{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:12:24Z","timestamp":1790244744569,"version":"4.1.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Inborn Errors of Immunity (IEI) are associated with an increased risk of malignancy due to impaired immune surveillance, genetic instability and chronic inflammation, However, comprehensive epidemiological data from large national cohorts remain limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a multicenter, retrospective-prospective observational study involving 4,540 pediatric and adult patients with IEI, followed across 30 Italian referral centers, with the aim of evaluating those who developed cancer. Clinical, immunological, genetic, and oncological data were prospectively collected from October 2023 to October 2025, while the retrospective period covered January 2000 to September 2023. These findings were then compared with data from Italian population-based cancer registries (AIRTUM\/AIRC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Out of 4,540 patients with IEI, 248 developed malignancies: 133 females and 115 males, comprising 195 adults and 53 children. The overall prevalence of malignancy within the IEI cohort was 5.5% (95% CI: 4.8\u20136.2), with an incidence rate of 3.4 cases per 1,000 person-years. Common variable immunodeficiency represented the largest IEI subgroup and showed the highest prevalence of malignancy 11.7%, (95% CI: 10.1\u201313.4). Malignancies occurred significantly earlier than in the general Italian population, at a median age of 44 years (range: 1\u201382), particularly in patients with ataxia-telangiectasia, 8.5 years (range 4-23). In contrast, patients with IgA deficiency displayed the highest median age at first malignancy, 52 years (range: 18- 57), compared to other IEI categories. In 30.2% of cases, cancer represented the first clinical manifestation leading to the IEI diagnosis. A different oncological profile compared to Italian population-based data was observed, with Non-Hodgkin lymphoma (21.7%) as the most frequent cancer, followed by skin cancers (11.2%) and gastric adenocarcinoma (10.4%), The overall 10-year survival rate was 94%, with no significant differences between hematologic and solid malignancies, or between adult and pediatric cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The multicenter, registry-based design of our study enabled a reliable estimation of cancer incidence among IEI patients and a direct comparison with the general population, while the longitudinal dataset provided valuable insights into the cancer spectrum and outcomes across different IEI subtypes. Tailored surveillance strategies, early IEI diagnosis and multidisciplinary management are essential to improve long-term outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1948296","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:54:51Z","timestamp":1790243691000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Malignancies in inborn errors of immunity: a retrospective-prospective study on a large Italian cohort of pediatric and adult patients"],"prefix":"10.3389","volume":"17","author":[{"given":"Cinzia","family":"Milito","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, \u201cSapienza\u201d University of Rome","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"D\u2019Anzieri","sequence":"additional","affiliation":[{"name":"Department of Translational and 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