Cutaneous melanoma in children and adolescents is an extremely rare malignancy that poses significant diagnostic and therapeutic challenges due to limited clinical evidence and a lack of specific treatment guidelines. This document, developed by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT), updates and systematizes previous recommendations by integrating recent advances. It particularly emphasizes the need for accurate diagnosis through expert pathology review, multidisciplinary discussion, appropriate surgical management, and the important role of systemic treatments now available, also in pediatric age. A strengthened collaboration with adult oncologists is fundamental to optimizing strategies and improving outcomes.

Primary lung carcinomas and bronchial carcinoid tumors (BC) are very rare malignancies in childhood. While typical BC and mucoepidermoid carcinomas are mostly low-grade, localized tumors with a more favorable prognosis than in adults, necessitating avoidance of overtreatment, adenocarcinomas of the lung are often diagnosed at advanced disease stages with low survival rates. This paper presents consensus recommendations on the diagnosis and treatment of pediatric patients with primary lung carcinomas and BC, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) in collaboration with the European Reference Network for Pediatric Oncology (ERN PaedCan).

Pediatric very rare tumors (VRTs) are a highly heterogeneous group of neoplasms defined by an annual incidence of <2 cases per million children under 18 years. Their rarity precludes prospective clinical trials, resulting in limited evidence-based guidelines and largely individualized treatment approaches. Olfactory neuroblastoma (ON) is an exceptionally rare pediatric VRT arising from the olfactory neuroepithelium, typically affecting adults. In children, ON is locally aggressive and may present with regional or distant metastases. Prognosis depends on stage, histology, and multimodal treatment. Owing to the absence of pediatric-specific guidelines, this project aims to develop internationally harmonized consensus recommendations for diagnosis and management.

OBJECTIVE:To map real-world management of paediatric differentiated thyroid carcinoma (DTC) across Europe and identify targets for harmonization. DESIGN:Cross-sectional, web-based survey of centres providing paediatric DTC care. SETTING & PARTICIPANTS:One consolidated response per centre was requested from a clinician overseeing paediatric DTC. The instrument covered centre profile/multidisciplinary tumour (MDT) board organization; staging and guideline use; risk stratification and dynamic response; diagnostics; surgery/lymph node management; radioactive iodine therapy (RAIT) policy and activity selection; and thyroid-stimulating hormone targets, follow-up, shared-care/transition. Analyses were descriptive at centre level. RESULTS:Forty-two centres from 18 countries participated in the survey. Response denominators varied by item. Among responding centres, ≈75% were university or academic hospitals, ≈70% used a paediatric age cut-off of ≤18 years, and ≈60% reported having a dedicated MDT board. Staging and guideline use were heterogeneous: centres most often reported mixed or centre-specific guidance, followed by the American Thyroid Association (ATA) 2015 guideline, national guidelines, and the European Thyroid Association (ETA) 2022 guideline. Dynamic response-to-therapy categories were commonly used. For unilateral presumed low-risk disease, hemithyroidectomy was the usual initial surgery in approximately two-thirds to three-quarters of centres, whereas total thyroidectomy was less common. For low-risk patients, RAIT policy were split between de-escalation and risk-adapted use. When administered, RAIT activity was determined using weight-based, dosimetric, or fixed empirical approaches. Country-level patterns suggested clustering around ETA-leaning, ATA-leaning, and national guideline frameworks. CONCLUSIONS:Across Europe, centres broadly endorse risk-adapted care but diverge at key decision nodes-extent of surgery, formal risk framework, and RAIT in low-risk disease-reflecting guidance plurality and organizational context. Leveraging existing infrastructures offers pragmatic avenues to reduce unwarranted variation while generating paediatric-specific evidence to refine recommendations.

Abstract Background Neuroepithelial tumors (NEpT) harboring PATZ1 gene fusions represent a rare and biologically heterogeneous group of central nervous system neoplasms characterized by marked histopathological variability and incompletely defined clinical behavior. Historically, tumor classification relied predominantly on histopathological assessment. The introduction of next-generation sequencing (NGS) has significantly improved tumor stratification by identifying recurrent molecular alterations, enabling more precise diagnosis, prognostication, and potential therapeutic targeting. PATZ1 fusion tumors are most frequently supratentorial and are generally associated with favorable outcomes, although clinical experience remains limited due to their rarity. Methods We present a case of a pediatric patient with tumor reclassification following molecular diagnostics and provide a review of the current literature on NEpT with PATZ1 gene fusions, including clinical, histopathological, and molecular characteristics. Results A 16-year-old female was initially diagnosed with anaplastic ganglioglioma (WHO grade III) located in the right frontal lobe. Following surgical resection, she received multimodal oncological treatment consisting of chemotherapy according to a national protocol (lomustine and temozolomide) and adjuvant radiotherapy to the tumor bed (59.4 Gy in 33 fractions). Clinical evaluation revealed features consistent with neurofibromatosis type 1 based on established diagnostic criteria. Comprehensive molecular testing results became available after completion of oncological treatment and identified an EWSR1::PATZ1 gene fusion, leading to final reclassification as neuroepithelial tumor with PATZ1 fusion. Conclusions This case highlights the critical role of molecular diagnostics in the accurate classification of rare pediatric CNS tumors. Identification of PATZ1 gene fusions may significantly impact diagnostic interpretation, prognostic assessment, and future therapeutic decision-making. Increasing integration of molecular profiling into routine clinical practice is essential to improve diagnostic precision and optimize individualized patient management in rare neuroepithelial tumors.

Serratia species are Gram-negative pathogens responsible for a wide range of nosocomial infections. This multicenter nationwide retrospective study aimed to describe the epidemiology, clinical characteristics, antimicrobial susceptibility, and outcomes of Serratia infections in pediatric oncology patients and hematopoietic stem cell transplantation (HSCT) recipients in Poland between 2012 and 2023. A total of 36 Serratia infection episodes were identified in patients under 20 years of age, including 30 cases (83.3%) in the oncological (OHD) group and six (16.7%) among HSCT recipients. The median age was 4.30 years. The most common underlying diseases were acute lymphoblastic leukemia (36.1%) and central nervous system tumors (16.7%). Bloodstream infections predominated in OHD patients (33.3%), whereas urinary tract infections were most frequent in HSCT recipients (83.3%). S. marcescens was the most commonly isolated species. More than half of isolates (53.3%) showed antimicrobial resistance, with extended-spectrum β-lactamase (ESBL)-producing strains in 26.7% and AmpC β-lactamase-producing strains in 13.3%. Multidrug resistance occurred in 30%. Treatment most often included amikacin, piperacillin/tazobactam, and carbapenems. Five deaths occurred in the OHD group and one in the HSCT group, none directly related to Serratia infection. Although uncommon, Serratia infections remain clinically relevant due to their high antimicrobial resistance, underscoring the need for antimicrobial stewardship.

Pediatric gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are extremely rare and clinically heterogeneous. Management has largely been extrapolated from adult practice. This European Standard Clinical Practice Guideline (ESCP), developed by the EXPeRT network in collaboration with adult NEN experts, provides (adult) evidence-informed and consensus-driven recommendations. Using a literature review and GRADE methodology, we address clinical evaluation, imaging pathology, genetics, surgical and systemic therapies, and long-term surveillance. Surgical resection is the cornerstone in localized disease. Systemic treatments are largely adapted from adult data, including somatostatin analogues, radiopharmaceutical therapy, and targeted agents. Multidisciplinary care, genetic counseling, and lifelong follow-up are essential to optimize outcomes.

Enterococcal bacteremia (EB) is a relevant healthcare-associated complication in children receiving anticancer therapy or undergoing hematopoietic stem cell transplantation (HSCT), yet nationwide pediatric data remain scarce. To assess the incidence, microbiology, antimicrobial resistance, timing, and outcomes of EB in pediatric oncology and HSCT patients in Poland. We performed a retrospective multicenter nationwide survey across 17 pediatric hematology-oncology and transplant centers in Poland between 2014 and 2021. Children under 19 years of age treated with chemotherapy for malignancy or undergoing HSCT were included. Only the first EB episode per patient was analyzed. Species identification and antimicrobial susceptibility testing were performed locally and interpreted according to EUCAST criteria. EB was identified in 94/7300 (1.28

BACKGROUND/AIM:Following approval from the European Medicines Agency, selumetinib has emerged as a targeted therapy for pediatric patients aged ≥3 years with inoperable, symptomatic NF1-related plexiform neurofibromas (PNs). In Poland, this treatment has been reimbursed since January 2024 under a national therapeutic program funded by the National Health Service. Nevertheless, the efficacy and safety of selumetinib in subgroups within the pediatric population remain unclear. This study aimed to evaluate the efficacy and safety of selumetinib treatment in adolescents (≥16 years old) compared with younger children with NF1-related PNs. PATIENTS AND METHODS:A total of 111 patients were included in the program over a two-year period. Patients were divided into two groups according to age: adolescents (≥16 years of age) and children (<16 years of age). Demographic characteristics, PN location, treatment efficacy and adverse effects were analyzed and compared between the two groups. RESULTS:Response rates at the first and second evaluation time point were similar between the groups. However, at the third time point, the response rate was significantly higher in children vs. adolescents (56.0% vs. 18.2%; odds ratio=5.7; 95% confidence interval=1.02-32; p=0.035). Skin-related adverse effects were the most common in both groups, and only isolated cases required selumetinib dose reduction. CONCLUSION:Early response to selumetinib therapy is achieved faster in children than in adolescents. Selumetinib is generally well tolerated in both age groups.

As part of the European Cooperative Study Group for Paediatric Rare Tumours initiative, we developed standard clinical practice guidelines for ovarian sex cord stromal tumors, based on comprehensive national and international cohort analyses, literature review, and a final expert consensus conference. Complete tumor resection is the cornerstone of treatment, with meticulous attention to preventing tumor spillage. Risk stratification of adjuvant chemotherapy decisions incorporates tumor stage and critical parameters, including histological differentiation and mitotic rate. Optimal patient management requires treatment within cooperative networks providing centralized histopathological review and comprehensive genetic testing, multidisciplinary tumor board evaluation, and prospective registry enrollment to advance knowledge for these exceptionally rare malignancies.

Solid pseudopapillary neoplasm of the pancreas (SPN) is a rare low-grade malignant exocrine pancreatic tumor, mostly discovered during the second decade of life in females, with a very good prognosis, provided microscopically complete surgical excision is achieved. This manuscript presents harmonized recommendations for the diagnosis, treatment, and long-term management of pediatric SPN established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) in collaboration with the European Reference Network for Pediatric Oncology (ERN PaedCan) after careful review of the literature and experts' opinions refined by selected external reviewers.

IntroductionMitogen-activated protein kinase pathway inhibitors (MAPKi) are an important therapeutic option for patients with unresectable, symptomatic or progressive pediatric low-grade gliomas (pLGGs). Despite high disease control rates during treatment, tumor regrowth following MAPKi discontinuation has been reported. This phenomenon, termed rebound regrowth (RR), appears biologically and clinically distinct from classic off-therapy progression or acquired resistance to MAPKi. However, the incidence, timing, and predictors of RR remain poorly defined. This systematic review synthesizes evidence on RR following MAPKi discontinuation in pLGG.MethodsA systematic literature review was conducted according to PRISMA 2020 guidelines. Eligible studies included clinical trials, cohort studies, and case reports/series, involving patients aged 0–25 years with NF1-associated or sporadic pLGG, who experienced RR after MAPKi dose reduction or discontinuation. RR was defined as radiological progression within 6 months after treatment cessation. Cohort-level and individual patient-level data were extracted.ResultsTwenty publications met inclusion criteria. Among ten studies involving ≥10 patients, RR was documented in at least 23 of 131 evaluable individuals. Additionally, individual-level data of 21 patients were analyzed. Most RR events occurred early after MAPKi cessation, were detected radiologically and clinically asymptomatic. RR was reported most frequently in tumors harboring the BRAFV600E variant. Most patients responded to MAPKi rechallenge, suggesting preserved drug sensitivity.ConclusionRR is a reproducible and clinically relevant phenomenon following MAPKi discontinuation in pLGG. Standardized definitions, structured post-discontinuation surveillance, and prospective evaluation of treatment duration and dose-tapering strategies are needed to optimize MAPKi discontinuation and long-term disease management in patients with pLGG.

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare neoplasm primarily affecting the craniofacial skeleton in infants. Management can be challenging in unresectable, multiply recurrent, or metastatic cases. Diagnosis requires local imaging assessment with magnetic resonance imaging (MRI) and computed tomography (CT) and histopathological confirmation. Surgery is the mainstay of treatment, achieving 80%-90% cure rates. Chemotherapy may be considered for advanced disease, whereas radiotherapy is generally avoided in young children. These recommendations were developed within European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) and European Reference Network Paediatric Cancer (ERN PaedCan) using a structured consensus process based on focused literature review and expert agreement. Multidisciplinary, risk-adapted management, and structured follow-up are essential.

BACKGROUND:The increasing number of patients and better outcomes indicate the need for studying long-term time-trends of childhood cancer incidence in Poland. The aim of the study was to analyse childhood cancer incidence by sex, age and site group in Poland over 25 years between 1996 and 2020. METHODS:Data for the analysis of childhood cancer incidence were obtained from the Polish Childhood Cancer Clinical Database. The analysis of childhood cancer incidence was carried out based on the age standardized incidence rate (ASR). The ASR coefficient values were determined for five-year periods: 1996-2000, 2001-2005, 2006-2010, 2010-2015, 2016-2020. RESULTS:In the years 1996-2020, a total of 26863 new cases of cancer were registered among children and adolescents up to 17 years of age of which 21904 cases were recorded in children up to the age of 14. The most frequently diagnosed cancers were leukaemia (27·5 %), CNS tumours (19·9 %), and lymphomas (13·75 %). In most groups of cancers the disease was diagnosed more frequently in boys than in girls. The standardized incidence rate of cancers (ASR) for children up to 14 years of age in the corresponding periods was: 128·7, 148·0, 148·8, 158·7, and 167·9. INTERPRETATION:In Poland, despite fluctuations between subsequent years in the period 1996-2020, the number of new cancer cases among children up to 17 years of age was at a similar level. At the same time, the number of children aged 0-17 years in Poland in that period decreased from 10'531'160-7'672'644. Overall, we can observe an increase in the incidence of childhood cancer in Poland between 1996 and 2020 based on ASR by 23·3 %.

BACKGROUND:The prognostic role of systemic inflammation markers in pediatric soft-tissue sarcomas (STS) remains unclear. PROCEDURE:This multicenter study investigated the prognostic significance of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), C-reactive protein (CRP), and lactate dehydrogenase (LDH) in 213 pediatric patients diagnosed with STS in years 2002-2023. Patients were categorized into groups: rhabdomyosarcoma (RMS, n = 126), RMS-like (n = 57), and non-RMS (n = 30). Clinicopathological data, including complete blood counts (CBCs), CRP, and LDH levels, were collected and age-adjusted. Optimal cutoffs for predicting outcomes were determined, and the prognostic value of the inflammatory markers was assessed using Kaplan-Meier survival analysis, log-rank tests, and Cox regression models. RESULTS:No significant differences in NLR, PLR, LMR, and CRP levels were observed between RMS, RMS-like, and non-RMS groups. However, LDH levels were significantly elevated in the RMS group compared with the RMS-like group. A consistent trend toward higher NLR, PLR, and CRP values was noted in patients with more advanced disease stages. Multivariate Cox regression analysis across the entire cohort identified CRP (HR 3.39, 95% CI 1.55-7.4, p = 0.002), NLR (HR 2.06, 95% CI 1.07-3.99, p = 0.03), and disease stage (HR = 0.49, 95% CI 0.26-0.95, p = 0.035) as independent prognostic factors for survival. Subgroup analyses revealed that the prognostic impact of these markers varied across histopathological subtypes, with limited utility in the RMS-like group. CONCLUSIONS:These findings highlight the prognostic value of systemic inflammatory markers in pediatric STS, emphasizing their potential to refine risk assessment and guide treatment.

BACKGROUND:Adrenal (formerly termed pheochromocytomas) and extra-adrenal paragangliomas (PGLs) in children and adolescents are rare neuroendocrine tumors characterized by unique biological behavior, a strong hereditary component, and significant risk of recurrence and metastatic progression. Their management requires specialized, multidisciplinary care. OBJECTIVE:This guidance provides harmonized, evidence-graded recommendations for the diagnosis, treatment, and follow-up of pediatric PGL, developed by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) as part of the European Standard Clinical Practice (ESCP) initiative. METHODS:Recommendations were formulated through structured consensus by a multidisciplinary panel of experts in pediatric oncology, endocrinology, surgery, nuclear medicine, genetics, and pathology, based on literature review, existing international guidelines, and integration of external adviser feedback. Levels of evidence and grades of recommendation follow a simplified GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system. RECOMMENDATIONS:Diagnosis should be based on plasma-free metanephrine and normetanephrine as first-line test, complemented by appropriate anatomical and functional imaging guided by biochemical phenotype and genotype. Germline genetic testing is recommended. Tumor resection remains the mainstay of curative treatment, with cortical-sparing adrenalectomy advised in bilateral hereditary cases (except SDHB). Management of metastatic disease should be individualized, incorporating radionuclide therapy, systemic treatments, focal therapies, and palliative care as appropriate. Lifelong surveillance is essential, tailored to genotype and disease characteristics. CONCLUSION:This European clinical guidance offers practical recommendations to support multidisciplinary management of pediatric PGL within European healthcare systems, complementing existing international consensus statements and supporting harmonization of care.

BACKGROUND:Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular tumor, typically affecting infants. Kasabach-Merritt phenomenon (KMP) is a frequent and serious complication of KHE. The study aimed to analyze clinical manifestations, treatment strategies, and outcomes in children with KHE treated in Poland between 2007 and 2024. PROCEDURE:Clinical data of 42 children with KHE treated in 15 Polish pediatric hematology/oncology and surgery centers between 2007 and 2024 were analyzed retrospectively. RESULTS:KMP was present in 27/42 children (64.3%). The median age at diagnosis in children with and without KMP was 2.5 and 8 months, respectively. A male predilection was observed (61.9%), particularly in patients without KMP (13/15, 86.7%). Diagnosis of KHE required a tumor biopsy in 20 patients, including 14/15 (93.3%) of patients without KMP. Treatment strategies varied significantly between patients, institutions, and treatment periods. Systemic treatment was administered in 39 (92.9%) children, with predominating role of chemotherapy and glucocorticoids in the first period (2007-2013), and with gradually increasing importance of sirolimus in the years 2014-2018 and 2019-2024. Three children were successfully treated with surgery only. Salvage therapies ultimately controlled KHE progression/relapse in 14/17 (82.4%) patients. Only one child with metastatic, treatment-resistant cardiac KHE died of disease progression. CONCLUSIONS:Management of childhood KHE is challenging since no unified treatment recommendations exist. To optimize KHE therapy in Poland, the Section of Childhood Vascular Anomalies was established in June 2021 as part of the Polish Society of Pediatric Oncology and Hematology. Its aim is to standardize therapeutic guidelines and provide education on vascular anomalies in Poland.

IntroductionVascular anomalies (VAs), comprising vascular tumors and malformations, are commonly diagnosed based solely on clinical evaluation and imaging. Soft-tissue sarcomas (STSs) may mimic VAs clinically and radiologically, leading to misdiagnosis, delayed treatment, and suboptimal outcomes. In this systematic review, we aimed to summarize patients with a pathological diagnosis of STSs who were initially misdiagnosed with benign VAs, highlighting diagnostic pitfalls.Materials and methodsIn this systematic review (PROSPERO ID: CRD42024615285), we followed the PRISMA 2020 guidelines. The inclusion criteria comprised patients with histologically confirmed STSs who had been initially misdiagnosed as benign VAs based on clinical or radiological features. Literature from five databases was reviewed without language or date restrictions. One additional case of alveolar soft-part sarcoma initially misdiagnosed and mistreated as an arteriovenous malformation from the authors’ institution was added to the analysis.ResultsThe systematic search yielded a total of 96 patients with STS initially misdiagnosed as benign VAs (95 from 77 publications and one from our own case). The median age at presentation was 6 months (range: newborn–88 years). The most frequent symptom was a swelling or mass (75%). In most cases, the misdiagnosis was both clinical and radiological. The median diagnostic delay was 5.5 months. Fifty-nine (61.5%) patients received treatment for the misdiagnosed benign VA, including local interventions (51.0%) and systemic therapies (17.7%). The most commonly misdiagnosed STS subtypes were infantile fibrosarcoma, alveolar soft-part sarcoma, rhabdomyosarcoma, dermatofibrosarcoma protuberans, angiosarcoma, and Ewing sarcoma.ConclusionSeveral STS subtypes may mimic benign VAs clinically and radiologically. The misuse of outdated terminology and limited awareness among clinicians contribute to diagnostic delays. To avoid misdiagnoses, the care for patients with benign VAs should be provided by specialists familiar with the classification and natural history of these lesions. In patients diagnosed with benign VAs based on clinical or imaging features only, all findings should clearly support the diagnosis. Any ambiguity warrants prompt referral to a tertiary center. A biopsy should be considered in doubtful or atypical cases.

Background/Objectives: This study involved an analysis of clinical data, histological types, genetic predisposition, treatment and outcomes in PPB in children. Patients and methods: We conducted a retrospective review of children treated for PPB at Polish pediatric oncology centers between 2011 and 2024. Results: A total of fifteen children (seven boys, eight girls; median age of 39 months; range: 27-64 months) were included. Type II solid/cystic PPB and type III solid PPB were diagnosed in six and eight children, respectively (one not known). Overall, 93% of patients were diagnosed at up to 4 years of age. Metastatic disease at diagnosis was confirmed in three (20%) patients, localized in bones, bone marrow and lymph nodes. Diagnosis was confirmed via central pathology review in 11 patients (73%). DICER1 pathogenic variants were identified in eight patients. All children presented with respiratory symptoms. The tumor dimensions were >10 cm (n = 7), 5-10 cm (n = 5) and <5 cm (n = 2). No bilateral lung involvement was observed. Tumor biopsy was performed in six children (40%), with subsequent resection (R0) in five patients. Primary resection (R0) was achieved in three patients (20%) with type II (n = 1) or type III (n = 2). In the other six patients, non-radical resection was performed: R1 in four (27%) children (with a tumor rupture in one patient) and R2 (subtotal resection) in two children (13%). All patients received postoperative chemotherapy. Maintenance chemotherapy was given to two patients. No patient received radiotherapy as first-line treatment. Progressive disease occurred in two patients in the CNS and lungs. Relapsed disease appeared in three patients, all with CNS involvement. Conclusions: PPB is a rare, malignant tumor of early childhood with an uncertain prognosis. Despite multimodal treatment, patients remain at risk of progression or CNS relapse. Complete surgical resection remains a key prognostic factor.