The pathological classification of pancreatic neuroendocrine neoplasms (PanNENs) has been revised based on the World Health Organization (WHO) 2017 classification. Well-differentiated PanNENs were previously classified as G1, G2, or G3 according to the Ki-67 labeling index (LI), which shows the cell proliferation ability. Although the Ki67 LI cut-off for G1 and G2 was changed from ≤2% to < 3% from WHO 2010 to 2017, there are few reports on the impact of G2 tumor malignancy associated with this change.
Patients with PanNENs G1/G2 classified by WHO 2017 Ki-67 LI cut-off who underwent pancreatic resection at our institution between July 1987 and March 2019 were retrospectively analyzed. We excluded patients with synchronous distant metastasis at the time of diagnosis. Their clinicopathological variables were analyzed.
Sixty-two patients (median age: 58 years; range: 18–84 years) were examined. The G1/G2 groups comprised 40/22 and 48/14 patients based on WHO 2010 and 2017 classifications, respectively. Eight patients were reclassified from G2 to G1, two of which were T2 or more based on TNM classification; one patient had lymph node metastasis positivity, and all patients survived without recurrence. Disease recurrence occurred in 4/4 G1/G2 patients according to both WHO 2010 and 2017. G2 patients had shorter 5- and 10-year disease-free survivals (DFSs) than those of G1 patients based on WHO 2010 (90.9% and 90.9% vs. 84.5% and 70.4%, p = 0.179) and significantly shorter DFS based on WHO 2017 (91.9% and 91.9% vs. 78.6% and 58.9%, p = 0.036). The Ki-67 LI cut-off by ROC analysis was 3%, supporting the WHO 2017 classification. In multivariate analysis for DFS, tumor size >25 mm and vascular invasion positivity, but not G2, were risk factors for recurrence. The high-risk group with these factors had significantly worse 5- and 10-year disease-specific survivals (DSSs) compared to the low-risk group (100% and 100% vs. 90.9% and 68.2%, p = 0.045).
Revision of the Ki-67 LI cut-off for PanNENs G1/G2 based on WHO 2017 may be appropriate but G2 is not a risk factor for DFS. Tumor size >25 mm and vascular invasion positivity are potential risk factors. High-risk patients should be closely monitored during follow-up.
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