Introduction. The development of technologies for molecular genetic typing of tumors of the central nervous system (CNS) has significantly increased the specificity of traditional histological and immunohistochemical research methods. As a result, completely new variants of tumors have appeared, as well as improved results of treatment of tumors with a long-term favorable prognosis. Thanks to new biomarkers, among morphologically similar small-cell embryonic CNS tumors, extremely rare tumors have been identified: ETMR (embryonic tumor with multiple rosettes C19MC), CNS NB-FOXR2 (CNS neuroblastoma (NB) with FOXR2-activation), CNS EFT-CIC (tumor of the CNS sarcoma family of sarcoma alteration), CNS HGNET-MN1 (neuroepithelial tumor of the CNS of high grade with MN1 alteration), CNS HGNET-BCOR (neuroepithelial tumor of the CNS of high grade with BCOR alteration).
The aim of the study was to assess the historical prerequisites for the emergence of a new rare nosological form “CNS NB with FOXR2- activation”, as well as presentation of own results of diagnostics and treatment of children with this tumor.
Materials and methods. The results of diagnosis and treatment of 7 patients with CNS NB with FOXR2-activation were studied. Tumor identification was carried out using a new DNA methylation technique for CNS tumor profiles using the Heidelberg (Germany) brain tumor classifier (www.molecularneuropathology.org), which has recently become available in Russia.
Results and discussion. Based on a review of international experience, the evolution of the appearance in the classification of CNS tumors, as well as the clinical and molecular features of CNS neuroblastoma with FOXR2-activation are presented. The authors present their own results of diagnostics and treatment of 7 patients with a rare tumor CNS neuroblastoma with FOXR2-activation.
Conclusion. Biomarkers have been proposed for the differential diagnosis of small-cell PNET-like tumors of the CNS in children. Due to the molecular identification of this tumor in children, it became clear that such patients, provided that the treatment protocol is adequately followed, have quite satisfactory long-term survival results.

Introduction. Infantile hemangiomas (IH) are the most common benign vascular tumor of children of the first year and are an interdisciplinary problem of neonatologists, pediatricians, pediatric cardiologists, oncologists, pediatric surgeons, dermatologists. Depending on the age of child, phase of pathological process, size, and localization of the IH, the management tactics of such children can be conservative (pharmaceuticals therapy) or invasive (laser therapy, surgical methods). Laser therapy with a pulsed dye laser has proven itself well to correct and minimize residual phenomena because of spontaneous involution and after the completion of pharmaceuticals treatment.
The purpose of the study is to analyze the experience of using Hemangiol® (oral solution) for the treatment of children with IH, obtained in 10 medical hospitals in 6 cities of Russia.
Materials and methods. Treatment with Hemangiol® was carried out in 6 cities of Russia on the basis of 10 medical hospitals (Children’s City
Clinical Hospital named after Z.A. Bashlyaeva of Moscow City Health Department, Research Institute of Pediatric Oncology and Hematology of N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia (Moscow), Russian Children’s Clinical Hospital of the N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia (Moscow), Children’s City Clinical Hospital named after N.F. Filatov of Moscow City Health Department, Saint Petersburg Clinical Scientific and Practical Center of Specialized Medical Assistance (Oncological) (S.-Petersburg), Almazov National Medical Research Centre, Ministry of Health of Russia (S.-Petersburg), Rostov Regional Clinical Hospital (Rostov-on-Don), Stavropol Regional Children’s Clinical Hospital (Stavropol), Samara Regional Clinical Hospital named after V.D. Seredavin, Children’s Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan (Kazan) in the Departments of Pediatric Cardiology, Surgery, Oncology, Pediatrics from January 2020 to December 2021. Therapy with Hemangiol® was received by 49 children with IH for at least 3 months. Before the start of treatment, the patients’ heart rate and blood pressure were measured, general and biochemical blood tests were performed, electrocardiography and ultrasound IH were performed. According to the indications, ultrasound of the liver and thyroid gland was performed to determine the parameters of the thyroid status. Before the start of therapy and during dynamic observation, photo documentation was performed against the background of treatment. In the absence of contraindications to treatment, Hemangiol® was prescribed. During a six-month course of treatment with Hemangiol®, effectiveness was evaluated based on the results of a clinical examination and based on photographs. The appearance of possible adverse reactions was monitored.
Results. In 33 (67.3 %) children with IH, therapy with Hemangiol® was completed within 6 months. The effect of treatment in the form of a pronounced regression of vascular tumor was achieved in 25 (75.8 %) of 33 patients. In 16 (32.7 %) of 49 children, treatment with Hemangiol® was continued for more than 6 months. The first symptoms of improvement were observed from the second to 10 days after the start of Hemangiol® therapy in 45 patients, which was (91.8 %). Rebound syndrome (recurrence of IH) was detected in 2 (6.0 %) of 33 children who completed therapy. Transit adverse reactions (decreased heart rate, increased excitability, lethargy) on therapy of Hemangiol® were observed in 8 (16.3 %) children. The duration of therapy with Hemangiol® depended on the prevalence, the depth of the IH lesion, as well as on the presence of prematurity in a child with IH (r = 0.533, p < 0.05). Successful laser treatment with a pulsed laser on a dye after the completion of systemic Hemangiol® therapy, were on 5 children of Research Institute of Pediatric Oncology and Hematology at N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia.
Conclusion. The results of the using of Hemangiol® as a modern means of systemic pharmacotherapy of IH therapy in 10 medical hospitals in 6 cities of Russia have demonstrated its high efficiency and safety.

Introduction. Neuroblastoma (NB) is the most common embryonic extracranial malignant neoplasm in children. The contribution of the NF1 gene to the development of NB is discussed in the literature, but there is no evidence of the pathogenetic role of NF1 gene aberrations in NB. According to various literature sources, the occurrence of pathogenic variants in the NF1 gene in the general cohort of patients with NB does not exceed 1–6 %.
Materials and methods. The molecular genetic examination by next generation sequencing (NGS) was performed in 77 patients with NB during the period from April 2019 to July 2021 in the Laboratory of Molecular Oncology Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology. The staging of patients was carried out within the framework of the international staging system, stratification into risk groups and therapy according to the protocol of the German Group for the study of NB GPOH NB-2004. International criteria of the response assessment system for patients with NB were used to assess the response to treatment. Calculations of event-free and overall survival by the Kaplan–Mayer method for the follow-up period up to 12.01.2022 were performed.
Results and discussion. The cohort of patients included in the study was represented by patients with an initially unfavorable prognosis. Patients were divided into 3 groups: without pathogenic variants in genes belonging to the RAS-RAF-MEK pathway and TP53 – “RAS-/ TP53-” (n = 43), with clinically significant variants in the NF1 gene – “NF1+” (n = 12), clinically significant variants in the genes of RAS-RAF-MEK and TP53 pathway – “RAS+/TP53+” except NF1 (n = 22). The median age for the entire group of patients at the time of diagnosis was 41 months (0.1–173 months). Boys prevailed over girls with a ratio of 1.5:1. Patients with stage 4 of the disease according to the INSS classification prevailed – 81.8 % (63/77), high-risk groups according to the NB-2004 protocol – 77.9 % (60/77).
In our study 13 clinically significant variants in NF1 were identified in 12 patients (15.6 %), of which 4 were germinal, 9 were somatic. The frequency of detection of pathogenic aberrations in the NF1 gene was much higher than the literature data, which can be associated with a selective cohort of studied patients with an unfavorable prognosis and patients with suspected hereditary genetic syndrome. The presentation of adverse events was observed in 83.3 % of patients, more often against the background of specific therapy (in 60 % of cases), which may be due to the rapid acquisition of NB chemoresistance, among other things. When comparing the three groups, it was shown that the frequency of objective responses to induction therapy was statistically significantly lower in the group of patients “NF1+”, when compared with other groups (p = 0.015; p = 0.024), which may also indicate the chemoresistance of NF1-aberrated NB. When analyzing survival there was no statistical difference between the compared groups.
Conclusions. The data obtained by us do not allow us to consider the presence of genetic variants in NF1 separately as a prognostic factor, however, it can be assumed that a group of patients with an unfavorable prognosis may be enriched with cases with mutations in the NF1 gene. Refractory course of the disease/development of adverse events in the presence of genetic variants of NF1, causing the activation of the RASRAF- MEK signaling pathway, leads to the induction of tumor chemoresistance. The presence of clinical significance of aberrations in the NF1 gene does not lead to a statistically significant difference in prognosis when compared with patients with aberrations in other components of the RAS-RAF-MEK pathway, however, longer catamnestic follow-up of patients is necessary.
Currently, there are no effective drugs for the treatment of NF1-associated NB in clinical practice that requires further study of the mechanisms of chemoresistance development in such patients. Understanding the molecular and genetic features of the course of NF1-associated NB can become the basis for the development of personalized therapy in the future.

Materials and methods. The study included 18 samples of patients with ACC stages I–III who received treatment from 2003 to 2021. Samples from 6 (33 %) patients with stage I, 5 (28 %) patients with stage II, and 7 (39 %) patients with stage III ACC were analyzed. The average age of patients is 61.6 (12–216) months. Four subgroups of patients were identified: with an isolated mutation in the TP-53 gene, with an isolated mutation in the IGF-2 gene, with simultaneous mutations in the TP-53 and IGF-2 genes and no mutations in the studied genes.
Results. In 12 out of 18 (67 %) of the studied samples, mutations in the TP-53 and IGF-2 genes and their combination were detected. A mutation in the TP-53 gene was present in 8 patients, in the IGF-2 gene in 8 patients, and a combination of TP-53 + IGF-2 in 4 patients. The five-year OS and DFS in the groups of patients with mutations in TP-53 and/or IGF-2 were 45.5 % and 41.6 % versus 83.3 % and 83.3 % in the group without mutations (p = 0.15 and p = 0.18, respectively). The five-year overall (OS) and disease-free (DFS) survival in the TP-53 group compared with the group without the mutation was 50 % and 50 % versus 62.2 % and 66.7 % (p = 0.6 and p = 0.5, respectively). The five-year OS and DFS in the IGF-2 group compared with the group without mutation was 14.3 % and 0 % versus 90 % and 90 % (p = 0.001 and p = 0.0009, respectively). The five-year OS and DFS in the group in which the combination of mutations in the TP-53 + IGF-2 genes was present compared with patients without the combination of these mutations was 0 % vs. 75.2 % and 76.9 % (p = 0.002 and p = 0.003, respectively).
Conclusion. The presence of a mutated IGF-2 gene is combined with a high Ki-67 index and is a factor in poor prognosis in children with localized forms of ACC. The simultaneous presence of mutations in the TP-53 and IGF-2 genes in the tumor also significantly negatively affects survival rates. Further prospective studies are needed to confirm the data and develop tactics for this group of patients.

Introduction. Despite significant advances in prevention, chemotherapy-induced (cytostatic therapy) nausea and vomiting (CINV) continues present a significant clinical problem for patients oncohematological profile, while often remaining outside areas of attention of pediatric oncologists and hematologists.
The aim of the study – frequency comparison of occurrence CINV according to data obtained from the medical database documentation (retrospective group) and data obtained in the process assessment of CINV using a modified questionnaire and specialized scales (prospective group).
Materials and methods. The retrospective group included 52 patients who received 178 cycles of highly emetogenic anticancer therapy with standard antiemetic prophylaxis from 02/01/2020 to 08/01/2020, in prospective – 88 patients who received 456 cycles of a similar anticancer therapy with standard CINV prophylaxis from 10/01/2020 until 07/01/2021.
Results. Although the groups were comparable in terms of key patient characteristics, chemotherapy regimens, and regimen prevention of CINV, the frequency of complete control of CINV between them is significantly was different: when analyzing the primary documentation, it turned out that the complete control of CINV in the acute, delayed and general periods is observed in 82 %, 86 %, 82 % cycles, while when assessing CINV using specialized questionnaires, the absence of these complications was noted only in 68 %, 52 %, 43 % of cycles. Thus, if we focus on standard tools fixing complications (diary entries, prescription lists), in more than 80 % of children receiving highly emetogenic cytostatic therapy it is possible to achieve complete control of CINV, and this complication does not really pose a clinically significant problem. However, when using a questionnaire and specialized scales, it becomes obvious that that more than half of children continue to suffer from CINV despite the standard prophylaxis of this complication.
Conclusion. In this way, the analysis performed shows that the frequency of development of CINV during routine antiemetic prophylaxis is clearly underestimated, and, in part, due to this CINV and remains outside the attention of pediatric oncologists and hematologists. For an adequate assessment of the true incidence of CINV and, accordingly, determining the need for improvement of existing approaches to their prevention, a key role should be played specialized questionnaires and scales that fully allow “visualize” this complication.

Neurofibromatosis type 1 (NF1) is a hereditary tumor syndrome caused by a mutation in tumor suppressor gene NF1. The disease occurs with a frequency of 1:3000 of the population. Typical manifestations of NF1 are multiple cutaneous, subcutaneous and plexiform neurofibromas, which cause serious cosmetic defects in the appearance of patients. Since an effective method for the treatment of NF1 has not yet been introduced into clinical practice, which makes it possible to completely get rid of multiple neoplasms, surgical removal or the use of photodestruction methods remains the method of choice for the treatment of cutaneous and subcutaneous neurofibromas. However, plexiform neurofibromas infiltratively grow into the surrounding tissues, so their complete excision is often impossible. Therefore, surgical excision is indicated for localized forms of plexiform neurofibromas and in emergency situations when they are located near vital structures or in the presence of a mass effect. Moreover, excision of cutaneous and subcutaneous neurofibromas may initiate formation and growth of new tumors. This is due to the degranulation of mast cells in response to tumor damage, since the pathology of the immune system plays an important role in the development of neurofibromas. In order to avoid dissemination of tumors, it is also important to adhere to the principles of antiblastic surgery. Therefore, the most promising is the complex treatment of NF1 with the combined use of a classical approach, surgical laser, ketotifen, and an inhibitor of mitogen-activated kinase. This method can be recommended for the treatment of malignant peripheral nerve sheath tumors, as well as sporadic neoplasms, the resistance of which is caused by a somatic mutation in the NF1 gene. The goal of NF1 treatment is to improve the quality of life of the patient as a whole and reduce pain using an integrated multidisciplinary approach.

Genodermatoses are a heterogeneous group of hereditary diseases that are characterized by predominantly skin lesions. To date, there are more than 200 genetically determined skin diseases, representing about 35 % of all hereditary syndromes. In some cases, skin lesions may be the only manifestation of the disease, but still more often, they occur in combination with disorders of other organ systems. In many cases, genodermatoses are associated with an increased risk of malignancy which makes early detection of hereditary syndromic pathology especially important for cancer prevention.
This review provides a brief description of the dermatological manifestations as well as other phenotypic features of a number of genodermatoses, their genetic nature, and the strategy of management.

Malignant rhabdoid tumor (MRT) is a rare malignant neoplasm of childhood, characterized by an aggressive course and an extremely unfavorable prognosis. The frequency of MRT outside the central nervous system (extracranial MRT) is 0.02–0.03 per 100,000 children. In most cases, MRT is based on an inactivating mutations of the tumor suppressor gene SMARCB1, which leads to the absence of expression of the SMARCB1 ((INI1/hSNF5/BAF47) protein in tumor cells. Aberrations of the SMARCA4 gene, which is an extremely rare molecular event, have been described among the MRTs expressing SMARCB1 (INI1). Few case reports have been described in the international literature.
This article contains a description of a clinical case of a patient diagnosed with soft tissue MRT with SMARCA4 gene alteration. The distinctive features of the presented case are the congenital nature of the tumor, atypical localization, and extremely aggressive clinical course of the disease. On the example of the described clinical case, diagnostics of SMARCA4-associated MRT are presented, as well as the place of molecular methods in diagnosis verification. In addition, it is highlighted that the detection of somatic changes in the SMARCB1 and SMARCA4 genes requires additional investigation of their germinal status to exclude or confirm the rhabdoid tumor predisposition syndrome.

Despite improved understanding of the biology of the disease and the use of multicomponent chemotherapy, the prognosis for children with relapsed or refractory B-line acute lymphoblastic leukemia (B-ALL) remains poor. Currently, the only definitive treatment for these patients is allogeneic hematopoietic stem cell transplantation (allo-HSCT), which can be performed after achieving immunohematological remission. Conducting highintensity polychemotherapy (PCT) blocks to achieve negative values of minimal residual disease (MRD) is often limited due to high toxicity. The developed monoclonal antibodies targeting cell surface antigens, such as CD19 and CD20, are actively used in children with relapsed/refractory B-ALL as part of “bridge therapy”, which allows achieving MRD-negative status without the use of intensive chemotherapy. However, new strategies are needed to improve the prognosis of these patients. The drug Inotuzumab ozogamicin has demonstrated efficacy in relapses of B-ALL and is actively used to achieve a negative MRD status before the allo-HSCT stage in children. In the presented article, in addition to a brief review of the literature, clinical experience with the use of this drug is demonstrated.

Relevance. Retinoblastoma (RB) is the most common primary intraocular tumor in children. The incidence of RB ranges from 1:14,000 to 1:20,000 newborns. To date, the survival rates of patients with RB reach almost 100 % with timely and adequate diagnosis. Among childhood oncological diseases, RB accounts for 2.3–4.5 % and 85–90 % among intraocular tumors in children. According to the volume of tumor spread, intra- and extraocular forms of the disease are distinguished. Extraocular RB is the spread of the tumor beyond the eye with invasion of the orbital tissues, as well as the possible involvement of adjacent areas, including intracranial without and with regional and/or remote metastases. The main method of treatment of children with extraocular RB is neoadjuvant chemotherapy (CT) with planning of surgical intervention and adjuvant therapy. High-dose CT (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT), it allows to increase relapse-free survival in patients without metastatic lesions of the brain and spinal cord, but with their defeat, the prognosis of survival is extremely unfavorable, the nature of the disease is recurrent with 100 % lethality.
Description of the clinical case. We report a case of bilateral RB: OD – with extraocular and intracranial spread of the tumor along the optic nerve with a lesion of the chiasm and a transition to the initial parts of the visual tracts. Secondary glaucoma. OS – with intraocular tumor growth in a 3-year-old child. After neoadjuvant chemotherapy, including intrathecal, a simultaneous two-stage operation was performed in the volume of bone-plastic (temporo-orbito-zygomatic) pterionic craniotomy on the right with prechiasmal resection of the right optic nerve and enucleation of the right eye. In the postoperative period, adjuvant chemotherapy was performed, followed by HDCT with auto-HSCT. Radiation therapy has become the final stage of treatment. Brachytherapy for OS tumor and remote radiotherapy for craniospinal region, right orbit, optic nerve stump with chiasm and pituitary pedicle were successively performed. After 14 months from the beginning of treatment and 5 months after its completion, a leptomeningeal relapse of the disease was detected.
Conclusion. Rare observations of RB with damage to the visual tracts do not allow us to sufficiently study the features of the course of the tumor process, as well as to develop a single effective approach to antitumor treatment. Among the causes of mortality in patients with extraocular RB, the main one is metastasis, metastasis in the brain and spinal cord.