胰岛素瘤是罕见的、功能性的胰腺神经内分泌肿瘤。大多数胰岛素瘤经手术治愈后是不侵害的，但10-15%的病例表现出侵袭性或恶性肿瘤的行为，并且局部或远处器官有转移。并发转移的胰岛素瘤患者的存活时间显著缩短。识别侵袭性胰岛素瘤有助于预测预后，指导治疗，并确定手术后的随访强度。本综述介绍了对温和和侵袭性胰岛素瘤在临床、病理、遗传和表观遗传学方面的重大差异的文献总结。侵袭性胰岛素瘤表现为症状急剧发作、肿块较大、ARX和α-1-抗胰蛋白表达增加，而胰岛素、PDX1和GLP-1R的免疫组化表达减少或缺失。此外，侵袭性胰岛素瘤通常携带ATRX或DAXX突变、替代端粒长度表型（ALT）和染色体不稳定性（CIN）。肿瘤分级以及MEN1和YY1突变对预测行为的有效性要低一些。侵袭性胰岛素瘤和正常的α-细胞和非功能性胰腺神经内分泌肿瘤有相似之处，而温和的胰岛素瘤则与正常的β-细胞密切相关。总之，温和和侵袭性胰岛素瘤是不同的实体，鉴别这两者在未来对确定预后和治疗将具有临床价值。

Insulinomas are rare functional pancreatic neuroendocrine tumors. While most insulinomas are indolent and cured after surgery, 10-15% of cases show aggressive or malignant tumor behavior and metastasize locally or to distant organs. Patients with metastatic insulinoma survive significantly shorter. Recognizing aggressive insulinomas can help to predict prognosis, guide therapy and determine follow-up intensity after surgery. This review offers a summary of the literature on the significant clinical, pathological, genetic and epigenetic differences between indolent and aggressive insulinomas. Aggressive insulinomas are characterized by rapid onset of symptoms, larger size, expression of ARX and alpha-1-antitrypsin; and decreased or absent immunohistochemical expression of insulin, PDX1 and GLP-1R. Moreover, aggressive insulinomas often harbor ATRX or DAXX mutations, the alternative lengthening of telomeres phenotype (ALT) and chromosomal instability (CIN). Tumor grade and MEN1 and YY1 mutations are less useful for predicting behavior. Aggressive insulinomas have similarities to normal alpha-cells and non-functional pancreatic neuroendocrine tumors, while indolent insulinomas remain closely related to normal beta-cells. In conclusion, indolent and aggressive insulinoma are different entities, and distinguishing these will have future clinical value in determining prognosis and treatment.