Epidemiology: 

• Account for 7-8% of all B-cell lymphomas 
• 50% of primary gastric lymphoma 
• Median age- 61 years 
• Slight female preponderance 

Etiology: 

• Precursor lesions 
  • H. pylori associated chronic gastritis. 
  • Sjogren syndrome 
  • Hashimoto’s thyroiditis 
  • BorreliaBurgdorferi -  Cutaneous MALToma 
  • Chlamydia psittasi- Conjuctical MALToma 
  • Campylobacter jejuni-Small intestinal MALToma(Immunoproliferative small intestinal disease-IPSID) 

Sites 

• GIT (Most Common)- 50% of all MALTomas occur in stomach  (MC in GIT)
• Lung -14%
• Other organs: ocular adnexa, thyroid, breast, Small intestine, salivary gland, skin 

Pathogenesis: 

H. Pylori infection

↓

Severe gastritis and activation of CagA gene

↓

Activation of B lymphocytes

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H. Pylori related lymphoma

Clinical Features: 

• Dyspepsia 
• Reflux esophagitis 
• Abdominal pain 
• Nausea 
• Weight loss 

Complication: 

• Transformation into DLBCL 

Investigations:

• Endoscopic biopsy
  • Lymphoma cells infiltrate around reactive B-cell follicles, external to preserved follicle mantle, in a marginal zone distribution and spread out to form larger confluent areas which eventually over run most of the follicles. 
    • Marginal zone B cells are small to medium sized. Their nuclei are slightly irregular with moderately dispersed chromatin and inconspicuous nucleoli. Cytoplasm is abundant and pale (Monocytoid appearance). Sometimes Plasmacytic differentiation is present (1/3rd cases) 
    • Larger cells resembling centroblasts or immunoblasts are usually present. 
    • Lympho epithelial lesions- Aggregates of 3 / more marginal zone cells with distortion of the epithelium, often together with eosinophilic degeneration of epithelial cells 
• Immunophenotyping by immunohistochemistry
  • Positive- Immunoglobulin light chain restriction,  IgM, CD20, CD79a, dim-moderate- CD11c , Marginal zone associated antigens (CD21, CD35) 
  • Negative- CD5, CD23, CD10, CD103, Cyclin D1, aberrant CD43 
• H. Pylori testing 
  • Biopsy 
  • Urea breath test 
• BM examination- Involved in 10% of cases 
• S. LDH- Increased in advanced stages 
• S. Beta 2 microglobulin- Increased in advanced stages 
• CT scan- Chest, abdomen, pelvis 
• Endoscopic ultrasound- To evaluate regional lymph nodes and gastric wall infiltration
• Molecular studies: 
  • Antigen receptor genes- Rearrangement and mutations in Ig light and heavy chain genes, in variable region, consistent with derivation from post germinal centre memory B cell
• Cytogenetics
  • Trisomy 3 
  • t (11 : 18) – Fusion of API2 with MLT leading to activation of NFk beta. It is present in 40% cases and is associated with failure to respond to eradication of H. Pylori. 
  • del 6q23 involving TNF-AIP-3 
• FISH Panel 
  • t (1:14) 
  • t (3:14) 
  • t (11:14) 
  • t (11:18) 
  • t (14:18) 

Staging: Lugano staging system for GI lymphomas 

• Stage I- Confined to GI tract (I1- Mucosa, submucosa, I2- Muscularispropria, serosa )
• Stage II- Extending into abdomen (II1- Local nodal involvement, II2- Distant nodal involvement) 
• Stage IIE- Penetration of serosa to involve adjucent organs or tissues 
• Stage IV- Disseminated extranodal involvement or concomitant supradiaphragmatic nodal involvement. 

Prognosis: 

• Indolent course 

Indications for Treatment: 

• Symptomatic patients 
• GI bleeding 
• Threatened end organ function 
• Bulky disease 
• Steady/ rapid progression 
• Patient preference 

Pretreatment Work-up: 

• History 
  • B-Symptoms 
• Examination 
  • LN: 
  • Spleen: 
• WHO P. S. 
• BSA 
• IHC 
• H. Pylori Stain 
• BMA and Bx 
• CT (CAP) 
• Stage 
• Hemoglobin 
• TLC, DLC 
• Platelet count 
• LFT: Bili- T/D   SGPT:     SGOT: Albumin:     Globulin: 
• Creatinine
• Electrolytes: Na:      K:      Ca: Mg:   PO4:   
• Uric acid:
• LDH 
• HIV:
• HBsAg:
• HCV: 
• UPT 
• Cytogenetics 
• FISH for t(11;18) in H.Pylori +ve cases 
• Urea Breath/ Stool Antigen (For HP Stain -ve Cases) 
• ECHO (If anthracyclines planned) LVEF-               %
• Chemotherapy consent after informing about disease, prognosis, cost of therapy, side effects, hygiene, food and contraception
• Fertility preservation
• PICC line insertion and Chest X ray after line insertion
• Tumor board meeting and decision
• Attach supportive care drug sheet
• Inform primary care physician

Treatment Plan: 

Large cell transformation of MALToma, has to be treated like DLBCL.

Treatment of MALToma at other sites is planned based on: 

• Site and stage of disease 
• Whether tumor can be surgically excised 
• Ease of administering locoregional ISRT 
• Chemotherapy for advanced stages 

About Each Modality of Treatment: 

• Radiotherapy: 
  • 30-40 Gygiven over 4 weeks 
  • Adjacent nodes should be included 
• H. Pylori eradication: Includes PPI with following antibiotics for 14 days 
  • 1st line: 
    • Clarythromycin- 500mg- BD 
    • Amoxycillin- 1000mg- BD 
  • 2nd line 
    • Metronidazole- 500mg- 1-1-1 
    • Tetracycline- 500mg- QID 
    • Bismuth subcitrate- 120mg- QID 
• Note: Gastrectomy has not been shown to achieve superior results in comparison to organ preserving strategies. 

Monitoring After Treatment/ Follow-up: 

• Repeat endoscopy twice a year for 2 years 
• Then once a year