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.