Approach Considerations
Mucosa-associated lymphoid tissue (MALT) lymphomas (MALTomas) are classified as extranodal marginal-zone lymphomas of MALT type. [19] Management differs, depending on whether the MALToma is gastric or nongastric.
Gastric MALTomas are the most common and well-studied MALTomas. These neoplasms are intimately associated with Helicobacter pylori infection, which is present in more than 90% of pathologic specimens of MALTomas. [14] Generally, in terms of outcome and quality of life, conservative treatment is preferable to surgical therapy or radiotherapy in patients with these lesions. [25]
Nongastric MALTomas most commonly occur in the head and neck, [26, 27, 28] lung, [29] and orbit. [22, 30] These nongastric MALTomas are not associated with H pylori and are treated with standard modalities, including radiation therapy, chemotherapy, and administration of monoclonal antibodies. In general, patients with stage IE-II disease can be treated with locoregional radiation therapy or surgery.
Patients whose condition subsequently recurs, as well as those with stage III/IV disease at presentation, are treated with regimens typically used for follicular lymphoma (eg, rituximab, CVP [chlorambucil, vincristine, prednisone], fludarabine, and FND [fludarabine, mitoxantrone, dexamethasone]). However, patients who have nongastric MALToma that has transformed to large B-cell lymphoma should be treated with regimens that are appropriate for the latter disease (eg, R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone]).
A study that followed patients with gastric MALTomas who were treated with anti–H pylori antibiotic therapy found an excellent remission rate for the gastric MALTomas but an increased risk of developing gastric cancer later. In addition, this population had an increased risk of developing non-Hodgkin lymphoma. [31] A study by Gong et al suggests that H pylori eradication therapy may be worthwhile as an initial treatment for gastric MALTomas even in patients who test negative for H pylori, regardless of stage. [32, 33]
Inappropriately aggressive surgical, radiation, or medical therapy that results in serious injury or long-term disability is a potentially serious medicolegal hazard in the management of MALTomas.
Pharmacologic Therapy
Proton pump inhibitors and antibiotics
Treatment with a proton pump inhibitor (PPI) and antibiotics to eradicate H pylori is the most important modality used in the therapy of gastric MALTomas. Triple therapy with a combination of amoxicillin, clarithromycin, and a PPI results in eradication rates of 70-85%; for penicillin-allergic patients, an alternative regimen of metronidazole, clarithromycin, and PPIs achieves the same result. This approach results in regression in more than 75% of cases of low-grade MALToma [34] and a minority of cases of intermediate-grade MALToma.
The presence of t(11;18)(q21;q21) translocations has been shown to predict a poor response to therapy. In cases in which no initial response to anti–H pylori therapy is observed, an alternative regimen is recommended for use during the second course of treatment.
Treatment with chemotherapy, surgery, or radiotherapy (alone or in combination) has not been demonstrated to be superior to antibiotic treatment. Because of this, a conservative approach, with oncologic and endoscopic follow-up, is advisable.
Because most gastric MALTomas are low-grade lesions, they may remain localized and may not progress for several years. Locally advanced disease that has infiltrated the muscularis mucosa, serosa, or perigastric lymph nodes has a significantly lower response rate.
Patients who are stage IE-II disease who are H pylori–negative typically receive radiation therapy or rituximab.
Chemotherapy
Chemotherapy for MALTomas has not been studied extensively, but historically, the usual treatment has been the chemotherapy used for low-grade non-Hodgkin lymphoma (NHL).
The traditional monotherapy regimens employed for MALTomas have included chlorambucil, cyclophosphamide, or fludarabine. In addition, standard combination regimens such as CHOP have been used successfully. Conjunctival MALTomas have been treated with interferon alfa-2a. Gastrointestinal MALTomas are first treated with an antibiotic regimen designed to eradicate H pylori.
It is widely recommended that chemotherapy should be used in cases where antibiotic regimens fail, though this practice has not been extensively studied. The treating physician’s clinical judgment is crucial in this circumstance; he or she should choose secondary regimens that work against other NHLs.
The single agents chlorambucil and cyclophosphamide have been reported to achieve remissions in three quarters of patients with low-grade gastric MALTomas. The anti-CD20 monoclonal antibody rituximab has been reported to achieve remissions in patients with gastric MALTomas who either were not responsive to anti–H pylori therapy or were not infected with H pylori.
Amiot et al conducted a single-center retrospective study to evaluate effectiveness of gastric MALToma treatment in 106 H pylori–negative patients. Outcomes of oral alkylating monotherapy, rituximab monotherapy, and combination therapy with both drugs were compared. At 2-year followup, both complete remission and overall response were significantly better in patients who received combination therapy (92% and 100% respectively) than in those treated with alkylating agents alone (66% and 68%) or rituximab alone (64% and 73%). However fewer adverse effects were reported with rituximab alone than with either regimen containing alkylating agents. [35]
In a randomized controlled trial by Zucca et al, complete remission at 5-year followup was better in patients treated with chlorambucil plus rituximab than in those treated with chlorambucil alone (78% vs 65%, respectively) but overall response rates were similar (90% vs 87%). However, the differences in remission rates did not translate into improved survival; both groups had an overall survival rate of 89%. [36]
The large-cell, intermediate-grade forms of MALToma require standard chemotherapy similar to that used for other intermediate-grade NHLs (eg, diffuse large B-cell lymphoma).
Radiation Therapy
The efficacy of radiation therapy for gastric MALTomas has been demonstrated in several small trials. Patients with gastric MALToma who will receive the maximal benefit from radiation therapy are those whose disease is in a limited area that could be incorporated in a single radiation treatment field and in whom antibiotic treatment has failed. [37]
Treatment with radiation therapy has achieved long-term remissions (lasting for 8 years or longer in one series) in selected patients with gastric MALToma. The optimal radiation dose, the patient characteristics determining candidacy for radiotherapy, and the role of radiation in the treatment armamentarium for gastric MALToma are not well delineated, but the dose generally recommended is in the range of 30-36 Gy.
Secondary malignancies may occur in a small fraction of patients with gastric MALToma who undergo radiotherapy. Caution is warranted in patients with tumor infiltration into the serosa; successful treatment may lead to gastric perforation, necessitating immediate surgical intervention. With the increased availability of systemic therapies, in general, radiation therapy is currently not favored as an upfront treatment option for this disease.
Radiotherapy may be very effective for orbital soft-tissue MALTomas.
Gastrectomy, Debulking, and Excisional Biopsy
Surgery has an important, but extremely limited, role in the treatment of gastric MALTomas. The morbidity associated with a partial or total gastrectomy is considerable, and in most cases, neither operation is typically necessary. The efficacy of antibiotics, chemotherapy, and monoclonal antibody therapy has dramatically reduced the need for these procedures. Similarly, debulking is almost never required.
Surgery management of nongastrointestinal MALToma predominantly involves excisional biopsy of the lungs or orbital soft tissue for diagnostic purposes. It has little impact as an actual treatment.
Long-Term Monitoring
Patients with MALTomas should continue to receive serial examinations at increasing frequencies for several years after the successful completion of therapy. A gastroenterologist is an integral member of the treatment team for follow-up of the results of therapy for gastric MALTomas. No special diet is required for patients with MALTomas.
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Low magnification micrograph of a lymphoepithelial lesion of the gastrointestinal tract in the setting of a primary gastrointestinal tract lymphoma. H&E stain. Colonic biopsy (descending colon). Lymphoepithelial lesions are strongly associated with mucosa-associated lymphoid tissue lymphomas (MALT lymphomas); however, they may appear in other types of lymphomas.
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High magnification micrograph of a lymphoepithelial lesion of the gastrointestinal tract in the setting of a primary gastrointestinal tract lymphoma. H&E stain. Colonic biopsy (descending colon). Lymphoepithelial lesions are strongly associated with mucosa-associated lymphoid tissue lymphomas (MALT lymphomas); however, they may appear in other types of lymphomas.
