[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.

[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.

[Hepatopulmonary syndrome: a rare manifestation of cirrhosis in patient with diencephalic obesity and nonalcoholic fatty liver disease after surgery for craniopharyngioma].

We describe a 15-year girl, who developed panhypopituitarism and diencephalic obesity after surgical excision of craniopharyngioma, followed by nonalcoholic fatty liver disease and cirrhosis 5 years after surgery. Cirrhosis in this case manifested by hypoxia due to hepatopulmonary syndrome, and despite cure of craniopharyngioma by surgery and radiosurgery treatment and adequate hormonal substitution therapy patient died 9 years after surgery. Growth hormone substitutional therapy in patients with hypopituitarism, and steatohepatitis may decrease liver triglyceride accumulation and prevent end-stage liver disease.

[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.

[Modern diagnosis and treatment in children with congenital basal encephalocele]. / Sovremennye metody diagnostiki i lecheniia detei s vrozhdennymi bazal'nymi cherepno-mozgovymi gryzhami.

Basal encephalocele is a rare disease that predominantly occurs in children. Its most common symptoms include nasal liquorrhea, difficulty in nasal breathing, and deformity of the naso-orbital region. MATERIAL AND METHODS: The study group included 19 patients with basal encephalocele, aged 2 months to 18 years. Ten (59%) patients were operated on through a transnasal endoscopic approach; 3 (17.5%) patients were operated on through a transcranial approach; 4 (23.5%) patients were operated on using a combined approach: the patients underwent simultaneous elimination of a cranio-orbital region deformity using the basal transcranial approach as well as hernial sac resection and hernioplasty using the transnasal endoscopic approach. Two children had no surgery due to minimal symptoms and a lack of cerebrospinal fluid leak. RESULTS: Application of the algorithms for diagnosis and treatment of encephalocele, suggested by the authors, enabled making the timely diagnose, defining the optimal surgical tactics, and achieving good treatment results. CONCLUSION: A differentiated approach to the choice of a surgical technique for basal encephalocele, the use of auto-tissues for skull base reconstruction, intraoperative and postoperative lumbar drainage, and simultaneous elimination of deformity of the fronto-naso-orbital region enable avoiding complications and achieving good functional and aesthetic results.

[Transient enlargement of craniopharyngioma cysts after stereotactic radiotherapy and radiosurgery]. / Tranzitornoe uvelichenie ob''ema kist kraniofaringiom posle stereotaksicheskoi luchevoi terapii i radiokhirurgii.

Stereotactic radiotherapy/radiosurgery (RT/ES) is an effective technique for treating craniopharyngiomas (CPs). However, enlargement of the cystic part of the tumor occurs in some cases after irradiation. The enlargement may be transient and not require treatment or be a true relapse requiring treatment. MATERIAL AND METHODS: In this study, we performed a retrospective analysis of 79 pediatric patients who underwent stereotactic RT or RS after resection of craniopharyngioma. RESULTS: Five-year relapse-free survival after complex treatment of CP was 86%. In the early period after irradiation, 3.5 months (2.7-9.4) on average, enlargement of the cystic component of the tumor was detected in 10 (12.7%) patients; in 9 (11.4%) of them, the enlargement was transient and did not require treatment; in one case, the patient underwent surgery due to reduced visual acuity. In 8 (10.1%) patients, an increase in the residual tumor (a solid component of the tumor in 2 cases and a cystic component of the tumor in 6 cases) occurred in the long-term period after irradiation - after 26.3 months (16.6-48.9) and did not decrease during follow-up in none of the cases, i.e. continued growth of the tumor was diagnosed. A statistical analysis revealed that differences in the terms of transient enlargement and true continued growth were statistically significant (p<0.01). CONCLUSION: Enlargement of a craniopharyngioma cyst in the early period (up to 1 year) after RT/RS is usually transient and does not require surgical treatment (except cases where worsening of neurological symptoms occurs, or occlusive hydrocephalus develops).

[Basal ganglia germinomas in children. Four clinical cases and a literature review].

UNLABELLED: Basal ganglia germinomas are a specific group of intracranial germinomas. Their early diagnosis is complicated due to their atypical localization and diversity of neuroimaging and clinical signs. MATERIAL AND METHODS: We describe 4 cases of basal ganglia germinoma in boys of 13, 14, 15, and 16 years of age. The medical history data, clinical features, neuroimaging and histological characteristics of basal ganglia germonomas, and preliminary results of the treatment are presented. CONCLUSION: Basal ganglia germinomas are usually verified at the late stage of the disease when patients are detected with extended lesions of the basal ganglia and severe neurological and neuroendocrine deficits. This situation is due to clinical and imaging signs that are untypical of common germinomas.

[A giant hyperostotic parasagittal meningioma in a child with neurofibromatosis type II (a case report and literature review)]. / Gigantskaya giperostoticheskaya parasagittal'naya meningioma u rebenka s neirofibromatozom II tipa (sluchai iz praktiki i obzor literatury).

Large parasagittal meningiomas, in particular hyperostotic ones, in children are rare and problematic in the differential diagnosis. The literature reports only single clinical cases related to this issue; opinions about the indications, surgical treatment options, and prognosis are contradictory. This paper presents a clinical case of a hyperostotic parasagittal meningioma with intra-extracranial growth in a 10-year-old boy with neurofibromatosis type II significantly worsening the prognosis. We discuss the epidemiological and clinical features of childhood meningiomas and issues of their diagnosis, treatment, and prognosis.

[Comparative characteristics of genetic aberrations in glioblastomas in children and adults].

Glioblastomas in children and adults are a heterogeneous group of tumors that can be divided into at least three different subgroups: pediatric glioblastomas, IDH1-mutant glioblastomas in adults (the most favorable prognostic subtype), and IDH1-wild type glioblastomas in adults. According to the frequency of detected cytogenetic aberrations (amplification of the MYC/MYCN, EGFR and PDGRFA oncogenes, homozygous deletion of the CDKN2A gene, and deletion of the PTEN gene), pediatric glioblastomas bear analogy to the subgroup of IDH1-mutant glioblastomas in adults.

[Biological features and long-term results of comprehensive treatment of brain tumors in infants].

UNLABELLED: Complete removal is the treatment standard for most brain tumors. Outcomes of subsequent comprehensive treatment depend on biological features, the histological structure of the tumor, and radicality of surgery. The aim of this work was to study the morphological features of brain tumors in infants and to analyze long-term outcomes of surgical and comprehensive treatment. MATERIAL AND METHODS: The study included 80 infants with brain tumors aged from 1 to 12 months who had been operated on at the Burdenko Neurosurgical Institute during the period from 2000 to 2010. RESULTS: Maximal radicality was achieved in the group of tumors of the lateral and third ventricles (85%), in the group of tumors of hemispheric localization (82%), and in the group of tumors of the posterior fossa (83%). The lowest percentage of radical tumor removal (15%) accrued to tumors of the chiasmosellar area, most of which were large visual pathway gliomas. The overall five-year survival rate associated with the treatment in the studied series of patients was 92 and 48% for Grade I-II and Grade III-IV tumors, respectively. CONCLUSION: The features of biology of brain tumors in infants include the increased proliferative activity (high Ki-67 index of 10% and higher) revealed at the diagnosis of choroid papillomas, a series of pilocytic astrocytomas of the chiasm and Grade III astrocytomas, which do not affect the clinical course. The best long-term results of the treatment were obtained in infants with complete resection of Grade I and III astrocytomas and in infants with choroid papillomas. Radical removal of such histological forms as anaplastic astrocytoma, choroidal carcinoma, and anaplastic ependymoma improves the prognosis, provides favorable conditions for adjuvant therapy, and increases the period of progression-free survival in infants.

[Blood loss in surgery of brain tumors in infants].

Functional immaturity of all organs and systems result in a high risk of complications in surgery of brain tumors in infants. One of the most serious complications is a massive blood loss and developing on its background severe disorders of hemostasis. In modern series of observations perioperative mortality in these children varies from 13 to 33%. The purpose of this paper--based on an analysis of topography, morphology and features of the operations to determine risk groups of blood loss in surgery of brain tumors in infants and suggest the best options for surgical tactics. When operating blood loss exceed 300% of the calculated blood volume persistent violations of coagulation homeostasis develop, which can lead to uncontrolled bleeding and death on the operating table, or post-operative bleeding. Intraoperative blood loss could be reduced by surgical techniques improvement, as well as by improving of anesthesia. First type includes preoperative embolization of the afferent vessels, careful planning of surgical approach, including using neuronavigation, deep stromal tumor coagulation during debulking, primary coagulation of main feeding blood vessels, two-stage surgery, and optimization of speed of tumor removal. All these methods has reduced the overall operational and post-operative mortality rate from 13 to 5%.

[Characteristics of medulloblastoma in children under age of three years].

We present a series of 51 medulloblastoma in children under three years, collected in N.N. Burdenko Neurosurgical Institute from 2000 to 2010. 57% of the tumors showed desmoplastic/nodular histology. Performed fluorescence in situ hybridization (FISH) analysis revealed the MYC oncogene amplification in 4%, the MYCN oncogene amplification - in 8%, isochromosome 17q - in 16% of cases. 9q deletion was found in 8% of desmoplastic/ nodular medulloblastomas. Our results showed that desmoplastic/nodular medulloblastoma has a positive predictive value for progression-free survival. Another feature of a biology of medulloblastomas in children younger than three years is the lack of nuclear accumulation of beta-catenin, and 6q deletion. Medulloblastomas with MYCN oncogene amplification often exhibit desmoplastic/nodular histology and a relatively favorable outcome. The most unfavorable prognostic marker is the MYC oncogene amplification, which in our series of 100% combined with the large cell/anaplastic medulloblastoma and isochromosome 17q - such tumors should be included in the "high risk" protocol.

[Migrating choroid plexus papilloma of the lateral ventricle in infant--modern approaches to surgical treatment].

Choroid plexus papilloma (CPP) are rare in adults and accounted for only 0.4-1% of all intracranial tumors and even though found in all age groups, it is first of all a pediatric tumor--in children of the first year of life they account for 12-14% of all brain tumors. The preferential localization of CPP--lateral ventricles of the brain. Our paper describes a rare case of an infant with a "migrating" choroid plexus papilloma of the lateral ventricle and reviews modern approaches to surgical treatment.

[Glioneuronal tumor with neuropil-like islands in a neonate]. / Glioneironal'naia opukhol' s uchastkami neiropilia u rebenka grudnogo vozrasta.

Glioneuronal tumor with neuropil-like islands - GTNI is a rare histopatological subtype of anaplastic astrocytoma. English-language literature contains only 43 observations, among them only 4 observations in children up to 18 years. Neuropil is an eosinophilic stained a cellular foci of tumor tissue. These cells demonstrate less proliferation activity than prevailing glial component, which is characterized by a high degree of atypia - Gr III according to WHO classification. Single reports about verification of the glioneuronal tumor with neuropil-like islands in children are supplemented with an observation of the case with tumor, located in lateral ventricular in infant with the onset of hypertension symptoms at the age of 11 months. The potential for complete removal of these tumors despite its large size and young age of the child is presented. However, the prognosis in infants with GTNI despite completeness of removal and chemotherapy might be extremely unfavorable - in case of intraventricular localization progression in the form of tumor implantation on ventricular ependyma is possible.

[Thyrotropin secreting pituitary adenoma in a child: case report and literature review].

We present a case of 11-year old boy with Type 1 Autoimmune Polyglandular Syndrome and thyrotropin secreting pituitary adenoma, which was diagnosed by elevated TSH and thyroid hormones levels and MRI signs of pituitary tumor and without clinical symptoms of hyperthyroidism. He underwent partial resection of the tumor via transnasal approach and subsequent radiation therapy. Consequently 1 year after XRT patient developed growth hormone deficiency, 3.5 years later patient became euthyroid, and 5.5 years after treatment - hypothyroid. This is the first described case of coexistence of this 2 rare endocrine diseases in the same patient.

[Stereotactic radiotherapy and radiosurgery in treatment of patients with deep-seated pilocytic astrocytomas].

Pilocytic astrocytoma (PA) is a low-grade glial tumor (WHO grade I) with predominant occurrence in pediatric patients. According to many authors, stereotactic radiosurgery (SRS) and radiotherapy (SRT) promote long-term remission or retardation of tumor progression in patients with in inoperable lesions after incomplete resection or recurrence. Therefore it is essential to determine the role of SRS and SRT in complex management of patients with deep-seated PA. Since April 2005 till May 2010 101 patient with intracranial PA was treated in department for radiation therapy of Burdenko Neurosurgical Institute. The series consisted of 70 pediatric patients (below 17 years inclusively) and 31 adults, of them--51 male and 50 female patients. Mean age was 15.1 years (9.8 years in children and 28.7 in adults). In 90 patients (89.2%) tumors were previously histologically verified (tumor resection in 83 cases and biopsy in 7). In 11 (10.8%) patients diagnosis of PA was based on clinical and neurovisualization data. In most cases SRT (66 (66.3%) patients) was preformed, the rest 35 (34.7%) patients were treated by SRS. Median follow-up from the onset of disease reached 52 months (2-228 months). Catamnestic data were available in 88 (87%) patients. By the end of catamnestic follow-up (December 2010) 87 (98.8%) patients treated by SRS and SRT were alive. Median follow-up from the start of radiation treatment was 22.7 months (6-60 months). Progression of tumor was observed in 20 patients (22.7%), in 18 of them due to cyst growth. 18 patients were reoperated. In 12 operated patients histological examination and its comparative analysis were performed. We found that alterations in the tumor tissue, accompanied by regression of solid component and progression of cystic portion, represent reactive-degenerative changes in the tumor as a consequence of radiation-induced pathomorphism. SRS and STR are effective techniques for treatment of patients with primary and recurrent PA despite regardless of localization of the tumor. There procedures should be performed shortly after non-radical resection. Control of tumor growth by the present time (median follow-up is 22.7 months) reaches 98%. "Progression" of the tumor due to enlargement of cystic portion shortly after SRT and SRS represents reactive-degenerative alterations in the tumor tissue and should not be evaluated as true recurrence; without neurological deterioration these cases do not require special treatment.

[Implantation metastasizing of craniopharyngioma].

The paper describes two cases of implantation metastasizing of craniopharyngioma after its resection using combined (transcallosal and subfrontal) and pterional approach. The mechanisms of metastasizing and possible ways of prevention are discussed.

[A new entity in WHO classification of tumors of the central nervous system--embryonic tumor with abundant neuropil and true rosettes: case report and review of literature].

Embryonic tumor with abundant neuropil and true rosettes (ETANTR) is a very aggressive rare tumor with unique histologic and molecular features occurring in very young children. At present approximately 80 cases of ETANTR have been documented in the literature since first description in 2000. We report seven patients with ETANTR below 4 years of age who underwent surgical resection in the Burdenko Neurosurgery Institute between 2005 and 2010. Four children have received different modality chemotherapy and radiotherapy and two patients were treated by chemotherapy alone. One child did not receive any adjuvant treatment. All children had local relapses, two of them were operated twice. A 2 year old girl underwent subtotal resection thrice. Histological examination showed that all tumors were composed of true multilayered rosettes admixed with large areas of paucicellular neuropil. By analysis of recurrences we have found that large areas of neuropil and number of true rosettes were lost and tumors acquired a resemblance to central nervous system primitive neuroectodermal tumors. In four cases frozen tumor material was available for array-based comparative genomic hybridization, which discovered trisomy of chromosome 2 and amplification at the 19q13.42 chromosome locus. Fluorescence in situ hybridization revealed amplification at the 19q13.42 chromosome locus in all cases.