Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, Australia; Douglass Hanly Moir, Macquarie Park, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia; NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia.
Pathology. 2022 Dec;54(7):855-862. doi: 10.1016/j.pathol.2022.05.008. Epub 2022 Jul 13.
Pancreatic neuroendocrine tumours (NETs) are currently graded using the World Health Organization (WHO) 2019 system, which is based solely on mitotic count and Ki-67 proliferative index. Although necrosis is a well recognised adverse prognostic feature that is included in the grading systems of NETs of certain types such as pulmonary carcinoid and medullary thyroid carcinoma, there is currently insufficient evidence to support its inclusion in the grading of pancreatic NETs. Therefore, we sought to investigate the prognostic significance of tumour necrosis in our cohort of resected pancreatic NETs, with a view to providing evidence to support its incorporation into the WHO grading scheme. Under our proposal, pancreatic NETs without necrosis would continue to be graded based solely on mitotic count and Ki-67 index using the established WHO cut-offs, while NETs with tumour necrosis would be classified as grade 3, irrespective of proliferative activity. Using this system in our cohort of 110 resected pancreatic NETs, overall survival (OS) was 250, 198, and 151 months (p=0.039) and disease-free survival (DFS) was 180 months, 117 months, and 38 months (p<0.0001) for grades 1, 2, and 3, respectively. In contrast, there was no significant difference in OS (p=0.231) or DFS (p=0.058) between low grade (grade 1) and intermediate-high grade (grade 2/3) tumours using the current WHO system which does not consider necrosis. Interobserver concordance for assessment of necrosis was excellent. In conclusion, necrosis is an independent predictor of OS and DFS for pancreatic NETs, and our findings strongly support its addition to the grading scheme for this tumour.
胰腺神经内分泌肿瘤（NETs）目前采用 2019 年世界卫生组织（WHO）系统进行分级，该系统仅基于有丝分裂计数和 Ki-67 增殖指数。虽然坏死是一种公认的不良预后特征，已被纳入某些类型的 NETs 分级系统，如肺类癌和甲状腺髓样癌，但目前尚无足够证据支持将其纳入胰腺 NETs 的分级。因此，我们试图在我们的胰腺 NET 切除患者队列中研究肿瘤坏死的预后意义，以期提供支持将其纳入 WHO 分级方案的证据。根据我们的建议，无坏死的胰腺 NETs 将继续仅根据有丝分裂计数和 Ki-67 指数进行分级，使用既定的 WHO 截止值，而有肿瘤坏死的 NETs 将被归类为 3 级，无论增殖活性如何。在我们的 110 例胰腺 NET 切除患者队列中使用该系统，总生存期（OS）分别为 250、198 和 151 个月（p=0.039），无疾病生存期（DFS）分别为 180、117 和 38 个月（p<0.0001），分别为 1 级、2 级和 3 级。相比之下，根据目前不考虑坏死的 WHO 系统，低级别（1 级）和中高级别（2/3 级）肿瘤之间的 OS（p=0.231）或 DFS（p=0.058）无显著差异。评估坏死的观察者间一致性极好。总之，坏死是胰腺 NETs OS 和 DFS 的独立预测因子，我们的研究结果强烈支持将其纳入该肿瘤的分级方案。
