Diversity of malignancies in patients with different types of inborn errors of immunity

Abstract

Genetic defects in the development, maturation, and/or function of the immune cells can lead to Inborn errors of immunity (IEI) which may predispose patients to malignancies. The overall risk for cancer in children with IEI ranges from 4 to 25% and the type of malignancy is highly dependent on the specific mutant gene underlying IEI. We investigated 3056 IEI patients registered in the Iranian national registry between the years 1999 and 2020 in this retrospective cohort study. The frequency of malignancy and its association with the type of IEI in these patients were evaluated. A total of 82 IEI patients with malignancy were enrolled in this study. Among them, predominantly lymphoma was the most common type of malignancy (67.1%), followed by leukemia (11%), and cancers of the head and neck (7.3%). Among identified lymphoma cancers, non-Hodgkin’s lymphomas were the most frequent type (43.9%) followed by different subtypes of Hodgkin’s lymphoma (23.2%). Solid tumors (18.3%) appeared to be very heterogeneous by type and localization. The correlation between the type of malignancy and survival status and the association between the type of malignancy and IEI entities were unremarkable. The awareness of the association between the presence of IEI and cancer highlights the importance of a synergistic effort by oncologists and immunologists in the early diagnosis of malignancy and personalized therapeutic strategies in IEI patients.

Malignancies and Lymphoproliferations in Children With Primary Immune Deficiency—A Single-center Experience

“…Our study revealed a notably higher prevalence with a rate of 3.0%. NHL emerged as the most frequently occurring type of malignancy in our study, consistent with existing research 6,7,9,10 . A study conducted by Tavakol et al 6 among 82 patients with PID diagnosed with malignancy reported similar results, with lymphoma being the most common type, NHL in 36 cases (43.9%), and leukemia in 9 cases (11%).…”

“…7 They have a 1.42-fold higher relative risk of developing cancer when compared with healthy individuals. 6,7,9,10 In a study conducted in Turkey, researchers found that the prevalence of malignancy was identified as an occurrence rate of 0.9%. 4 Our study revealed a notably higher prevalence with a rate of 3.0%.…”

“…Children with PID are not only at an elevated risk of malignancy but also experience its onset at a younger age compared with those with a healthy immune system 7 . They have a 1.42-fold higher relative risk of developing cancer when compared with healthy individuals 6,7,9,10 . In a study conducted in Turkey, researchers found that the prevalence of malignancy was identified as an occurrence rate of 0.9% 4 .…”

“…5 In patients with PID, malignancy is most reported to be non-Hodgkin lymphoma (NHL), followed by Hodgkin lymphoma (HL) and leukemia. [6][7][8] In the literature, there are publications stating that common variable immune deficiency (CVID) and ataxia-telangiectasia (AT) are the most common immunodeficiencies associated with malignancy. [8][9][10] We aimed to evaluate the frequency of malignancy and/or benign lymphoproliferation in PID, the types of PID that cause malignancy and/or benign lymphoproliferation, and their prognoses.…”

“…In patients with PID, malignancy is most reported to be non–Hodgkin lymphoma (NHL), followed by Hodgkin lymphoma (HL) and leukemia 6–8 . In the literature, there are publications stating that common variable immune deficiency (CVID) and ataxia-telangiectasia (AT) are the most common immunodeficiencies associated with malignancy 8–10 .…”