An overview of neuroendocrine neoplasms and their connections with primary and secondary immunodeficiency conditions. Neuroendocrine malignancies are widely recognized to be linked with genetic disorders such as multiple endocrine neoplasia type 1, von Hippel–Lindau syndrome, neurofibromatosis type 1, and tuberous sclerosis. This article addresses neuroendocrine tumors (NETs) that arise in different immunocompromised conditions, as well as the X-linked variant of hyper-IgM syndrome (XHIGM) caused by mutations in the CD40Ligand gene (CD40LG). NETs appear to be unique to XHIGM patients among all primary immune deficiency disorders. The outcomes for XHIGM patients with NETs are dismal, and the mechanism behind this connection is unknown. NET was most common in individuals with HIV or AIDS, the autoimmune illness systemic lupus erythematosus, and solid organ transplant recipients in secondary immune deficiency states. Nongastroenteropancreatic NETs, such as Merkel cell carcinoma and small-cell lung carcinoma, were more common in XHIGM patients, whereas non gastroenteropancreatic NETs, such as Merkel cell carcinoma and small-cell lung carcinoma, were more common in HIV/AIDS patients. Chronic infections and inflammation, as well as CD40–CD40L interactions, are addressed as potential explanations for the nature of these relationships. Given that many of these patients arrive late in their illness course and have poor outcomes, it is critical to maintain a high index of suspicion when early signs and symptoms appear.
NETs appear to be unique to XHIGM among other primary immunodeficiency disorders, and the mechanism behind this connection is unknown. The prognosis for XHIGM patients with NETs is poor, and it is critical to maintain a high index of suspicion at the onset of early signs and symptoms.