Monoclonality and Immunophenotype of Intraepithelial Lymphocytes in Lymphocytic Gastritis

Review Article

Austin J Clin Pathol. 2014;1(1): 1003.

Monoclonality and Immunophenotype of Intraepithelial Lymphocytes in Lymphocytic Gastritis

M Rodriguez-Justo1*,Z Avila1, I Proctor1, D Thind1, T Diss1, C Santonja2

1Department of Histopathology, University College London, University Street, London WC1E 6JJ, UK. Tel: (+44) (0) 20 7679 6015;

2Department of Anatomic Pathology, Fundacion Jimenez Diaz, Madrid, Spain;

*Corresponding author: M Rodriguez-Justo, Department of Histopathology, University College London, University Street, London WC1E 6JJ, UK. Tel: (+44) (0) 20 7679 6015; USA

Received: February 09, 2014; Accepted: March 11, 2014; Published: March 22, 2014


Aims: To investigate the clonality and immunophenotype of intraepithelial lymphocytes (IELs) in lymphocytic gastritis (LG).

Methods and Results: The study included 47 cases of LG. Clinical information regarding Helicobacter pylori (Hp) infection and coeliac disease (CD) were recorded. Immunohistochemistry for Hp, CD3, CD4 and CD8 (single and double-staining with CD3); and PCR amplification of the T-cell receptor gamma (TCR-?) gene was performed in each case. 11/47 cases were positive for Hp and 2/47 cases had CD. In all cases the IELs showed a CD3+ CD4- CD8+ immunophenotype. DNA quality allowed PCR analysis in 34/47 cases: in 5/34 a monoclonal expansion of T-cells was demonstrated. Three cases were associated with Hp and the remaining cases had no evidence of Hp or CD. None of the patients have developed lymphoma (median follow up 64 months).

Conclusions: Hp infection may trigger LG and induce infiltration of T-lymphocytes into the gastric mucosa. In a significant proportion of cases (15% overall and 43% of Hp+ cases in our series) a T-cell clonal expansion may develop. Some patients with monoclonal T-cell expansion are not Hprelated and other host-related factors may play a role. Although clonal LG, when isolated, appear to be a monoclonal benign disease, there is still need to characterize LG on an immunophenotypical and molecular clonal/level in larger scale follow-up studies. TCR gene rearrangement testing in the diagnosis of a histologically gastric biopsy that only shows features of LG, might contribute to identify patients which may require close follow-up.

Keywords: Gastritis; Immunophenotyping; T-cell gene rearrangement; Helicobacter pylori; Celiac disease; Etiology; Gastric lymphoma


IELs: Intraepithelial Lymphocytes; LG: Lymphocytic Gastritis; Hp: Helicobacter pylori; CD: Celiac Disease; TCR-?: T-cell receptor gamma; EATL: Enteropathy-associated T-cell lymphoma; H&E: Haematoxylin and Eosin; PCR: Polymerase Chain Reaction.


Lymphocytic gastritis (LG) is an uncommon histopathological subtype of chronic gastritis. It is characterised by a marked increase in the number of intraepithelial lymphocytes (IELs) in the gastric surface and foveolar epithelium, together with a variable increase in lymphocytes within the lamina propria [1]. IELs in LG are primarily CD3+/CD8+ cytotoxic T-cells [2,3] and 25 or more IELs per 100 gastric epithelial cells are usually considered diagnostic [4]. The disorder may affect the whole stomach and the reported prevalence varies from 0.83% of unselected patients undergoing endoscopy, to 1.6-4.5% of patients with histological chronic active gastritis [5,6] and 1-8% of patients with dyspepsia [7].

The pathogenesis of LG is poorly understood and its etiology is unknown in a high proportion of cases. It is associated with endoscopic findings of varioliform gastritis [8] (prominent mucosal folds in the gastric fundus with nodules and chronic superficial erosions) although some cases have normal endoscopic appearances.Helicobacter pylori (Hp) infection has been detected histologically or serologically in 40-80% of cases of LG in some studies and it has been suggested that LG may represent an atypical immune response to a local antigen such as Hp [9]. In addition, LG has been associated with gastric adenocarcinoma (prevalence 12%) and primary gastric lymphoma (prevalence 14%-32%) [10,11] two conditions also linked with Hp infection.

Gluten is another suspected inciting agent in some cases of LG. Studies have shown that 36-45% of cases of patients with coeliac disease (CD) may have LG [12-14]. The intraepithelial lymphocytosis in the small bowel in CD has been the focus of much attention. Ulcerative jejunitis and refractory CD are complications and characterised by loss of response to a gluten-free diet and the presence of a cytologically normal, non-invasive, monoclonal intraepithelial T-cell population. Detection of this clonal intraepithelial T-cell population is associated with poor outcome and higher risk of developing enteropathyassociated T-cell lymphoma (EATL) [15]. Bagdi et al [l6] showed that the monoclonal T cell-populations observed in ulcerative jejunitis and refractory CD share an identical aberrant immunophenotype with the monoclonal T-cell population in the lymphoma and adjacent enteropathic mucosa in EATL. Thus the intrepithelial lymphocytosis in refractory CD and ulcerative jejunitis is considered a neoplastic T-cell disorder. In addition, refractory CD is recognised as a diffuse gastrointestinal disease: one study detected a monoclonal T-cellpopulation in 62%, 80% and 44% of gastric, colonic and blood samples respectively from patients with refractory CD [17].