Marginal zone lymphomas (MZLs) comprise 3 distinct entities: extranodal MZL of mucosa-associated lymphoid tissue (MALT), splenic MZL, and nodal MZL. Gastric MALT lymphoma is the most common extranodal MZL and often develops as a result of chronic Helicobacter pylori gastritis. Such cases frequently respond to antibiotics directed against H. pylori. Antigen-driven lymphomatous disease can also be seen in the association of Borrelia burgdorferi with MALT lymphoma of the skin, Chlamydia psittaci with MALT lymphoma of the ocular adnexa, Campylobacter jejuni with immunoproliferative disease of the small intestine, and hepatitis C with splenic MZL. This article discusses the pathogenesis and clinical features of MZL and the treatment options available to patients.

If the inline PDF is not rendering correctly, you can download the PDF file here.

Article Details

Correspondence: Alexandra M. Levine, MD, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Room 3468, Los Angeles, CA 90033. E-mail:


  • 1.

    HarrisNLJaffeESSteinH. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood1994;84:13611392.

  • 2.

    JaffeESHarrisNLSteinH. World Health Organization classification of tumours: pathology and genetics of tumours of haematopoietic and lymphoid tissues. Lyon, France: IARC Press; 2001:351.

  • 3.

    A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood1997;89:39093918.

  • 4.

    IsaacsonPWrightDH. Malignant lymphoma of mucosa-associated lymphoid tissue: a distinctive type of B-cell lymphoma. Cancer1983;52:14101416.

  • 5.

    JonssonVWiikAHou-JensenK. Autoimmunity and extranodal lymphocytic infiltrates in lymphoproliferative disorders. J Intern Med1999;245:277286.

  • 6.

    ZuccaEBertoniFRoggeroE. Molecular analysis of the progression from Helicobacter pylori-associated chronic gastritis to mucosa-associated lymphoid tissue lymphoma of the stomach. N Engl J Med1998;338:804810.

  • 7.

    WotherspoonACOrtiz-HidalgoCFalzonMR. Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma. Lancet1991;338:11571176.

  • 8.

    DoglioniCWotherspoonACMoschiniA. High incidence of primary gastric lymphoma in northeastern Italy. Lancet1992;339:834835.

  • 9.

    WyattJIRathboneBJ. Immune response of the gastric mucosa to Campylobacter pylori. Scand J Gastroenterol1998(suppl);142:4449.

  • 10.

    QinYGreinerATrunkMJ. Somatic hypermutation in low-grade mucosa-associated lymphoid tissue-type B-cell lymphoma. Blood1995;86:3528–3534.

  • 11.

    WotherspoonACDoglioniCIsaacsonPG. Regression of primary low-grade gastric lymphoma of mucosa-associated lymphoid tissue after eradication of Helicobacter pylori. Lancet1993;342: 575577.

  • 12.

    ChanJK. Gastrointestinal lymphomas: an overview with emphasis on new findings and diagnostic problems. Semin Diagn Pathol1996;13:260296.

  • 13.

    ThiedeCWundischTAlpenB. Long-term persistence of monoclonal B cells after cure of Helicobacter pylori infection and complete histologic remission in gastric mucosa-associated lymphoid tissue B-cell lymphoma. J Clin Oncol2001;19:16001609.

  • 14.

    YeHLiuHAttygalleA. Variable frequencies of t(11;18)(q21;q21) in MALT lymphomas of different sites: significant association with CagA strains of H pylori in gastric MALT lymphoma. Blood2003;102:10121018.

  • 15.

    StreubelBSimonitsch-KluppIMullauerL. Variable frequencies of MALT lymphoma-associated genetic aberrations in MALT lymphomas of different sites. Leukemia2004;18:17221726.

  • 16.

    InagakiHNakamuraTLiC. Gastric MALT lymphomas are divided into three groups based on responsiveness to Helicobacter pylori eradication and detection of API2-MALT1 fusion. Am J Surg Pathol2004;28:15601567.

  • 17.

    LevyMCopie-BergmanCGameiroC. Prognostic value of translocation t(11;18) in tumoral response of low-grade gastric lymphoma of mucosa-associated lymphoid tissue type to oral chemotherapy. J Clin Oncol2005;23:50615066.

  • 18.

    YeHDoganAKarranL. BCL10 expresion in normal and neoplastic tissue: nuclear localization in MALT lymphoma. Am J Pathol2000;157:11471154.

  • 19.

    FarnhaPGascoyneRD. Molecular pathogenesis of mucosa-associated lymphoid tissue lymphoma. J Clin Oncol2005;23:63706378.

  • 20.

    StarostikPPatznerJGreinerA. Gastric marginal zone B-cell lymphomas of MALT type develop along 2 distinct genetic pathways. Blood2002;99:39.

  • 21.

    RohatinerAd'AmoreFCoiffierB. Report on a workshop convened to discuss the pathological and staging classifications of gastrointestinal tract lymphoma. Ann Oncol. 1994;5:397400.

  • 22.

    SteinbachGFordRGloberG. Antibiotic treatment of gastric lymphoma of mucosa-associated lymphoid tissue: an uncontrolled trial. Ann Intern Med1999;131:8895.

  • 23.

    RoggeroEZuccaEPinottiG. Eradication of Helicobacter pylori infection in primary low-grade gastric lymphoma of mucosa-associated lymphoid tissue. Ann Intern Med1995;122:767769.

  • 24.

    BayerdorfferENeubauerARudolphB. Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection: MALT Lymphoma Study Group. Lancet1995;345:15911594.

  • 25.

    MognerAMiehlkeSFishbachS. Complete remission of primary high-grade B-cell gastric lymphoma after cure of Helicobacter pylori infection. J Clin Oncol2001;19:20412048.

  • 26.

    SteinbachGFordRGloberG. Antibiotic treatment of gastric lymphoma of mucosa-associated lymphoid tissue. Ann Intern Med1999;131:8895.

  • 27.

    LiuHYeHRuskone-FourmestrauxA. t(11;18) is a marker for all stage gastric MALT lymphomas that will not respond to H pylori eradication. Gastroenterology2002;122:12861294.

  • 28.

    SchechterNRPortlockCSYahalomJ. Treatment of mucosa-associated lymphoid tissue lymphoma of the stomach with radiation alone. J Clin Oncol1998;16:19161921.

  • 29.

    TsangRWGospodarowiczMKPintilieM. Localized mucosa-associated lymphoid tissue lymphoma treated with radiation therapy has excellent clinical outcome. J Clin Oncol2003;21:41574164.

  • 30.

    de MascarelARuskone-FourmestrauxAVavergne-SloveA. Clinical, histological and molecular follow-up of 60 patients with gastric marginal zone lymphoma of mucosa-associated lymphoid tissue. Virchows Arch2005;446:219224.

  • 31.

    JagerGNeumeisterPBrezinschekR. Treatment of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type with cladribine: a phase II study. J Clin Oncol2002;20: 38723877.

  • 32.

    MartinelliGLaszloDFerreriAJ. Clinical activity of rituximab in gatric marginal zone NHL resistant to or not eligible for anti-Helicobacter pylori therapy. J Clin Oncol2005;23:19791983.

  • 33.

    O'ConnerOAWrightJMoskowitzC. Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma and mantle cell lymphoma. J Clin Oncol2005;23:676684.

  • 34.

    Alpha-chain disease and related small intestinal lymphoma: a memorandum. Bull World Health Organ197654:615624.

  • 35.

    IsaacsonPG. Gastrointestinal lymphoma. Hum Pathol1994;25: 10201029.

  • 36.

    RamotBShahinNBubisJJ. Malabsorption syndrome in lymphoma of small intestine: a study of 13 cases. Isr Med J1965;47:221226.

  • 37.

    RambaudJCHalphenMGalianATsapisA. Immunoproliferative small intestinal disease (IPSID): relationships with alpha-chain disease and ``Mediterranean'' lymphomas. Springer Semin Immunopathol1990;12:239250.

  • 38.

    KhojastehAHaghighiP. Immunoproliferative small intestinal disease: portrait of a potentially preventable cancer from the Third World. Am J Med1990;89:483490.

  • 39.

    LecuitMAbachinEMartinA. Immunoproliferative small intestinal disease associated with Campylobacter jejuni. N Engl J Med2004;350:239248.

  • 40.

    Ben-AyedFHalphenMNajjarT. Treatment of alpha chain disease: results of a prospective study in 21 Tunisian patients by the Tunisian-French intestinal Lymphoma Study Group. Cancer1989;63:12511256.

  • 41.

    AkbulutHSoykanIYakaryilmazF. Five-year results of the treatment of 23 patients with immunoproliferative small intestinal disease: a Turkish experience. Cancer1997;80:814.

  • 42.

    GarbeCSteinHDienemannD. Borrelia burgdorferi-associated cutaneous B cell lymphoma: clinical and immunohistologic characterization of four cases. J Am Acad Dermatol1991;24:584590.

  • 43.

    CerroniLZochlingNPutzBKerlH. Infection by Borrelia burgdorferi and cutaneous B-cell lymphoma. J Cutan Pathol1997;24:457461.

  • 44.

    RoggeroEZuccaEMainetiiC. Eradication of Borrelia burgdorferi infection in primary marginal zone B-cell lymphoma of the skin. Hum Pathol2000;31:263268.

  • 45.

    FerreriAJGuidoboniMPonzoniM. Evidence for an association between Chlamydia psittaci and ocular adnexal lymphomas. J Natl Cancer Inst2004;96:586594.

  • 46.

    FerreriAJPonzoniMGuidoboniM. Regression of ocular adnexal lymphoma after Chlamydia psittaci-eradicating antibiotic therapy. J Clin Oncol2005;23:50675073.

  • 47.

    IsaacsonPGMatutuesCBurkeM. The histopathology of splenic lymphoma with villous lymphocytes. Blood1994;84: 38283834.

  • 48.

    ChaconJIMollefoMMunozE. Splenic marginal zone lymphoma: Clinical characteristics and prognostic factors in a series of 60 patients. Blood2002;100:16481654.

  • 49.

    TroussardXValenciFDuchayneE. Splenic lymphoma with villous lymphocytes: clinical presentation, biology and prognostic factors in a series of 100 patients. Br J Haematol1996;93:731736.

  • 50.

    BergerFFelmanPThieblemontC. Non-MALT marginal zone B-cell lymphomas: a description of clinical presentation and outcome in 124 patients. Blood2000;95:19501956.

  • 51.

    AudouinJLe TourneauAMolinaT. Patterns of bone marrow involvement in 58 patients presenting primary splenic marginal zone lymphoma with or without circulating villous lymphocytes. Br J Haematol2003;122:404412.

  • 52.

    HernandezJMGarciaJLGutierrezNC. Novel genomic imbalances in B-cell splenic marginal zone lymphomas revealed by comparative genomic hybridization and cytogenetics. Am J Pathol2001;158:18431850

  • 53.

    RosenwaldAOttGStilgenbauerS. Exclusive detection of the t(11:18)(q21;q21) in extra-nodal marginal zone B cell lymphomas (MZBK) of MALT type in contrast to other MZBL and extra-nodal large B cell lymphomas. Am J Pathol1999;155:18171821.

  • 54.

    Sanchez-IzquierdoDBuchonnetGSiebertR. MALT1 is deregulated by both chromosomal translocation and amplification in B-cell non-Hodgkins lymphoma. Blood2003;101:45394546.

  • 55.

    SoleFSalidoMEspinetB. Splenic marginal zone B-cell lymphomas: two cytogenetic subtypes, one with gain of 3q and the other with loss of 7q. Haematologica2001;86:7177.

  • 56.

    Gruska-WestwoodAMMatutesECoignetLF. The incidence of trisomy 3 in splenic lymphoma with villous lymphocytes: a study by FISH. Br J Haematol1999;104:600604.

  • 57.

    OscierDGGardinerAMouldS. Structural abnormalities of chromosome 7q in chronic lymphoproliferative disorders. Cancer Genet Cytogenet1996;92:2427.

  • 58.

    AlgaraPMateoMSSanchez-BeatoM. Analysis of the IgV(H) somatic mutations in splenic marginal zone lymphoma defines a group of unmutated cases with frequent 7q deletion and adverse clinical course. Blood2002;99:12991304.

  • 59.

    MeleAPulsoniABiancoE. Hepatitis C virus and B cell non-Hodgkin lymphomas: an Italian multicenter case-control study. Blood2003;102:996999.

  • 60.

    SaadounDSuarezFLefrereF. Splenic lymphoma with villous lymphocytes, associated with type II cryoglobulinemia and HCV infection: a new entity?Blood2005;105:7476.

  • 61.

    VallisaDBernuzziPArcainiL. Role of anti-hepatitis C virus (HCV) treatment in HCV-related, low-grade, B-cell, non-Hodgkin's lymphoma: a multicenter Italian experience. J Clin Oncol2005;23:468473.

  • 62.

    CatovskyDMatutesE. Splenic lymphoma with circulating villous lymphocytes/splenic marginal-zone lymphoma. Semin Hematol1999;36:148154.

  • 63.

    ThieblemontCFelmanPCallet-BauchuE. Splenic marginal-zone lymphoma: a distinct clinical and pathological entity. Lancet Oncol2003;4:95103.

  • 64.

    MulliganSPMatutesEDeardenC. Splenic lymphoma with villous lymphocytes: natural history and response to therapy in 50 cases. Br J Haematol1991;78:206209.

  • 65.

    BolamSOrchardJOscierD. Fludarabine is effective in the treatment of splenic lymphoma with villous lymphocytes. Br J Haematol1995;99:158161.

  • 66.

    LefrereFHermineOBelangerC. Fludarabine: an effective treatment in patients with splenic lymphoma with villous lymphocytes. Leukemia2000;14:573575.

  • 67.

    VirchisAMehtaA. Splenic lymphoma with villous lymphocytes (SLVL) responding to 2-chlorodeoxyadenosine (2-CdA). Br J Haematol1998;100:609.

  • 68.

    LefrereFHermineOFrancoisS. Lack of efficacy of 2-chlorodeoxyadenoside in the treatment of splenic lymphoma with villous lymphocytes. Leuk Lymphoma2000;40:113117.

  • 69.

    ArcainiLOrlandiEScottiM. Combination of rituximab, cyclophosphamide, and vincristine induces complete hematologic remission of splenic marginal zone lymphoma. Clin Lymphoma2004;4:250252.

  • 70.

    ThomasDO'BrianSCortesJ. Treatment of splenic lymphoma with villous lymphocytes (SLVL) and marginal zone lymphoma (MZL) with single agent Rituximab [abstract]. Blood2001;98:134a.

  • 71.

    NathwaniBNAndersonJRArmitageJO. Marginal zone B-cell lymphoma: a clinical comparison of nodal and mucosa-associated lymphoid tissue types: nNon-Hodgkin's Lymphoma Classification Project. J Clin Oncol1999;17:24862492.

  • 72.

    SheibaniKBurkeJSSwartzWG. Monocytoid B-cell lymphoma: clinicopathologic study of 21 cases of a unique type of low-grade lymphoma. Cancer1988;62:15311538.

  • 73.

    KohLPLimLCThngCH. Retreatment with chimeric CD 20 monoclonal antibody in a patient with nodal marginal zone B-cell lymphoma. Med Oncol2000;17:225228.

Article Information


Google Scholar

Related Articles


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 38 38 26
PDF Downloads 3 3 3
EPUB Downloads 0 0 0