Histologic characterization and improved prognostic evaluation of 209 gastric neuroendocrine neoplasms

Gastric neuroendocrine neoplasms differ considerably in histology, clinicopathologic background, stage, and patient outcome, implying a wide spectrum of therapeutic options, hence the need for improved diagnostic and prognostic criteria to select appropriate therapy. Here, we tested the European NeuroEndocrine Tumor Society and the novel World Health Organization 2010 grade and stage classifications together with additional clinicopathologic and histologic parameters in a series of 209 gastric neuroendocrine neoplasms with a median follow-up of 89 months. Fifty-one grade 3 neuroendocrine carcinomas and 15 mixed endocrine-exocrine carcinomas of poor outcome were separated from 143 neuroendocrine tumors, including 132 G1 or G2 enterochromaffin-like (ECL) cell neoplasms and 11 G1 gastrin-cell, somatostatin-cell, or serotonin-cell tumors. Most G1 cases had excellent prognosis, even when metastatic, whereas G2 and G3 neoplasms had worse or very severe prognosis, respectively. The European NeuroEndocrine Tumor Society-World Health Organization 2010 proliferative grading system well correlated with patient survival. Structural histologic parameters were equally predictive and when combined with the European NeuroEndocrine Tumor Society-World Health Organization 2010 grading system in a "global grade" improved tumor prognostic stratification. The European NeuroEndocrine Tumor Society-World Health Organization 2010 staging system proved effective. Introduction of novel T (T(1a) and T(1b) or deep submucosal) and N categories (N(1), <3 nodes metastases; N(2), ≥3) allowed a simplified, equally informative 3-stage TNM system. Such improved diagnostic and prognostic criteria for gastric neuroendocrine neoplasms are proposed and discussed.