REVIEW Primary immunodeficiencies and their associated risk of malignancies in children: an overview Samuele Renzi 1,2 & Karin Petra Sabine Langenberg-Ververgaert 3 & Nicolas Waespe 1,4,5 & Salah Ali 1,2 & Jack Bartram 1,6 & Orli Michaeli 1,2 & Julia Upton 2,7 & Michaela Cada 1,2 Received: 12 November 2019 /Revised: 5 February 2020 /Accepted: 24 February 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020 Abstract Primary immunodeficiency disorders represent a heterogeneous spectrum of diseases, predisposing to recurrent infections, allergy, and autoimmunity. While an association between primary immunodeficiency disorders and increased risk of cancer has been suggested since the 1970s, renewed attention has been given to this topic in the last decade, largely in light of the availability of large registries as well as advances in next generation sequencing. In this narrative review, we will give an insight of the primary immunodeficiencies that are commonly responsible for the greater number of cancers in the primary immunodeficiency disorders population. We will describe clinical presentations, underlying genetic lesions (if known), molecular mechanisms for carcinogen- esis, as well as some management considerations. We will also comment on the future directions and challenges related to this topic. Conclusion: The awareness of the association between several primary immunodeficiencies and cancer is crucial to provide the best care for these patients. What is Known: • Patients with primary immunodeficiency have an increased risk of malignancy. The type of malignancy is highly dependent on the specific primary immunodeficiency disorder. What is New: • Survival in patients with primary immunodeficiency disorders has been improving, and conversely also their lifetime risk of malignancy. • International collaboration and multinational registries are needed to improve our knowledge and therapeutic strategies. Samuele Renzi and Karin Petra Sabine Langenberg-Ververgaert contrib- uted equally to this work. Communicated by Peter de Winter * Samuele Renzi samuele.renzi@sickkids.ca Karin Petra Sabine Langenberg-Ververgaert K.P.S.Langenberg@prinsesmaximacentrum.nl Nicolas Waespe nicolas.waespe@ispm.unibe.ch Salah Ali salah.ali@sickkids.ca Jack Bartram Jack.Bartram@gosh.nhs.uk Orli Michaeli Orlimi@gmail.com Julia Upton julia.upton@sickkids.ca Michaela Cada michaela.cada@sickkids.ca 1 Division of Haematology/Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G1X8, Canada 2 University of Toronto, Toronto, Ontario, Canada 3 Department of Translational Research, Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands 4 Swiss Childhood Cancer Registry, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland 5 CANSEARCH Research Laboratory, Department of Pediatrics, Faculty of Medicine, University of Geneva, Geneva, Switzerland 6 Department of Haematology, Great Ormond Street Hospital for Children, London, UK 7 Division of Immunology, The Hospital for Sick Children, Toronto, Ontario, Canada European Journal of Pediatrics https://doi.org/10.1007/s00431-020-03619-2