What are the implications of mild chronic lymphocytic infiltration in the lamina propria of the gastric antral mucosa on a stomach biopsy?

Mild Chronic Lymphocytic Infiltration in Gastric Antral Lamina Propria

Mild chronic lymphocytic infiltration in the lamina propria of the gastric antral mucosa represents a nonspecific finding that most commonly indicates chronic gastritis, typically associated with Helicobacter pylori infection, but requires systematic evaluation to exclude more significant pathology including early gastric MALT lymphoma, autoimmune gastritis, or lymphocytic gastritis.

Primary Diagnostic Considerations

Most Common Etiology: Chronic Gastritis

• Chronic lymphocytic infiltration is the hallmark of chronic gastritis, characterized by increased lymphocytes and plasma cells in the lamina propria, particularly between the base of crypts and muscularis mucosae (basal plasmacytosis) 1.
• H. pylori-associated chronic gastritis shows diffuse or continuous inflammatory infiltrate composed of lymphocytes, plasma cells, and neutrophils in the antral mucosa 1.
• Test for H. pylori infection immediately, as this is present in the majority of chronic gastritis cases and guides treatment 1.

Critical Differential: Gastric MALT Lymphoma

• The interpretation of lymphoid infiltrates in gastric biopsies can be very difficult, as early MALT lymphoma may appear similar to benign chronic gastritis 1.
• Distinguishing features favoring lymphoma include: (1) marked increase in density of lymphoid infiltrate, (2) massive substitution of gastric glands by lymphoid infiltration, and (3) lymphoepithelial lesions where lymphocytes infiltrate and partially destroy isolated glands 2.
• In 44% of gastric lymphoma cases, lymphoma was discovered in only one or two tissue portions, emphasizing the need for adequate sampling 2.

Other Important Considerations

• Lymphocytic gastritis requires ≥25 intraepithelial lymphocytes per 100 epithelial cells, with lymphocytic infiltration of the lamina propria, and has strong associations with celiac disease and H. pylori infection 3, 4.
• Autoimmune gastritis shows diffuse lymphoplasmacytic infiltration with increased IgG4/IgG ratio, particularly in the lower lamina propria, though this typically affects the corpus more than antrum 5.
• Lymphoid aggregates are common in H. pylori-associated gastritis and increase with age, but are not exclusively related to H. pylori infection 6.

Algorithmic Management Approach

Step 1: Assess Adequacy of Biopsy

• Ensure multiple biopsies were obtained (ideally 6 specimens from different locations including antrum and corpus) to exclude patchy disease 7.
• Review whether the pathologist commented on: crypt architecture, presence of lymphoepithelial lesions, density of infiltrate, and distribution pattern 1, 2.

Step 2: Test for H. pylori

• Perform H. pylori testing on all patients with chronic lymphocytic infiltration using histology, rapid urease test, or stool antigen 1.
• If positive, initiate eradication therapy with appropriate antibiotic regimens plus proton pump inhibitor 1.
• Confirm eradication 4-8 weeks after treatment completion 1.

Step 3: Evaluate for Atrophic Changes and Intestinal Metaplasia

• Assess for gastric atrophy and intestinal metaplasia, as these represent progression along the gastric cancer cascade and require surveillance 1.
• Atrophic gastritis shows shrunk, vanishing glands with foci of intestinal metaplasia surrounded by fibromuscular tissue in the lamina propria 1.
• Patients with severe atrophic gastritis should be considered for endoscopic surveillance for early gastric cancer detection 1.

Step 4: Exclude MALT Lymphoma

• If lymphoid infiltrate is dense, diffuse, or shows any lymphoepithelial lesions, strongly consider MALT lymphoma and request immunohistochemistry for B-cell markers and clonality studies 1, 2.
• MALT lymphoma shows centrocyte-like cells producing: marked increase in lymphoid density, massive gland substitution, and lymphoepithelial lesions 2.
• Even after H. pylori eradication, sequential gastric biopsies remain essential as residual lymphoid infiltrates can be difficult to interpret 1.

Step 5: Consider Associated Conditions

• Screen for celiac disease if lymphocytic gastritis is suspected (≥25 intraepithelial lymphocytes per 100 epithelial cells), as there is strong positive correlation 4.
• Evaluate for autoimmune pancreatitis if diffuse lymphoplasmacytic infiltration is prominent, particularly in the lower lamina propria 5.

Follow-Up Strategy

For H. pylori-Positive Chronic Gastritis

• Repeat endoscopy with biopsies 2-3 months after eradication to document bacterial clearance and assess histologic improvement 1.
• If atrophy or intestinal metaplasia present, establish surveillance based on extent and severity 1.

For Persistent Lymphoid Infiltrate

• If stable residual lymphoid infiltrate persists without progression, a watch-and-wait policy is safe with long-term endoscopic follow-up every 12-18 months 1.
• Transient histological relapses are occasionally observed and are often self-limiting, especially without H. pylori reinfection 1.

Critical Pitfalls to Avoid

• Do not assume all lymphocytic infiltration is benign chronic gastritis—adequate tissue sampling and careful morphologic assessment are essential to exclude early MALT lymphoma 2.
• Avoid inadequate biopsy sampling—obtain at least 6 specimens from multiple locations, as lymphoma may be focal in 44% of cases 7, 2.
• Do not overlook the surrounding gastric mucosa—evaluate entire stomach for atrophy, intestinal metaplasia, and synchronous lesions 1.
• Recognize that lymphoid aggregates are not exclusively related to H. pylori—they can occur in autoimmune gastritis and other conditions 6, 5.
• Remember that interpretation of post-treatment lymphoid infiltrates is very difficult—there are no uniform criteria for histologic remission, requiring comparison with previous biopsies 1.