Prognostic features of gastro-entero-pancreatic neuroendocrine neoplasms in primary and metastatic sites: Grade, mesenteric tumour deposits and emerging novelties

J Neuroendocrinol. 2021 Aug;33(8):e13000. doi: 10.1111/jne.13000. Epub 2021 Jul 16.

Abstract

Updates in classification of gastro-entero-pancreatic neuroendocrine neoplasms better reflect the biological characteristics of these tumours. In the present study, we analysed the characteristics of neuroendocrine tumours that could aid in a more precise stratification of risk groups. In addition, we have highlighted the importance of grade (re)assessment based on investigation of secondary tumour lesions. Two hundred and sixty-four cases of neuroendocrine tumours of gastro-entero-pancreatic origin from three centres were included in the study. Tumour morphology, mitotic count and Ki67 labelling index were evaluated in specimens of primary tumours, lymph node metastases and distant metastases. These variables were correlated with overall survival (OS) and relapse-free survival (RFS). Tumour stage, number of affected lymph nodes, presence of tumour deposits and synchronous/metachronous metastases were tested as possible prognostic features. Mitotic count, Ki-67 labelling index, primary tumour site, tumour stage, presence of tumour deposits and two or more affected lymph nodes were significant predictors of OS and RFS. At the same time, mitotic count and Ki-67 labelling index can be addressed as continuous variables determining prognosis. We observed a very high correlation between the measures of proliferative activity in primary and secondary tumour foci. The presence of isolated tumour deposits was identified as an important determinant of both RFS and OS for pancreatic (hazard ratio [HR] = 7.61, 95% confidence interval [CI] = 3.96-14.6, P < 0.0001 for RFS; HR = 3.28, 95% CI = 1.56-6.87, P = 0.0017 for OS) and ileal/jejunal neuroendocrine tumours (HR = 1.98, 95% CI = 1.25-3.13, P = 0.0036 for RFS and HR 2.59, 95% CI = 1.27-5.26, P = 0.009 for OS). The present study identifies the presence of mesenterial tumour deposits as an important prognostic factor for gastro-entero-pancreatic neuroendocrine tumours, provides evidence that proliferative parameters need to be treated as continuous variables and further supports the importance of grade determination in all available tumour foci.

Keywords: GEP-NEN; Ki-67; mesenteric tumour deposit; mitotic count; prognosis; tumour deposit.

MeSH terms

  • Cell Proliferation
  • Extranodal Extension / diagnosis
  • Follow-Up Studies
  • Humans
  • Intestinal Neoplasms / diagnosis*
  • Intestinal Neoplasms / mortality
  • Intestinal Neoplasms / pathology*
  • Italy / epidemiology
  • Mesentery / pathology
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neuroendocrine Tumors / diagnosis*
  • Neuroendocrine Tumors / mortality
  • Neuroendocrine Tumors / pathology*
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology*
  • Peritoneal Neoplasms / diagnosis
  • Peritoneal Neoplasms / mortality
  • Peritoneal Neoplasms / secondary
  • Prognosis
  • Retrospective Studies
  • Stomach Neoplasms / diagnosis*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*
  • Survival Analysis

Supplementary concepts

  • Gastro-enteropancreatic neuroendocrine tumor