Definition/General
Introduction:
Gastric lymphoma represents the most common primary extranodal lymphoma location
It accounts for 60-75% of all gastrointestinal lymphomas
The majority are B-cell lymphomas with two main types
MALT lymphoma (mucosa-associated lymphoid tissue) and diffuse large B-cell lymphoma (DLBCL).
Origin:
Arises from acquired mucosa-associated lymphoid tissue in gastric mucosa
Normal gastric mucosa lacks organized lymphoid tissue
Chronic inflammation leads to lymphoid tissue development
Helicobacter pylori infection is the most important trigger for MALT lymphoma development.
Classification:
MALT lymphoma (marginal zone lymphoma) comprises 60-70% of gastric lymphomas
DLBCL accounts for 25-35% of cases
Mantle cell lymphoma and follicular lymphoma are rare
T-cell lymphomas are extremely rare in stomach.
Epidemiology:
Peak incidence in 6th decade of life
Slight male predominance (1.5:1)
Strong association with H
pylori infection (>90% MALT cases)
Geographic variation correlates with H
pylori prevalence
Increasing incidence in developing countries including India.
Clinical Features
Presentation:
Epigastric pain and discomfort (70-80% cases)
Dyspepsia and early satiety (60-70%)
Nausea and vomiting (40-50%)
Weight loss (30-40% cases)
Gastrointestinal bleeding (hematemesis, melena)
B-symptoms rare except in DLBCL.
Symptoms:
Chronic epigastric pain similar to peptic ulcer disease
Postprandial fullness and bloating
Anorexia and weight loss
Fatigue and weakness
Iron deficiency anemia from chronic bleeding
Palpable abdominal mass in advanced cases.
Risk Factors:
Helicobacter pylori infection (strongest risk factor)
Chronic gastritis and gastric atrophy
Immunodeficiency states (HIV, immunosuppression)
Autoimmune disorders (Sjogren syndrome, Hashimoto thyroiditis)
Family history of lymphoma
Previous gastric adenocarcinoma.
Screening:
No routine screening protocols
Upper GI endoscopy for persistent dyspepsia
H
pylori testing in all gastric lymphoma patients
CT/PET scanning for staging
Bone marrow biopsy in selected cases
Flow cytometry of peripheral blood.
Master Gastric Lymphoma Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
MALT lymphoma: Subtle mucosal thickening, shallow ulcerations, nodular appearance
DLBCL: Large ulcerated masses, polypoid lesions, diffuse wall thickening
Both types may show multicentric involvement.
Characteristics:
MALT lymphoma shows preserved mucosal architecture with subtle changes
DLBCL demonstrates obvious mass lesions with ulceration
Cut surface shows gray-white tissue with fish-flesh appearance typical of lymphoma.
Size Location:
MALT lymphoma often involves antrum and body (multifocal in 20-30%)
DLBCL typically presents as solitary large mass (>5 cm)
Cardia involvement more common in DLBCL
Size varies from microscopic to >10 cm.
Multifocality:
Multicentric disease more common in MALT lymphoma (20-30%)
Skip lesions may be present throughout stomach
Duodenal involvement in 10-15% of cases
Regional lymph node involvement variable depending on type and stage.
Microscopic Description
Histological Features:
MALT lymphoma: Small to medium lymphoid cells infiltrating around reactive follicles
Lymphoepithelial lesions (lymphocytes invading epithelium)
Marginal zone pattern around follicles
DLBCL: Large lymphoid cells with vesicular nuclei and prominent nucleoli.
Cellular Characteristics:
MALT lymphoma: Centrocyte-like cells with irregular nuclei
Marginal zone cells with abundant pale cytoplasm
Plasma cell differentiation common
DLBCL: Large cells >2x normal lymphocyte size
Vesicular nuclei with prominent nucleoli.
Architectural Patterns:
MALT lymphoma: Marginal zone pattern around reactive follicles
Lymphoepithelial lesions characteristic
Plasma cell differentiation
DLBCL: Diffuse growth pattern
Destruction of normal architecture
High mitotic activity.
Grading Criteria:
MALT lymphoma is indolent/low-grade lymphoma
DLBCL is aggressive/high-grade lymphoma
Large cell transformation can occur in MALT lymphoma
High-grade areas require separate reporting and staging.
Immunohistochemistry
Positive Markers:
B-cell markers: CD20 (99% positive), CD79a, PAX5
MALT lymphoma: CD21 highlights follicular dendritic cells
DLBCL: CD10 (30-40%), BCL6 (60-70%), MUM1 (70-80%)
Plasma cells: CD138, kappa/lambda light chains.
Negative Markers:
T-cell markers: CD3, CD5 (negative in most cases)
CD10 negative in MALT lymphoma
Cyclin D1 negative (excludes mantle cell lymphoma)
CD23 negative
TdT negative.
Diagnostic Utility:
CD20 confirms B-cell lineage
Light chain restriction demonstrates clonality
CD21 highlights follicular colonization in MALT
CD10/BCL6/MUM1 classify DLBCL subtypes
Ki-67 shows proliferation rate (low in MALT, high in DLBCL).
Molecular Subtypes:
DLBCL subtypes: Germinal center B-cell (GCB) vs non-GCB
GCB: CD10+, BCL6+, MUM1-
Non-GCB: CD10-, MUM1+
Double-hit lymphomas: MYC and BCL2 or BCL6 rearrangements
Triple-hit lymphomas have worst prognosis.
Molecular/Genetic
Genetic Mutations:
MALT lymphoma: t(11;18)(q21;q21) API2-MALT1 fusion (20-30%)
t(1;14)(p22;q32) BCL10-IGH (5%)
t(14;18)(q32;q21) IGH-MALT1 (15%)
DLBCL: MYC rearrangements (10-15%), BCL2 rearrangements (20-30%), BCL6 rearrangements (30-40%).
Molecular Markers:
MALT lymphoma: Nuclear BCL10 expression in t(1;14) cases
Nuclear MALT1 expression in some cases
DLBCL: MYC overexpression (40-50%)
BCL2 overexpression (50-60%)
p53 mutations (20-30%)
EBV association rare except in immunocompromised.
Prognostic Significance:
MALT lymphoma: t(11;18) associated with H
pylori independence and antibiotic resistance
Advanced stage and large cell transformation indicate poor prognosis
DLBCL: MYC/BCL2 double expression indicates poor prognosis
Double-hit lymphomas have worst outcomes.
Therapeutic Targets:
H
pylori eradication first-line for early MALT lymphoma
Anti-CD20 therapy (rituximab) for advanced disease
BTK inhibitors (ibrutinib) for relapsed MALT
R-CHOP chemotherapy for DLBCL
CAR-T therapy for refractory DLBCL.
Differential Diagnosis
Similar Entities:
Reactive lymphoid hyperplasia (H
pylori gastritis)
Gastric adenocarcinoma (poorly differentiated)
Other lymphomas (mantle cell, follicular)
Metastatic lymphoma from nodal sites
Inflammatory myofibroblastic tumor.
Distinguishing Features:
MALT lymphoma: Monoclonal B-cells
MALT lymphoma: Lymphoepithelial lesions
MALT lymphoma: Light chain restriction
Reactive hyperplasia: Polyclonal
Reactive hyperplasia: Preserved architecture
Adenocarcinoma: Cytokeratin positive
Adenocarcinoma: Mucin production.
Diagnostic Challenges:
Distinguishing early MALT lymphoma from reactive hyperplasia
Identifying large cell transformation in MALT lymphoma
Separating primary gastric DLBCL from secondary involvement
Flow cytometry and molecular studies often required.
Rare Variants:
Mantle cell lymphoma (cyclin D1 positive, t(11;14))
Follicular lymphoma (CD10+, BCL2+, t(14;18))
Burkitt lymphoma (starry-sky pattern, MYC rearrangement)
T-cell lymphomas (peripheral T-cell lymphoma NOS, EATL).
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
[specimen type], measuring [size] cm in greatest dimension
Diagnosis
[MALT lymphoma/DLBCL], [grade/subtype]
WHO Classification
Extranodal marginal zone lymphoma (MALT type) / Diffuse large B-cell lymphoma
Histological Features
[describe cellular morphology, growth pattern, architectural features]
Immunophenotype
CD20: [+/-], CD79a: [+/-], Light chain restriction: [kappa/lambda], Ki-67: [%]
H. pylori Status
H. pylori: [present/absent] by [method]
Staging
Ann Arbor Stage: [IE/IIE/IIIE/IVE]
Molecular Studies
FISH/PCR: [specify results if performed]
Prognostic Factors
Stage, grade, H. pylori status, response to therapy
Final Diagnosis
Primary gastric [lymphoma type], Ann Arbor Stage [stage]