肺类癌/NET G3 的临床病理及预后验证:高分化神经内分泌肿瘤中一个独特亚组的证据
Clinicopathological and prognostic validation of pulmonary carcinoid/NET G3: evidence for a distinct subgroup of well-differentiated neuroendocrine neoplasms.
作者
作者单位
- Department of Pathology, Caen-Normandie University Hospital, Avenue de la Côte de Nacre, 14000 Caen, France.
- Department of Pathology, Caen-Normandie University Hospital, Avenue de la Côte de Nacre, 14000 Caen, France; Normandie University, UNICAEN, CNRS, ISTCT UMR6030, GIP Cyceron, 14000 Caen, France.
- Department of Pathology, Caen-Normandie University Hospital, Avenue de la Côte de Nacre, 14000 Caen, France; Normandie University, UNICAEN, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Institut Brain, Blood and Memory @ Caen-Normandie (BBM@C), GIP Cyceron, 14000 Caen, France. Electronic address: dubois-fa@chu-caen.fr.
- Department of Pathology, Caen-Normandie University Hospital, Avenue de la Côte de Nacre, 14000 Caen, France. Electronic address: jeanjacques-b@chu-caen.fr.
摘要
中文
肺神经内分泌肿瘤(NENs)构成从高分化类癌到低分化神经内分泌癌的生物学谱系。2026 年,国际肺癌研究协会(IASLC)提出更新分类,将肺类癌/NET G3 引入作为一种独特的高分化肿瘤类别,其增殖活性增加,将 Ki-67 纳入诊断框架并使肺 NENs 与其他器官系统对齐。然而,这一新提出实体的临床病理特征和预后意义仍尚未完全明确。我们对 2007–2024 年诊断的肺神经内分泌肿瘤进行回顾性单中心研究,收集临床、组织病理学、免疫组化和生存数据。使用预设研究标准(核分裂计数 > 10/2 mm² 和/或 Ki-67 > 20%)识别具有高分化形态但增殖活性增加的肿瘤。在 2026 年 IASLC 提案发表后,这些肿瘤在修订稿件中统称为类癌/NET G3。进行 RB1 和 p53 免疫组化检测,使用 Kaplan-Meier 估计和 Cox 回归分析生存。在 155 例肺神经内分泌肿瘤中,8 例(5.2%)符合类癌/NET G3 标准。这些肿瘤尽管增殖活性升高,仍呈现高分化形态,保留 RB1 表达,具有野生型 p53 免疫表型,区别于 LCNEC。临床上,类癌/NET G3 表现出介于传统类癌与 LCNEC 之间的中间预后。核分裂计数和 Ki-67 仅呈中等相关性,Ki-67 可识别额外具有生物学相关性的核分裂活性相对较低的肿瘤。我们的发现为最近提出的 IASLC 类癌/NET G3 概念提供了独立的临床病理验证。整合形态学、Ki-67、RB1 和 p53 可改善肺神经内分泌肿瘤的诊断分类和预后分层,同时支持新兴的肺类癌/NET G1–G3 框架的实施。
English
Pulmonary neuroendocrine neoplasms (NENs) comprise a biological spectrum ranging from well-differentiated carcinoid tumors to poorly differentiated neuroendocrine carcinomas. In 2026, the International Association for the Study of Lung Cancer (IASLC) proposed an updated classification introducing pulmonary carcinoid/NET G3 as a distinct category of well-differentiated tumors with increased proliferative activity, incorporating Ki-67 into the diagnostic framework and aligning pulmonary NENs with other organ systems. However, the clinicopathological characteristics and prognostic significance of this newly proposed entity remain incompletely defined. We conducted a retrospective single-center study of pulmonary neuroendocrine neoplasms diagnosed between 2007 and 2024. Clinical, histopathological, immunohistochemical, and survival data were collected. Tumors with well-differentiated morphology and increased proliferative activity were identified using predefined study criteria (mitotic count > 10/2 mm2 and/or Ki-67 > 20 %). Following publication of the 2026 IASLC proposal, these tumors are referred to as carcinoid/NET G3 throughout the revised manuscript. RB1 and p53 immunohistochemistry was performed, and survival was analyzed using Kaplan-Meier estimates and Cox regression. Among 155 pulmonary neuroendocrine neoplasms, eight (5.2 %) fulfilled criteria for carcinoid/NET G3. These tumors exhibited well-differentiated morphology despite elevated proliferative activity, retained RB1 expression, and a wild-type p53 immunophenotype, distinguishing them from LCNEC. Clinically, carcinoid/NET G3 showed an intermediate prognosis between conventional carcinoids and LCNEC. Mitotic count and Ki-67 demonstrated only moderate correlation, and Ki-67 identified additional biologically relevant tumors with relatively low mitotic activity. Our findings provide independent clinicopathological validation of the recently proposed IASLC carcinoid/NET G3 concept. Integration of morphology, Ki-67, RB1 and p53 may improve diagnostic classification and prognostic stratification of pulmonary neuroendocrine neoplasms while supporting implementation of the emerging pulmonary carcinoid/NET G1-G3 framework.
分类与指标
- 研究类型
- 临床研究
- 病种
- 肺癌
- JCR 分区
- Q1
- 影响因子
- 5.3
- 新锐分区
- 2区