What are the recommended diagnostic evaluation and treatment strategies for extranodal marginal‑zone (MALT) lymphoma?

Extranodal Marginal Zone Lymphoma (MALT Lymphoma): Diagnostic Evaluation and Treatment

Diagnostic Approach

Diagnosis requires histopathologic evaluation of multiple biopsies from the affected site, with gastric MALT lymphoma necessitating samples from each gastric region, duodenum, and gastroesophageal junction. 1, 2

Essential Diagnostic Components

• Histopathology must follow WHO classification criteria with confirmation by an expert hematopathologist, including immunohistochemistry panel with CD20, CD10, CD5, and cyclin D1 to differentiate from other indolent lymphomas 1

• H. pylori status determination is mandatory through histochemistry, urea breath test, stool antigen test, or serology if histochemistry is negative 1, 2

• FISH or PCR for t(11;18) translocation should be performed to identify patients unlikely to respond to antibiotic therapy and potentially unresponsive to alkylating agents 1, 2

Staging Workup

• Endoscopic ultrasound to evaluate regional lymph nodes and depth of gastric wall infiltration 1, 2

• CT chest, abdomen, and pelvis with contrast 1, 2

• Complete blood count and biochemical studies including LDH and β2-microglobulin 1, 2

• Bone marrow aspirate and biopsy 1, 2

• PET scan has little clinical utility and is not recommended 1

Treatment Algorithm

For H. pylori-Positive Localized Gastric MALT Lymphoma

H. pylori eradication with antibiotics is the sole initial treatment for localized H. pylori-positive gastric MALT lymphoma. 1, 2

• Use PPI-based triple therapy with clarithromycin plus either amoxicillin or metronidazole for 10-14 days 2

• Confirm eradication with urea breath test or stool antigen test at least 6 weeks after therapy and 2 weeks after PPI withdrawal 2

• If eradication fails, attempt second-line triple or quadruple therapy with alternative antibiotic combinations 1, 2

• Wait at least 12 months before initiating alternative treatment in patients achieving clinical and endoscopic remission with H. pylori eradication, even if histological lymphoma persists 1

• Molecular persistence of monoclonal B-cells after histologic regression warrants watchful waiting rather than active treatment 1, 2

For Antibiotic-Resistant or H. pylori-Negative Localized Disease (Stage I-II)

Involved-field radiotherapy with 24-30 Gy delivered over 3-4 weeks to the stomach and perigastric lymph nodes is the optimal treatment for localized disease resistant to antibiotics. 3, 2

• Radiation therapy achieves excellent disease control with minimal morbidity and preserves gastric function 3

• Surgery has not demonstrated superior results compared to conservative approaches and may impair quality of life 3, 2

For Systemic Disease (Stage III-IV)

For symptomatic systemic disease, chemoimmunotherapy with rituximab plus chemotherapy is the most appropriate treatment. 3, 2

• Oral alkylating agents (cyclophosphamide or chlorambucil) or purine nucleoside analogs (fludarabine, cladribine) are options 2

• Rituximab plus chlorambucil has proven efficacy in randomized studies 2

• For asymptomatic systemic disease, watchful waiting is a valuable option and may continue for several years 4

Follow-Up Protocol

• Endoscopy with multiple biopsies 2-3 months after treatment to document H. pylori eradication 2

• Endoscopy with biopsies at least twice yearly for 2 years to monitor histological regression 2

• Long-term annual blood counts and appropriate imaging 2

Critical Clinical Considerations

• Patients with t(11;18) translocation are unlikely to respond to antibiotics and will probably be unresponsive to alkylating agents as sole treatment 3, 2

• The term "high-grade MALT lymphoma" is obsolete; cases with solid proliferation of transformed large cells must be diagnosed as diffuse large B-cell lymphoma 1

• Lymphoepithelial lesions, while typical, are neither essential for diagnosis nor pathognomonic 1

Common Pitfalls to Avoid

• Do not increase antibiotic dosing for truly antibiotic-resistant disease—this delays appropriate definitive therapy 3

• Do not rely on single-site biopsies—multiple biopsies from different regions are essential for accurate diagnosis 1, 2

• Do not pursue surgery as first-line therapy—it has not shown superior outcomes and may worsen quality of life 3, 2

• Do not initiate active anticancer treatment for persistent molecular disease after histologic regression—watchful waiting is appropriate unless disease is symptomatic or progressive 2