Stomach
Gastritis
Autoimmune gastritis
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PubMed Search: Autoimmune gastritis[TI] stomach pathology
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Positive stains | Negative stains | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Franklin MM, Hanson JA. Autoimmune gastritis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stomachautoimmunegastritis.html. Accessed March 22nd, 2023.
Definition / general
- Chronic atrophic gastritis characterized by destruction of oxyntic glands in gastric body with circulating antiparietal cell (APC) and anti-intrinsic factor (AIF) antibodies
Essential features
- Immune mediated destruction of oxyntic glands with progressive atrophy and metaplasia of gastric body
- Preneoplastic syndrome: predisposes to well differentiated neuroendocrine tumors (type 1) and gastric adenocarcinoma
- Associated with type 1 diabetes, autoimmune thyroid disease and other polyglandular autoimmune syndromes
- Iron deficiency and vitamin B12 deficiency (pernicious anemia)
- Serum tests: increased gastrin, decreased pepsinogen 1/pepsinogen 2 ratio, APC and AIF antibodies, B12 deficiency
Terminology
- Metaplastic chronic atrophic gastritis
- Chronic autoimmune atrophic gastritis
- Type A gastritis (Autoimmun Rev 2014;13:459)
ICD coding
- ICD-10: K29.40 - Chronic atrophic gastritis without bleeding
Epidemiology
- F:M = 3:1 (Autoimmun Rev 2019;18:215)
- Commonly presents in patients > 60 years old
- Prevalence: 2% in general population (Best Pract Res Clin Endocrinol Metab Dec 11 [Epub ahead of print])
- Higher frequency in patients with type 1 diabetes mellitus, autoimmune thyroid disease, thyrogastric autoimmune disease and other polyglandular autoimmune syndromes
Sites
- Atrophic and metaplastic changes restricted to oxyntic mucosa in gastric body and fundus
- Gastric antrum may demonstrate reactive gastropathy-like features but is not overtly inflamed
Pathophysiology
- Believed to arise through one of two mechanisms:
- Primary autoimmune disease with circulating antiparietal cell and anti-intrinsic factor antibodies
- Gastric H/K ATPase reactive CD4+ T cells involved in destruction of native oxyntic glands
- Chronic stimulation of B cells by T cells triggers formation of APC and AIF antibodies
- Achlorhydria induces G cell hyperplasia and overproduction of gastrin from G cells
- Increased gastrin stimulates ECL cell hyperplasia in the gastric body (predisposing to well differentiated, type I neuroendocrine tumors) (Clin J Gastroenterol 2019 Nov 28 [Epub ahead of print])
- Gastric body epithelium regenerates through metaplastic glands including pseudopyloric (most common), intestinal or pancreatic acinar type (Surg Pathol Clin 2017;10:801)
- Chronic immunologic process involving molecular mimicry, secondary to longstanding infection with Helicobactor pylori
- Cross reactive epitopes exist on beta subunit of H. pylori urease and beta subunit of ATPase on parietal cells (Autoimmun Rev 2019;18:215)
- Primary autoimmune disease with circulating antiparietal cell and anti-intrinsic factor antibodies
Etiology
- Exact causation is unknown but likely combination of genetic and environmental factors
Clinical features
- Iron deficiency anemia via malabsorption, due to achlorhydria (early finding) (Wien Med Wochenschr 2016;166:424)
- Acid maintains nonheme iron in more readily absorbable ferrous state (Autoimmun Rev 2014;13:459)
- Acid necessary to degrade protein bound iron
- Pernicious anemia via malabsorption, due to lack of intrinsic factor which binds B12 for absorption in the terminal ileum (late finding) (Wien Med Wochenschr 2016;166:424)
- Nonspecific upper gastrointestinal complaints such as dysmotility type dyspepsia (Autoimmun Rev 2019 Mar;18:215)
- Delayed gastric emptying due to achlorhydria
Diagnosis
- Relies on combination of clinical, serologic and histopathologic findings
- Presence of consistent serologic findings are not necessary diagnostic criteria if there are typical histologic lesions; autoantibodies may be absent in late stage
- Recommendations for biopsy (Best Pract Res Clin Endocrinol Metab 2019 Dec 11 [Epub ahead of print]):
- Body: 2 random
- Incisura: 1 random
- Antrum: 2 random
Laboratory
- Serologic findings may include (World J Gastroenterol 2015;21:12179):
- Elevated serum gastrin
- Decreased pepsinogen I (decreased pepsinogen I/pepsinogen II ratio) due to loss of zymogenic chief and mucous neck cells from oxyntic mucosa, while antral glands sustain pepsinogen II secretion
- APC antibodies: serum level correlates with inflammatory involvement of oxyntic mucosa
- AIF antibodies: serum level correlates with mucosal atrophy
- Hematologic findings may include:
- Pernicious anemia (macrocytic anemia)
- Iron deficiency anemia (microcytic anemia)
Case reports
- 3 year old boy with immune dysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome (BMC Pediatr 2018;18:191)
- 12 and 17 year old girls with iron deficiency anemia and negative family history for autoimmune disorders (Front Pediatr 2018;6:123)
- 41 year old woman with gastric neuroendocrine tumor and chronic autoimmune atrophic gastritis (Transl Gastroenterol Hepatol 2016;1:85)
- 53 year old woman with gastric neuroendocrine tumor and duodenal gastrinoma, with chronic autoimmune atrophic gastritis (Pancreas 2019;48:131)
- 62 year old woman with two types of gastric cancer caused by the same underlying condition (Gastroenterology 2018;154:1246)
Treatment
- No effective treatments directed against the gastritis
- B12 supplementation for pernicious anemia
- Antrectomy is definitive therapy for type 1 neuroendocrine tumors, though smaller tumors may be amenable to polypectomy
Gross description
- Early disease:
- No gross findings, stomach appears normal
- Late disease:
- Pseudopolypoid appearance due to patchy sparing of oxyntic glands surrounded by atrophy or irregular flattening of gastric rugae
- Diffuse erythema of the gastric body
- Loss of rugal folds
Microscopic (histologic) description
- Spectrum of disease can be described by 4 chronologic, sometimes overlapping, phases in oxyntic mucosa (World J Gastroenterol 2015;21:12179):
- Patchy lymphoplasmacytic infiltrate in the lamina propria, full thickness and bottom heavy; rare eosinophils and neutrophils
- Destruction of oxyntic glands with associated pseudopyloric metaplasia and dense, full thickness lymphoplasmacytic infiltrate in the lamina propria
- Progressive gland destruction accompanied by intestinal or pancreatic acinar metaplasia
- Complete replacement of oxyntic glands with metaplastic epithelium; lacks prominent inflammatory component due to destruction of target
- Other potential background findings include:
- Linear or nodular enterochromaffin-like (ECL) cell hyperplasia due to achlorhydria stimulating increased gastrin secretion from the antral G cells, which may lead to type 1 well differentiated neuroendocrine tumors
- Intestinal type dysplasia-adenocarcinoma sequence
- Antral changes often mimic reactive gastropathy and show G cell hyperplasia
Microscopic (histologic) images
Contributed by Joshua A. Hanson, M.D.
Atrophic gastric body
Gastrin stain, body
Chromogranin stain, body
Antrum in autoimmune gastritis
Gastrin stain, antrum
Virtual slides
Images hosted on other servers:
Autoimmune gastritis
Positive stains
- ECL cell hyperplasia can be highlighted by chromogranin IHC performed on atrophic oxyntic mucosa
Negative stains
Sample pathology report
- Stomach, body, biopsy:
- Gastric body mucosa with chronic atrophic gastritis, consistent with autoimmune gastritis (see comment)
- Comment: The gastric body demonstrates panmucosal chronic inflammation with pseudopyloric metaplasia and focal intestinal metaplasia. A negative gastrin IHC stain confirms the aforementioned biopsy location. A chromogranin stain shows linear and micronodular ECL cell hyperplasia and an H. pylori stain is negative. The features are consistent with autoimmune gastritis. Correlation with appropriate serologic studies is recommended.
Differential diagnosis
- Multifocal atrophic H. pylori gastritis:
- Involves antrum in addition to body and fundus
- Atrophic body / fundus changes can mimic autoimmune gastritis, especially if the antrum is not concurrently biopsied
- Long standing H. pylori infection is causative agent and can still be demonstrated by IHC stain
- ECL cell hyperplasia is not a feature of multifocal atrophic H. pylori gastritis
- Typical H. pylori gastritis:
- Predominantly involves gastric antrum demonstrating chronic or acute inflammation in top heavy band-like distribution
- Atrophy of oxyntic mucosa is not seen
- H. pylori visible on H&E or with IHC
Board review style question #1
A 45 year old woman presents with anemia and mild epigastric pain. A stomach biopsy is taken that demonstrates intestinal metaplasia. The pathologist is uncertain if this is antral mucosa or atrophic body mucosa. What immunohistochemical stain can be used to differentiate atrophic gastric body mucosa from gastric antral mucosa in this case of suspected autoimmune gastritis?
- Chromogranin
- CDX2
- CK7
- Gastrin
Board review style answer #1
Board review style question #2
What is the classic distribution of the inflammatory pattern typically seen in autoimmune gastritis?
- Antral predominant gastritis with mildly inflamed oxyntic mucosa
- Cardiac lymphoid aggregates and normal antral/oxyntic mucosa
- Diffuse antral and oxyntic gastritis with intestinal metaplasia of antral mucosa
- Oxyntic predominant gastritis with atrophic changes and intestinal metaplasia
Board review style answer #2
D. Oxyntic predominant gastritis with atrophic changes and intestinal metaplasia
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Reference: Autoimmune gastritis
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