Malignancies in the context of Inborn errors of immunity: an immunologist's view.

[INTRODUCTION] Inborn errors of immunity (IEIs), also known as primary immunodeficiency diseases (PIDs) since 2017 Inborn Errors of Immunity Committee classification, comprise a heterogeneous group of genetic disorders resulting in impaired immune development and function. Malignancy is a major challenge in IEIs, particularly in those with defects in DNA repair, tumor suppression, immune surveillance, or chronic inflammatory control, highlighting the close interplay between immune dysfunction and oncogenesis.

[AREAS COVERED] Hematologic malignancies, especially non-Hodgkin lymphomas, predominate in IEIs, though epithelial tumors also occur and present at younger ages with poorer outcomes. Both intrinsic factors - such as genomic instability and defective lymphocyte maturation - and extrinsic factors, including chronic inflammation, oncogenic viral infections, and iatrogenic exposures, contribute to cancer development. Subtypes such as ataxia-telangiectasia, Nijmegen breakage syndrome, Wiskott - Aldrich syndrome, and common variable immunodeficiency show particularly high malignancy rates. Defects in specific immune pathways, may predispose to organ-specific or virus-driven cancers.

[EXPERT OPINION] Although hematopoietic stem cell transplantation remains curative for selective IEIs, post-transplant malignancy risk persists. A deeper understanding of shared molecular pathways linking immunodeficiency and cancer is essential to refine early diagnosis, risk stratification, and targeted management in this vulnerable population.