Vol 25, No 3 (2026)

Objective – to evaluate the learning curve of laparoscopic liver resections in children using the risk-associated cumulative summary analysis (RA-CUSUM) method with one surgeon experience in performing these open operations in adults and children.

Materials and methods. A database consisting of 52 patients that were operated in 2018-2024 on the basis of one center was analyzed. Due to the rarity of liver tumors between children, the study included patients with liver diseases of various etiologies – benign and malignant neoplasms, metastatic lesions. The learning curves were analyzed using approximation methods, exponential function of the ratio of surgery time to the experience gained by the surgeon, and the method of RA-CUSUM. To calculate the risk of surgical intervention we’ve used a difficulty scoring system, that was developed and published by a team of authors. The time of the operation was compared, and the criteria for failure were pathological bleeding that led to the conversion.

Results. Evaluating the results relative to the time of surgical interventions, it was found that the maximum value of the approximating function is achieved at approximately 21 operations performed, the proportion of observations (coefficient of determination) explained by this model is R² = 90%. According to the results of the exponential function construction, the regression coefficient shows that with each new operation, its time decreases by an average of 1.39%, and after 10 operations by an average of 13.04%. The graph constructed by the method of RA-CUSUM gave a stable decline, starting with the 24^th operation performed.

Conclusion. As the number of laparoscopic liver resections increases, the time of surgery and the frequency of pathological bleeding that leads to conversion significantly decrease. A surgeon with experience in open liver resections will need about 20–25 operations to learn how to perform laparoscopic liver resections in children. A difficulty scoring system, that was developed in our center for predicting and assessing preoperative risk, has proved its effectiveness.

Introduction. Myoepithelial сarcinoma (MC) is a rare and highly malignant neoplasm. Primary soft tissue involvement predominates in pediatrics (MCST), while MC of bones has been described in isolated cases. The rarity of MC combined with its polymorphic phenotype significantly challenge diagnosis and determine the absence of standardized treatment approaches.

Aim: to analyze the specifics of diagnosis and treatment of children with MC at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Health of the Russian Federation.

Material and methods. The study included 7 patients aged 1.3 to 14.2 years who were diagnosed with MC and registered between 2017 and 2024.

Results and discussion. MC of soft tissue was diagnosed in 6/7 cases and MC of bones in 1/7. Five out of seven cases were localized, while 2/7 cases presented with distant metastases. In 3 cases a deletion of the SMARCB1 gene was identified, and in 1 case deletion of the EWSR1 gene was detected. Surgical resection proved to be the cornerstone of the treatment program for patients with MC (R0 – n = 3; R1 – n = 3; R2 – n = 1). 5 patients underwent external beam radiation therapy. In 4 cases of localized MC, courses of chemotherapy (ICpE) were administered as an adjuvant. In 1 case courses of ICpE and IVE were given perioperatively. In the first case of metastatic MCST courses of ICpE/IVE were also administered; and in the second case a combination of AP + vinorelbine was used. Follow-up outcomes: 4/7 patients are alive with 3/4 alive without events.

Conclusion. The results of our study mostly align with international experience and emphasize the significance of local control, as well as the leading role of a multidisciplinary approach and multicenter data sharing in improving the diagnostic and therapeutic outcomes for patients with MC.

Background. Neuroblastoma (NB) is one of the most common malignant solid tumors in childhood, in some cases presenting challenges for differential diagnosis at initial presentation. Serum tumor markers – neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) – have limited diagnostic accuracy. Circulating C18 lipoform of GD2 may represent a promising liquid biopsy marker for NB, however, multiparametric diagnostic models combining GD2 with serum markers remain largely unexplored.

Objective – to develop and internally validate a logistic regression model for noninvasive diagnosis of NB in children based on the combination of serum C18 lipoform GD2, NSE, and LDH levels, and to assess whether a neural network model (multilayer perceptron) improves diagnostic performance compared to logistic regression.

Materials and methods. Serum concentrations of C18 lipoform GD2 were measured using a validated high-performance liquid chromatography-tandem mass spectrometry method, NSE and LDH were determined by standard techniques in primary patients with suspected neurogenic tumor between July 2021 and March 2024 (32 months) at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Missing NSE and LDH data were handled by multiple imputation (m = 20). A logistic model with three continuous predictors (GD2, NSE, LDH) was fitted in each imputed dataset, and coefficients were pooled using Rubin's rules. As an alternative, a neural network model (3 inputs, one hidden layer with 2 neurons, logistic output) was trained on the 6^th imputation and applied to all 20 datasets. Model performance was assessed by AUC (95% confidence interval (CI)), as well as sensitivity, specificity, positive predictive value and negative predictive value for the logistic and neural network decision rules on the pooled multiply imputed dataset at the probability threshold determined by the Youden index. Internal validation was performed using strict 5-fold cross-validation on each imputed dataset. Differences in AUC between the two decision rules were assessed using DeLong's test.

Results. This prospective single-center diagnostic cohort study included 155 patients aged 0–18 years with clinical and instrumental suspicion of a neurogenic tumor prior to specific therapy (89 with NB, 66 controls). The logistic model demonstrated an AUC of 0.842 (95% CI 0.829–0.856); only C18 lipoform GD2 remained a significant predictor (OR 1.07 per 1 nM; 95% CI 1.04–1.11; p < 0.001). The mean AUC under strict 5-fold cross-validation was 0.838 (range – 0.812–0.867). The neural network decision rule showed a similar AUC on pooled data (0.841; 95% CI 0.828–0.855) but a lower and more variable mean AUC under cross-validation (0.759; range – 0.684–0.841). DeLong's test revealed no statistically significant difference between the AUCs of the logistic and neural network models (p = 0.904).

Conclusion. Circulating C18 lipoform GD2 may serve as a key component of the diagnostic model in patients with suspected neurogenic tumor, while NSE and LDH contribute minimal additional value. The neural network model does not provide a significant AUC advantage and is less stable than logistic regression. Given the comparable discriminatory ability, greater robustness, and interpretability, the logistic regression model was selected as the final decision rule for noninvasive NB diagnosis and implemented as an online risk calculator.

Background. Germ cell tumors (GCT) in children represent a group of chemosensitive malignant neoplasms. However, for a small subset of patients with refractory, relapsed, or disseminated GCT, the prognosis remains extremely poor, with overall survival rates potentially not exceeding 45%. High-dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is considered a treatment strategy with the potential to improve outcomes in this patient population.

Objective – to analyze the experience of HDCT with auto-HSCT in children with poor-prognosis GCT, with assessment of the efficacy and safety of this therapeutic approach.

Materials and methods. This single-center retrospective study enrolled 20 children (9 boys and 11 girls) with relapsed (n = 9), refractory (n = 3), and disseminated (n = 8) forms of GCT who received HDCT followed by auto-HSCT. The median age is 2 (1–18) years. All patients had a graft of adequate cellularity collected prior to transplantation: the median CD34⁺ cell dose was 3.6 (range 2.0–8.1) ×10⁶/kg body weight. A tandem HDCT regimen was administered to 14 patients (first course: carboplatin 1200 mg/m², etoposide 1500 mg/m², second course: etoposide 1500 mg/m² and thiotepa 900 mg/m²). Six patients received a single-course HDCT regimen (etoposide 1500 mg/m² and thiotepa 900 mg/m²). The median follow-up was 27 (range 1–61) months.

Results. All patients achieved hematopoietic recovery following auto-HSCT. Febrile neutropenia developed in 11 patients (55.0%) during the early post-transplant period, with a mean duration of fever of 4 (range 0–6) days. Oropharyngeal mucositis and gastrointestinal mucositis were observed in all 20 patients (100.0%), and dermatological toxicity was noted in 16 patients (80.0%). In the majority of cases, the severity of toxic and infectious complications did not exceed grade 2. At a median follow-up of 2.7 years, overall survival was 84.0%, event-free survival was 78.0%, and relapse-free survival was 81.0%. Disease progression after auto-HSCT was documented in 3 patients, 2 of whom remain alive. Two patients died: one due to disease progression, and one due to an infectious episode at the place of residence 6 months after the completion of therapy.

Conclusion. HDCT with auto-HSCT in children with poor-prognosis GCT may be considered an effective therapeutic approach with an acceptable toxicity profile.

Introduction. Graft failure (GF) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a life-threatening complication, with an incidence of 5–20% in pediatric patients with acute leukemia. Macrophage activation syndrome (MAS)/secondary hemophagocytic lymphohistiocytosis (sHLH) represents one of the most aggressive triggers of GF, being closely associated with cytokine storm, multiple organ dysfunction, and high transplant-related mortality. In the setting of primary or secondary GF, a second allo-HSCT remains the only potentially curative treatment option; however, performing it against a background of hyperinflammation carries substantial risks of fatal complications and recurrent non-engraftment.

The aim of the study – to evaluate factors influencing the rates of non-engraftment, overall survival, and relapse-free survival following second allo-HSCT in pediatric patients with acute leukemia who suffered primary or secondary GF after their first allo-HSCT.

Materials and methods. This retrospective single-center study included 44 pediatric patients (median age 9.4 years) with acute myeloid leukemia (n = 11), acute lymphoblastic leukemia (n = 28), and myeloproliferative neoplasms (n = 5). Primary GF was diagnosed in 65.9% of patients, while secondary GF/rejection occurred in 34.1%. Key triggers of MAS/sHLH included viral infections (Epstein–Barr virus, cytomegalovirus, human herpes virus 6, parvovirus B19), bacterial/fungal complications, and cytokine release syndrome. Prior to the second HSCT, conditioning regimens consisted of reduced-intensity conditioning in 79.5% and anti-thymocyte globulin-based conditioning in 20.5%; a subset of patients received anti-cytokine therapy. A switch to a different HLA-matched donor was performed in 47.7% of cases. The median follow-up was 3 years.

Results. The cumulative incidence of engraftment was 73% (median time to neutrophil recovery – 15 days). One-year overall survival was 64% (95% confidence interval (CI) 48–76), relapse-free survival was 57% (95% CI 41–70), and non-relapse mortality was 34% (95% CI 20–48). The main causes of death were infectious complications (n = 7), hepatic veno-occlusive disease/sinusoidal obstruction syndrome/transplant-associated thrombotic microangiopathy (n = 6), acute respiratory distress syndrome (n = 3), and cerebrovascular accident (n = 2). The incidence of grade II–IV acute GVHD was 61%, with grade III–IV occurring in 36%. HLA donor switch, stem cell source, and conditioning regimen, including anti-thymocyte globulin use, did not demonstrate a statistically significant impact on overall survival.

Conclusion. A second allo-HSCT in pediatric patients with GF complicated by MAS/sHLH demonstrates acceptable engraftment and survival outcomes, remaining the only available option for long-term disease control. The high incidence of early immunological complications and non-relapse mortality necessitates exactly pre-transplant optimization, performing of weekly serum ferritin and inflammatory marker monitoring, and morphological confirmation of hemophagocytosis during the early post-transplant period (days +14 to +21), particularly in the absence of hematopoietic recovery. Optimization of targeted anti-cytokine therapy and intensified prophylaxis/management of infectious complications represent priority strategies to reduce transplant-related mortality.

Introduction. Myxopapillary ependymoma (MPE) is a rare ependymal neoplasm arising predominantly from the conus medullaris, cauda equina, and filum terminale. In the pediatric population, MPE accounts for less than 10% of all ependymomas and approximately 1–2% of all primary central nervous system tumors. Compared to adults, pediatric MPE displays a more aggressive clinical course, with higher rates of leptomeningeal dissemination at diagnosis (reported in up to 35–58% of cases in some series) and higher rates of local and metastatic recurrence following surgical treatment. In accordance with the 2021 World Health Organization Classification of Central Nervous System Tumors, MPE has been reclassified as a Grade 2 neoplasm. Large pediatric cohorts with concurrent analysis of clinical and morphological features and treatment outcomes remain scarce, and national data from Russian institutions are virtually absent from the international literature.

The aim of this study was to analyze the clinical and morphological characteristics of pediatric MPE and to evaluate the impact of extent of surgical resection and radiation therapy (RT) on disease outcomes.

Materials and methods. This retrospective study included 49 patients under 18 years of age with histologically confirmed MPE at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (Moscow) between 2013 and 2025. Parameters analyzed included patient demographics, tumor localization, metastatic staging per Chang classification (M0–M3), extent of surgical resection, use of RT. The primary endpoint was event-free survival (EFS), defined as time from diagnosis to disease progression or relapse. A morphological sub-analysis was performed in 28 patients with available archival histological material, evaluating candidate anaplasia features: high cellularity, mucin reduction, high mitotic activity (≥5 mitoses per high-power field at ×400 or Ki-67 ≥10%), endothelial proliferation, spontaneous necrosis, and heterogeneous GFAP expression. A composite anaplasia index was calculated. Statistical analyses were performed in R 4.5.2 using Kaplan–Meier estimation, log-rank testing, and multivariate Cox proportional-hazards regression.

Results. Of 49 patients, 57.1% were male and the median age at diagnosis was 12.8 years (range 5.8–18.0). The predominant tumor location was the lumbosacral spinal cord (85.7%). Metastatic dissemination at diagnosis was identified in 8/49 (16.3%) patients. Gross total resection was achieved in 28/49 (57.1%) patients. RT was administered to 23/49 (46.9%) patients. At the time of analysis, all 49 patients were alive (overall survival – 100%), with a median follow-up of 4.2 years. Disease progression or relapse occurred in 12/49 (24.5%) patients. The 3- and 5-year EFS for the entire cohort were 77.6% and 69.4%, respectively. On multivariate Cox analysis, adjuvant RT was an independent statistically significant predictor of EFS (hazard ratio 0.05; 95% confidence interval 0.01–0.44; p = 0.007). The greatest benefit from RT was observed in patients with incomplete resection: 5-year EFS increased from 22.2% with surgery alone to 66.7% with the addition of RT. In contrast, patients achieving R0 resection without RT already demonstrated a favorable 5-year EFS of 75.6%. In the morphological subgroup, a composite anaplasia index ≥2 was significantly associated with inferior EFS: 44.0% vs. 81.0% (log-rank p = 0.046; adjusted hazard ratio 4.44; 95% confidence interval 1.04–19.0; p = 0.044).

Conclusion. Pediatric MPE is characterized by excellent overall survival but heterogeneous EFS outcomes determined primarily by extent of resection and adjuvant RT. A risk-adapted strategy – reserving RT for patients with residual disease – is supported by the results of this study and is consistent with EANO guidelines for spinal ependymomas. Routine RT following gross total resection appears unnecessary, given the well-documented long-term radiation toxicity in growing children. The proposed composite morphological anaplasia index represents a promising tool for additional risk stratification in pediatric MPE, pending validation in larger, prospective, and preferably multicenter cohorts.

Introduction. Hereditary spherocytosis (HS) is a hereditary hemolytic anemia caused by defects in erythrocyte membrane and cytoskeleton due to mutations mainly in five genes: ANK1, SPTB, SPTA1, SLC4A1, and EPB42. The genetic landscape of HS is characterized by considerable interpopulation variability.

Aim – to investigate the molecular genetic spectrum of HS in the Russian population.

Materials and methods. The study included 240 patients under 21 years of age with genetically confirmed HS. We analyzed the distribution of pathogenic variants by gene, mutation type, frequency of recurrent and previously undescribed variants, and also assessed the genotype–phenotype correlation with disease severity.

Results. Pathogenic variants in the SPTB gene were identified in 45.8% of the patients, in the ANK1 gene in 34.6%, in the SLC4A1 gene in 11.3%, and in the SPTA1 gene in 8.3%. In the SPTB and ANK1 genes, loss-of-function mutations, such as nonsense, frameshift, and splice-site mutations, predominated. In the SLC4A1 gene, missense mutations were the most common, whereas in the SPTA1 gene there was a heterogeneous mutation spectrum, including the frequent intronic mutation with low aLEPRA expression. Novel mutations accounted for 54.2% of all variants. In SPTA1-associated HS, complex genotypes were frequently observed: compound heterozygous variants and digenic variants were found in 35% and in 20% of the patients, respectively. Our clinical severity analysis showed that patients with SPTB- and ANK1-associated HS had mostly moderate disease, patients with SLC4A1-associated HS had a mild course with no severe cases, while SPTA1-associated HS was characterized by a relatively high proportion of severe cases.

Conclusion. The Russian cohort belongs to populations with an SPTB-dominant mutation pattern and represents one of the largest national cohorts of patients with genetically confirmed HS worldwide.

Aim of the study – comparison of results of flow cytometric minimal residual disease (MRD) detection in B-lineage acute lymphoblastic leukemia in two Russian laboratories of the Moscow–Berlin study group.

Materials and methods. Ring trial was performed in three rounds. Four flow cytometry specialist from Dmitry Rogachev Center (Moscow) and two from Regional Children Hospital (Ekaterinburg) were suggested to analyze cytometric files of 70 studies of bone marrow samples obtained at various time-points during different treatment phases.

Results and discussion. Although false-positive and false-negative results were obtained by single specialists in exact cases, the overall comparability of MRD data was very high. Found discrepancies were observed mainly in cases with very low MRD burden (below 0.01%). Also discordant results were observed in patients with CD10-negative immunophenotype. Nevertheless, in all samples the majority of the documented results were right. Presence of the most experienced expert in each laboratory, who is responsible for the final conclusion on MRD samples, led to the high inter-laboratory concordance.

Conclusion. Therefore, discussion of all complicated cases with the most experienced specialists, centralization of the primary immunophenotyping, clinical application of the most reproducible MRD thresholds, as well as further improvement of flow cytometry methodology and technology harmonization will allow achieving perfect reproducibility of the flow cytometric MRD detection in patients with B-lineage acute lymphoblastic leukemia.

Introduction. With adequate initial therapy, germ cell tumors (GCTs) have a relatively favorable prognosis; however, approximately 20–25% of patients experience relapse or refractory disease. Currently, there are several potentially curative treatment options for this patient population but the optimal approach remains undetermined in both adult and pediatric practice. A particular challenge is the management of patients who have not responded to multiple lines of systemic therapy. Although most GCTs are considered as a primarily systemic disease, in this population with an extremely low chance of cure with systemic treatment alone, local control modalities may offer a chance of cure. Clinical experience demonstrates the effectiveness of not only surgical but also radiotherapeutic approaches, despite the fact that non-seminomatous/non-dysgerminomatous GCTs were previously considered radioresistant.

Clinical case. Here, we report a clinical case of a 16-year-old female adolescent with secreting malignant ovarian germ cell tumor. The patient received 3 cycles of multi-agent chemotherapy according to the MAKEI-05 protocol, followed by surgical treatment (left-sided salpingo-oophorectomy). After surgery, a radiological complete response was achieved, however, alpha-fetoprotein (AFP) levels did not normalize. Later, the patient showed a rise in AFP levels and a metabolically active tumor on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT). Therefore, second-line therapy was administered according to the TIGER protocol, after which AFP levels normalized. One month after the completion of multi-modal treatment, an increase in AFP was observed, and PET/CT again revealed metabolically active lesions. To achieve systemic disease control, the girl received chemotherapy with the GOP regimen (gemcitabine, oxaliplatin, paclitaxel), followed by surgical exploration of the abdominal cavity, which revealed no pathological findings. Given the inability to rule out the presence of viable tumor cells, a multidisciplinary decision was made to administer radiation therapy to the metabolically active lesions visualized on PET/CT (in the region of the right uterine adnexa). The patient underwent radiation therapy to the right adnexal bed to a total dose of 50.4 Gy. The girl was discharged for follow up. At the time of this report, the patient remains in complete unmaintained remission for 30 months.

Conclusion. This clinical case illustrates successful curative local treatment of the patient with recurrent disease after multiple surgeries in the same area, who had exhausted all available systemic curative options.

Introduction. This study presents the first experience of robotic fenestration of a liver cyst using the Versius system and assesses the feasibility and safety of this procedure in children.

Clinical case. The study presents a case of successful treatment of a simple liver cyst in a 15-year-old boy who had been complaining of discomfort in the right hypochondrium and occasional pain for 6 months prior to admission to the children's hospital. Visualization data confirmed the ultrasound finding and identified a simple liver cyst with a diameter of 7 cm with a thin avascular capsule filled with liquid contents. The operation was performed using the Versius robotic system developed by CMR (UK). The main stages of the operation included: cyst puncture and aspiration of its contents; excision of the cyst dome (fenestration) as close to the liver parenchyma as possible; destruction of the remaining epithelium of the posterior wall of the cyst using argon plasma photocoagulation to prevent recurrence of the disease. The patient's age at the time of surgery was 15 years. The cyst was located in segment VI of the right lobe of the liver. The duration of the surgery was 130 min, the robot installation time was 15 min, the main console time was 115 min. The total blood loss was no more than 5 ml. The surgery was not accompanied by conversion to laparoscopic or open surgery. During the surgical interventions, no complications associated with trauma to the bile ducts, liver vessels, or adjacent anatomical structures were noted. Recovery was smooth and quick, and the patient was discharged from the hospital on the 3rd postoperative day. Pathological examination of the resected sample showed a benign liver cyst.

Conclusion. Robot-assisted fenestration combined with simultaneous argon plasma photocoagulation of the residual cavity is a feasible option for the treatment of simple liver cysts and is accompanied by a favorable course of the postoperative period.

This paper presents, to our knowledge, the first reported case of desmoplastic small round cell tumor harboring a somatic missense variant in the EGFR gene in exon 21, c.2620G>C (p.Gly874Arg), which did not demonstrate sensitivity to treatment with the EGFR inhibitor osimertinib. Additionally, we describe a clinical case of a patient with ovarian desmoplastic small round cell tumor carrying a pathogenic PIK3CA variant, c.263G>A (p.Arg88Gln).

Thiamine-responsive megaloblastic anemia (Rogers syndrome; OMIM #249270) is a rare autosomal recessive disorder caused by pathogenic variants in the SLC19A2 gene, which encodes the high-affinity thiamine transporter type 1. The disease is characterized by the classic triad of symptoms: megaloblastic anemia, non-autoimmune diabetes mellitus, and progressive sensorineural hearing loss. We report two sibling brothers of Ingush origin with genetically confirmed Rogers syndrome. In the older brother (3 years), the disease manifested with the classic triad in combination with cardiomyopathy, cardiac arrhythmias, and ophthalmologic pathology; the diagnosis was established in the setting of a fully developed clinical picture. In the younger brother (11 months), the disease was suspected based on a positive family history and early laboratory abnormalities (anemia, hyperglycemia, hyperlactatemia), which allowed initiation of thiamine replacement therapy prior to the onset of irreversible clinical symptoms. In both patients, whole genome sequencing identified a homozygous SLC19A2 variant c.1223+1G>A. At follow-up 1.5 years later, the younger brother, while on continuous thiamine therapy, retained normal hearing and showed no evidence of anemia or diabetes mellitus.

Nephron-sparing surgery for renal tumors in children are a modern and effective method of radical treatment. However, the opportunity of application of these technologies is clearly regulated by the international treatment protocols SIOP and COG and depends on the characteristics of the initial tumor in the kidney. Also, the method of dividing the renal parenchyma, the need for stenting of the upper urinary tract, the relationship to multivisceral resections, and the possibility of simultaneous bilateral resection have not been fully determined. At the same time, there are many studies demonstrating satisfactory treatment results for patients whose tumors are beyond international protocols. This publication demonstrates the modern understanding of kidney resections for tumor lesions.