Diagnostic value of whole-mount crypt analysis of ileal biopsy specimens for the patients with familial small intestinal neuroendocrine tumors
Therapeutic advances in medical oncology(2023)
摘要
Background and Aims: Early-stage small intestinal neuroendocrine tumors (SI-NETs) are generally asymptomatic and difficult to diagnose. As a result, patients often present with late-stage incurable disease. SI-NETs originate from enterochromaffin (EC) cells, which develop enteroendocrine cell (EEC) clusters consisting of a subset of EC cells at the crypt bottom at an early stage of tumor progression. In a familial form of SI-NET, EEC clusters arise in a multifocal and polyclonal fashion. We sought to determine whether early detection and analysis of cryptal EEC clusters could provide insight into the development of SI-NETs and allow successful pre-symptomatic screening for at risk family members of patients with SI-NETs. Methods: Isolated crypts from endoscopic ileal biopsies or surgically removed specimens from 43 patients with familial SI-NET and 20 controls were formalin-fixed, immunostained for chromogranin A, and examined by confocal three-dimensional analysis for the presence of EEC cluster formations. Results: Examination of multiple areas of macroscopic tumor-free mucosa in surgically resected specimens from patients with familial SI-NET revealed widely distributed, independent, multifocal EEC micro-tumor formations of varying sizes. Consistent with this finding, randomly sampled ileal biopsy specimens identified aberrant crypt containing endocrine cell clusters (ACECs) in patients. ACECs were found exclusively in patients (23/43, 53%) and not in controls (0/20). Furthermore, analysis of positions and numbers of EECs in crypts and ACECs indicated significant increases in EECs at the crypt bottom, predominantly at positions 0 and 1 ' (p < 0.0001 compared to controls), suggesting the progression of EEC accumulation below +4 position as the early process of ACEC formation. These findings also suggested that ACECs were precursors in the development of micro-tumors and subsequent macro-tumors. Conclusion: This study indicates that SI-NETs develop from deep crypt EC cells to become ACECs, micro-tumors, and ultimately gross tumors. This process occurs widely throughout the distal small intestine in patients with familial SI-NETs consistent with but not exclusively explained by germline disease. Finally, analysis of crypts from ileal biopsies could contribute in part to earlier diagnostic screening processes avoiding late-stage presentation of incurable disease.
更多查看译文
关键词
biopsy,carcinoid,crypt,enterochromaffin,familial,ileal,multifocal,neuroendocrine
AI 理解论文
溯源树
样例
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要