Pancreatic grade 3 neuroendocrine tumors behave similarly to neuroendocrine carcinomas following resection: a multi-center, international appraisal of the WHO 2010 and WHO 2017 staging schema for pancreatic neuroendocrine lesions.

Background: In 2017, the WHO updated their 2010 classification of pancreatic neuroendocrine tumors, introducing a well-differentiated, highly proliferative grade 3 tumor, distinct from neuroendocrine carcinomas. The aim of this study was to investigate the clinical significance of this update in a large cohort of resected tumors.

Methods: Using a multicenter, international dataset of patients with pancreatic neuroendocrine lesions, patients were classified both according to the WHO 2010 and 2017 schema. Multivariable survival analyses were performed, and the models were evaluated for discrimination ability and goodness of fit.

Results: Excluding patients with a known germline MEN1 mutation and incomplete data, 544 patients were analyzed. The performance of the WHO 2010 and 2017 models was similar, however surgically resected grade 3 tumors behaved very similarly to neuroendocrine carcinomas.

Conclusion: The addition of a grade 3 NET classification may be of limited utility in surgically resected patients, as these lesions have similar postoperative survival compared to carcinomas. While the addition may allow for a more granular evaluation of novel treatment strategies, surgical intervention for high grade tumors should be considered judiciously.