Not all that is corpus restricted is necessarily autoimmune

We read with interest the paper by Rugge et al on the longterm natural history in Helicobacter pylori (Hp)negative patients with autoimmune gastritis (AIG) whose main findings were that (1) corpusrestricted inflammation, pseudopyloric (PPM) rather than intestinal metaplasia (IM), and enterochromaffin like (ECL)cell hyperplasia and neoplasia were the main histopathological hallmarks associated with AIG; (2) patients with AIG seem not to have an increased gastric cancer (GC)risk when previous/current Hp infection is thoroughly excluded, but surveillance for type1 gastric neuroendocrine tumours (t1gNETs) risk may be performed. We fully agree that corpusrestricted inflammation, ECLcell hyperplasia, t1gNETs and PPM are findings commonly associated with AIG, although not exclusively present. ECLcell hyperplasia is the consequence of increased gastrin and a result of impaired gastric acid secretion due to oxyntic glands atrophy, over time possibly leading to t1gNETs occurrence. ECLcell hyperplasia and, occasionaly, t1gNETs may occur in patients with Hprelated corpuspredominant gastric atrophy and on longterm treatment with proton pump inhibitors, thus questioning its role as a histopathological marker for AIG. PPM is a histopathological alteration considered a benign, regenerative adaptation to gastric mucosal injuries including autoimmune and Hpinduced gastritis. When injury persists, this adaptive response may progress to IM or, sometimes, to metaplastic lineages with incomplete transition endpoint metaplasia likely representing the preneoplastic field of cancerisation. In the cited study, 25% of patients with AIG were at an early stage (20% with nonatrophic oxyntic mucosa, 5% with nonmetaplastic atrophy) and the PPM score (95%) was higher than IM (76%). PPM seems to protect from neoplastic development in corpus atrophic gastritis, while neoplastic progression seems to be associated with IM, in particular when present without PPM. In addition to the accurate exclusion of Hp infection, the high prevalence of benign PPM together with the early stage of AIG might provide a further explanation for the lack of GC findings at followup. Considerable efforts were done to include a ‘pure’, possibly unbiased population of patients with AIG based not only on the histopathological key feature of corpusrestricted atrophy with a spared antrum (considered alone sufficient to diagnose AIG) but also on parietal cells autoantibodies (PCA)positivity and Hpnegativity at several tests including molecular tests. But, corpusrestricted atrophy is always linked to gastric autoimmunity only? Chronic Hp gastritis may show a pylorocardial extension and, over time, progression of corpus atrophic lesions may be associated with antral mucosa healing, possibly ending up as severe corpusrestricted atrophic gastritis resembling AIG. In severe corpus atrophic gastritis, histopathological detection of Hp is challenging and commonly available serology assays and noninvasive tests for diagnosis of Hp infection (urea breath test, stool antigen tests) may be unreliable. Considering the high prevalence of Hp infection, a causal or casual association may be indistinguishable. PCA are considered serological hallmarks of AIG but are found in about 20% of the general population. In patients with clinical suspicion of corpus atrophic gastritis, PCA yielded a specificity and sensitivity of 88%–77% showing suboptimal diagnostic reliability decreasing with increasing age. In conclusion, the cited paper raises two points: (1) clearly defined and universally shared diagnostic criteria for AIG are urgently needed, as corpusrestricted atrophy, PCA positivity, and/or Hpnegativity with the commonly available tests may be insufficient to accurately diagnose AIG; (2) clearcut criteria to assess or to rule out Hp in corpusrestricted atrophic gastritis should be defined (including histopathology, accurate personal history of previous eradication treatment, serology and/or other tests). This should lead to unbiased studies on AIG avoiding misdiagnosis/misclassification and yielding comparable results to correctly understand the natural history of this intriguing condition.