Introduction
Autoimmune atrophic gastritis (AAG) is an immune-mediated disorder characterized by atrophy of the gastric corpus mucosa and preservation of the antrum. This condition is marked by the replacement of specialized oxyntic glands with pseudopyloric metaplasia (PPM) and/or intestinal metaplasia (IM) (1,2). Two main subtypes of gastric IM have been described: complete (cIM) which resembles the epithelium of the small intestine, containing Paneth cells (PanC), absorptive cells with a brush border (BB), and goblet cells (gobC), and incomplete (icIM) which exhibits histological features similar to the colonic epithelium, typically lacking PanC and/or absorptive cells (3,4). Gastric IM may progress to dysplasia (GD) and ultimately to cancer (GC), with the icIM subtype being more strongly associated with an elevated risk of neoplastic transformation (2,5).Surveillance of atrophic gastritis is particularly recommended in icIM (6,7). AAG has been reported to be associated to cIM rather than icIM(8) and also for this reason GC risk in AAG has been reported to be negligible (9).
Aims & Methods
To characterize the IM subtype in AAG patients who developed GC or GD in order to clarify the relationship between cIM or icIM and gastric neoplastic lesions in AAG.
We conducted a case-control study by performing histopathological assessment of gastric IM on formalin-fixed paraffin-embedded gastric corpus mucosa biopsies obtained from two groups:
1) cases (AAG GC+ or GD+): AAG pts (n=15, F 86%, median age 69) who developed GC (n=8) or GD (n=8) at AAG diagnosis or during long-term follow-up (FU) (median 7, range 0-13 yrs).
2) controls (AAG GC-GD-): AAG pts (n=38, F 60%, age 56 yrs) monitored for at least once 3 yrs after diagnosis who did not develop GC or GD over long-term FU (median 6 yrs, 3-17).
AAG was histologically diagnosed (1,2) and pts (cases or controls) with H.pylori (Hp) positivity at histology and/or serology and/or previous history of Hp were excluded.
Histopathological subtyping of gastric IM was performed on haematohylin-eosin-stained slides. cIM was defined by the presence intestinal metaplastic epithelium containing Paneth cells (PanC), goblet cells (gobC) and absorptive enterocytes with a brush border (BB)(9).
Results
AAG GC+GD+ (cases, n=15) and AAG GC-GD- (controls, n=37) were similar for sex, age, 1st degree family history of GC, parietal cell autoantibodies positivity, presence of PPM and long-term FU.
The presence of PanC (13/15, 87% vs 31/37, 84%, p=0.80), gobC (15/15, 100% vs 37/37, 100%, p=1.00), and BB (14/15, 93% vs 35/37, 95%, p=0.86) was similar in AAG GC+GD+ and AAG GC-GD- pts. The presence of all 3 markers of cIM (PanC, gobC, BB) was found in 12/15 (80%) AAG GC+GD+ and 31/37 (81%) AAG GC-GD- pts (p=0.75). Also, the various combinations of these markers (PanC+gobC, PanC+BB, gobC+BB) were similar between groups: 87% vs 81%, 67% vs 81%, and 93% vs 95%, respectively (p>0.05). All pts had at least 2 of 3 markers.
Conclusion
Eighthy percent of AAG pts with GC or GD exhibited all defining histological features of cIM, including the presence of PanC, gobC, and absorptive cells with a BB, compared to 81% of AAG pts without neoplastic lesions.
In AAG with and without GC or GD, cIM is more common than icIM and gastric neoplastic lesions may occur in the absence of icIM. Therefore, icIM is not reliable as predictor for neoplastic risk and further studies are needed to identify new markers of neoplastic progression in AAG pts.
References
1) Lenti MV et al. Autoimmune gastritis. Nat Rev Dis Primers 2020
2) Rugge M et al. RE.GA.IN: the Real-world Gastritis Initiative-updating the updates. Gut 2024
3) El Zimaity HMT et al. Gastric intestinal metaplasia: subtypes and natural history. J Clin Pathol 2001
4) Sugano K et al. Gastric Intestinal Metaplasia: Real Culprit or Innocent Bystander as a Precancerous Condition for Gastric Cancer? Gastroenterology 2023
5) Du S et al. Gastric Cancer Risk of Intestinal Metaplasia Subtypes: A Systematic Review and Meta-Analysis of Cohort Studies. Clinical and Translational Gastroenterology 2021
6) Shah SC et al. AGA Clinical Practice Update on the Diagnosis and Management of Atrophic Gastritis: Expert Review. Gastroenterology. 2021
7) Dinis-Ribeiro M et al. Management of epithelial precancerous conditions and early neoplasia of the stomach (MAPS III): European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter and Microbiota Study Group (EHMSG) and European Society of Pathology (ESP) Guideline update 2025. Endoscopy 2025
8) Genta R et al. Incomplete Intestinal Metaplasia Is Rare in Autoimmune Gastritis. Dig Dis 2023
9) Rugge M et al. Autoimmune gastritis: long-term natural history in naïve Helicobacter pylori-negative patients. Gut 2023