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Summary: Background: Genomic characterisation has led to an improved understanding of adult melanoma. However, the aetiology of melanoma in children is still unclear and identifying the correct diagnosis and therapeutic strategies remains challenging. Methods: Exome sequencing of matched tumour-normal pairs from 26 paediatric patients was performed to study the mutational spectrum of melanomas. The cohort was grouped into different categories: spitzoid melanoma (SM), conventional melanoma (CM), and other melanomas (OT). Findings: In all patients with CM (n = 10) germline variants associated with melanoma were found in low to moderate melanoma risk genes: in 8 patients MC1R variants, in 2 patients variants in MITF, PTEN and BRCA2. Somatic BRAF mutations were detected in 60% of CMs, homozygous deletions of CDKN2A in 20%, TERTp mutations in 30%. In the SM group (n = 12), 5 patients carried at least one MC1R variant; somatic BRAF mutations were detected in 8.3%, fusions in 25% of the cases. No SM showed a homozygous CDKN2A deletion nor a TERTp mutation. In 81.8% of the CM/SM cases the UV damage signatures SBS7 and/or DBS1 were detected. The patient with melanoma arising in giant congenital nevus (CNM) demonstrated the characteristic NRAS Q61K mutation. Interpretation: UV-radiation and MC1R germline variants are risk factors in the development of conventional and spitzoid paediatric melanomas. Paediatric CMs share genomic similarities with adult CMs while the SMs differ genetically from the CM group. Consistent genetic characterization of all paediatric melanomas will potentially lead to better subtype differentiation, treatment, and prevention in the future. Funding: Found in Acknowledgement.

This case describes a 9-year-old male who presented to general surgical clinic with a 3-year history of persistent natal cleft swelling, previously unsuccessfully treated as a pilonidal abscess in the community with multiple courses of antibiotics. In clinic, a 50 × 30-mm soft tissue swelling was found in the natal cleft and a clinical diagnosis of a pilonidal cyst was made. A cream-coloured solid mass measuring 50 × 35 × 30 mm was subsequently excised under general anaesthetic, with specialist histology and immunostaining confirming an unexpected diagnosis of a subcutaneous extraspinal myxopapillary ependymoma, a tumour usually found in the neuraxis. Given the atypical anatomical site of the tumour, the case presented a unique management challenge. Ultimately, the patient underwent a re-operation after specialist multi-disciplinary discussion and is currently disease free at 18 months post-surgery. The authors wish to contribute their experiences of managing this rare extraspinal ependymoma to the few existing reports in the literature. [ABSTRACT FROM AUTHOR]

Background: Genomic characterisation has led to an improved understanding of adult melanoma. However, the aetiology of melanoma in children is still unclear and identifying the correct diagnosis and therapeutic strategies remains challenging., Methods: Exome sequencing of matched tumour-normal pairs from 26 paediatric patients was performed to study the mutational spectrum of melanomas. The cohort was grouped into different categories: spitzoid melanoma (SM), conventional melanoma (CM), and other melanomas (OT)., Findings: In all patients with CM (n = 10) germline variants associated with melanoma were found in low to moderate melanoma risk genes: in 8 patients MC1R variants, in 2 patients variants in MITF, PTEN and BRCA2. Somatic BRAF mutations were detected in 60% of CMs, homozygous deletions of CDKN2A in 20%, TERTp mutations in 30%. In the SM group (n = 12), 5 patients carried at least one MC1R variant; somatic BRAF mutations were detected in 8.3%, fusions in 25% of the cases. No SM showed a homozygous CDKN2A deletion nor a TERTp mutation. In 81.8% of the CM/SM cases the UV damage signatures SBS7 and/or DBS1 were detected. The patient with melanoma arising in giant congenital nevus (CNM) demonstrated the characteristic NRAS Q61K mutation., Interpretation: UV-radiation and MC1R germline variants are risk factors in the development of conventional and spitzoid paediatric melanomas. Paediatric CMs share genomic similarities with adult CMs while the SMs differ genetically from the CM group. Consistent genetic characterization of all paediatric melanomas will potentially lead to better subtype differentiation, treatment, and prevention in the future., Funding: Found in Acknowledgement., Competing Interests: Declaration of interests Outside of submitted work: IBB: Institutional grant from Biontech. O.R. and C.Sc.: grants: Deutsche Forschungsgemeinschaft (DFG), Deutsche Krebshilfe (DKH), European Union (EU), grants to the institution from Illumina and BMS Stiftung Immunonkologie. U.L.S: grants: MSD; support for attending meeting and/or travel: Sun Pharma, Pierre Fabre; participation on a Data Safety Monitoring Board or Advisory Board: MSD, Novartis, Sun Pharma, Almirall, Roche, Sanofi; ADO board member. T.E.: Consulting fees: Bristol-Myers Squibb, MSD, Novartis, Almirall, Hermal, CureVac, Immunocore, Sanofi. S.O.: grants: DFG, Deutsche Luft und Raumfahrt Gesellschaft (DLR), European Union (EU), Bundesministerium für Bildung und Forschung (BMBF), Deutsche Krebshilfe, Bundesministerium für Arbeit und Soziales (BMSA); presentation: Illumina; support for attending meeting and/or travel: Oxford Nanopore Technologies. S.F.: grants: NeraCare, Skyline Dx, Biontech,; speakers honoraria: Kyowa Kirin, Recordati, Takeda Pharmaceuticals., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background Thymomas and thymic carcinomas belong to a group of thymic epithelial tumours arising from the anterior mediastinum and, are extremely rare in children in which no therapeutic guidelines have been established. The aim is to describe paediatric characteristics of these tumours and give some therapeutic indications. Methods Retrospective analysis of clinical data and therapeutic characteristics of paediatric patients less than 18 years with thymic tumours treated between 2000 and 2012 registered in the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) database of the cooperating national rare paediatric tumour working groups from France, Italy, Germany and Poland. Results Sixteen children with thymoma, median age 11 years and 20 patients with thymic carcinoma, median age 14 years were enrolled into study. At diagnosis complete primary resection was possible in 11 patients with thymoma and one with thymic carcinoma; resection with microscopic residue was performed in three cases and incomplete resection with macroscopic residue in four patients. Chemotherapy with various regimens was administered to 22 children; 17 of them as neoadjuvant chemotherapy. Eight patients with thymic carcinoma received additional radiotherapy. Seventeen children died (15 thymic carcinoma, two thymoma). Five-year overall survival for patients with thymic carcinoma is 21.0 ± 10.0%. Conclusions This study confirms the possibility to perform European retrospective analysis even in very rare paediatric tumours. Thymic carcinoma is associated with paediatric patients to give a very poor prognosis independently despite multimodal management. Multidisciplinary, multicenter approach and collaboration with adults’ physician are necessary in order to propose homogenous guidelines. [ABSTRACT FROM AUTHOR]

Abstract: Background: Pancreatoblastoma is a very rare malignant tumour typically occurring in the early years of life. Due to its rarity, standardised diagnostic and therapeutic guidelines are not available for pancreatoblastoma. Methods: The newborn cooperative group denominated EXPeRT – European cooperative study group for paediatric rare tumours – combined in a joint analysis of all cases registered between 2000 and 2009 by the national groups of Italy, France, United Kingdom, Poland and Germany. Results: Twenty patients <18years old (median age 4years) were analysed: nine had distant metastases at diagnosis. Seventeen patients had tumour resection, at initial or delayed surgery. Eighteen received chemotherapy (response rate 73%), seven received radiotherapy. For the whole series, 5-year event-free survival and overall survival were 58.8% and 79.4%, respectively. Outcome did not correlate with tumour site and size, but was strongly influenced by the feasibility of tumour complete resection. Conclusions: This international study confirms the rarity of the disease, the critical role of surgical resection both as therapy and as a prognostic variable, and the potential efficacy of chemotherapy. The adoption of an intensive multidisciplinary approach is required, as well as the referral to highly experienced centres. Further international cooperation is needed to collect larger series and stimulate biological studies to improve our understanding of the biology and the natural history of PBL. [Copyright &y& Elsevier]

Abstract: A national cooperative project on rare paediatric tumours (the TREP project) was launched in 2000 in Italy, with a view to improving the clinical management and the basic research on these ‘orphan’ tumours, defined as those childhood solid malignancies characterised by an annual incidence <2/million and not considered in other clinical trials. This paper describes the process that the group developed and the problems it had to face, and aims to stimulate a debate on the rationale, scientific relevance and feasibility of running scientific research programs on rare childhood neoplasms. In the first phase of its activity, the project developed diagnostic and therapeutic recommendations for each rare tumour and established a collaborative network between ‘experts’ dedicated to each histotype and other specialists (i.e. adult oncologists, surgeons) involved in the management of these tumours. From 2000 to 2005, 297 patients have been registered from 35 Italian centres. This experience demonstrates the feasibility of a national multidisciplinary cooperation on rare paediatric malignancies and suggests that international studies could be realised. [Copyright &y& Elsevier]