Lymphocytic Gastritis

Background

Lymphocytic gastritis is a rare gastritis primarily diagnosed by the surgical pathologist. There is a peculiar infiltration of benign lymphocytes into the glands and surface mucosa. It may be associated with celiac disease and Helicobacter infection of the stomach. There are case reports of clearing of the disease by treatment for Helicobacter infection in the stomach.

OUTLINE

Epidemiology

Disease Associations Celiac disease

Pathogenesis Helicobacter

Laboratory/Radiologic/Other Diagnostic Testing

Histopathological Features and Variants

Differential Diagnosis Graft versus host disease

Prognosis General
Malignancy

Treatment Helicobacter eradication

Commonly Used Terms

Internet Links

EPIDEMIOLOGY CHARACTERIZATION

SYNONYMS

INCIDENCE/PREVALENCE

Lymphocytic gastritis: a study of its frequency and review of the literature.

Ribeiro VL, Barbosa AJ.

Department of Pathological Anatomy and Forensic Medicine, Federal University, Minas Gerais School of Medicine, FM-UFMG, Belo Horizonte, MG, Brazil.

Arq Gastroenterol 1998 Jan-Mar;35(1):26-31 Abstract quote
Lymphocytic gastritis is currently recognized as a special type of chronic gastritis characterized by a large number of intraepithelial lymphocytes in antral or oxyntic mucosa.

The frequency of lymphocytic gastritis rarely exceeds 5% of the histologic diagnosis of gastric biopsies. This diagnosis can be easily made by intraepithelial lymphocyte counts in preparations stained with hematoxylin and eosin. Very little is known about the etiopathogeny, clinical significance and evolution of the disease.

The objective of the present study was to investigate the frequency of lymphocytic gastritis in gastric mucosa biopsies from the antrum and body in patients submitted to upper digestive endoscopy in Belo Horizonte, MG, Brazil. Histological sections of antral and oxyntic mucosa from 400 patients with no gastric ulcer or neoplasia of the gastrointestinal tract were analyzed retrospectively. The following lymphocyte numbers per 100 epithelial cells were obtained: 0 a 5 lymphocytes in 366 patients (91.5%); 6 to 15 lymphocytes in 22 patients (5.5%); 16 to 29 lymphocytes in eight patients (2.0%), and 30 or more lymphocytes in four patients (1%). Patients with 30 or more lymphocytes were considered to have lymphocytic gastritis.

Three of these four cases with lymphocytic gastritis presented an endoscopic diagnosis of enanthematous pangastritis, and one presented erosive pangastritis.

DISEASE ASSOCIATIONS CHARACTERIZATION

CELIAC DISEASE

The pattern of involvement of the gastric mucosa in lymphocytic gastritis is predictive of the presence of duodenal pathology.

Hayat M, Arora DS, Wyatt JI, O'Mahony S, Dixon MF.

Centre for Digestive Diseases, General Infirmary, Leeds, UK.

J Clin Pathol 1999 Nov;52(11):815-9 Abstract quote
AIM: To determine whether the pattern of involvement of the gastric mucosa in lymphocytic gastritis is predictive of the presence or absence of duodenal pathology.

METHODS: 50 cases (M:F, 26:24; median age 57 years) diagnosed as lymphocytic gastritis between 1986 and 1998 with concurrent duodenal (D2) biopsies were identified from a computer search of the pathology records and validated by counting gastric intraepithelial lymphocytes. Gastric and duodenal intraepithelial lymphocyte counts were performed on haematoxylin and eosin (H&E) and anti-CD3 stained sections. D2 biopsies were assessed for villous atrophy and chronic inflammatory cell infiltration by subjective grading, and gastritis was classified and graded according to the updated Sydney system. A case was designated corpus predominant when the corpus chronic inflammation grade exceeded that of the antrum. If it was less, then the case was antrum predominant, and if they were equal it was diffuse (pan-) gastritis. The ratio between the corpus and antral intraepithelial lymphocyte count in individual patients was calculated.

RESULTS: Of 50 cases of lymphocytic gastritis, 21 were classified as corpus predominant. With one exception (a case of mild villous atrophy), all were accompanied by normal duodenal morphology. Cases with a corpus predominant gastritis had median duodenal intraepithelial lymphocyte counts of 19 (H&E) and 14.1 (CD3), whereas 29 subjects with an antrum predominant or diffuse gastritis had median counts of 39.9 (H&E) and 37.9 (CD3). Fifteen of these 29 cases (52%) showed villous atrophy; all were graded as moderate or severe. Patients with any degree of villous atrophy had a mean corpus/antrum intraepithelial lymphocyte ratio (H&E) of 0.59 (representing antral predominance), while those with normal duodenal morphology had a ratio of 2.39 (p < 0.0001).

CONCLUSIONS: The pattern of involvement of gastric mucosa in lymphocytic gastritis is closely related to the associated duodenal pathology. Those with the corpus predominant form are unlikely to have duodenal pathology, while those with an antral predominant or diffuse form should have distal duodenal biopsies taken to exclude villous atrophy.

Lymphocytic gastritis and coeliac disease: evidence of a positive association.

Feeley KM, Heneghan MA, Stevens FM, McCarthy CF.

Department of Pathology, University College Hospital, Galway, Ireland.

J Clin Pathol 1998 Mar;51(3):207-10 Abstract quote
AIMS: To investigate the prevalence of lymphocytic gastritis in patients with coeliac disease.

METHODS: Gastric biopsies from 70 patients with coeliac disease were examined by light microscopy for the presence of lymphocytic gastritis, defined as 25 or more intraepithelial lymphocytes/100 gastric columnar epithelial cells.

RESULTS: Lymphocytic gastritis was found in seven cases. Positive cases had a mean of 32.1 intraepithelial lymphocytes/100 columnar cells, compared with a mean of 13.9 in negative cases, and 5.15 in noncoeliac controls. No differences were found for age, sex, gastric corpus or antrum, or degree of inflammation in the gastric lamina propria. All intraepithelial lymphocytes were of T cell lineage. Cases not showing lymphocytic gastritis did however show significantly increased gastric intraepithelial lymphocytes compared with non-coeliac controls. Eighteen of 70 cases were positive for Helicobacter pylori, and four of seven cases of lymphocytic gastritis were H pylori positive; no significant difference was observed between H pylori positive and negative patients. Three cases had concomitant ulcerative enteritis, of which none showed lymphocytic gastritis, while five cases had concomitant enteropathy associated T cell lymphoma, of which one showed lymphocytic gastritis.

CONCLUSIONS: Lymphocytic gastritis occurred in 10% of patients with coeliac disease. Cases without lymphocytic gastritis nevertheless showed increased gastric intraepithelial lymphocytes. Coeliac disease may on occasion be a diffuse lymphocytic enteropathy occurring in response to gluten. Lymphocytic gastritis outside coeliac disease may involve an immune response to luminal antigens, such as H pylori, not unlike the response to gluten in patients with coeliac disease.

Lymphocytic gastritis: a positive relationship with celiac disease.

De Giacomo C, Gianatti A, Negrini R, Perotti P, Bawa P, Maggiore G, Fiocca R.

Clinica Pediatrica, Universita di Pavia, Italy.

J Pediatr 1994 Jan;124(1):57-62 Abstract quote
Lymphocytic gastritis is characterized by lymphocytic infiltration of the surface and pit epithelium. Its cause has not been established, but an association with Helicobacter pylori infection or celiac disease has been suggested.

We evaluated the histologic features of both gastric and duodenal biopsy specimens from 245 consecutive children and adolescents, and found chronic gastritis in 60 children and celiac disease in 25. Chronic gastritis was associated with H. pylori infection in 36 children and with celiac disease in 15. Lymphocytic gastritis was found in nine children with celiac disease. Children with lymphocytic gastritis had a mean of 40.64 lymphocytes per 100 epithelial cells, compared with a mean of 3.92 lymphocytes per 100 epithelial cells in children with H. pylori-associated gastritis and 5.15 lymphocytes in normal control subjects.

Immunohistochemical studies showed that the intraepithelial lymphocytes in lymphocytic gastritis were T cells. No child with lymphocytic gastritis had serologic evidence of past H. pylori infection.

We conclude that lymphocytic gastritis in children is associated with celiac disease. Dyspeptic symptoms are frequent; the endoscopic appearance is not characteristic.

COLLAGENOUS GASTRITIS

Collagenous gastritis associated with lymphocytic gastritis and celiac disease.

Stancu M, De Petris G, Palumbo TP, Lev R.

Department of Pathology and Laboratory Medicine, Roger Williams Medical Center, Boston University, Providence, RI 02908, USA.
Arch Pathol Lab Med 2001 Dec;125(12):1579-84 Abstract quote
Collagenous gastritis is a rare disorder, with only 8 cases reported in the literature, 2 in children and 6 in adults. We report an additional case of collagenous gastritis in a 42-year-old man with celiac disease. A thickened (>10 microm) subepithelial collagen band with entrapped capillaries, fibroblasts, and inflammatory cells was seen in the stomach, associated with lymphocytic gastritis.

The duodenal mucosa showed severe villous atrophy but no subepithelial collagen deposition. No evidence of lymphocytic or collagenous colitis was found in the colon. The patient became symptom-free on a gluten exclusion diet and showed partial improvement of histopathologic findings after 3 months.

Collagenous gastritis is a rare disease, but a wider recognition of its histopathologic features and clinical associations may bring more cases to light and provide additional clues in determining its etiology and pathogenesis.

PATHOGENESIS CHARACTERIZATION

GRANZYME B

High proportion of granzyme B-positive (activated) intraepithelial and lamina propria lymphocytes in lymphocytic gastritis.

Oberhuber G, Bodingbauer M, Mosberger I, Stolte M, Vogelsang H.

Department of Clinical Pathology, University of Vienna, Medical School, Austria.

Am J Surg Pathol 1998 Apr;22(4):450-8 Abstract quote
Intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LpLs) have not been well studied in gastric mucosa, particularly in lymphocytic gastritis. Therefore, they were immunohistologically characterized with antibodies recognizing CD3, CD8, CD57, T cell-restricted intracellular antigen (TIA-1), and granzyme B (GrB).

The TIA-1 labels cytotoxic granules of resting and activated T-cells, whereas GrB decorates activated cytotoxic T cells. Thirty patients with celiac disease, including 20 taking gluten and 10 on a gluten-free diet, 15 patients with nonceliac disease-associated lymphocytic gastritis, and 20 controls were studied. Stained cells were counted and results were given as IELs/100 epithelial cells or percentage of lamina propria cells. Sixty percent to 90% of CD3+ IELs and up to 12% of lamina propria cells contained TIA-1-positive cytotoxic granules.

The number of GrB+ IELs and LpLs was increased in Helicobacter pylori-positive controls (p < 0.03 vs. H pylori-negative controls) and celiac disease patients taking gluten (p < 0.05 vs. controls). The highest number of GrB+ IELs and LpLs was found in nonceliac disease-associated lymphocytic gastritis (p < 0.009 vs. controls, p < 0.05 vs. celiac disease). This study shows that a high proportion of gastric IELs and LpLs is potentially cytotoxic in nature.

Through stimuli not yet identified, a proportion of them becomes activated after H pylori infestation and in lymphocytic gastritis.

HELICOBACTER INFECTION

Effects of Helicobacter pylori eradication on the natural history of lymphocytic gastritis.

Hayat M, Arora DS, Dixon MF, Clark B, O'Mahony S.

Centre for Digestive Diseases, The General Infirmary at Leeds, Leeds, UK.

Gut 1999 Oct;45(4):495-8 Abstract quote
BACKGROUND: Lymphocytic gastritis is characterised by an accumulation of lymphocytes in the surface epithelium of the stomach. Lymphocytic gastritis has been linked to coeliac disease and Helicobacter pylori infection.

AIMS: To determine whether H pylori eradication leads to resolution of the lymphocytic infiltrate and clinical improvement in patients with lymphocytic gastritis, and to determine their HLA status.

METHODS: The Leeds Dyspepsia Questionnaire (LDQ) was administered to 13 patients with lymphocytic gastritis. H pylori serology, (13)C urea breath test (UBT), and upper gastrointestinal endoscopy with sampling of the duodenum, antrum, and corpus were done in all cases and the HLA status was determined. Eleven patients had at least one positive test for H pylori. Patients with lymphocytic gastritis and H pylori infection were treated with a one week course of omeprazole, clarithromycin, and metronidazole. Gastric and duodenal intraepithelial lymphocyte (IEL) counts were performed, along with histological assessment of gastric and duodenal biopsies before and after H pylori eradication.

RESULTS: Two months after treatment there was a significant reduction in gastric IEL counts in both antrum and corpus. There was no significant change in duodenal IEL counts before and after eradication. According to the Sydney grading there was significant improvement in corpus inflammation after eradication. The patients histologically H pylori positive before treatment became H pylori negative. Dyspepsia scores also improved significantly after treatment.

CONCLUSIONS: H pylori eradication treatment in patients with lymphocytic gastritis causes significant improvement in the gastric IEL infiltrate, corpus inflammation, and dyspeptic symptoms. H pylori serology is frequently positive when histology and UBT are negative. Lymphocytic gastritis may represent a specific immune response to H pylori infection.

Helicobacter pylori genotypes may determine gastric histopathology.

Nogueira C, Figueiredo C, Carneiro F, Gomes AT, Barreira R, Figueira P, Salgado C, Belo L, Peixoto A, Bravo JC, Bravo LE, Realpe JL, Plaisier AP, Quint WG, Ruiz B, Correa P, van Doorn LJ.

Institute of Molecular Pathology and Immunology and the Faculty of Medicine, University of Porto, Porto, Portugal.

Am J Pathol 2001 Feb;158(2):647-54 Abstract quote
The outcome of Helicobacter pylori infection has been associated with specific virulence-associated bacterial genotypes.

The present study aimed to investigate the gastric histopathology in Portuguese and Colombian patients infected with H. pylori and to assess its relationship with bacterial virulence-associated vacA, cagA, and iceA genotypes. A total of 370 patients from Portugal (n = 192) and Colombia (n = 178) were studied. Corpus and antrum biopsy specimens were collected from each individual.

Histopathological features were recorded and graded according to the updated Sydney system. H. pylori vacA, cagA, and iceA genes were directly genotyped in the gastric biopsy specimens by polymerase chain reaction and reverse hybridization. Despite the significant differences between the Portuguese and Colombian patient groups, highly similar results were observed with respect to the relation between H. pylori genotypes and histopathology. H. pylori vacA s1, vacA m1, cagA+ genotypes were significantly associated with a higher H. pylori density, higher degrees of lymphocytic and neutrophilic infiltrates, atrophy, the type of intestinal metaplasia, and presence of epithelial damage. The iceA1 genotype was only associated with epithelial damage in Portuguese patients.

These findings show that distinct H. pylori genotypes are strongly associated with histopathological findings in the stomach, confirming their relevance for the development of H. pylori-associated gastric pathology.

LABORATORY/RADIOLOGIC/
OTHER TESTS
CHARACTERIZATION

RADIOLOGIC

LABORATORY MARKERS

MALABSORPTION

Lymphocytic gastritis and protein-losing gastropathy.

Perardi S, Todros L, Musso A, David E, Repici A, Rizzetto M.

Department of Gastroenterology, San Giovanni Battista Hospital of Turin, Italy.
Dig Liver Dis 2000 Jun-Jul;32(5):422-5 Abstract quote
Lymphocytic gastritis is a histopathological entity of unknown aetiology which is characterized by dense surface and foveolar epithelial T-cell infiltration.

We report here an uncommon clinical presentation in a young female presenting with unexplained recurrent weight loss and peripheral oedema. Endoscopic and histological features before and after successful therapy with omeprazole are described.

HISTOLOGICAL TYPES CHARACTERIZATION

GENERAL

Lymphocytic gastritis: association with etiology and topology.

Wu TT, Hamilton SR.

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA.

Am J Surg Pathol 1999 Feb;23(2):153-8 Abstract quote
Lymphocytic gastritis (LG) is an uncommon chronic gastritis characterized by lymphocytosis of foveolar and surface epithelium. Lymphocytic gastritis is associated with celiac disease, Helicobacter pylori (HP) gastritis, and varioliform gastritis, but its topology and severity with respect to the associated entities have not been studied in detail.

Therefore, we studied 103 patients with LG classified according to the associated entities, including the distribution and severity of LG in the 70 patients from whom biopsy specimens of both antrum and body were available. In 84 patients (82%), a distinct associated entity was identified, including 39 with celiac disease, 30 with HP infection, 4 with varioliform gastritis, 2 each with inflammatory polyp, Crohn's disease, human immunodeficiency virus infection, lymphoma, and esophageal carcinoma, and 1 with lymphocytic gastroenterocolitis.

Lymphocytic gastritis was found in 33% of patients with celiac disease and 4.1% of histopathologically defined HP gastritis. The severity of intraepithelial lymphocytosis was greater in antrum than in body in 83% (20 of 24) of LG associated with celiac disease, but in only 19% (4 of 21) of LG associated with HP infection (p < 0.00002). All four patients with varioliform gastritis had more severe involvement of body. Lymphocytic colitis was common (38%, 5 of 13) in celiac disease with LG.

Our results indicate that lymphocytic gastritis most commonly occurs in celiac disease and HP infection, but rarely with other entities. The topology of LG can direct the clinical evaluation for associated disease.

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES

GRAFT VERSUS HOST DISEASE

Lymphocytic gastritis resembling graft-vs.-host disease following autologous hematopoietic cell transplantation.

Tzung SP, Hackman RC, Hockenbery DM, Bensinger W, Schiffman K, McDonald GB.

Division of Clinical Research, Fred Hutchinson Cancer Research Center and the University of Washington, Seattle 98109-1024, USA.

Biol Blood Marrow Transplant 1998;4(1):43-8. Abstract quote
Although cutaneous graft-vs.-host disease (GVHD) has been noted after autologous hematopoietic cell transplantation, intestinal involvement has not been well documented.

We evaluated 197 patients undergoing autologous transplantation for intestinal symptoms; the source for hematopoietic cells was marrow (n=32), peripheral blood stem cells (n=146), or both (n=19). Patients with persistent nausea, vomiting, and anorexia after day 20 underwent upper intestinal endoscopy and mucosal biopsy. Eight patients (4.1%) had diffuse edema, erythema of gastric mucosa, and histological evidence of lymphocytic gastritis with focal apoptosis of crypt epithelial cells-typical of the findings in acute GVHD.

All studies for viral, fungal, or bacterial causes were negative. Two patients showed evidence of GVHD in skin and liver, respectively. All patients received 1 mg/kg/day of oral prednisone for 10 days; symptomatic improvement often occurred within days of therapy onset. At the end of corticosteroid treatment, complete resolution of symptoms was seen in all eight patients. In one patient, elevated serum alkaline phosphatase levels gradually normalized over the ensuing 3-4 weeks. When followed up 3 months after treatment, all patients remained symptom-free without evidence of recurrent intestinal symptoms.

We concluded that recipients of autologous hematopoietic cells may develop intestinal symptoms caused by a lymphocytic gastritis that is typical of acute GVHD. Patients with this syndrome promptly responded to treatment of a short course of prednisone. The pathogenesis of gastric epithelial damage after autologous transplant is unknown.

PROGNOSIS CHARACTERIZATION

GENERAL

Ten year follow up study of lymphocytic gastritis: further evidence on Helicobacter pylori as a cause of lymphocytic gastritis and corpus gastritis.

Niemela S, Karttunen T, Kerola T, Karttunen R.

Department of Internal Medicine, University Hospital of Oulu, Finland

J Clin Pathol 1995 Dec;48(12):1111-6 Abstract quote
AIMS--To examine the course of lymphocytic gastritis and its relation to Helicobacter pylori (H pylori) infection in a 10 year follow up.

METHODS--Ninety six patients were originally examined for dyspepsia in 1981. Gastroscopies with stepwise biopsies were performed on all the patients initially and after an interval of 10 years.

RESULTS--Nine per cent of the patients (9/96) had features of lymphocytic gastritis in gastric biopsy at the first examination, and 12.5% (12/96) at the second examination; 7/9 patients (78%) had persistent lymphocytic gastritis during the follow up; in two the diagnostic features of lymphocytic gastritis had disappeared, and five had a new diagnosis of lymphocytic gastritis at the second examination. At the second examination 9/12 lymphocytic gastritis patients (75%) were H pylori positive histologically, while all had specific antibodies to H pylori. The lymphocytic gastritis patients had higher grades of gastritis (p = 0.009), neutrophilic and eosinophilic granulocytes, mononuclear inflammatory cells, and foveolar hyperplasia in the corpus mucosa, but smaller numbers of H pylori, than the H pylori positive patients without lymphocytic gastritis. The appearance of lymphocytic gastritis during the 10 year interval was associated with increases in the grades of corpus gastritis and neutrophilic granulocytes (p = 0.043 for both). During the follow up, the patients with lymphocytic gastritis, but not the H pylori positive patients without lymphocytic gastritis, appeared to have a significant increase in the grade of intestinal metaplasia in the corpus mucosa (p = 0.043).

CONCLUSIONS--In some patients H pylori may cause a gastritis that predominates in the corpus and is associated with an increase in the intraepithelial lymphocyte count. This form of gastritis may cause progression of intestinal metaplasia.

MALIGNANCY

Lymphocytic gastritis, gastric adenocarcinoma, and primary gastric lymphoma.

Griffiths AP, Wyatt J, Jack AS, Dixon MF.

Department of Histopathology, Neath General Hospital, West Glamorgan.
J Clin Pathol 1994 Dec;47(12):1123-4 Abstract quote
A series of primary gastric lymphomas and adenocarcinomas was reviewed to assess the prevalence of lymphocytic gastritis in these conditions.

Lymphocytic gastritis was more prevalent in patients with gastric adenocarcinoma (16 of 130 cases; 12.3%) and primary gastric lymphoma (six of 45 cases; 13.7%) than in unselected patients undergoing endoscopy (0.83-2.5%).

This suggests that these two disparate gastric tumours may share an immunological dysfunction or a common pathogenesis, and this is of interest given that Helicobacter pylori is thought to have a role in the evolution of gastric adenocarcinoma and lymphoma.

TREATMENT CHARACTERIZATION

GENERAL

HELICOBACTER TREATMENT

Healing of lymphocytic gastritis by eradication of Helicobacter pylori.

Muller H, Volkholz H, Stolte M.

Institute of Pathology, Klinikum Bayreuth, D-95445 Bayreuth, Germany.

Digestion 2001;63(1):14-9 Abstract quote
BACKGROUND: It is not yet clear whether lymphocytic gastritis might not be a sequela of Helicobacter pylori (Hp) infection. The aim of the present pilot study was, therefore, to investigate whether lymphocytic gastritis can be cured by Hp eradication, which, if affirmed, would provide indirect evidence for an etiopathogenic relationship.

PATIENTS AND METHODS: 98 of 220 patients with lymphocytic gastritis diagnosed between 1988 and 1998 were investigated at least twice, with 61 of them undergoing Hp eradication treatment. In 29 of these patients, the pretreatment histological work-up using the Warthin-Starry silver stain revealed Hp colonisation, while in the remaining 32 patients the biopsies from the antrum and corpus were negative for Hp. The other 37 patients received no treatment, and served as a control group.

RESULTS: Both in the group with Hp-positive, and in the group with Hp-negative histology prior to treatment, eradication treatment led to healing of the gastritis, i.e. to regression of the gastritis parameters including normalisation of the intra-epithelial lymphocyte count, in 93.1% and 84.3% of the cases, respectively. In the control group the histological findings did not change.

CONCLUSIONS: The results of our retrospective study support the notion that most cases of lymphocytic gastritis might be a consequence of Hp infection. This, however, needs to be clarified definitively by a prospective, randomized, double-blind study.

Treatment of Helicobacter pylori in patients with lymphocytic gastritis.

Niemela S, Karttunen TJ, Kerola T.

Department of Internal Medicine, Oulu University Hospital, 90220, Oulu, Finland.
Hepatogastroenterology 2001 Jul-Aug;48(40):1176-8 Abstract quote
BACKGROUND/AIMS: Lymphocytic gastritis is a subtype of chronic gastritis characterized by a marked increase in the number of intraepithelial lymphocytes in the gastric mucosa. Its etiology is unknown, but a proportion of these patients have Helicobacter pylori infection. The aim was to assess the significance of H. pylori treatment in lymphocytic gastritis patients.

METHODOLOGY: The 10 patients with lymphocytic gastritis and either serologically or histologically diagnosed H. pylori infection were treated with a triple therapy and followed by serology and histology after 6-18 months.

RESULTS: The levels of IgG antibodies for H. pylori decreased below 50% of the pretreatment values in all patients. The maximum numbers of intraepithelial lymphocytes decreased significantly (P = 0.005) from the pretreatment values.

CONCLUSIONS: Treatment of H. pylori infection cures lymphocytic gastritis associated with H. pylori infection. H. pylori appears to be one etiological cause of lymphocytic gastritis.

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Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
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PATHOGENESIS	CHARACTERIZATION
GRANZYME B
High proportion of granzyme B-positive (activated) intraepithelial and lamina propria lymphocytes in lymphocytic gastritis. Oberhuber G, Bodingbauer M, Mosberger I, Stolte M, Vogelsang H. Department of Clinical Pathology, University of Vienna, Medical School, Austria.	Am J Surg Pathol 1998 Apr;22(4):450-8 Abstract quote Intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LpLs) have not been well studied in gastric mucosa, particularly in lymphocytic gastritis. Therefore, they were immunohistologically characterized with antibodies recognizing CD3, CD8, CD57, T cell-restricted intracellular antigen (TIA-1), and granzyme B (GrB). The TIA-1 labels cytotoxic granules of resting and activated T-cells, whereas GrB decorates activated cytotoxic T cells. Thirty patients with celiac disease, including 20 taking gluten and 10 on a gluten-free diet, 15 patients with nonceliac disease-associated lymphocytic gastritis, and 20 controls were studied. Stained cells were counted and results were given as IELs/100 epithelial cells or percentage of lamina propria cells. Sixty percent to 90% of CD3+ IELs and up to 12% of lamina propria cells contained TIA-1-positive cytotoxic granules. The number of GrB+ IELs and LpLs was increased in Helicobacter pylori-positive controls (p < 0.03 vs. H pylori-negative controls) and celiac disease patients taking gluten (p < 0.05 vs. controls). The highest number of GrB+ IELs and LpLs was found in nonceliac disease-associated lymphocytic gastritis (p < 0.009 vs. controls, p < 0.05 vs. celiac disease). This study shows that a high proportion of gastric IELs and LpLs is potentially cytotoxic in nature. Through stimuli not yet identified, a proportion of them becomes activated after H pylori infestation and in lymphocytic gastritis.
HELICOBACTER INFECTION
Effects of Helicobacter pylori eradication on the natural history of lymphocytic gastritis. Hayat M, Arora DS, Dixon MF, Clark B, O'Mahony S. Centre for Digestive Diseases, The General Infirmary at Leeds, Leeds, UK.	Gut 1999 Oct;45(4):495-8 Abstract quote BACKGROUND: Lymphocytic gastritis is characterised by an accumulation of lymphocytes in the surface epithelium of the stomach. Lymphocytic gastritis has been linked to coeliac disease and Helicobacter pylori infection. AIMS: To determine whether H pylori eradication leads to resolution of the lymphocytic infiltrate and clinical improvement in patients with lymphocytic gastritis, and to determine their HLA status. METHODS: The Leeds Dyspepsia Questionnaire (LDQ) was administered to 13 patients with lymphocytic gastritis. H pylori serology, (13)C urea breath test (UBT), and upper gastrointestinal endoscopy with sampling of the duodenum, antrum, and corpus were done in all cases and the HLA status was determined. Eleven patients had at least one positive test for H pylori. Patients with lymphocytic gastritis and H pylori infection were treated with a one week course of omeprazole, clarithromycin, and metronidazole. Gastric and duodenal intraepithelial lymphocyte (IEL) counts were performed, along with histological assessment of gastric and duodenal biopsies before and after H pylori eradication. RESULTS: Two months after treatment there was a significant reduction in gastric IEL counts in both antrum and corpus. There was no significant change in duodenal IEL counts before and after eradication. According to the Sydney grading there was significant improvement in corpus inflammation after eradication. The patients histologically H pylori positive before treatment became H pylori negative. Dyspepsia scores also improved significantly after treatment. CONCLUSIONS: H pylori eradication treatment in patients with lymphocytic gastritis causes significant improvement in the gastric IEL infiltrate, corpus inflammation, and dyspeptic symptoms. H pylori serology is frequently positive when histology and UBT are negative. Lymphocytic gastritis may represent a specific immune response to H pylori infection.
Helicobacter pylori genotypes may determine gastric histopathology. Nogueira C, Figueiredo C, Carneiro F, Gomes AT, Barreira R, Figueira P, Salgado C, Belo L, Peixoto A, Bravo JC, Bravo LE, Realpe JL, Plaisier AP, Quint WG, Ruiz B, Correa P, van Doorn LJ. Institute of Molecular Pathology and Immunology and the Faculty of Medicine, University of Porto, Porto, Portugal.	Am J Pathol 2001 Feb;158(2):647-54 Abstract quote The outcome of Helicobacter pylori infection has been associated with specific virulence-associated bacterial genotypes. The present study aimed to investigate the gastric histopathology in Portuguese and Colombian patients infected with H. pylori and to assess its relationship with bacterial virulence-associated vacA, cagA, and iceA genotypes. A total of 370 patients from Portugal (n = 192) and Colombia (n = 178) were studied. Corpus and antrum biopsy specimens were collected from each individual. Histopathological features were recorded and graded according to the updated Sydney system. H. pylori vacA, cagA, and iceA genes were directly genotyped in the gastric biopsy specimens by polymerase chain reaction and reverse hybridization. Despite the significant differences between the Portuguese and Colombian patient groups, highly similar results were observed with respect to the relation between H. pylori genotypes and histopathology. H. pylori vacA s1, vacA m1, cagA+ genotypes were significantly associated with a higher H. pylori density, higher degrees of lymphocytic and neutrophilic infiltrates, atrophy, the type of intestinal metaplasia, and presence of epithelial damage. The iceA1 genotype was only associated with epithelial damage in Portuguese patients. These findings show that distinct H. pylori genotypes are strongly associated with histopathological findings in the stomach, confirming their relevance for the development of H. pylori-associated gastric pathology.

Epidemiology
Disease Associations	Celiac disease
Pathogenesis	Helicobacter
Laboratory/Radiologic/Other Diagnostic Testing
Histopathological Features and Variants
Differential Diagnosis	Graft versus host disease
Prognosis	General Malignancy
Treatment	Helicobacter eradication
Commonly Used Terms
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EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS
INCIDENCE/PREVALENCE
Lymphocytic gastritis: a study of its frequency and review of the literature. Ribeiro VL, Barbosa AJ. Department of Pathological Anatomy and Forensic Medicine, Federal University, Minas Gerais School of Medicine, FM-UFMG, Belo Horizonte, MG, Brazil.	Arq Gastroenterol 1998 Jan-Mar;35(1):26-31 Abstract quote Lymphocytic gastritis is currently recognized as a special type of chronic gastritis characterized by a large number of intraepithelial lymphocytes in antral or oxyntic mucosa. The frequency of lymphocytic gastritis rarely exceeds 5% of the histologic diagnosis of gastric biopsies. This diagnosis can be easily made by intraepithelial lymphocyte counts in preparations stained with hematoxylin and eosin. Very little is known about the etiopathogeny, clinical significance and evolution of the disease. The objective of the present study was to investigate the frequency of lymphocytic gastritis in gastric mucosa biopsies from the antrum and body in patients submitted to upper digestive endoscopy in Belo Horizonte, MG, Brazil. Histological sections of antral and oxyntic mucosa from 400 patients with no gastric ulcer or neoplasia of the gastrointestinal tract were analyzed retrospectively. The following lymphocyte numbers per 100 epithelial cells were obtained: 0 a 5 lymphocytes in 366 patients (91.5%); 6 to 15 lymphocytes in 22 patients (5.5%); 16 to 29 lymphocytes in eight patients (2.0%), and 30 or more lymphocytes in four patients (1%). Patients with 30 or more lymphocytes were considered to have lymphocytic gastritis. Three of these four cases with lymphocytic gastritis presented an endoscopic diagnosis of enanthematous pangastritis, and one presented erosive pangastritis.

LABORATORY/RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
RADIOLOGIC
LABORATORY MARKERS
MALABSORPTION
Lymphocytic gastritis and protein-losing gastropathy. Perardi S, Todros L, Musso A, David E, Repici A, Rizzetto M. Department of Gastroenterology, San Giovanni Battista Hospital of Turin, Italy.	Dig Liver Dis 2000 Jun-Jul;32(5):422-5 Abstract quote Lymphocytic gastritis is a histopathological entity of unknown aetiology which is characterized by dense surface and foveolar epithelial T-cell infiltration. We report here an uncommon clinical presentation in a young female presenting with unexplained recurrent weight loss and peripheral oedema. Endoscopic and histological features before and after successful therapy with omeprazole are described.

PROGNOSIS	CHARACTERIZATION
GENERAL
Ten year follow up study of lymphocytic gastritis: further evidence on Helicobacter pylori as a cause of lymphocytic gastritis and corpus gastritis. Niemela S, Karttunen T, Kerola T, Karttunen R. Department of Internal Medicine, University Hospital of Oulu, Finland	J Clin Pathol 1995 Dec;48(12):1111-6 Abstract quote AIMS--To examine the course of lymphocytic gastritis and its relation to Helicobacter pylori (H pylori) infection in a 10 year follow up. METHODS--Ninety six patients were originally examined for dyspepsia in 1981. Gastroscopies with stepwise biopsies were performed on all the patients initially and after an interval of 10 years. RESULTS--Nine per cent of the patients (9/96) had features of lymphocytic gastritis in gastric biopsy at the first examination, and 12.5% (12/96) at the second examination; 7/9 patients (78%) had persistent lymphocytic gastritis during the follow up; in two the diagnostic features of lymphocytic gastritis had disappeared, and five had a new diagnosis of lymphocytic gastritis at the second examination. At the second examination 9/12 lymphocytic gastritis patients (75%) were H pylori positive histologically, while all had specific antibodies to H pylori. The lymphocytic gastritis patients had higher grades of gastritis (p = 0.009), neutrophilic and eosinophilic granulocytes, mononuclear inflammatory cells, and foveolar hyperplasia in the corpus mucosa, but smaller numbers of H pylori, than the H pylori positive patients without lymphocytic gastritis. The appearance of lymphocytic gastritis during the 10 year interval was associated with increases in the grades of corpus gastritis and neutrophilic granulocytes (p = 0.043 for both). During the follow up, the patients with lymphocytic gastritis, but not the H pylori positive patients without lymphocytic gastritis, appeared to have a significant increase in the grade of intestinal metaplasia in the corpus mucosa (p = 0.043). CONCLUSIONS--In some patients H pylori may cause a gastritis that predominates in the corpus and is associated with an increase in the intraepithelial lymphocyte count. This form of gastritis may cause progression of intestinal metaplasia.
MALIGNANCY
Lymphocytic gastritis, gastric adenocarcinoma, and primary gastric lymphoma. Griffiths AP, Wyatt J, Jack AS, Dixon MF. Department of Histopathology, Neath General Hospital, West Glamorgan.	J Clin Pathol 1994 Dec;47(12):1123-4 Abstract quote A series of primary gastric lymphomas and adenocarcinomas was reviewed to assess the prevalence of lymphocytic gastritis in these conditions. Lymphocytic gastritis was more prevalent in patients with gastric adenocarcinoma (16 of 130 cases; 12.3%) and primary gastric lymphoma (six of 45 cases; 13.7%) than in unselected patients undergoing endoscopy (0.83-2.5%). This suggests that these two disparate gastric tumours may share an immunological dysfunction or a common pathogenesis, and this is of interest given that Helicobacter pylori is thought to have a role in the evolution of gastric adenocarcinoma and lymphoma.