The need for differential diagnosis of skin tumors in children and adolescents determines the relevance of improving age-adapted research methods. Dermatoscopic analysis rightfully belongs to the method of choice as a non-invasive approach today. The study presents the experience of dermatoscopic examination of skin tumors in pediatric patient`s cohort, assessment of the method informativeness and visualization of the probability of a diagnostic error by constructing a mathematical matrix.

Introduction. Early diagnosis of oncological diseases is one of the most important tasks of public health, because improves the quality of medical care for patients and the prognosis of the disease. Despite advances in oncology, pediatric tumors continue to be diagnosed at advanced stages, which may be associated with a delayed visit to a doctor and a delay in diagnosis due to several factors. Many foreign articles are devoted to the search and analysis of significant factors of untimely diagnosis of oncological diseases, but few similar works in Russia.
Purpose of the study – to identify factors of late diagnosis and treatment of children with retinal tumors using the example of a common childhood tumor of retinoblastoma (RB).
Material and methods. A retrospective cohort study of patients diagnosed with RB at the of the Research Institute of Pediatric Oncology and Hematology at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia (Research Institute of Pediatric Oncology and Hematology) was performed using the database of the hospital cancer registry. The study group included RB patients from Russia with a first diagnosis in the period from 2016 to 2019 and receiving treatment at the Research Institute of Pediatric Oncology and Hematology. Time intervals were calculated based on the dates of the first symptom of RB, the initial medical consultation, the date of the final diagnosis by an oncologist or ophthalmologist, and the date of the first therapy for a child with RB. The intervals were calculated in days.
Results. Data from 197 patients (aged 0 to 15 years) were analyzed, which corresponded to 262 cases and the number of eyes with bilateral or unilateral Rb. The median diagnostic interval for patients with localized RB (groups A and B) was 30 days, for patients with locally advanced RB (groups C, D and E) 41 days. The median treatment initiation interval for localized and locally advanced RB was 15 days. Age (p = 0.0067) and patient gender were statistically significantly correlated with the diagnostic interval. For strabismus, the median diagnostic interval was 91 days (p < 0.0001), and when RB was detected during a preventive medical examination, the median diagnostic interval was 17 days (p < 0.0001). The event-free survival of the eyes depended on the prevalence of the process (in groups A, B, C) and the duration of the doctors’ interval (p = 0.0394). The distance to the cancer center was not statistically significant.
Conclusion. Predictors of late diagnosis and initiation of treatment in our study: gender, age of the patient at the time of diagnosis, and the first specific symptom of RB.

Introduction. Adrenal cortical carcinoma (ACC) is a rare cancer with a very poor prognosis. Surgery remains the best treatment modality for adrenocortical carcinoma in the early stages. The appropriate treatment for metastatic ACC is not well established, and the effectiveness of chemotherapy and radiotherapy, is not proven. Five-year survival for patients with stage IV tumors ranged from 0 to 17 %. The data regarding the effectiveness of surgery in the management of metastatic tumor remain scarce.
Aim of the study – to present our results of surgical treatment for metastatic ACC in children and to determine the risk factors of local relapse.
Materials and methods. The results of treatment of 10 patients with a median age of 5.8 (1.5–15.1) years with stage IV ACC were retrospectively analyzed. The tumors were hormone-producing in 6 of 10 cases. Four (40 %) patients experienced a Cushing syndrome. Primary tumor resection R1 and R0 was performed in 8 (80 %) and 5 (50 %) patients respectively. The median volume of resected tumor was 183 (3.6–1608) cm³. All patients received mitotane combined in 80 % with systemic chemotherapy consisted of etoposide, doxorubicin, cisplatin (EDP-M).
Results. Two (20 %) of 10 patients are alive with tumor in 14.1 and 28.8 months respectively. The median follow-up in the hole group was 21.8 (10.4–33.9) months and the median period to disease progression was 11.3 (6.4–17.9) months. The risk of local relapse in the first 8 months after surgery was 33.3 % vs. 100 % in R0 and R1/R2 groups respectively. The period from diagnosis to death from tumor progression was significantly longer in 7 patients with 2 and more EDP-M courses compared to 3 patients who received one EDP-M or no further treatment (24.9 vs. 14.4 months, p = 0.02). Two and five-year overall survive were 57.1 % and 0 % respectively.
Conclusion. The radical surgical resection (R0) significantly reduced the risk and incidence of local relapse in children with stage IV ACC. Adjuvant EDP-M therapy did not affect the unfavorable prognosis of the disease, but positively influenced life expectancy of patients with disseminated ACC.

Acute lymphoblastic leukemia is the most common tumor of childhood. Using of modern treatment chemotherapy regimens, we can reach about 90 % of 5-year survival. An important problem – patients with relapses of the disease, as well as children with the persistence of minimal residual disease (MRD), which is absolutely necessary in hematopoietic stem cell transplantation aspects. The possibilities of continuous intensive chemotherapy are limited by high toxicity, and therefore targeted drugs are used to achieve MRD-negative remission in children, in particular, a bispecific antibody – blinatumomab.
This article presents our own experience of using blinatumomab in patients using various financial sources, the technical features of using within the federal medical center. Also, undesirable effects of the drug and their therapy are mentioned.

Neuroblastoma (NB) is a rare malignant tumor characterized by highly variable biological behavior, including spontaneous and induced regression, maturation, and progression. To assess the prognosis and response to therapy in NB, the determination of a number of oncological markers is used, such as neuron-specific enolase, lactate dehydrogenase, ferritin. Nevertheless, the models for assessing the prognosis developed so far do not fully predict the specificity of the course of the disease. In this regard, the creation of methods for monitoring tumor status in real time, based on the analysis of circulating tumor biomarkers, seems to be extremely urgent. A characteristic feature of NB is the expression of various gangliosides on the surface of tumor cells. In particular, the content of disialoganglioside GD2 reaches up to 30 % of all gangliosides. At the same time, the level of GD2 expression depends on the differentiation of neurogenic tumors: the highest concentrations are determined on NB cells, the lowest – on ganglioneuroblastoma and ganglioneuroma. The phenomenon of “shedding”, the so-called flushing, of GD2 from the NB cell membrane made it possible to estimate its concentration in the peripheral bloodstream. The article discusses the evolutionary path of the methodology for detecting GD2 in blood serum, with an emphasis on the recently introduced liquid chromatography/ tandem mass spectrometry technique, which can be used as a starting point for the emergence of GD2 as a soluble biomarker of the tumor process, which is undoubtedly a powerful application in the clinical practice that offers hope for improved diagnosis, prognosis and riskadapted therapy strategies based on well-defined, measurable determinants in accordance with the concept of evidence-based medicine.

Inspite of great successes in treatment and high incidence of surveillance in pediatric acute lymphoblastic leukemia (ALL), patients are addicted to many drugs adverse events, which sometimes indicate to decrease the dose or even cytotoxic drug interruption with following risk of secondary disease relapse. Besides, researches found significant inter-individual variability of drugs toxicity and disease outcome. This fact specify a role of pharmacogenetics (PGx) in genetic polymorphism revealing in gene-candidates for treatment optimization. Global wide initiated studies of correlation analysis between genetic polymorphism and toxicity effects of ALL treatment in different ethnic groups of patients. In Russia such studies are rare.
In the current review we present annotations of gene-candidates of drugs with highest degree of proof their role in different types of clinical toxicity variants and recommendations for following PGx use in individualization of treatment protocols for pediatric ALL.

In the last 50 years there has been significant improvement in survival for children with cancer, achieved by the implementation of cooperative clinical research trials that found an opportunity to standardize and to control treatment of childhood cancer. Combined modalities in treatment approaches, intensification of chemotherapy regimens for high-risk disease allow to reach 70 % survival rate of all cases. Yet there is still a need to improve outcomes and decrease side effects of anticancer treatment in groups of unfavorable prognosis. The most promising point is personification of treatment with a special focus on targeted drug therapies and immunotherapy. We reviewed recent international advances and unique options in precision medicine for pediatric cancers.

Asparaginase drugs are integrated to multicomponent chemotherapy protocols for acute lymphoblastic leukemia (ALL) in children and adults. Despite the use of different treatment protocols for ALL therapy, drugs are the same there and the differences include the doses and the frequency of administration of cytostatics. Native L-asparaginase obtained from Escherichia coli was the first asparaginase drug for the treatment of ALL. With accumulated knowledge about undesirable and side effects another asparaginase drugs with less expressed side effects were created: pegylated form (PEG-asparaginase), asparaginase derived from Erwinia chrysanthemi (erwinase) and pegylated form of erwinase (crisantaspase).
This review is devoted to modern ideas about the mechanisms of action of various asparaginase drugs, pharmacological properties and adverse effects. There is a particular attention to the development of new forms of asparaginase, which will help minimize side effects and increase the effectiveness of the drug. Of no less importance is drug monitoring of asparaginase in the blood to detect side effect at the time and to understand the effectiveness of the therapy. The introduction of drug monitoring will help to individualize and improve the effectiveness of ALL treatment.

Factor XIII deficiency is one of the rare bleeding disorders with an approximate prevalence about 1 per 3 million. A characteristic feature of this deficiency is the high frequency of severe bleeding, including intracranial hemorrhages. This coagulopathy is not detected using a standard coagulation tests, measuring of factor XIII activity is required. The world practice of treating this hemorrhagic condition is the use of plasma and recombinant concentrate. These drugs are not registered in the territory of the Russian Federation. In our country, cryoprecipitate is used. This article describes the clinical case, diagnosis and unsatisfactory results of cryoprecipitate therapy in a patient with diagnosis of factor XIII deficiency. Prompt registration of the XIII factor concentrates is required.

Peutz–Jeghers syndrome (PJS) is a rare autosomal dominant disease (genodermatosis) caused by germline mutations in STK11 gene. The article describes an algorithm for PJS diagnostics in children using a clinical case as an example. A 5-year-old female patient without any family history underwent a genetic testing because of the buccal mucosa pigmentation, which is the one of the major signs of PJS. De novo mutation in the STK11 gene was found (c.543C> G, p.N181K). Taking into account the high risk of polyposis in PJS, an endoscopic examination of the gastrointestinal tract was performed. Gastric polyps were found, including multiple hamartoma polyps, which fully met the clinical criteria of the disease.
The reported case shows an importance of multidisciplinary approach to PJS management. Multidisciplinary team should include dermatologist, clinical geneticist, endoscopist, and pediatric oncologist due to the high risk of developing malignancies as the child grows older.