Hackeng Wenzel M, Brosens Lodewijk A A, Dreijerink Koen M A
Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Department of Endocrinology, Amsterdam University Medical Centers, VU University Medical Center, Amsterdam, The Netherlands.
Endocr Relat Cancer. 2023 Mar 27;30(5). doi: 10.1530/ERC-22-0321. Print 2023 May 1.
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 and chromosomal instability. 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.
胰岛素瘤是罕见的功能性胰腺神经内分泌肿瘤。虽然大多数胰岛素瘤生长缓慢，手术后可治愈，但10% - 15%的病例表现出侵袭性或恶性肿瘤行为，并发生局部转移或远处器官转移。转移性胰岛素瘤患者的生存期明显较短。识别侵袭性胰岛素瘤有助于预测预后、指导治疗并确定术后随访强度。本综述总结了关于惰性和侵袭性胰岛素瘤在临床、病理、遗传和表观遗传方面显著差异的文献。侵袭性胰岛素瘤的特征为症状出现迅速、肿瘤体积较大、ARX和α1抗胰蛋白酶表达、胰岛素、PDX1和GLP - 1R免疫组化表达降低或缺失。此外，侵袭性胰岛素瘤常存在ATRX或DAXX突变、端粒替代延长表型和染色体不稳定。肿瘤分级以及MEN1和YY1突变对预测肿瘤行为的作用较小。侵袭性胰岛素瘤与正常α细胞和无功能性胰腺神经内分泌肿瘤有相似之处，而惰性胰岛素瘤仍与正常β细胞密切相关。总之，惰性和侵袭性胰岛素瘤是不同的实体，区分它们在确定预后和治疗方面将具有未来临床价值。
