Analysis of risk factors for recurrence after curative resection of well‐differentiated pancreatic neuroendocrine tumors based on the new grading classification

Abstract

It is difficult to predict the malignant potential of pancreatic neuroendocrine tumors (PNETs) precisely. This study investigated the validity of a new grading system adopted by the World Health Organization 2010 classification to determine risk factors for recurrence of PNETs. Data of 70 patients with PNETs who underwent curative resection were retrospectively examined by uni- and multivariate analyses. Histopathological findings were re-reviewed by experienced pathologists. NET G1 was defined as mitotic count <2 per 10 high power fields (HPF) and/or ≤2% Ki67 index, and NET G2 as 2-20 mitosis per 10 HPF and/or 3-20% Ki67 index. There were 58 patients with NET G1 and 12 with NET G2. Incidence of recurrence was 11.4%. Univariate analysis demonstrated significant risk factors for recurrence including NET G2 of histological grade (P = 0.0089), male gender (P = 0.0333), tumor size ≥ 20 mm (P = 0.0117), lymph node metastasis (P = 0.0004), liver metastasis (P < 0.0001), lymphatic invasion (P = 0.046), and neural invasion (P = 0.0002). By multivariate analysis, histological grade (hazard ratio; 59.76, P = 0.0022) and neural invasion (hazard ratio; 147.49, P = 0.0016) were significantly associated with recurrence of PNETs. This study confirmed the prognostic relevance of the new grading classification and that evaluation of perineural invasion and histological grade should be considered as prognostic predictors in well-differentiated PNETs (NET G1 and G2).