Pancreatic neuroendocrine tumors (PanNETs) and lung NETs (LNETs) represent a rare but clinically significant subgroup of neoplasms. While the majority is sporadic, approximately 17% of PanNETs and a subset of LNETs develop in the context of monogenic familial tumor syndromes, especially multiple endocrine neoplasia type 1 (MEN1) syndrome. Other inherited syndromes associated with PanNETs include MEN4, von Hippel–Lindau (VHL) syndrome, neurofibromatosis type 1 (NF1), and tuberous sclerosis complex (TSC). These syndromes are highly penetrant and their clinical manifestations may vary even among members of the same family. They are attributed to genetic mutations involving key molecular pathways regulating cell growth, differentiation, and angiogenesis. Pancreatic NETs in hereditary syndromes are often multiple, develop at a younger age compared to sporadic tumors, and are associated with endocrine and nonendocrine tumors derived from multiple organs. Lung NETs are not as common as PanNETs and are mostly encountered in MEN1 syndrome and include typical and atypical lung carcinoids. Early detection of PanNETs and LNETs related to inherited syndromes is crucial, and specific follow-up protocols need to be employed to optimize diagnosis and management. Genetic screening is recommended in childhood, and diagnostic screening starts often in adolescence, even in asymptomatic mutation carriers. Optimal management and therapeutic decisions should be made in the context of a multidisciplinary team in specialized centers, whereas specific biomarkers aiming to identify patients denoted to follow a more aggressive course need to be developed.
胰腺神经内分泌肿瘤（PanNETs）与肺神经内分泌肿瘤（LNETs）是一类罕见但具有重要临床意义的肿瘤亚群。尽管多数为散发性病例，但约17%的PanNETs及部分LNETs发生于单基因遗传性肿瘤综合征背景下，尤其多见于多发性内分泌腺瘤病1型（MEN1）综合征。其他与PanNETs相关的遗传综合征包括MEN4型、希佩尔-林道综合征（VHL）、1型神经纤维瘤病（NF1）以及结节性硬化症（TSC）。这些综合征具有高外显率，其临床表现即使在同家族成员间也存在差异。其发病机制涉及调控细胞生长、分化及血管生成的关键分子通路基因突变。遗传综合征相关的胰腺神经内分泌肿瘤常呈多发性，较散发性肿瘤发病年龄更早，且常伴发多器官来源的内分泌及非内分泌肿瘤。肺神经内分泌肿瘤较PanNETs少见，主要见于MEN1综合征，包括典型与非典型肺类癌。早期发现与遗传综合征相关的PanNETs和LNETs至关重要，需采用特定随访方案以优化诊疗。建议在儿童期进行基因筛查，诊断性筛查通常始于青少年期，即使对无症状突变携带者亦应如此。最佳治疗决策应在专科中心的多学科团队协作下制定，同时需开发特异性生物标志物以识别可能进展为侵袭性病程的患者群体。
Hereditary Syndromes Associated with Pancreatic and Lung Neuroendocrine Tumors
肿瘤(癌症)患者之家