Introduction: Introduction: Renal cell carcinoma (RCC) is a very rare pediatric renal tumor. Robust evidence to guide treatment is lacking and knowledge on targeted therapies and immunotherapy is mainly based on adult studies. Currently, the International Society of Pediatric Oncology–Renal Tumor Study Group (SIOP‐RTSG) 2016 UMBRELLA protocol recommends sunitinib for metastatic or unresectable RCC.Methods: This retrospective study describes the effects of tyrosine kinase inhibitors (TKI), anti‐programmed cell death 1 (PD‐(L)1) monoclonal antibodies, and immunotherapeutic regimens in advanced‐stage and relapsed pediatric RCC.Results: Of the 31 identified patients (0–18 years) with histologically proven RCC, 3/31 presented with TNM stage I/II, 8/31 with TNM stage III, and 20/31 with TNM stage IV at diagnosis. The majority were diagnosed with translocation type RCC (MiT‐RCC) (21/31) and the remaining patients mainly presented with papillary or clear‐cell RCC. Treatment in a neoadjuvant or adjuvant setting, or upon relapse or progression, included mono‐ or combination therapy with a large variety of drugs, illustrating center specific choices in most patients. Sunitinib was often administered as first choice and predominantly resulted in stable disease (53%). Other frequently used drugs included axitinib, cabozantinib, sorafenib, and nivolumab; however, no treatment seemed more promising than sunitinib. Overall, 15/31 patients died of disease, 12/31 are alive with active disease, and only four patients had a complete response. The sample size and heterogeneity of this cohort only allowed descriptive statistical analysis.Conclusion: This study provides an overview of a unique series of clinical and treatment characteristics of pediatric patients with RCC treated with targeted therapies.

The clinical case of a giant congenital germ cell tumor (immature teratoma, 2 grade) of soft tissues of the head and neck with destruction of the large wing of the sphenoid bone, with spreading to the oral cavity with the transition beyond the middle line, infiltration of the tongue, complete obstruction of the nasopharyngeal the child 15 days of life. The article describes Specific features of performing surgical intervention are described taking into account the prevalence of the tumor process. The discussed issues of teratoma classification, methods of diagnosis, provision of modern principles of therapy for patients with this disease.

Cancer predisposition syndromes (CPSs) account for 8.5–18% of all childhood cancer cases. Most of them are inherited in an autosomal dominant pattern; consequently, there is a 50% risk of transmission to offspring. Early detection of CPSs is crucial for choosing patient treatment strategies and for counseling in the family. This study enrolled 886 pediatric patients with hematologic and solid neoplasms from prospective and retrospective cohorts (2018–2025). Clinical exome or multigene panel sequencing was used to analyze blood DNA. Overall, 186 pathogenic/likely pathogenic (PLP) variants in cancer-associated genes were identified in 176/886 (20%) of patients, and the most frequently mutated were the NF1 (n = 35) and TP53 (n = 18) genes. Among the 186 PLP variants, 126/886 (14.2%) were causative for pediatric neoplasms, while 56/886 (6.3%) were heterozygous mutations associated with adult-onset CPSs affecting DNA repair. The highest total mutation rate was revealed in retinoblastoma (80%), peripheral nerve sheath tumors (60%), and pheochromocytoma/paraganglioma (47%), while the lowest rate was found in hematologic malignancies (4.6%) and neuroblastoma (12%). The wide range and high frequency of deleterious variants in pediatric patients, especially in those with solid tumors, highlights the importance of multigene panel sequencing for the accurate determination of CPSs.

Mosaic RASopathies are rare conditions caused by postzygotic mutations in RAS/MAPK signaling pathway genes arising during embryonic development. They are mainly characterized by a combination of epidermal nevi with extra-cutaneous manifestations. Choosing between different entities can be challenging because of their substantial clinical and genetic overlap. Our aim was to demonstrate the importance of genetic background in accurate diagnosis and further prognostic assessment of disease progression by analyzing genotype–phenotype correlations within this clinical group. The study enrolled 18 patients (10 males, 8 females) aged from 1 month to 21 years with congenital nevi of craniofacial localization and variable extracutaneous abnormalities. DNA isolated from peripheral blood lymphocytes and affected tissues (nevus, tumor) was analyzed using a targeted next-generation sequencing (NGS) panel covering RAS/MAPK pathway genes, followed by Sanger sequencing. Eight patients were diagnosed with Schimmelpenning–Feuerstein–Mims syndrome caused by postzygotic mutations in the HRAS (n=4) or KRAS (n=4) genes. Seven patients were clinically diagnosed with phacomatosis pigmentokeratotica, and mosaic mutations were identified in the HRAS (n=4), KRAS (n=2), or BRAF (n=1) genes. Two patients with similar phenotypes carried somatic mutations in the PIK3CA and FGFR2 genes, respectively, and in one case no mutation was detected in the affected skin. We compared the spectrum of extracutaneous anomalies depending on the mutation in a specific gene by combining our data with data from other clinical cases of mosaic RASopathies described in the literature. In summary, 53 cases with HRAS postzygotic mutations and 41 cases with KRAS mutations were involved in the analysis of genotype–phenotype correlations. Hypophosphatemic rickets and malignant tumors were associated with mutations in the HRAS gene, while ophthalmological, neurological, cardiovascular, and renal disorders were more common in KRAS-mutant patients. Thus, genetic testing of affected tissue is essential for accurate diagnosis of these mosaic disorders. Taking into account clinical manifestations and the identified genotype–phenotype correlations may further assist in prognosis and patient management.

PIK3CA-Related Overgrowth Spectrum (PROS) refers to rare syndromes, which are characterized by malformations and excessive tissue growth and caused by somatic mutations in the PIK3CA gene occurring during embryogenesis. This article discusses the pathogenesis, clinical picture, diagnosis and treatment of these syndromes.Some of the illustrations used in this article are copied from other resources, the rights of the authors are respected and not violated. The appropriate permissions from the journals have been obtained.

B-cell lymphoma is unclassifiable, with signs intermediate between diffuse large-cell B-cell lymphoma and Hodgkin's lymphoma (LH), is a rare aggressive lymphoma with an uncertain prognosis that has specific morphological and immunophenotypic characteristics characteristic of both diffuse B-large-cell lymphoma and Hodgkin's lymphoma. In this article, the comparative characteristics of NIVCL and various variants of large cell B-cell lymphomas are presented, as well as a description of the clinical case of NVCL in a child of 3 years. Patient's parents agreed to use personal dats and photos in research and publications.