What is the recommended diagnostic work‑up and treatment for a patient with pyloric or duodenal wall thickening suspected to be primary gastrointestinal lymphoma?

Diagnostic Work-Up and Treatment for Pyloric/Duodenal Wall Thickening Suspected to be Primary GI Lymphoma

For suspected primary gastrointestinal lymphoma presenting with pyloric or duodenal wall thickening, perform esophagogastroduodenoscopy with extensive biopsies from all gastric regions, duodenum, and gastroesophageal junction, followed by H. pylori testing, endoscopic ultrasound, complete staging CT, and bone marrow biopsy—then treat H. pylori-positive localized gastric MALT lymphoma with antibiotic eradication as first-line therapy, while H. pylori-negative or duodenal cases require radiation therapy (24-30 Gy) for localized disease or systemic chemoimmunotherapy for advanced stages. 1, 2

Initial Diagnostic Approach

Endoscopic Evaluation

• Perform comprehensive esophagogastroduodenoscopy with multiple biopsies taken from each region of the stomach (antrum, body, fundus), duodenum (bulb and second portion), gastroesophageal junction, and any abnormal-appearing sites 1
• Obtain at least 6-8 biopsies to ensure adequate tissue sampling, as lymphoma may be patchy and endoscopic appearance is often nonspecific (gastritis-like or peptic ulcer appearance) 1, 3
• Request endoscopic ultrasound to evaluate gastric/duodenal wall infiltration depth and assess perigastric/periduodenal lymph node involvement 1

Pathological Assessment

• Ensure histopathologic evaluation includes routine histology, immunohistochemistry (minimum panel: CD20, CD10, CD5, cyclin D1), and assessment for lymphoepithelial lesions 1, 4
• Order FISH or PCR testing for t(11;18) translocation, as this identifies patients unlikely to respond to antibiotic therapy and helps guide treatment decisions 1, 2
• Confirm H. pylori status through histochemistry on biopsy specimens, supplemented by urea breath test or stool antigen test 1, 2

Staging Work-Up

• Obtain complete blood counts and biochemical studies including lactate dehydrogenase and β2-microglobulin 1, 2
• Perform CT scan of chest, abdomen, and pelvis to assess for systemic disease and lymphadenopathy (lymph nodes on CT strongly predict neoplastic lesions) 1, 5
• Complete staging with bone marrow aspirate and biopsy 1, 2
• Consider PET-CT if clinical or laboratory data suggest transformation to high-grade histology 1

Treatment Algorithm Based on Location and H. Pylori Status

For Gastric MALT Lymphoma (H. Pylori-Positive, Localized)

• Initiate H. pylori eradication as sole first-line treatment using proton-pump inhibitor plus clarithromycin-based triple therapy with either amoxicillin or metronidazole for 10-14 days 1, 2
• Confirm eradication with urea breath test or stool antigen test at least 6 weeks after therapy completion and 2 weeks after PPI withdrawal 2
• If initial eradication fails, attempt second-line therapy with alternative triple- or quadruple-therapy regimens 1, 2

For H. Pylori-Negative or Antibiotic-Resistant Gastric MALT Lymphoma

• For localized disease (stage I-II), administer involved-field radiotherapy with 24-30 Gy delivered over 3-4 weeks to the stomach and perigastric lymph nodes 6, 2
• This achieves excellent disease control with minimal morbidity and preserves gastric function 6
• Patients with t(11;18) translocation are particularly unlikely to respond to antibiotics and should proceed directly to radiation or systemic therapy 6, 2

For Primary Duodenal MALT Lymphoma

• Duodenal MALT lymphoma is very rare and typically resistant to H. pylori eradication alone 7
• For localized duodenal disease, radiation therapy (24-30 Gy) to the duodenum and regional nodes is the preferred approach 6
• For symptomatic or advanced disease, systemic chemotherapy with CVP (cyclophosphamide, vincristine, prednisolone) or rituximab-based regimens achieves remission 7

For Systemic or Advanced Disease

• Administer systemic chemoimmunotherapy with rituximab plus chemotherapy (such as rituximab-chlorambucil or rituximab-CVP) for symptomatic systemic disease 6, 2
• Oral alkylating agents (cyclophosphamide or chlorambucil) or purine nucleoside analogs (fludarabine, cladribine) are alternative options 1, 2
• Rituximab monotherapy has shown activity in phase II studies for less aggressive cases 1, 2

Follow-Up Protocol

Post-Treatment Surveillance

• Perform endoscopy with multiple biopsies 2-3 months after treatment to document H. pylori eradication and assess histologic response 1, 2
• Continue endoscopic surveillance with biopsies at least twice yearly for 2 years to monitor histological regression 1, 2
• For persistent but stable residual disease after antibiotic therapy, adopt a watchful waiting approach with continued endoscopic surveillance, as long-term persistence of monoclonal B-cells may occur without clinical significance 1, 2
• Maintain long-term follow-up with annual blood counts and appropriate imaging 2

Critical Clinical Pitfalls to Avoid

• Do not delay definitive therapy by repeatedly attempting antibiotic regimens in truly antibiotic-resistant disease or patients with t(11;18) translocation 6
• Avoid surgery as primary treatment, as it has not demonstrated superior results compared to conservative approaches and may impair quality of life 1, 6, 2
• Do not assume all gastric wall thickening is gastric in origin—duodenal involvement requires different management considerations and is less responsive to H. pylori eradication 8, 7
• Ensure adequate biopsy sampling, as the distinction between MALT lymphoma and reactive lymphoid hyperplasia can be problematic in small specimens 4
• Recognize that bowel wall thickening on CT warrants endoscopic follow-up regardless of location, especially when associated with lymphadenopathy (positive predictive value for malignancy of 0.36) 5