[Supratentorial neuroepithelial tumor with PLAGL1 gene fusion - a new type of morphologically variable pediatric brain neoplasm defined by a distinct DNA methylation class. A case report and literature review]. / Supratentorial'naya neiroepitelial'naya opukhol' so sliyaniem gena PLAGL1 u detei ­ novyi tip opukholi mozga s raznoobraznoi morfologicheskoi kartinoi i otlichitel'nym metilyatsionnym profilem(sluchai iz praktiki i obzor literatury).

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.

[Chordoid gliomas of the third ventricle]. / Opyt lecheniya khordoidnykh gliom III zheludochka.

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.

[Total DNA methylation profile in assessing the MGMT gene promoter status in malignant gliomas]. / Rezul'taty i perspektivy ispol'zovaniya obshchego profilya metilirovaniya DNK dlya otsenki statusa promotora gena MGMT v zlokachestvennykh gliomakh.

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.

[Perifocal edema and glymphatic system dysfunction: quantitative assessment based on diffusion tensor magnetic resonance imaging]. / Peritumoroznyi otek i disfunktsiya glimfaticheskoi sistemy golovnogo mozga: kolichestvennaya otsenka na osnove diffuzionno-tenzornoi MRT.

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, TEmin=102 ms, FOV=240 mm, isotropic voxel size 3×3×3 mm3, 60 directions of diffusion gradients. Measurements were carried out at b-factor 0 and 1000 s/mm2. 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.

[Factors influencing peritumoral edema in meningiomas: CT- and MRI-based quantitative assessment]. / Peritumoroznyi otek pri meningiomakh i faktory, vliyayushchie na ego formirovanie: kolichestvennaya otsenka na osnove KT i MRT.

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.

[Verification of the diagnosis of supratentorial ependymomas by real-time PCR]. / Verifikatsiya diagnoza supratentorial'nykh ependimom metodom PTsR v rezhime real'nogo vremeni.

BACKGROUND: Differential diagnosis of supratentorial ependymomas is of particular difficulty in neurooncology due to nonspecific clinical and radiographic findings, a rare seen «classic¼ 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.

[Astrocytoma with 1p19q codeletion]. / Astrotsitoma s kodeletsiei 1p19q.

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.

[Expression of estrogen and progesterone receptors in vestibular schwannomas]. / Analiz ekspressii retseptorov estrogena i progesterona v vestibulyarnykh shvannomakh.

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.

[IDH-mutant brainstem glioma]. / IDH-mutantnaya glioma stvola.

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.

[Multiple gliomas]. / Mnozhestvennye gliomy.

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.

[The DNA methylation profiling in the study and treatment of patients with meningiomas of the craniovertebral junction]. / Znachenie analiza metilirovaniya DNK v issledovanii i lechenii patsientov s meningiomami oblasti kraniovertebral'nogo perekhoda.

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.

[Novel BRAF::EPB41L2 gene fusion in posterior fossa pilocytic astrocytoma. Brief communication]. / Novyi tip sliyaniya genov BRAF::EPB41L2 v piloidnoi astrotsitome zadnei cherepnoi yamki. Kratkoe soobshchenie.

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.

[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.

[Significance of DNA methylation assessment in the morphological diagnosis of brain tumours]. / Znachenie otsenki metilirovaniya DNK v morfologicheskoi diagnostike opukholei TsNS.

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.

[Application of high throughput sequencing in pediatric neurooncology]. / Primenenie tekhnologii sekvenirovaniya v pediatricheskoi neiroonkologii.

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.

[Current diagnostic methods in molecular classification of brain tumors at the Burdenko Neurosurgical Center]. / Sovremennye diagnosticheskie vozmozhnosti molekulyarnogo issledovaniya opukholei mozga v Tsentre neirokhirurgii im. akad. N.N. Burdenko.

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.

[Diffuse brainstem tumors in children. Tumor biology and hope for a better outcome. Current state of the problem]. / Diffuznye opukholi stvola golovnogo mozga u detei. Biologiya opukholi i nadezhda na luchshii iskhod. Sovremennoe sostoyanie problemy.

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.

[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.

[Central neurocytomas: long-term treatment outcomes]. / Tsentral'nye neirotsitomy golovnogo mozga: otdalennye rezul'taty lecheniya.

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.

[Influence of resection quality on postoperative outcomes in children with atypical teratoid-rhabdoid tumor of the central nervous system]. / Vliyanie radikal'nosti operativnogo vmeshatel'stva na rezul'taty lecheniya atipichnoi teratoidno-rabdoidnoi opukholi tsentral'noi nervnoi sistemy u detei.

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-look¼ 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.