Rodger C. Haggitt Slide Seminar: Lesions of Esophagus, Stomach, and Duodenum
Moderators: Dr. Cecilia Fenoglio-Preiser and Dr. Wendy Frankel
Case 1 -
Drs. Jean-François FLEJOU, Adriana HANDRA-LUCA
Service d'Anatomie Pathologique, hôpital Saint-Antoine
Assistance Publique-Hôpitaux de Paris
Université Pierre et Marie Curie
74 yrs old man. Recent anorexia and weight loss, with upper abdominal pain. Moderate arterial
hypertension, no other past medical history. Under NSAIDs for vague rheumatismal pain. On upper
digestive endoscopy, large eroded folds in the gastric body.
Two slides of gastric biopsies are submitted: (1) body; (2) antrum.
Case 1 - Slide 1
Case 1 - Slide 2
Gastric biopsies were performed in the antrum and in the fundus. They show typical features of
lymphocytic gastritis. The fundic mucosa (1) shows diffuse inflammatory changes, present on all 4
specimens. There is an increased number of intraepithelial lymphocytes (IELs) in the surface and crypt
epithelium, that is confirmed by immunohistochemistry. IEL number is higher than 30 per 100 epithelial
cells, and IELs express CD3 and CD8. The lamina propria shows an increase in inflammatory cells, mostly
lymphocytes and plasma cells. There is also focal surface erosion, with fibrin deposit and neutrophils.
There is no glandular atrophy nor intestinal metaplasia.
In the antrum (2), the lesions are similar, with increased IELs, but there is no erosion. There is no
Helicobacter pylori (H. pylori) infection. Biopsies taken from the small
intestine are normal.
Diagnosis: Lymphocytic gastritis
Lymphocytic gastritis was described initially by Haot et al in 1985
It is an uncommon form
of chronic gastritis with a distinctive histological picture but still a poorly understood
Histological and immunohistological features
The diagnostic feature of lymphocytic gastritis is a marked intraepithelial lymphocytosis. The count
has to be made on the surface epithelium, on 400 to 500 epithelial cells. A number of 25 IELs per 100
epithelial cells is considered as a threshold for the diagnosis of lymphocytic gastritis. However, this
number is much higher in most cases, with a mean number about 50 IEL for 100 epithelial cells in most
series, i.e., 10 times higher as in other types of chronic gastritis and 20 times higher as in normal
mucosa. In typical cases, the surface epithelium is crowded with dark nuclei surrounded by a clear halo,
typical of normal IEL. This increased number of IEL is only present in the surface and foveolar
epithelium with no involvement of the glandular layer.
Lymphocytic gastritis can be present in the antrum and/or the body, depending upon the associated
conditions and endoscopic features (see infra).
Immunophenotype of IELs (8)
In typical cases of lymphocytic gastritis, immunostaining is not necessary to make the diagnosis.
IELs in lymphocytic gastritis have the phenotype of normal IELs: a mast majority are CD3+ T lymphocytes,
and 70-80% express CD8 in the cell surface. Most of these IELs are activated cytotoxic T-lymphocytes, as
shown by their expression of TIA-1, a cytotoxic granule-associated protein. B lymphocytes are absent
from the epithelium in lymphocytic gastritis.
The typical increased IELs are usually associated with a chronic inflammatory infiltrate in the lamina
propria, of variable intensity, and composed of lymphocytes and plasma cells. The foveolar pits may be
tortuous and elongated. In a number of cases, erosions are present. Eroded areas contain fibrin
deposits and active inflammation with neutrophils, that may obscure the IEL infiltrate.
Clinical and endoscopic features
Lymphocytic gastritis has a frequency of 1.5% to 4% of chronic gastritis , and is found in about 1%
of dyspeptic patients undergoing upper GI endoscopy. Although most cases have been reported in Europe
and United States, lymphocytic gastritis has also been described in other parts of the world. It is seen
in most cases in adults, although there have been also case reports in children. A slight female
predominance is present.
Associated conditions will be discussed later. They include celiac disease, Helicobacter pylori (H. pylori) infection, and to a lesser extent Crohn's disease,
HIV infection, gastric lymphoma, and esophageal carcinoma.
Clinical features are highly variable, from dyspepsia to the rapid development of an alarming
symptomatology suggestive of a gastric neoplasm, with abdominal pain, anorexia, severe weight loss. In a
small subset of patients there may be protein-losing gastroenteropathy with peripheral oedema.
Endoscopic features are also variable, ranging from a normal aspect to the highly suggestive aspect of
varioliform gastritis, showing enlarged gastric folds with nodules that contain central erosion. The
correlation between endoscopic varioliform gastritis and lymphocytic gastritis is high in cases with
diffuse and corporeal endoscopic lesions (53 of 55 cases diagnosed by endoscopy corresponding to
lymphocytic gastritis in a series by Haot et al)
 but is much weaker in antral varioliform gastritis
(1 of 11 cases in the same series). On the other hand, 20 to 50% of cases of lymphocytic gastritis do
not present as varioliform gastritis on endoscopy.
Frontier cases with Ménétrier's disease
Some cases presenting clinically (low acid secretion and protein loss) and endoscopically (giant
gastric folds) as Ménétrier's disease show histologically lymphocytic gastritis in addition to the
classical features of Ménétrier's disease. On the other hand, many authors have reported an association
between lymphocytic gastritis and protein-losing gastropathy. It appears therefore that there is an
overlap between lymphocytic gastritis and Ménétrier's disease, with a spectrum of lesions ranging from
pure lymphocytic gastritis to classical Ménétriers's disease, trough intermediate lesions of
"hypertrophic" lymphocytic gastritis.
Collagenous gastritis is a very uncommon form of chronic gastritis with about 20 cases reported in the
literature to date. Its aetiology is unknown, and it is defined histologically by the presence on
gastric biopsies of a thickened subepithelial collagen band in association with an increased number of
inflammatory cells in the lamina propria. In view of the relationship between the two types of
microscopic colitides, i.e. lymphocytic colitis and collagenous colitis, there is a possibility that
collagenous and lymphocytic gastritis are linked in some way. In a series of 6 cases we have reported,
an increased number of IELs was present in the stomach in 2 cases .
Lymphocytic gastritis and celiac disease
Celiac disease is an important cause of lymphocytic gastritis. Approximately half of the patients
with celiac disease and a flat duodenal mucosa meet the criteria of lymphocytic gastritis. Conversely,
significantly higher IEL counts are found in the duodenal mucosa of patients with lymphocytic gastritis
and half of them have evidence of abnormal small intestinal permeability. These data indicate that in
some cases lymphocytic gastritis represents a reaction of the gastric mucosa to gluten ingestion.
Links with H. pylori infection
In most published series, H. pylori infection is present in a minority of
cases (20 to 40%) of lymphocytic gastritis. Moreover, in H. pylori-positive
cases with lymphocytic gastritis, H. pylori colonization is often minimal or
focally localized mainly in the corpus. Conversely, the majority of adult patients with lymphocytic
gastritis will have positive levels of serum anti-H. pylori antibodies.
This may be due to the cytotoxic effects of activated T lymphocytes on H.
pylori leading to reduction or even complete elimination of the bacteria.
The histological picture of lymphocytic gastritis is distinctive, and once the pathologist is aware of
this entity, the diagnosis is easily made in most cases. Diagnostic difficulties may occur in cases with
multiple erosions, due to non specific inflammatory changes (necrosis, polymorphs etc.) that may obscure
the increase in IELs. Celiac disease and Ménétrier's disease are not differential diagnoses but
associated or linked conditions in most cases.
In gastric MALT lymphomas there is epithelial destruction by the lymphoid infiltrate, which does not
occur in lymphocytic gastritis, and the neoplastic lymphoid cells are CD20 positive and CD3 negative.
In chronic active H. pylori gastritis, the surface and crypt epithelium
may be infiltrated by neutrophils, but the number of IEL is usually less than 5 per 100 epithelial cells.
Evolution and treatment
Spontaneous resolution of the disease is possible, but in most cases, lymphocytic gastritis follows a
protracted course and must be considered a chronic disease. Patients with ulcers and/or erosions are
treated with proton pump inhibitors (PPI). But in cases associated with other conditions, the main part
of the treatment is directed against those conditions: gluten-free diet in celiac disease, and
antibiotics with PPI in H. pylori gastritis. Very interestingly, it has
been reported in the only randomized-controlled anti-H. pylori trial of
lymphocytic gastritis that the healing rate was comparable high irrespective of the H. pylori status at baseline .
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