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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.

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.

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

Withdrawal of radiotherapy in patients with brain tumors under four years decreases chance for cure. AutoHSCT in a series of pilot studies demonstrated a potential to improve outcomes in these patients. The study included 50 patients with median age of 39 months (7-53). Medulloblastoma (n = 28, 56%), ETMR (n = 9, 18%) and other histological types (n = 13, 26%) were most commonly diagnosed. Forty two patients (84%) received tandem autoHSCT by HIT-MED protocol, and single autoHSCT was performed in eight children (16%). Adjuvant radiotherapy was administered in 25 (50%) children and treatment of relapse included radiotherapy in 6 (12%). Median follow-up was 39.6 months (6-121). Long-term CIR was 37%, and TRM - 6%. Five-year OS was 71% in medulloblastoma, 37% in ETMR and in other tumors - 51% (p = 0.07). Irradiation-free OS at 5 years for children with medulloblastoma was 24%. For the whole cohort of CNS tumors, independently of histology, OS and PFS at five years were 60% and 46%, respectively Young children with medulloblastoma, following tandem autoHSCT, demonstrate OS comparable to older children. Patients with other histological types demonstrate suboptimal long-term survival rates after autoHSCT and one should assess whether these patients benefit from autoHSCT., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

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.

Background: The implementation of standardized protocols for combined treatment of cancer into clinical practice inevitably leads to a long-term consequence., Aims: To study the prevalence of endocrine disorders, to assess the prevalence and degree of decline of bone mineral density (BMD) in individuals who have undergone combined treatment of malignant brain tumors in childhood and adolescence., Materials and Methods: A retrospective study was conducted with 59 young adults (31 men; 28 women) who have undergone surgical treatment of malignant brain tumour followed by radiation treatment (craniospinal radiation in combination with or without polychemotherapy). Group I consisted of 37 patients, who were treated between the ages of 3 and 16 years. Group II included 22 patients who received treatment between the ages of 16 and 38 years., Results: GH deficiency according to the results of the insulin hypoglycemia test was diagnosed in 48 patients (81%), 22 -patients had secondary adrenal insufficiency (37%). The majority of those examined (33 patients (56%)) did not achieve the target growth. Only 5 people from I group was treated with recombinant GH. Correlation analysis demonstrates that age of treatment is the main factor affecting final growth (r=0,619, p<0,001). Many cases of hypothyroidism (n=39 (66%)) and hypogonadism (19 women; 17 men) were detected. According to the DXA, a decrease of BMD ≤-2.0 SD (Z-score) in L1-L4 was found in 35 of 59 patients (59%). The BMD in the I group was significantly lower than in patients treated at an older age (p<0.001). A moderate correlation was discovered between BMD in L1-L4 at the time of examination and the level of estradiol in women (r=0.596, p<0.05) and testosterone in men (r=0.472, p<0.05). Direct correlation between BMD and age of diagnosis was revealed (r=0.781, p<0.01)., Conclusions: The results show that patients need to be monitored annually and for life after the combined treatment of malignant brain tumors in order to detect the long-term effects of the treatment. The high incidence of osteopenic conditions determines the relevance and need for early diagnosis to prevent further bone loss, reduced bone strength and the risk of fractures.

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-look» 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.

Medulloblastoma (MB) is the most common brain malignancy in children occurring in the posterior cranial fossa. This tumor is characterized by high risk of metastasis along the CSF pathways. Significant progress in research of this tumor and appropriate treatment is associated with determining the various molecular categories of primary medulloblastomas. This analysis includes certain factors of cytogenetic and transcriptional proliferation. Modern treatment approaches for patients older than 3 years include advanced resection, craniospinal irradiation with a boost on the postoperative bed followed by platinum-based chemotherapy. Conventional radiotherapy including craniospinal irradiation results a significant number of complications. Morbidity rate is increased throughout long-term follow-up. Secondary tumors including glioblastomas are under special attention since their occurrence is associated with a fatal outcome. This may partially explaine the fact that chemotherapy without repeated morphological verification doesn't always ensure tumor growth control in patients with recurrent medulloblastomas. The authors consider irradiation-induced glioblastomas secondary to primarily verified medulloblastomas in patients who had previously undergone craniospinal irradiation as a component of combined treatment after tumor resection. It was found that the incidence of this phenomenon is significant and made up about 10% among patients with recurrent medulloblastomas. This value is significantly higher compared to previous data. The authors analyzed patterns of occurrence of irradiation-induced glioblastomas depending on the molecular genetic group and clinical characteristics of patients after primary surgery. Treatment outcomes were estimated too. It was concluded that morphological verification is necessary if long-term recurrence is diagnosed after combined treatment of medulloblastoma.

Background: The glucagon test (GT) is a promising alternative to the insulin hypoglycemia test (IHT) in diagnosis of secondary adrenal insufficiency (SAI)., Aim: To study the feasibility of using the GT in patients after craniospinal irradiation and to determine the cut-off value to rule out SAI., Methods: A total of 28 patients (14 males and 14 females) with the median age of 19 years (17; 23) who had undergone combination treatment (surgery, craniospinal irradiation (35 Gy) with boost to the tumor bed, and polychemotherapy) of extrapituitary brain tumors no later than 2 years before study initiation and 10 healthy volunteers of matching sex and age were examined. All the subjects underwent the GT and IHT with an interval of at least 57 days. The cortisol, ACTH, and glucose levels were measured., Results: Twelve out of 28 patients were diagnosed with SAI according to the IHT results. ROC analysis revealed that cortisol release during the GT 499 nmol/L ruled out SAI [100% sensitivity (Se); 62% specificity (Sp)], while the absence of a rise 340 nmol/l verified SAI (Sp 100%; 55% Se). For GT, the area under a curve (AUC) was 93.6%, which corresponds to a very good diagnostic informativity. In 19 patients, the IHT and GT results were concordant (in ten patients, the release of cortisol occurred above the cut-off value in both tests; no release was detected in nine patients). In nine cases, the results were discordant: the maximum cortisol level detected in the GT was 500 nmol/l, but the IHT results ruled out SAI (the GT yielded a false positive outcome). Contrariwise, in three (10.7%) patients the release of cortisol detected in the GT was adequate, while being insufficient in the IHT test. Adverse events (nausea) were reported during the GT test in 9 (25%) subjects; one patient had hypoglycemia (1.8 mmol/l)., Conclusion: GT is highly informative and can be used as a first-level stimulation test for ruling out SAI in patients exposed to craniospinal irradiation performed to manage brain tumors. The cortisol level of 500 nmol/L is the best cut-off value for ruling out SAI according to the GT results. The insulin hypoglycemia test is used as the second-level supporting test in patients with positive GT results.

Background: The most of the current studies include patients who are different by the etiology of secondary adrenal insufficiency (SAI), or investigate SAI among other late effects of the radiation therapy., Aims: To describe the features of SAI and to select the best method of screening SAI in adult patients followed complex treatment of nonpituitary brain tumors in childhood., Materials and Methods: It was the retrospective cross-sectional study. 31 patients after the complex treatment of nonpituitary brain tumors in childhood and 20 healthy volunteers were examined. Age and sex ratio were comparable between the groups. Biochemical and clinical blood tests, levels of cortisol, ACTH, DHEA-C were evaluated. The insulin tolerance test (ITT) was performed for all patients and 11 volunteers., Results: The prevalence of SAI by ITT was 45.2%. The levels of basal cortisol (BC) were significantly higher in patients without SAI in comparison with the SAI group and volunteers (505 [340; 650] vs 323 [233; 382] and 372 [263; 489] nmol / l; pSAI- without_SAI=0.001; pwihtout_SAI-healthy = 0.04). The SAI group had DHEA-C significantly lower than in other groups one (3.1 [1.8; 3.4] vs 5.1 [2.5; 6.4] and 6.8 [4.1; 8.9]; рSAI- without_SAI = 0.036; pSAI-healthy = 0.001). ROC analysis showed that BC and DHEA-S can be used as high-quality screening tests for SAI (AUC = 89.3% and 88.3%). The maximum level of cortisol (656 [608-686] vs 634 [548-677]; p = 1) and the time of its increase (45 and 60 min) did not differ during ITT in patients without SAI and volunteers. Side effects: delayed hypoglycemia occurred in 4/14 patients of the SAI group 4090 minutes late of injection 60-80 ml of 40% glucose solution for stopping hypoglycemia in the test., Conclusions: 45.2% of patients followed craniospinal irradiation had SAI that is characterized by a decrease in DHEA-C levels. A highly normal level of basal cortisol was observed in 45% of patients without SAI. DHEA-C and blood cortisol can be used for SAI screening.

In most cases, oncogene amplification are prognostic and predictive markers for various tumors, therefore DNA probes are unable to reveal changes in the copy numbers should not be used to diagnose malignant tumors., Objective: To comparatively analyze DNA probes from different manufacturers to detect MYC gene amplification in routine practice., Material and Methods: The study material was formalin-fixed paraffin-embedded medulloblastoma fragments from 4 patients, with discrepancies in the results in the detection of MYC gene amplification., Results: MYC gene amplification was determined using DNA probes: Kreatech MYC (8q24)/SE 8, Vysis LSI MYC SO, Vysis CEP 8 (D8Z2) SG, and Zytolight SPEC MYC/CEN 8 Dual Color Probe. The use of the probes Kreatech TERC (3q26)/MYC (8q24)/SE7 Triple-Color probe failed to detect MYC gene amplification; this probe showed a balanced profile of chromosome 8., Conclusion: In routine practice, fluorescence in situ hybridization with the DNA probes Kreatech MYC (8q24)/SE 8, Vysis LSI MYC SO, Vysis CEP 8 (D8Z2) SG and Zytolight SPEC MYC/CEN 8 Dual Color Probe can be the method of choice for studying the copy number of the MYC gene. However, the authors strongly recommend that the Kreatech TERC (3q26)/MYC (8q24)/SE7 Triple-Color should not be used for this purpose. In addition, probes for fluorescence in situ hybridization must be necessarily tested in large reference laboratories dealing with one or another area of oncopathology.

Aim: To evaluate the character of growth disorders and risk factors of their development after treatment of acute lympho- blastic leukemia (ALL) patients in childhood., Materials and Methods: In this study 25 patients (16 women and 9 men) who had undergone treatment for ALL in childhood were assessed. Patients underwent polychemo- therapy and cranial irradiation. Average age at the time of the survey - 21,2±3,9 years; average age at the time of treatment - 6,9±3,4 years; average follow-up - 13,8±4,9 years. Healthy volunteers were included in the control group (10 women and 6 men) at the age of 25,9±3,6 years. Patients' anthropometric and laboratory parameters were measured., Results: SDS of the final height in ALL survivors was significantly lower in comparison with the control group (p=0,009). ALL survivors had significantly higher difference between final and target height compared to control (p=0,049). 4 of 8 men (50,0% CI: 24,5% - 75,5%) and 13 of 15 women (86,7% CI:68,1-95,7%) have reached the target height. 73,9% (CI: 56,3% - 86,8%) of ALL survivors have reached target height which is significantly lower than in the control group (p<0,001). We found a significant backward correlation be- tween the age at the time of treatment and reaching of the target height (r=-0,415, p=0,049). ALL survivors also suffered from obesity - 12%, dyslipidemia - 36,8%, insulin resistance - 66,7%., Conclusion: Treatment for ALL in childhood causes a de- crease of final height. Its main risk factor is the age at the time of the treatment. ALL survivors are diagnosed with the other endocrine disorders and they need an endocrinologist's observation.

A total of 40 patients (median age 6 years, range 1-28 years) with high-risk malignant brain tumors received a single (n = 35) or tandem (n = 5) high-dose chemotherapy (HDCT) with autologous hemopoietic stem cell transplantation (auto-HSCT). The 2-year OS and DFS are 52% and 47%, accordingly, with median follow-up of 24 (range 2-96) months. The patients without complete response at the time of auto-HSCT had worst prognosis with 53% DFS in patients with partial remission and 25% in patients with disease stabilization (p = 0.001). Patients with relapsed tumor had worse prognosis, than high-risk patients in the first remission with DFS 26% and 62%, accordingly (p=0.02). The relapse rate also correlated with patient's age (38% DFS in patients younger, than 4 years and 60% in older patients, p = 0.005) and tumor morphology (63% DFS in patients with medulloblastoma, 60% in patients with germ-cell tumors, 45% in other embryonal CNS tumors, p = 0.05). The 4th-grade transplant-related toxicity and mortality rates were observed in 13% and 18% of patients, accordingly. Therefore, HDCT with auto-HSCT in young patients with high-risk CNS tumors is characterized by acceptable toxicity and allows improving overall therapy results.

A six-year-old patient with non-germinomatous germ cell tumor of the chiasmatic-sellar area developed polyuria and polydipsia as the first symptoms of the disease. Then there were signs of precocious puberty and vision impairment. MRI examination revealed a shiasmatic sellar tumor and occlusive hydrocephalus. Tumor marker levels in blood serum were elevated. The alpha-fetoprotein level was increased 5-fold; human chorionic gonadotropin 20-fold. These levels increased over time. The patient received 2 cycles of PEI multiagent chemotherapy (Ifosfamide 1.5 g/m(2), Cisplatin 20 mg/m(2), Etoposide 100 mg/m(2)) during 5 days and 1 cycle of second-line multiagent chemotherapy (Cisplatin 100 mg/m(2) for 1 day and Endoxan 1500 mg/m(2) for 2 days). Despite the decrease in tumor marker levels to normal values, the patient's vision still deteriorated. MRI examination revealed that tumor size increased and its structure changed. Total tumor resection led to vision improvement and regression of intracranial hypertension. Histological analysis of tumor tissue only revealed a mature teratoma. This phenomenon, known as growing teratoma syndrome, is very rare among patients with intracranial non-germinomatous germ cell tumors.

Objective: the study objective was to improve the quality of detection of medulloblastoma metastases., Material and Methods: Magnetic resonance imaging (MRI) of the spinal cord in a child with medulloblastoma of the posterior cranial fossa, which was performed on the first day after surgery, detected contrast-positive thickenings of the meninges in the cervical, thoracic, and lumbar spinal cord that might be erroneously diagnosed as metastasis. These lesions spontaneously regressed within 3 weeks, which was verified by control MRI., Conclusion: In the case of misinterpretation of a MRI picture of contrast-positive thickenings of the meninges, a patient is erroneously regarded as having tumor metastases and is subject to more intensive treatment. However, the lesions spontaneously disappear or greatly reduce after 2-3 weeks. The article presents a case of this phenomenon, describes the putative mechanisms of its development, and provides recommendations for its differential diagnosis from metastases.

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.

Medulloepithelioma is a rare malignant tumor arising in cerebral hemispheres. Microscopically, medulloepithelioma is characterized by epithelial structures that mimic the embryonic neural tube. Immunohistochemical analysis revealed that tumor cells are immunopositive for LIN28A and fluorescence in situ hybridization showed an amplification of a miRNA cluster at 19q13.42. Presence of these both aberrations suggesting that medulloepithelioma, ependymoblastoma and embryonal tumor with multilayered rosettes are the same entity.

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.

The Turcot syndrome is a rare disease which is characterized by a combination of a brain tumor with a y at which the neoplasm of the colon. About 150 of such observations are described in world literature. Our own observation and a literature review are presented in this article.

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.

The day hospital proved effective for diagnosis and treatment of pediatric cancer. It is more cost-effective and less emotionally traumatic for patients than the usual hospital.