Nicolaides Rory E, de la Morena M Teresa
aDepartment of Pediatrics bDepartment of Internal Medicine, Division of Allergy and Immunology cChildren's Health, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Curr Opin Allergy Clin Immunol. 2017 Dec;17(6):431-442. doi: 10.1097/ACI.0000000000000406.
Overview of neuroendocrine neoplasms in the context of their associations with primary and secondary immunodeficiency states.
Malignancies of neuroendocrine origin are well known to be associated with hereditary syndromes, including multiple endocrine neoplasia type 1, von Hippel-Lindau syndrome, neurofibromatosis type 1, and tuberous sclerosis. This review includes the X-linked form of hyper-IgM syndrome (XHIGM), due to mutations in the CD40Ligand gene (CD40LG), as an additional inherited disorder with susceptibility to such malignancies, and discusses neuroendocrine tumors (NETs) arising in other immunocompromised states. Of all primary immune deficiency diseases, NETs appear to be unique to XHIGM patients. Outcomes for XHIGM patients with NETs is poor, and the mechanism behind this association remains unclear. In secondary immune deficiency states, NET occurrences were primarily in patients with HIV or AIDS, the autoimmune disease systemic lupus erythematosus and solid organ transplant recipients. Gastroenteropancreatic NETs were most frequent in XHIGM patients, whereas nongastroenteropancreatic-NETs, like Merkel cell carcinoma and small-cell lung carcinoma, affected HIV/AIDS patients. Possible mechanisms as to the nature of these associations are discussed, including chronic infections and inflammation, and CD40-CD40L interactions. Many questions remain, and further studies are needed to clarify the predisposition of patients with XHIGM to the development of NETs. Given that many of these patients present late in their disease state and have poor outcomes, it is imperative to keep a high index of suspicion at the advent of early signs and symptoms. Regular monitoring with laboratory or imaging studies, including tumor markers, may be warranted, for which further studies are needed.
Of all primary immunodeficiency diseases, NETs appear to be unique to XHIGM, and the mechanism behind this association remains unclear. Outcome for XHIGM patients with NETs is poor, and it is imperative to keep a high index of suspicion at the advent of early signs and symptoms.
概述神经内分泌肿瘤与原发性和继发性免疫缺陷状态的关联。
神经内分泌起源的恶性肿瘤与遗传性综合征相关，这是众所周知的，包括1型多发性内分泌腺瘤病、冯·希佩尔-林道综合征、1型神经纤维瘤病和结节性硬化症。本综述将因CD40配体基因（CD40LG）突变导致的X连锁高IgM综合征（XHIGM）作为另一种易患此类恶性肿瘤的遗传性疾病纳入其中，并讨论了在其他免疫功能低下状态下发生的神经内分泌肿瘤（NETs）。在所有原发性免疫缺陷疾病中，NETs似乎是XHIGM患者所特有的。XHIGM合并NETs患者的预后较差，这种关联背后的机制仍不清楚。在继发性免疫缺陷状态下，NETs主要发生于艾滋病病毒（HIV）感染者、获得性免疫缺陷综合征（AIDS）患者、自身免疫性疾病系统性红斑狼疮患者以及实体器官移植受者。胃肠道胰腺NETs在XHIGM患者中最为常见，而像默克尔细胞癌和小细胞肺癌这样非胃肠道胰腺NETs则多见于HIV/AIDS患者。文中讨论了这些关联本质的可能机制, 包括慢性感染与炎症以及CD40 - CD40L相互作用。许多问题仍然存在，需要进一步研究以阐明XHIGM患者发生NETs的易感性。鉴于这些患者中的许多人在疾病晚期才出现症状且预后不佳，在出现早期体征和症状时必须保持高度怀疑。可能有必要通过实验室检查或影像学检查（包括肿瘤标志物）进行定期监测，对此还需要进一步研究
在所有原发性免疫缺陷疾病中，NETs似乎是XHIGM所特有的，这种关联背后的机制仍不清楚。XHIGM合并NETs患者的预后较差，在出现早期体征和症状时必须保持高度怀疑。
