Histologic changes in type A chronic atrophic gastritis indicating increased risk of neuroendocrine tumor development: the predictive role of dysplastic and severely hyperplastic enterochromaffin-like cell lesions

Hum Pathol. 2013 Sep;44(9):1827-37. doi: 10.1016/j.humpath.2013.02.005. Epub 2013 May 2.


The role of putative preneoplastic enterochromaffin-like cell lesions, either hyperplastic or dysplastic, in the genesis of type 1 enterochromaffin-like cell neuroendocrine tumors associated with type A chronic atrophic gastritis, their actual neoplastic risk, and their precise histogenetic mechanism deserve further clarification by specific histopathologic studies coupled with patient follow-up. A total of 100 patients with severe type A chronic atrophic gastritis, enterochromaffin-like cell hyperplasia, and antral G-cell hyperplasia were endoscopically and histologically followed up for a median of 90.1 months (total of 9118 person-months). Preneoplastic enterochromaffin-like cell lesions and newly developed neuroendocrine tumors were investigated histologically and histochemically, in parallel with enterochromaffin-like cell lesions found in nontumor mucosa of another 32 well-characterized and previously reported type 1 neuroendocrine tumors. Both neuroendocrine and nonneuroendocrine mucosa changes were analyzed and statistically evaluated. During follow-up, 7 of 100 patients developed neuroendocrine tumors: 5 were in a group of 20 cases with previous enterochromaffin-like cell dysplasia and 2 were among 80 cases showing only enterochromaffin-like cell hyperplasia throughout the study (hazard ratio, 20.7; P < .001). The severity of enterochromaffin-like cell hyperplasia at first biopsy, with special reference to linear hyperplasia with 6 chains or more per linear millimeter, also increased the risk of neuroendocrine tumor development during follow-up (hazard ratio, 13.0; P < .001). Enterochromaffin-like cell microinvasive dysplastic lesions arising at the epithelial renewal zone level, in connection with immature proliferating mucous-neck cells, were found to be linked to early intramucosal neuroendocrine tumor histogenesis. Both enterochromaffin-like cell dysplasia and severe hyperplasia indicate increased risk of neuroendocrine tumor development in type A chronic atrophic gastritis with hypergastrinemia/G-cell hyperplasia.

Keywords: Dysplasia; ECL cell; Hyperplasia; Neuroendocrine tumor; Preneoplastic lesions; Stomach.

MeSH terms

  • Comorbidity
  • Disease Progression
  • Endoscopy, Gastrointestinal
  • Enterochromaffin Cells / pathology*
  • Follow-Up Studies
  • Gastric Mucosa / pathology*
  • Gastritis, Atrophic / complications
  • Gastritis, Atrophic / mortality
  • Gastritis, Atrophic / pathology*
  • Humans
  • Hyperplasia
  • Italy / epidemiology
  • Kaplan-Meier Estimate
  • Neuroendocrine Tumors / etiology
  • Neuroendocrine Tumors / mortality
  • Neuroendocrine Tumors / pathology*
  • Precancerous Conditions / pathology*
  • Prognosis
  • Pyloric Antrum / pathology
  • Risk Factors
  • Stomach Neoplasms / complications
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*
  • Survival Rate