Histologic features in an autoimmune gastritis patient with hypergastrinemia: Call for a grading system for G cell hyperplasia

Abstract Introduction/Objective Autoimmune gastritis (AG) is characterized by oxyntic glands destruction, metaplasia, enterochromaffin-like endocrine cell abnormality and G-cell hyperplasia with hypergastrinemia. The gastrin level can be extraordinarily high in certain cases to justify suspicion of Zollinger-Ellison syndrome. We herein report one such case and discuss clinical implication of a grading system for G-cell hyperplasia to correlate histology with gastrin levels. Methods/Case Report The patient was a symptomatic 65 year-old female with hypergastrinemia (2,068 pg/mL), negative abdomen/pelvis CT scan, positive anti-intrinsic factor and anti-parietal cell antibodies. Under esophagogastroduodenoscopy, biopsies were obtained from gastric cardia, fundus, corpus, incisura angularis, and antrum. Morphology and immunostains confirmed autoimmune gastritis. Diffuse linear pattern G-cell hyperplasia was evident in antrum and incisura angularis, counting up to 200 G-cells per linear millimeter. One study defined G-cell hyperplasia as >140 gastrin-positive cells per linear millimeter while another proposed a 2-tier stratification, i.e., simple hyperplasia (4-5 cells for each gland) and linear hyperplasia (continuous chain-like distribution of G-cells). Such scoring, however, was largely qualitative and fell short in delineating the extent of G-cell hyperplasia and correlation with gastrinemia. Results (if a Case Study enter NA) NA Conclusion Lack of G-cell grading system hindered our unequivocal determination of the G-cell hyperplasia as underlying or contributing cause of hypergastrenemia. The unique features of our case highlighted the necessity for installing a practical grading system that incorporates G-cell density, pattern (linear vs. nodular), extent of involved areas, other features of AG to correspond to gastrin level. With accumulation of clinical information, one such grading system is feasible and will improve our knowledge and patient care.

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Progression From Antral G-Cell Hyperplasia to Gastric Neuroendocrine Tumor in a Patient With Autoimmune Gastritis

ACG Case Reports Journal ◽

10.14309/crj.0000000000000649 ◽

2021 ◽

Vol 8 (8) ◽

pp. e00649

Author(s):

Patrick Brown ◽

Bhavana Tetali ◽

Suraj Suresh ◽

Adarsh Varma

Keyword(s):

Neuroendocrine Tumor ◽

Autoimmune Gastritis ◽

Cell Hyperplasia ◽

G Cell

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Marked Hypergastrinemia with G-cell Hyperplasia in Two Autoimmune Gastritis Patients

Internal Medicine ◽

10.2169/internalmedicine.3009-19 ◽

2020 ◽

Vol 59 (6) ◽

pp. 799-803

Author(s):

Hirotaka Watanabe ◽

Sho Yoneda ◽

Yuichi Motoyama ◽

Kosuke Mukai ◽

Yosuke Okuno ◽

...

Keyword(s):

Autoimmune Gastritis ◽

Cell Hyperplasia ◽

G Cell

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Clinical Usefulness of the Serological Gastric Biopsy for the Diagnosis of Chronic Autoimmune Gastritis

Clinical and Developmental Immunology ◽

10.1155/2012/520970 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 25

Author(s):

Antonio Antico ◽

Marilina Tampoia ◽

Danilo Villalta ◽

Elio Tonutti ◽

Renato Tozzoli ◽

...

Keyword(s):

Atrophic Gastritis ◽

Intrinsic Factor ◽

Vitamin B12 Deficiency ◽

Chronic Atrophic Gastritis ◽

Autoimmune Gastritis ◽

Parietal Cell Antibodies ◽

B12 Deficiency ◽

Gastric Biopsies ◽

High Concentrations ◽

Highly Correlated

Aim. To assess the predictive value for chronic autoimmune gastritis (AIG) of the combined assay of anti-parietal-cell antibodies (PCA), anti-intrinsic-factor antibodies (IFA), anti-Helicobacter pylori(Hp) antibodies, and measurement of blood gastrin.Methods. We studied 181 consecutive patients with anemia, due to iron deficiency resistant to oral replacement therapy or to vitamin B12 deficiency.Results. 83 patients (45.8%) tested positive for PCA and underwent gastroscopy with multiple gastric biopsies. On the basis of the histological diagnosis, PCA-positive patients were divided into 4 groups: (1) 30 patients with chronic atrophic gastritis; they had high concentrations of PCA and gastrin and no detectable IFA; (2) 14 subjects with metaplastic gastric atrophy; they had high PCA, IFA, and gastrin; (3) 18 patients with nonspecific lymphocytic inflammation with increased PCA, normal gastrin levels, and absence of IFA; (4) 21 patients with multifocal atrophic gastritis with “borderline” PCA, normal gastrin, absence of IFA and presence of anti-Hp in 100% of the cases.Conclusions. The assay of four serological markers proved particularly effective in the diagnostic classification of gastritis and highly correlated with the histological profile. As such, this laboratory diagnostic profile may be considered an authentic “serological biopsy.”

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Autoimmune Gastritis

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2019-0345-ra ◽

2019 ◽

Vol 143 (11) ◽

pp. 1327-1331 ◽

Cited By ~ 6

Author(s):

Sara N. Hall ◽

Henry D. Appelman

Keyword(s):

Intrinsic Factor ◽

Chronic Atrophic Gastritis ◽

Autoimmune Gastritis ◽

Cell Hyperplasia ◽

Oxyntic Mucosa ◽

Factor Deficiency ◽

Proper Diagnosis ◽

Gastric Biopsies ◽

Intrinsic Factor Deficiency ◽

Important Disease

Context.— Autoimmune gastritis (AG) is a corpus-restricted chronic atrophic gastritis associated with intrinsic factor deficiency, either with or without pernicious anemia. Autoimmune gastritis is a microscopic disease because patients present with no or vague symptoms, and clinicians rarely find endoscopic changes. Autoimmune gastritis only becomes a clinical disease when pathologists diagnose it in gastric biopsies performed for a variety of clinical indications. Unfamiliarity with this disease can result in misdiagnosis of patients, and thus inadequate patient management. Objective.— To review the pathogenesis, clinical features, diagnostic criteria, differential diagnoses, sequelae, and surveillance recommendations for AG. Data Sources.— The sources of the study include a review of the pertinent literature for AG. Conclusions.— Autoimmune gastritis is an important disease characterized by a loss of oxyntic mucosa and presence of metaplastic epithelium and enterochromaffin-like cell hyperplasia. Awareness and proper diagnosis are critical to prevent mismanagement of patients.

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Expression of the C-terminal flanking peptide of human progastrin in human gastroduodenal mucosa, G-cell hyperplasia and islet cell tumours producing gastrin

Molecular and Cellular Probes ◽

10.1016/0890-8508(87)90010-7 ◽

1987 ◽

Vol 1 (1) ◽

pp. 95-108 ◽

Cited By ~ 3

Author(s):

M. Hara ◽

I.M. Varndell ◽

A.E. Bishop ◽

M. Aitchison ◽

J. Rode ◽

...

Keyword(s):

Islet Cell ◽

Cell Hyperplasia ◽

G Cell ◽

Gastroduodenal Mucosa ◽

Islet Cell Tumours

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The Input-Output Organization Of a Pair of Giant Neurones in the Mollusc, Anisodoris Nobilis (MACFARLAND)

Journal of Experimental Biology ◽

10.1242/jeb.51.3.615 ◽

1969 ◽

Vol 51 (3) ◽

pp. 615-634

Author(s):

A. L. F. GORMAN ◽

M. MIROLLI

Keyword(s):

Synaptic Contact ◽

Excitatory Input ◽

Cell Functions ◽

G Cells ◽

G Cell ◽

Intracellular Stimulation ◽

Peripheral Cells ◽

P Cells ◽

Post Synaptic Potential ◽

Stimulation Of

1. Each of the two gastro-oesophageal ganglia of the nudibranch mollusc, Anisodoris nobilis, contains one giant neurone (G cell) whose axon is directed toward the oesophagus in the gastro-oesophageal nerve. 2. In the absence of stimulation the G cells are normally silent. However, they receive inhibitory and excitatory synaptic inputs from more central ganglia and a predominantly excitatory input from the periphery. The inputs from the central ganglia are bilaterally distributed to both G cells, whereas the inputs from the periphery are limited to the ipsilateral G cell. 3. Intracellular stimulation shows that there is no interaction between the G cells, nor between the G cell and other cells in the same or contralateral gastro-oesophageal ganglia. 4. The axon of the G cell makes synaptic contact with a series of peripheral cells (P cells). In most P cells the post-synaptic potential elicited by intracellular stimulation of the G cell is constant in amplitude and latency and probably results from a unitary monosynaptic contact. Intracellular stimulation shows that the P cells are not connected to the G cell. 5. The P cells are inter-connected by low-resistance electrotonic junctions which allow slow potentials of either polarity to spread between cells. These junctions exist between distant as well as adjacent peripheral neurones. 6. Our results show that the G cell functions as a command interneurone for an aggregate of electrically interconnected peripheral neurones.

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Single-cell transcriptional analyses of spasmolytic polypeptide-expressing metaplasia arising from acute drug injury and chronic inflammation in the stomach

Gut ◽

10.1136/gutjnl-2019-318930 ◽

2019 ◽

Vol 69 (6) ◽

pp. 1027-1038 ◽

Cited By ~ 6

Author(s):

Kevin A Bockerstett ◽

Scott A Lewis ◽

Kyle J Wolf ◽

Christine N Noto ◽

Nicholas M Jackson ◽

...

Keyword(s):

Gastric Mucosa ◽

Epithelial Cells ◽

Single Cell ◽

Chronic Inflammation ◽

Intrinsic Factor ◽

Drug Induced ◽

Cell Hyperplasia ◽

Tissue Samples ◽

Spasmolytic Polypeptide ◽

The Individual

ObjectiveSpasmolytic polypeptide-expressing metaplasia (SPEM) is a regenerative lesion in the gastric mucosa and is a potential precursor to intestinal metaplasia/gastric adenocarcinoma in a chronic inflammatory setting. The goal of these studies was to define the transcriptional changes associated with SPEM at the individual cell level in response to acute drug injury and chronic inflammatory damage in the gastric mucosa.DesignEpithelial cells were isolated from the gastric corpus of healthy stomachs and stomachs with drug-induced and inflammation-induced SPEM lesions. Single cell RNA sequencing (scRNA-seq) was performed on tissue samples from each of these settings. The transcriptomes of individual epithelial cells from healthy, acutely damaged and chronically inflamed stomachs were analysed and compared.ResultsscRNA-seq revealed a population Mucin 6 (Muc6)+gastric intrinsic factor (Gif)+ cells in healthy tissue, but these cells did not express transcripts associated with SPEM. Furthermore, analyses of SPEM cells from drug injured and chronically inflamed corpus yielded two major findings: (1) SPEM and neck cell hyperplasia/hypertrophy are nearly identical in the expression of SPEM-associated transcripts and (2) SPEM programmes induced by drug-mediated parietal cell ablation and chronic inflammation are nearly identical, although the induction of transcripts involved in immunomodulation was unique to SPEM cells in the chronic inflammatory setting.ConclusionsThese data necessitate an expansion of the definition of SPEM to include Tff2+Muc6+ cells that do not express mature chief cell transcripts such as Gif. Our data demonstrate that SPEM arises by a highly conserved cellular programme independent of aetiology and develops immunoregulatory capabilities in a setting of chronic inflammation.

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The Hidden Face of Pernicious Anemia: Age-Related Progression of Autoimmune Gastritis from Iron Deficiency to Cobalamin Depletion.

Blood ◽

10.1182/blood.v106.11.3603.3603 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3603-3603

Author(s):

Chaim Hershko ◽

Aharon Ronson ◽

Moshe Souroujon ◽

Yzhak Maschler ◽

Judith Heyd ◽

...

Keyword(s):

Iron Deficiency ◽

Atrophic Gastritis ◽

Pernicious Anemia ◽

Serum Gastrin ◽

Screening Method ◽

Intrinsic Factor ◽

Autoimmune Gastritis ◽

Deficiency Anemia ◽

Age Cohorts ◽

H Pylori

Abstract Because gastric acid secretion is critical for food iron absorption, iron deficiency is a known complication of the achlorhydria associated with pernicious anemia at presentation or following cobalamin (Cbl) treatment. In a previous study employing high serum gastrin and strongly positive antiparietal cell antibodies as a screening method for autoimmune atrophic gastritis, we have found a very high (27%) prevalence of atrophic gastritis among young subjects with iron deficiency anemia (IDA). The objectives of the present study were to explore the degree of overlap between patients presenting with atrophic gastritis and microcytic (MVC<80 fl) IDA on one hand, and those presenting with Cbl deficiency and normocytic (MCV 80–100 fl) or macrocytic (MCV>100 fl) anemia typical of pernicious anemia. Of 160 patients diagnosed with autoimmune gastritis presenting with iron, Cbl, or combined deficiency over the years 2001–2005, 83 presented with microcytic IDA, 48 with normocytic and 29 with macrocytic indices. Serum Cbl was abnormal in 100% of macrocytic, 92% of normocytic and 46% of microcytic subjects. IDA patients were 21 y younger (41 ±15 vs 62±15 y), predominantly female (78 vs 41%) and with a higher proportion of active H pylori infection (42 vs 21%). However, there were also marked similarities between all subgroups including a high prevalence of thyroid disease (20%) and diabetes (8%) known for their association with the autoimmune polyendocrine syndrome, and the rate of anti-intrinsic factor positivity was the highest (42% vs 31%) among IDA patients. Stratification by age cohorts from <20 to >60 y showed a very regular correlation, with progressive increase in MCV from 68±9 to 119±8 fl, serum ferritin from 4±2 to 37±41 μg/L, hypergastrinemia from 349±247 to 800±627 u/mL (normal 61±17), and a progressive decrease of Cbl from 392±179 in the youngest, to 108±65 pg/mL in the oldest age cohort. The prevalence of H pylori infection was 87.5% at age <20 y, 47% at 20–40 y, 37.5 % at 41–60 y and 12.5% at age > 60y implying a spontaneous elimination of H pylori by achlorhydria of increasing severity and duration. H pylori eradication by triple therapy in 24 patients resulted in a decrease in serum gastrin from 476±391 to 218±220 u/mL (paired t-test=0.00086) within 19± 12 months and complete remission of pernicious anemia in 2 patients. These findings challenge the common notion that pernicious anemia is a disease of the elderly manifested in megaloblastic anemia, and imply a disease starting many years before the establishment of clinical Cbl deficiency through an autoimmune mechanism directed against gastric parietal cells, likely triggered by H pylori by means of antigenic mimicry. Because of the added strain of young age and fertility on iron requirements, IDA may precede Cbl deficiency by many years until the crucial loss of remaining intrinsic factor in a proportion of patients terminating in typical pernicious anemia.

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