Oussama Abla, Stephen Peeke, Irem Eldem, Marianne D. van de Wetering, Jennifer Picarsic, Kseniya Petrova-Drus, Robert B. Lorsbach, Jan A M van Laar, Paul Geraeds Kemps, Sylvie Fraitag, Sébastien Héritier, Kristian T. Schafernak, Amy A. Swanson, Eli L. Diamond, Raf Sciot, Karen Ernestus, Mariko Suchi, Nabeel R. Yaseen, Sanda Alexandrescu, Laura Sophia Hiemcke-Jiwa, Matthew Collin, Ingrid S Tam, Sabrina Rossi, Benjamin H. Durham, F J Sherida H Woei-A-Jin, James A. Whitlock, Brianna Empringham, Laura Munoz-Arcos, Falko Fend, Olga Gryniewicz-Kwiatkowska, Majid Madni, Verena Wiegering, Kerry Turner, Dina El Demellawy, Gianpiero Tamburrini, Aditya Raghunathan, Lucas R. Massoth, Carel J. M. van Noesel, Robert Möhle, Cor van den Bos, Jacinthe Bonneau-Lagacherie, Somak Roy, Pasquale M Barbaro, Andreas Beilken, Stefania Gaspari, Jean-François Emile, David D. Grier, Claire Lamaison, Kee Kiat Yeo, Jean Donadieu, Jon M Brandt, Laure Farnault, Friedrich Feuerhake, Marie-Laure Jullie, Uta Flucke, Pancras C.W. Hogendoorn, Astrid G. S. van Halteren, Antje Bornemann, Bryan A. Sisk, Tina Méry, Joanna Weinstein, Ashish R Kumar, Robert M. Verdijk, V. Baykov, Alysa A Poulin, Mandy M Atkinson, VG Potapenko, Vaish Sridhar, Julien Haroche, Zofia Hélias-Rodzewicz, Shipra Garg, Susan Picton, Michael M. Henry, Jackie Allotey, Daniel Leino, Nishant Tiwari, Martin Ebinger, Jason L Hornick, Bożenna Dembowska-Bagińska, Marco Gessi, Dmitry A Evseev, Paediatric Oncology, CCA - Cancer biology and immunology, Pathology, CCA - Cancer Treatment and Quality of Life, Leiden University Medical Center (LUMC), Universiteit Leiden, Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Ambroise Paré [AP-HP], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pontchaillou [Rennes], CHU Marseille, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], CHU Pitié-Salpêtrière [AP-HP], National Institutes of Health, NIH, National Cancer Institute, NCI: P30 CA008748, R37 CA259260-01, Cincinnati Children's Hospital Medical Center, University of Saskatchewan, Leids Universitair Medisch Centrum, LUMC, Institut National Du Cancer, INCa: PRT-K19-143, P.G.K. received a grant from Leiden University Medical Center. A.G.S.v.H. is supported by Stichting 1000 kaarsjes voor Juultje. E.L.D. is supported by the National Institutes of Health/National Cancer Institute Core Grant (P30 CA008748), National Cancer Institute (R37 CA259260-01), the Frame Fund, Applebaum Foundation, and Joy Family West Foundation. J.-F.E. is supported by the Programme de Recherche Translationnelle sur le Cancer from the French National Cancer Institute (PRT-K19-143)., and The authors acknowledge the International Rare Histiocytic Disorders Registry (IRHDR, ClinicalTrial.gov number NCT02285582), which included some patients described in this study. The authors thank Chris Woods (Lead Analyst, Imaging Informatics) and the Research Pathology Laboratory at Cincinnati Children's Hospital Medical Center, John DeCoteau (molecular pathologist) at University of Saskatchewan, Sven van Kempen (senior laboratory technician) and Lennart Kester (clinical molecular biologist in pathology in training) at Princess M?xima Center for Pediatric Oncology, and Demi van Egmond (laboratory technician), Tom van Wezel (clinical molecular biologist in pathology), and Arjen Cleven (pathologist) at Leiden University Medical Center for technical assistance. The authors thank Els Wauters (pulmonologist and respiratory oncologist) at University Hospitals Leuven, Andreas Rosenwald (pathologist) at the Institute of Pathology of the University of W?rzburg, and Bipin Mathew (pathologist) at Leeds Teaching Hospitals for clinical care and/or diagnostics of patients described in this study. The authors thank Les Laboratoires Servier for allowing the use of their medical illustrations (Servier Medical Art, https://smart.servier.com) in the visual abstract. Figure 6 was created with BioRender.com. P.G.K. received a grant from Leiden University Medical Center. A.G.S.v.H. is supported by Stichting 1000 kaarsjes voor Juultje. E.L.D. is supported by the National Institutes of Health/National Cancer Institute Core Grant (P30 CA008748), National Cancer Institute (R37 CA259260-01), the Frame Fund, Applebaum Foundation, and Joy Family West Foundation. J.-F.E. is supported by the Programme de Recherche Translationnelle sur le Cancer from the French National Cancer Institute (PRT-K19-143).