尽管神经内分泌肿瘤（NEN）的研究已经取得了重要进展，但仍然缺乏关于其发病机制的一致数据。此外，不同的原发部位可能识别不同的发病机制。这篇综述分析了可能导致NEN在不同器官中发生和进展的可能的生物学和分子机制。通过广泛的文献研究，高胆固醇血症、炎症性肠病、慢性萎缩性胃炎等危险因素被评估为潜在的发病机制。关于散发性胃 NEN 和 MEN1 相关十二指肠胰腺 NEN 前驱病变有一致的证据，遗传-表观遗传突变可能在肿瘤发展和骨转移发病中发挥关键作用。在肺神经内分泌肿瘤（NET）中，支气管壁上神经内分泌细胞的弥漫性增殖（DIPNECH）被认为是一种癌前病变，而在肺神经内分泌癌中，尼古丁和烟雾可能是致癌过程的原因。此外，还对胸腺（T-NEN）和默克尔细胞癌（MCC）等罕见的原发性 NEN 进行了分析，发现了不同的可能发病机制。基因组学和表观基因组学的新技术为 NEN 的发病机制带来了新的认识，但还需要进一步的研究需要改善这些异质性肿瘤的预防和治疗。

Despite the fact that important advances in research on neuroendocrine neoplasms (NENs) have been made, consistent data about their pathogenetic mechanism are still lacking. Furthermore, different primary sites may recognize different pathogenetic mechanisms.This review analyzes the possible biological and molecular mechanisms that may lead to NEN onset and progression in different organs. Through extensive research of the literature, risk factors including hypercholesterolemia, inflammatory bowel disease, chronic atrophic gastritis are evaluated as potential pathogenetic mechanisms. Consistent evidence is available regarding sporadic gastric NENs and MEN1 related duodenopancreatic NENs precursor lesions, and genetic-epigenetic mutations may play a pivotal role in tumor development and bone metastases onset. In lung neuroendocrine tumors (NETs), diffuse proliferation of neuroendocrine cells on the bronchial wall (DIPNECH) has been proposed as a premalignant lesion, while in lung neuroendocrine carcinoma nicotine and smoke could be responsible for carcinogenic processes. Also, rare primary NENs such as thymic (T-NENs) and Merkel cell carcinoma (MCC) have been analyzed, finding different possible pathogenetic mechanisms.New technologies in genomics and epigenomics are bringing new light to the pathogenetic landscape of NENs, but further studies are needed to improve both prevention and treatment in these heterogeneous neoplasms.