aggressive behavior with early recurrence and unfavorable prognosis, which is not always captured by conventional histopathological grading. The present study evaluates the clinical, morphological, and molecular characteristics of clinically aggressive intracranial meningiomas Grade 1-2 in comparison with Grade 3 meningiomas, with particular emphasis on progression-free survival. Patients with clinically aggressive Grade 1-2 meningiomas and a comparison group of Grade 3 meningiomas were included. Standard histopathological examination was performed, along with molecular assessment of CDKN2A status using fluorescence in situ hybridization (FISH) with quantitative evaluation of the proportion of tumor cells harboring a CDKN2A deletion. Progression-free survival was defined as the interval between surgical resection and radiologically confirmed recurrence. In the clinically aggressive Grade 1-2 meningioma group, the median progression-free survival was approximately 36 months, with a wide range of values (21-144 months), reflecting pronounced clinical heterogeneity. In contrast, Grade 3 meningioma group demonstrated a substantially shorter median progression-free survival of approximately 19 months (range 4-34 months), with predominantly early recurrence. Shorter time to recurrence was more frequently observed in tumors with a high proportion of cells carrying CDKN2A deletion, whereas longer progression-free survival was generally associated with lower levels of CDKN2A loss. Notably, CDKN2A status did not consistently correspond to morphological tumor grade. These findings indicate that clinically aggressive Grade 1-2 meningiomas exhibit an intermediate progression-free survival profile between typical low-grade and overtly malignant Grade 3 meningiomas, supporting a continuum of biological aggressiveness. Quantitative assessment of CDKN2A may serve as a marker of biological risk associated with early recurrence; however, its greatest clinical value lies within an integrative prognostic framework combining clinical, morphological, and molecular parameters.

Gliomas are characterized by extremely aggressive growth and resistance to therapy. The tumor progression is known to be closely linked to its microenvironment, with stromal characteristics playing a key role. The aim of the study was to investigate the features of mesenchymal stroma in high-grade gliomas. A retrospective study was conducted on biopsy specimens from 31 patients with grade 4 astrocytic tumors at the A.L. Polenov Russian Scientific Research Institute of Neurosurgery. Based on molecular profiling, 10 patients were diagnosed with IDH-mutant astrocytoma, and 21 patients were diagnosed with IDH-wildtype glioblastoma. The tumor stroma was assessed using immunohistochemical (IHC) staining for IDH1R132h and vimentin and histochemical staining with Alcian Blue, Toluidine Blue, and Mallory’s trichrome. Analysis revealed statistically significant differences between the groups for all histochemical stains (p 0.05, Student’s t-test). The presence of desmoplastic stroma and high vimentin expression indicates a glial-mesenchymal transition in IDH-wildtype glioblastoma, which underlies its aggressive progression.

INTRODUCTION . Epilepsy is a major global health issue, and despite the availability of antiepileptic drugs, more than 30% of patients develop drug-resistant epilepsy and require surgical treatment. It is now known that disruption of the blood-brain barrier (BBB) is one of the manifestations of this disease, and in animal studies, the severity of epileptic seizures correlates with the degree of BBB disruption. Changes in the tight junctions of endothelial cells, specifically in the amount of claudin protein, which is a key component of the BBB, are of great interest. AIM. To investigate claudin immunoreactivity in the cerebral cortex and white matter of patients with drug-resistant epilepsy (DRE). MATERIALS AND METHODS . Biopsy material from fragments of the temporal lobe was obtained intraoperatively from 15 patients (5 women, 10 men) with locally-caused DRE, aged 20 to 42 years with an average age of 28.7 years. Autopsy material from 6 patients who died from somatic diseases and had no history of neurological disorders was used as a comparison group. Histological sections stained with hematoxylin and eosin, as well as immunohistochemical (IHC) reactions with antibodies to claudin, were studied. The results of the IHC reactions were assessed by calculating the densitometric density of stained basement membranes of vessels in 10 fields of view of the cortex and white matter of the resected temporal lobe in each patient. Statistical analysis was carried out using the Statistica v.10 program, and a difference was considered significant at pRESULTS . Histological analysis revealed focal cortical dysplasia in all patients. IHC reactions with claudin showed varying degrees of immunopositivity in the vascular endothelium of patients with DRE, with some cases showing complete loss of claudin. In the cortex, the level of claudin expression ranged from 0.072 to 0.554 (mean=(0.267±0.088)), and in the white matter, it ranged from 0.048 to 0.528 (mean=(0.181±0.064)). Statistical analysis showed no significant difference in claudin expression between patients with drug-resistant epilepsy and the comparison group (p-value = 0.43). However, a significant difference was found in the cortex according to the Mann – Whitney U test (p-value = 0.01). A correlation analysis using Spearman’s correlation coefficient revealed a medium-strength negative correlation. CONCLUSION . In patients with drug-resistant epilepsy, there is a decrease in claudin 5 immunoreactivity in the cerebral cortex. Defects in tight junction proteins, with a predominant effect on cortical vessels, may be both a primary and secondary factor in epilepsy and could potentially be a therapeutic target in this group of patients.

One of the main prognostic factors for meningioma recurrence is histological diagnosis with an assessment of tumor grade. Despite this, there are no clear microscopic criteria for recurrence prognosis in benign forms, and there is no common understanding of meningioma recurrence and continued growth clinical management. Objective. To evaluate neuroimaging, microscopic features and proliferative activity in meningioma recurrence and continued growth. Material and methods. Histological and immunohistochemical studies of tumor biopsies were performed in 16 patients with tumor progression who underwent surgery for recurrence and continued growth of intracranial meningiomas; the comparison group included 10 patients with newly diagnosed intracranial meningioma. All patients were performed pathomorphological and radiological examination assessment. Results. The average tumor volume in the meningioma progression group was 48.88±14.32 cm3; the average tumor volume was higher in the primary surgical treatment group — 51.51±14.48 cm3. Recurrent tumors were characterized by more pronounced cellular and tissue atypia, patterns of infiltrative growth with the involvement of large vessels. The meningioma proliferative activity, assessed by Ki-67(max) expression, was higher in the group with meningioma progression and amounted to 9.71±2.5%. Significant differences in the Ki-67 expression were noted by tumor localization, grade, and brain invasion (p<0.05) in the meningioma recurrence and continued growth group. Conclusion. Recurrent meningiomas are represented by different grade tumors, including benign typical meningioma (grade 1), which indicates the need for greater attention and patient follow-up with this pathology. There are differences in terms of grade progression and locally destructive growth in meningioma recurrence and continued growth. This indicates a more pronounced biological tumor aggression. The Ki-67 expression is an important prognostic factor in meningioma progression group.

Cells of the TMS cell line in the well with the addition of a PES inhibitor on the matrigel matrix.

Analysis of the mass-spectrometry data from isolated lipid rafts.

Preparing a tumor sample for confocal microscopy.

Motility of Hsp70-positive cells in a tumor sample.

List of proteins detected by mass spectrometric analysis of lipid rafts isolated from normal brain tissue (obtained from a patient with epilepsy).