Congenital mesoblastic nephroma (CMN) is a rare renal tumor of young children with intermediate biological behavior, accounting for 3.5-4% of all renal tumors in children. СMN is characterized by a favorable prognosis in case of radical surgical treatment. Relapses of CMN are considered to be quite a rare occurrence (4% of all cases), however, both local and metastatic relapses are possible. There are no fully standardized treatment approaches for patients with relapsed CMN. In our study, we performed a retrospective analysis of patients (n = 3) with a verified relapse of CMN who had received treatment at the D. Rogachev NMRCPHOI between 2012 to 2022 (132 months). At relapse, all the patients underwent at least one part of treatment at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. The diagnosis of CMN was established at the Pathology Department of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation, based on a histological examination. The patients with the cellular histological subtype of CMN underwent fluorescent in situ hybridization testing for ETV6 gene rearrangements. The demographic characteristics, clinical data, the extent of initial treatment and relapse therapy were assessed. Here, we describe three clinical cases of relapse in patients with CMN. The median age at initial diagnosis was 0.8 months (range 0.7–1.4). Our analysis of the extent of primary surgical treatment, including nephrectomy, in all cases revealed the following factors associated with a higher risk of relapse: preoperative tumor rupture – 1, intraoperative tumor rupture – 1, inability to confirm tumor-free margins – 1. The distribution of histological subtypes was as following: classical CMN (n = 1), cellular CMN (n = 1), and mixed CMN (n = 1). One patient had local stage II and 2 patients had local stage III. The median time from diagnosis to disease relapse was 0.8 months (range 2.3–4.3). One patient with mixed CMN died 10.6 months after diagnosis from complications of intensive therapy carried out for extremely aggressive relapse. Two patients are alive after repeated surgical treatment (R1 resection) and adjuvant therapy with actinomycin D and vincristine (AV regimen) for 27 weeks in one case, and neoadjuvant therapy (AV regimen for 4 weeks), delayed surgery (R0 resection), and adjuvant therapy (AV regimen for 4 weeks) in the other case. These patients were followed up for 92.2 and 21.3 months, respectively. By acknowledging the possibility of recurrent CMN, it seems important to provide multidisciplinary clinical care to young children with renal tumors involving a detailed planning of surgical procedures, radical surgeries in accordance with practice guidelines and standards in surgical oncology, and careful follow-up, especially during the first year after surgery. The patients' parents gave consent to the use of their children's data, including photographs, for research purposes and in publications.

Metanephric tumors (MTs) are a group of rare childhood kidney tumors consisting of epithelial and/or stromal cellular elements and characterized by a variety of histopathological features. MTs include metanephric adenoma (MA), metanephric adenofibroma (MAF), and metanephric stromal tumor (MST). This study aimed to retrospectively analyse clinical and molecular genetic characteristics of MTs, verified at the Pathology Department of the Dmitry Rogachev NMRCPHOI of Ministry of Healthcare of the Russian Federation. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. We performed a retrospective analysis of data on patients with MTs histologically confirmed between February 2015 and February 2024 (109 months). During this period, a total of 26 cases (patients aged 0–18 years) of histologically confirmed MA, MAF, and MST had been documented at the Pathology Department of the D. Rogachev Center. Out of these 26 cases, 16 patients with known clinical data were included in our analysis. The median age at diagnosis was 3.5 years (range: 0.4–15.2 years). The boys:girls ratio was 1:1. The analysis of primary complaints showed that the majority of patients (n = 8; 50%) were asymptomatic and their kidney masses were detected by chance. The rest of the patients presented with pain syndrome (n = 3; 19%), gross hematuria (n = 2; 13%), intoxication syndrome (n = 1; 6%), polycythemia (n = 1; 6%), an increased abdominal circumference (n = 1; 6%). Primary surgery was performed in 6 (37%) patients: partial nephrectomy (n = 4), total nephrectomy (n = 1), and a core needle biopsy of the mass followed by partial nephrectomy (n = 1). Ten patients (63%) underwent preoperative multiagent chemotherapy. The analysis of the extent of surgical treatment of all patients included in the analysis (n = 16) showed that total nephrectomy was performed in 9 cases, and partial nephrectomy – in 7 cases. R0 resection was achieved in 15 cases, R1 resection – in 1 case. The distribution by histological variants was as follows: MA – 10 (63%) patients, MST – 3 (19%) patients, MAF – 1 (6%) patient, MA in combination with clear cell papillary renal cell carcinoma – 1 (6%) patient, MAF in combination with papillary renal cell carcinoma – 1 (6%) patient. Sixteen patients underwent molecular genetic testing: a somatic V600E mutation in the BRAF gene was detected in 10/16 (62.5%) patients. Currently, all patients are alive, and no relapses of the disease have been observed. MTs are a group of rare kidney tumors in children, characterized by a variety of histological patterns, which creates difficulties in differential diagnosis with other kidney tumors, such as renal cell carcinoma and nephroblastoma. Molecular genetic testing aimed at identifying mutations in the BRAF gene can help in establishing the correct morphological diagnosis.

Growing teratoma syndrome (GTS) is a condition characterized by a paradoxical increase in tumor size during or after chemotherapy and/or surgical treatment for germ cell tumors. Due to its relative rarity, GTS may be misinterpreted as disease progression. However, a decrease in tumor markers (alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG)) in the blood, a paradoxical increase in tumor size during chemotherapy, and a verified histological diagnosis of mature teratoma after the tumor removal confirm GTS. Here we report a clinical case of a patient in whom we observed a decrease in tumor markers (AFP and hCG) in the blood during treatment, a paradoxical increase in the tumor size and normal AFP and hCG levels 5 months after the end of chemotherapy and a histologically verified diagnosis. These clinical features are consistent with the diagnostic criteria of GTS. The patient's parents gave consent to the use of their child's data, including photographs, for research purposes and in publications.

Germ cell tumors (GCT) are a heterogeneous group of neoplasms occurring predominantly in childhood and including several histological types characterized by different lesion localization and different clinical symptoms. Malignant GCT, such as yolk sac tumor (YST), in the head and neck region are extremely rare, therefore, only few clinical observations have been described in the literature. The aim of this study was to analyze the clinical data and treatment results of patients with yolk sac tumors of the head and neck region. Material and methods. During the period from 02.2012 to 02.2021 (108 months), 4 patients with YST of the head and neck area were treated at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. Median age at diagnosis was 22.2 months (range 6.9–36.2 months). Primary tumor was located in the orbit in 2 (50%) patients, in maxilla in 1 (25%) patient, and in nasal cavity in 1 (25%) case. Median alfa-fetoprotein (AFP) level before therapy was 4395 ng/ml (range 541–19453 ng/ml). The diagnosis was morphologically confirmed in all cases. Distant metastases in lungs were detected in 1 (25%) patient. The stage distribution was the following: II – 1 (25%), III – 2 (50%), IV – 1 (25%). Results. All the patients have received combined treatment according to the protocols of the German MAKEI group. Orbito-facial resections were required in 2 (50%) cases. By the time of the analysis, all patients are alive with no signs of recurrence and the median follow-up of 30.9 months (range 12.7–89.0). Conclusions. The main conclusion of this study is that the combined treatment, which is the standard of care, allows to achieve high overall survival rates, however, in some cases, complex anatomical localization of the tumor may require mutilation operations. Герминогенно-клеточные опухоли (ГКО) – гетерогенная группа новообразований, которая наблюдается преимущественно в детском возрасте, включает несколько гистологических типов, характеризуется раз- личной локализацией поражения и клинической симптоматикой. Злокачественные ГКО, такие как опухоль желточного мешка (ОЖМ), в области головы и шеи встречаются крайне редко, поэтому в литературе опи- сано мало клинических наблюдений. Целью настоящего исследования является изучение клинических данных и результатов терапии у пациентов c ОЖМ в области головы и шеи. Материал и методы. За период 02.2012–02.2021 гг. (108 месяцев) в ФГБУ НМИЦ ДГОИ им. Дмитрия Рогачева получали лечение 4 пациента с ОЖМ в области головы и шеи. Медиана возраста на момент постановки диагноза составила 22,2 месяца (разброс 6,9–36,2 месяца). Опухоль локализовалась в обла- сти орбиты у 2 (50%) пациентов, по 1 (25%) случаю пришлось на поражение верхней челюсти и полости носа. Медиана уровня α-фетопротеина до начала лечения – 4395 нг/мл (разброс 541–19453 нг/мл). Диагноз во всех случаях подтверждался результатами гистологического исследования. Отдаленные метастазы диагностированы у 1 (25%) пациента (легкие). Распределение по стадиям: II – 1 (25%), III – 2 (50%), IV – 1 (25%) пациент. Результаты. Всем пациентам проведено комбинированное лечение по протоколу MAKEI. У двух па- циентов потребовалось выполнение орбитофациальных резекций. На момент проведения настоящего анализа все пациенты живы без признаков заболевания, медиана длительности наблюдения составила 30,9 месяца (разброс 12,7–89,0). Выводы. Основным выводом настоящего исследование является то, что комбинированное лечение, яв- ляющееся стандартом терапии, позволяет добиться высоких показателей общей выживаемости, однако в ряде случаев сложная анатомическая локализация опухоли может требовать выполнения калечащих операций.

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.

1ФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России, Москва 2ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва 3ГУ «Республиканская детская клиническая больница» Министерства здравоохранения Республики Коми, Сыктывкар 4ГБУЗ «Самарская областная детская клиническая больница им. Н.Н. Ивановой», Самара

Succinate dehydrogenase-deficient renal cell carcinoma (SDH-deficient RCC) is histological variant of RCC recently recognized and included in the classification of renal tumors. SDH-deficient RCC constitutes only 0,02–0,5% of all RCC. The main role in the development of this malignant neoplasm (MN) belongs to mutations in the genes of succinate dehydrogenase (SDHx). The article presents a clinical case report of SDH-deficient RCC in the 15-year-old child. RCC developed as a consequence of the syndrome of hereditary pheochromocytoma and paraganglioma type 4. A literature review describes the histological and molecular genetic characteristics of SDH-deficient RCC, the clinical picture, approaches to therapy and monitoring of patients, as well as indications for genetic testing of patients and their relatives to identify cancer predisposition syndromes.

Cystic nephroma (CN) is a rare renal tumor occurring in children which belongs to a group of neoplasms linked with the inherited DICER1 syndrome. Given the rarity of CNs, it is important to describe clinical, radiological, and molecular genetic characteristics of these tumors in children and adolescents as well as to analyze treatment outcomes. We present our experience in managing 8 patients with histologically verified CN who received treatment and consultations at the D. Rogachev NMRCPHOI over a period of 9 years (2012–2020). The study was approved by the Independent Ethics Committee and the Scientific Council of the D. Rogachev NMRCPHOI. The patients’ parents gave their consent to the use of their child’s data, including photographs, for research purposes and in publications. We performed a retrospective analysis of clinical presentation, radiological findings, the extent of treatment given to patients, treatment outcomes, and the results of molecular genetic testing. The study included patients aged between 8.6 and 197 months at diagnosis (the median age was 14.2 months). The analysis of initial complaints revealed that six patients (75%) had an increased abdominal girth and a palpable mass in the abdomen, one patient (12.5%) presented with arterial hypertension, and another patient (12.5%) had a mass detected by a routine abdominal ultrasound examination. On contrast-enhanced computed tomography scans, CNs appeared as multicystic masses with thin, contrast-enhancing septa; the CN volume ranged from 59.7 to 1293.1 cm3 (the median volume was 626.3 cm3 ). In all cases, the diagnosis of CN was verified histologically. Surgical treatment included nephrectomy (n = 6) or partial resection of the affected kidney (n = 2) with the removal of the tumor. Some patients (n = 5) included in our analysis received pre-operative chemotherapy at the discretion of their treating physicians. Molecular genetic testing was carried out for 7 children: 4 out of 7 patients (57.1%) were found to have somatic and germline mutations in the DICER1 gene. Carriers of pathogenic DICER1 variant were identified in the family of 1 patient. The median duration of follow-up was 17.6 months (range: 1.7 to 58.9 months). Currently, all patients are alive, no relapses have occurred. Cystic renal neoplasms detected by radiological investigations should be reviewed at the reference centers for pediatric oncological diseases and included CN in the differential diagnosis. Initial surgery is the first line of treatment for cystic nephroma. The final diagnosis is made on the basis of a histological examination of tumor tissue. All patients with confirmed CN should be referred for genetic counseling and molecular genetic testing for germline mutations in the DICER1 gene and should receive surveillance recommendations for the early detection of other metachronous DICER1-associated tumors.

Growing teratoma syndrome (GTS) is reported to have an incidence of 1.9–7.6% among all germ cell tumours (GCT) and is often mistaken for tumor progression. There are no absolute signs or symptoms of GTS but it can be suspected based on the following criteria: the normalization of tumour markers, the enlargement of the mass and the presence in the tumour of mature teratoma cells alone. A delayed tumor resection in GTS can result in higher surgical risks and/or the infeasibility of complete resection. In 72–83% of cases, incomplete resection leads to relapses in the form of mature teratoma growth. A repeat biopsy is recommended in all patients with suspected GTS so that to avoid chemotherapy that would be ineffective in this disease. The article reports two clinical cases of GTS illustrating challenges inherent in the diagnosis of this syndrome. In each case, the parents gave consent to the use of their child's data, including photographs, for research purposes and in publications.

One of rare location of teratoma in children is head and neck region. Treatment options, including surgery, are determined by tumour location, its grade of differentiation, and patients age. This article presents case report of immature paratracheal neck teratoma in a 3-month old child, subjected for second-look surgery for residual tumour removal due to the risk of life-threatening complications.

Renal rhabdoid tumor (RRT) is the most malignant and aggressive renal tumors in children. The results of immunohistochemistry show co-expression of epithelial and mesenchymal markers with total loss of INI1 expression in tumor cells. Aim. To determine the frequency of WT1 expression in RRT using three different clones and to investigate WT1 gene status. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. 28 patients with RRT were included in our study from a period 2006–2019. Immunohistochemical staining included Vimentin, panCK, CK19, EMA, INI1, CD34, WT1 (clones: polyclonal, WT49, 6FH2). Additionally, in order to evaluate genetic events known to be significant in the RRT pathogenesis, molecular genetic testing by multiplex ligase-dependent probe amplification (NGS) and next-generation sequencing (NGS) of customized gene panel were conducted in 15 cases with available material. All tumors had classical rhabdoid morphology with co-expression of epithelial and mesenchymal markers and total loss of INI1 expression. Two tumors were WT1-positive (WT49 and Polyclonal). 5 out of 15 tumors harbored different in length SMARCB1 gene deletions. 7 cases studied by NGS for nucleotide substitutions and small indels included 5 patients lacking SMARCB1 deletions based on the MLPA data and 2 cases of RRT with WT1 protein nuclear expression. All evaluated patients had pathogenic or likely-pathogenic genetic variants in genes encoding core subunits of SWI/ SNF chromatin remodeling complex (predominantly, SMARCB1 and SMARCA4 genes). No pathogenic variants were revealed in WT1 gene. The literature describes isolated cases of WT1 expression in RRT elements. Often, the cellular elements of a rhabdoid tumor after preoperative chemotherapy are regarded as elements of the stromal component of nephroblastoma, maturing into rhabdomyoblasts. In the presence of WT1 expression, these tumors are considered as nephroblastomas. In this study we showed that RRTs are molecularly heterogeneous tumors with aberrant immunophenotype. Thus, our experience proves the importance of an integrated approach to differential diagnosis and the need for routine use of the INI1 antibody in panels for the study of kidney tumors in children to avoid misinterpretation of morphological data.

BK-virus has been identified as the main cause of polyomavirus-associated nephropathy, a major cause of renal allograft failure. Hemorrhagic cystitis is a major complication of BK-virus infection after hematopoietic stem cell transplantation. The reports of polyomavirus-associated nephropathy after hematopoietic stem cell transplantation (HSCT) are surprisingly very few. Here we describe two patients received an unrelated donor HSCT and developed a biopsy-proven BK nephropathy, which contributed to his renal failure.

Langerhans-cell histiocytosis (LCH) is a rare myeloid neoplasia (about 3 cases per 1 000 000 children yearly). Lung involvement is rare, usually as a part of multisystem disease. Clinically these lesions manifest with signs of respiratory insufficiency like dyspnea, cough and desaturation. Imaging shows nodules that are gradually transforming into thick- or thin-walled cysts. Rapture of these cysts leads to the pneumothorax which requires drainage. Our report shows clinical case of use of elective pleurodesis to prevent life-threatening complications of histologically confirmed LCH with lung involvement, which can develop either as a result of the disease or due to chemotherapy.

The malignant rhabdoid tumor (RT) is one of the most aggressive childhood neoplasm. RTs are characterized by the presence of inactivating mutations in the SMARCB1 (hSNF5/INI1/BAF47) gene – a tumor suppressor localized in 22q11.2. Up to 30 % of RTs caused by germline mutations of this gene, to date those cases are considered as a manifestation of the rhabdoid tumor predisposition syndrome type 1 (RTPS1). We have analyzed the SMARCB1 mutations by polymerase chain reaction and subsequent Sanger sequencing in 18 patients with RT in different localizations for improving of genetic laboratory diagnostics of the RTPS1, as well as searching of genotype-phenotype correlations in this disease. Three patients had de novo nonsense-mutations c.157C→T (p.R53*), c.669_670del (p.C223*) and c.843G→A (p.W281*), confirming RTPS1, which were associated with RT in the kidney, early age at diagnosis (median 2.6 months) and poor prognosis. Identification of germline SMARCB1 mutations in the patients with RTs is essential to assess the risk of metachronous tumors and for genetic counseling of other family members.

The malignant rhabdoid tumor (RT) is one of the most aggressive childhood neoplasm. RTs are characterized by the presence of inactivating mutations in the SMARCB1 (hSNF5/INI1/BAF47) gene – a tumor suppressor localized in 22q11.2. Up to 30 % of RTs caused by germline mutations of this gene, to date those cases are considered as a manifestation of the rhabdoid tumor predisposition syndrome type 1 (RTPS1). We have analyzed the SMARCB1 mutations by polymerase chain reaction and subsequent Sanger sequencing in 18 patients with RT in different localizations for improving of genetic laboratory diagnostics of the RTPS1, as well as searching of genotype-phenotype correlations in this disease. Three patients had de novo nonsense-mutations c.157C→T (p.R53*), c.669_670del (p.C223*) and c.843G→A (p.W281*), confirming RTPS1, which were associated with RT in the kidney, early age at diagnosis (median 2.6 months) and poor prognosis. Identification of germline SMARCB1 mutations in the patients with RTs is essential to assess the risk of metachronous tumors and for genetic counseling of other family members.

Extrarenal extracranial rhabdoid tumor (EERT) is a rare malignant pediatric tumor characterized by extremely aggressive behavior, rapid metastatic spread, low survival rates, and no targeted therapy. The morphological diagnosis of classical cases of EERT is not difficult and it is based on its characteristic histologic pattern and immunohistochemical findings in a relatively short time, which allows one to immediately initiate therapy. The paper describes two cases of ERRT in the complete absence of classical rhabdoid morphology, as revealed by light microscopy when the material was primarily assessed. The final diagnostic search could establish a diagnosis of EERT in both cases on the basis of immunohistochemical findings.