ArticleAnnals of surgical oncology2024
Subgrading of G2 Pancreatic Neuroendocrine Tumors as 2A (Ki67 3% to < 10%) Versus 2B (10% to ≤ 20%) Identifies Behaviorally Distinct Subsets in Keeping with the Evolving Management Protocols.
Article in Annals of surgical oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Neuroendocrine Tumors of the Gallbladder: A Multicenter Case Series and Systematic Literature Review Indicating Predominantly Non-Aggressive Tumor Behavior and a Common Association with Cholesterol Polyps and Cholesterolosis.Endocrine pathology · 2026Pooled it
- A case of small pancreatic neuroendocrine tumor of less than 10 mm showing metastasis to multiple organs.Clinical journal of gastroenterology · 2026Article
- Neuroendocrine Carcinoma of the Gallbladder: Clinicopathologic and Immunohistochemical Analysis of 31 Cases.The American journal of surgical pathology · 2026Article
- The Genomic Patterns of Well-Differentiated Pancreatic Neuroendocrine Tumors (NETs) Identify Sub-Sets for Rational Therapeutic Targeting.International journal of molecular sciences · 2026Article
- An Integrative RNA Spliceosomic Landscape of Pancreatic Neuroendocrine Tumors Identifies Clinically Relevant Molecular Subgroups.Endocrine pathology · 2026Article
- Predictors of disease progression in pancreatic neuroendocrine tumors after surgery.Updates in surgery · 2026Article
- Changes in the 6th edition of the World Health Organization classification of tumours of the digestive system.Histopathology · 2026Review
- Multi-omic profiles of neuroendocrine neoplasms of the pancreas: an integrated landscape.Molecular cancer · 2026Review
- Clinicopathological and molecular determinants of pancreatic neuroendocrine tumors: toward precision risk stratification.Journal of translational medicine · 2026Review
- The Role of the Mesopancreas in Pancreatic Neuroendocrine Neoplasms.Journal of clinical medicine · 2026Article
- The Paradox of Grade 2 Pancreatic Neuroendocrine Tumors: G2a/G2b Subdivision in Patients With and Without Liver Metastases: A Retrospective Single-Center Analysis.Annals of surgical oncology · 2026Article
- Endoscopic Ultrasound for the Management of Pancreatic Neuroendocrine Tumors: Diagnosis, Treatment, and Future Perspectives.Journal of gastroenterology and hepatology · 2026Review
- Concept of neuroendocrine neoplasms of all organs with a focus on grading, subtyping.Virchows Archiv : an international journal of pathology · 2026Review
- Interpretable machine learning prognostication of gastroenteropancreatic neuroendocrine tumors across Chinese and United States cohorts.Frontiers in oncology · 2026Article
- Differentiating well-differentiated neuroendocrine tumors grade 3 from poorly differentiated neuroendocrine carcinomas and adenocarcinoma with neuroendocrine differentiation: a comprehensive review.Virchows Archiv : an international journal of pathology · 2026Review
- Intratumoral Heterogeneity of Ki67 Index and Its Impact on the Diagnosis and Prognostication of Pancreatic Neuroendocrine Tumors: Hot-Spot Count Differs Significantly from Random-Area Count.Endocrine pathology · 2025Article
- Prognostic Features in Surgically Resected Well-Differentiated Pancreatic Neuroendocrine Tumors: an Analysis of 904 Patients with 7882 Person-Years of Follow-Up.Endocrine pathology · 2025Article
- Clinical and biological heterogeneity of Grade 2 digestive neuroendocrine neoplasms: prognostic significance of the 10% Ki-67 index cutoff and implications for treatment strategies. A longitudinal study.Journal of endocrinological investigation · 2025Article
- Management of patients with small pancreatic neuroendocrine tumors from a biomarker and surgical perspective.Endocrine-related cancer · 2025Review
- Retrospective analysis of criteria for oncological completion surgery of neuroendocrine tumors of the appendix.Langenbeck's archives of surgery · 2025Article
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Authors and funding
21 authors.
Funding
Abstract
backgroundGrade 1/2 PanNETs are mostly managed similarly, typically without any adjunct treatment with the belief that their overall metastasis rate is low. In oncology literature, Ki67-index of 10% is increasingly being used as the cutoff in stratifying patients to different protocols, although there are no systematic pathology-based studies supporting this approach.
methodsKi67-index was correlated with clinicopathologic parameters in 190 resected PanNETs. A validation cohort (n = 145) was separately analyzed.
resultsIn initial cohort, maximally selected rank statistics method revealed 12% to be the discriminatory cutoff (close to 10% rule of thumb). G2b cases had liver/distant metastasis rate of almost threefold higher than that of G2a and showed significantly higher frequency of all histopathologic signs of aggressiveness (tumor size, perineural/vascular invasion, infiltrative growth pattern, lymph node metastasis). In validation cohort, these figures were as striking. When all cases were analyzed together, compared with G1, the G2b category had nine times higher liver/distant metastasis rate (6.1 vs. 58.5%; p < 0.001) and three times higher lymph node metastasis rate (20.5 vs. 65.1%; p < 0.001).
conclusionsG2b PanNETs act very similar to G3, supporting management protocols that regard them as potential therapy candidates. Concerning local management, metastatic behavior in G2b cases indicate they may not be as amenable for conservative approaches, such as watchful waiting or enucleation. This substaging should be considered into diagnostic guidelines, and clinical trials need to be devised to determine the more appropriate management protocols for G2b (10% to ≤ 20%) group, which shows liver/distant metastasis in more than half of the cases, which at minimum warrants closer follow-up.
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