World Health Organization Classification (2004)-based Re-evaluation of 95 nonfunctioning malignant pancreatic endocrine tumors reported in Japan

The World Health Organization (WHO) classification (2004) defines pancreatic endocrine carcinoma as tumors with gross local invasion or metastasis, and the mere occurrence of angioinvasion or perineural invasion constitute insufficient criteria of malignancy. The significance of this classification remains to be assessed in Japan. Nonfunctioning malignant endocrine tumors hitherto reported in Japan were analyzed, reclassified according to the WHO criteria, and thereafter survival analyses were conducted. Ninety-five malignant endocrine tumors were reclassified into 40 cases of well-differentiated endocrine tumor, uncertain behavior (UB) and 55 cases of well-differentiated endocrine carcinoma (WEC) according to the WHO classification. The estimated overall 5-year survival of all patients was 86.0%. A univariate analysis revealed that the following factors were significant for overall survival: WHO classification (UB vs WEC; P = 0.001), lymph node metastasis (P = 0.008), distant metastasis (P = 0.023), and curability (P = 0.018). Of these, only the WHO classification was recorded as significant by a multivariate analysis (Cox proportional hazards regression; hazard ratio 6.2, 95% confidence interval 1.3-30, P = 0.025). These data confirm the validity of the malignancy criteria of the WHO classification, thus indicating its impact on the diagnosis and treatment of pancreatic endocrine tumors in Japan.