The malignant progression of pancreatic cystic lesions (PCLs) remains understudied with a knowledge gap, yet its exploration is pivotal for effectively stratifying patient risk and detecting cancer at its earliest stages. Within this review, we delve into the latest discoveries on the molecular level, revealing insights into the IPMN molecular landscape and revised progression model, associated histologic subtypes, and the role of inflammation in the pathogenesis and malignant progression of IPMN. Low-grade PCLs, particularly IPMNs, can develop into high-grade lesions or invasive carcinoma, underscoring the need for long-term surveillance of these lesions if they are not resected. AlthoughKRASandGNASremain the primary oncogenic drivers of neoplastic development in IPMNs, additional genes that are important in tumorigenesis have been recently identified by whole exome sequencing. A more complete understanding of the genes involved in the molecular progression of IPMN is critical for effective monitoring to minimize the risk of malignant progression. Complicating these strategies, IPMNs are also frequently multifocal and multiclonal, as demonstrated by comparative molecular analysis. Algorithms for preoperative cyst sampling and improved radiomic techniques are emerging to model this spatial and temporal genetic heterogeneity better. Here, we review the molecular pathology of PCLs, focusing on changes associated with malignant progression. Developing models of molecular risk stratification in PCLs which can complement radiologic and clinical features, facilitate the early detection of pancreatic cancer, and enable the development of more personalized surveillance and management strategies are summarized.
胰腺囊性病变（PCLs）的恶性进展机制仍存在研究空白，但其探索对于有效分层患者风险及实现癌症早期检测至关重要。本综述深入探讨了分子层面的最新发现，揭示了导管内乳头状黏液性肿瘤（IPMN）的分子图谱、修订的进展模型、相关组织学亚型，以及炎症在IPMN发病机制和恶性进展中的作用。低级别PCLs（尤其是IPMNs）可能发展为高级别病变或浸润性癌，这强调了未切除病变需长期监测的必要性。尽管KRAS和GNAS仍是IPMN肿瘤发生的主要驱动基因，但近期全外显子测序已鉴定出其他在肿瘤发生中至关重要的基因。更全面地理解参与IPMN分子进展的基因，对于通过有效监测降低恶性进展风险具有关键意义。分子比较分析表明，IPMNs常呈多灶性、多克隆性，这增加了诊疗策略的复杂性。新兴的术前囊液采样算法与改进的影像组学技术，正为更好地模拟这种时空遗传异质性提供支持。本文综述了PCLs的分子病理学特征，重点关注与恶性进展相关的变化，并总结如何建立PCLs分子风险分层模型。这些模型可补充影像学和临床特征，促进胰腺癌早期检测，并为制定更个体化的监测与管理策略提供依据。
Molecular Pathology of Pancreatic Cystic Lesions with a Focus on Malignant Progression
肿瘤(癌症)患者之家