Small neuroendocrine proliferations in columnar mucosa at or near the gastroesophageal junction: a finding potentially related to proton pump inhibitor use and/or gastroesophageal reflux disease

AIMS: Neuroendocrine proliferations have been described in gastrointestinal (GI) mucosa associated with chemoradiation and inflammatory bowel disease (IBD) and can also be seen in gastric mucosa in hypergastrinemic conditions. We have encountered small clusters of neuroendocrine cells in the lamina propria, designated herein as neuroendocrine micronodules (NMs), in biopsies taken at and around the gastroesophageal junction (GEJ) in patients without histories of chemoradiation, IBD or autoimmune metaplastic atrophic gastritis (AMAG) and sought to further characterize their clinicopathological features. METHODS: Nine patients with NMs were identified during routine signout. An additional 66 consecutive patients with GEJ biopsies containing ≥1 fragment of columnar mucosa were prospectively evaluated. NMs were identified on haematoxylin and eosin staining and confirmed with chromogranin A immunohistochemistry. RESULTS: NMs were identified in 8% (5/66) of GEJ biopsies in the prospective cohort. Of the 14 total patients with NMs, the median age was 51 years (range 25-78 years) with slight male predominance (1.7:1). 79% reported proton pump inhibitor (PPI) use, 71% had gastroesophageal reflux disease (GERD) and 36% had hiatal hernia. None had IBD, chemoradiation or prior neuroendocrine neoplasia. Associated histological findings included pancreatic metaplasia in 57%, intestinal metaplasia in 7% and linear neuroendocrine cell hyperplasia in 64%. Twelve patients had concurrently sampled oxyntic mucosa and all lacked evidence of AMAG. CONCLUSIONS: NMs at the GEJ can be found in up to 8% of unselected biopsies and may occur in patients without AMAG. Possible aetiologies include PPI-associated ECL hyperplasia and/or GERD-mediated injury; however, definitive characterization requires further studies.