Well differentiated neuroendocrine tumor

Author: Elliot Weisenberg, M.D. (see Authors page)

Revised: 6 November 2018, last major update August 2012

Copyright: (c) 2003-2018,, Inc.

PubMed Search: NET G1

Related Topics: Clear cell variant, ECL cell NETs (Enterochromaffin-like cell neuroendocrine tumors), Gastrin producing NET (Gastrinoma)
Cite this page: Weisenberg, E. Well differentiated neuroendocrine tumor. website. Accessed December 11th, 2018.
Definition / general
  • WHO defines as well differentiated neuroendocrine tumor (NET) composed of cells with features similar to those of normal gut endocrine cell, expressing general markers of neuroendocrine differentiation (usually diffuse and intense chromogranin A and synaptophysin) and hormones (usually intense but not necessarily diffuse) according to site, with mild to moderate nuclear atypia and a low number of mitoses (PubCan)
  • Proposed grading:
    • G1 (NET G1): mitotic count <2 per 10 high power fields (HPF) or Ki67 index ≤2%
    • G2 (NET G2): mitotic count 2 - 20 per 10 HPF or Ki67 index 3 - 20%
  • Enterochromaffin-like (ECL) cells:
    • Nonpeptide secreting endocrine cell of gastric fundus / body mucosa
    • Comprises 30% of endocrine cells
    • Releases histamine in response to gastrin production by G cells
    • Long term gastrin stimulation causes ECL hyperplasia

  • Type 1 gastric endocrine tumor:
    • In patients with autoimmune chronic atrophic gastritis (Am J Surg Pathol 1995;19(S1):S20)
    • Occur in 5 - 10%, usually women, mean age 63 years
    • Arise due to enterochromaffin-like cell hyperplasia and hypergastrinemia secondary to parietal cell loss, in fundus / body
    • 57% multifocal
    • 97% < 1.5 cm
    • 91% limited to mucosa or submucosa
    • Only 2 - 5% associated with liver metastases
    • Nearly always grade 1, indolent course, almost never causes death

  • Type 2 gastric endocrine tumor:
    • In patients with Zollinger-Ellison syndrome, usually also MEN1 (abnormality of menin gene on 11q13)
    • No gender predilection, mean age 50 years
    • Associated with ECL cell hyperplasia and hypergastrinemia
    • Usually multicentric in body / fundus
    • 23% > 1.5 cm, 30% with local nodal metastases, 10% with liver metastases
    • Death more likely from gastrinomas of Zollinger-Ellison syndrome than from the carcinoid tumors

  • Type 3 gastric endocrine tumor:
    • Sporatic, not related to hypergastrinemia or ECL cell hyperplasia
    • Usually solitary, may not be in body / fundus
    • 74% in men, mean age 55 years
    • 76% deeply invasive, 71% have nodal metastases, distant metastases common

  • Type 4 gastric endocrine tumor:
    • Very rare, due to defective gastric acid secretion
    • Metastases only to regional lymph nodes and liver, but patients may still have long term survival
Clinical features
Case reports
Gross description
  • Small, sharply outlined, covered by flattened mucosa
  • Resemble polyps
Microscopic (histologic) description
  • Glandular, trabecular or rarely insular patterns
  • Bland nuclei with salt and pepper chromatin, rare mitotic figures, prominent vessels, no necrosis
Negative stains
Electron microscopy description
  • Dense core secretory granules