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Clinical manifestations, pathologic features, and diagnosis of extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT)

Authors
Arnold S Freedman, MD
Jon C Aster, MD
Section Editor
Andrew Lister, MD, FRCP, FRCPath, FRCR
Deputy Editor
Rebecca F Connor, MD

INTRODUCTION

The non-Hodgkin lymphoma subtype of marginal zone lymphoma represents a group of lymphomas that have been historically classified together because they appear to arise from post-germinal center marginal zone B cells and share a similar immunophenotype: positive for B cell markers CD19, CD20, and CD22, and negative for CD5, CD10, and usually CD23.

Several marginal zone lymphoma subtypes are recognized in the World Health Organization classification of lymphoid neoplasms:

Extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT lymphoma)

Nodal marginal zone lymphoma

Splenic marginal zone lymphoma

                        
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Literature review current through: Oct 2017. | This topic last updated: Oct 11, 2017.
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References
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  1. Novak U, Basso K, Pasqualucci L, et al. Genomic analysis of non-splenic marginal zone lymphomas (MZL) indicates similarities between nodal and extranodal MZL and supports their derivation from memory B-cells. Br J Haematol 2011; 155:362.
  2. Ruland J, Duncan GS, Elia A, et al. Bcl10 is a positive regulator of antigen receptor-induced activation of NF-kappaB and neural tube closure. Cell 2001; 104:33.
  3. Ruefli-Brasse AA, French DM, Dixit VM. Regulation of NF-kappaB-dependent lymphocyte activation and development by paracaspase. Science 2003; 302:1581.
  4. Ruland J, Duncan GS, Wakeham A, Mak TW. Differential requirement for Malt1 in T and B cell antigen receptor signaling. Immunity 2003; 19:749.
  5. Ho L, Davis RE, Conne B, et al. MALT1 and the API2-MALT1 fusion act between CD40 and IKK and confer NF-kappa B-dependent proliferative advantage and resistance against FAS-induced cell death in B cells. Blood 2005; 105:2891.
  6. Hu S, Du MQ, Park SM, et al. cIAP2 is a ubiquitin protein ligase for BCL10 and is dysregulated in mucosa-associated lymphoid tissue lymphomas. J Clin Invest 2006; 116:174.
  7. Bertoni F, Zucca E. Delving deeper into MALT lymphoma biology. J Clin Invest 2006; 116:22.
  8. Sagaert X, De Wolf-Peeters C, Noels H, Baens M. The pathogenesis of MALT lymphomas: where do we stand? Leukemia 2007; 21:389.
  9. Dierlamm J, Baens M, Wlodarska I, et al. The apoptosis inhibitor gene API2 and a novel 18q gene, MLT, are recurrently rearranged in the t(11;18)(q21;q21) associated with mucosa-associated lymphoid tissue lymphomas. Blood 1999; 93:3601.
  10. Yonezumi M, Suzuki R, Suzuki H, et al. Detection of AP12-MALT1 chimaeric gene in extranodal and nodal marginal zone B-cell lymphoma by reverse transcription polymerase chain reaction (PCR) and genomic long and accurate PCR analyses. Br J Haematol 2001; 115:588.
  11. Zhang Q, Siebert R, Yan M, et al. Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32). Nat Genet 1999; 22:63.
  12. Willis TG, Jadayel DM, Du MQ, et al. Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types. Cell 1999; 96:35.
  13. Yeh KH, Kuo SH, Chen LT, et al. Nuclear expression of BCL10 or nuclear factor kappa B helps predict Helicobacter pylori-independent status of low-grade gastric mucosa-associated lymphoid tissue lymphomas with or without t(11;18)(q21;q21). Blood 2005; 106:1037.
  14. Wlodarska I, Veyt E, De Paepe P, et al. FOXP1, a gene highly expressed in a subset of diffuse large B-cell lymphoma, is recurrently targeted by genomic aberrations. Leukemia 2005; 19:1299.
  15. Sagardoy A, Martinez-Ferrandis JI, Roa S, et al. Downregulation of FOXP1 is required during germinal center B-cell function. Blood 2013; 121:4311.
  16. Sagaert X, de Paepe P, Libbrecht L, et al. Forkhead box protein P1 expression in mucosa-associated lymphoid tissue lymphomas predicts poor prognosis and transformation to diffuse large B-cell lymphoma. J Clin Oncol 2006; 24:2490.
  17. Khalil MO, Morton LM, Devesa SS, et al. Incidence of marginal zone lymphoma in the United States, 2001-2009 with a focus on primary anatomic site. Br J Haematol 2014; 165:67.
  18. Perry AM, Diebold J, Nathwani BN, et al. Non-Hodgkin lymphoma in the developing world: review of 4539 cases from the International Non-Hodgkin Lymphoma Classification Project. Haematologica 2016; 101:1244.
  19. Radaszkiewicz T, Dragosics B, Bauer P. Gastrointestinal malignant lymphomas of the mucosa-associated lymphoid tissue: factors relevant to prognosis. Gastroenterology 1992; 102:1628.
  20. Zucca E, Bertoni F, Roggero E, Cavalli F. The gastric marginal zone B-cell lymphoma of MALT type. Blood 2000; 96:410.
  21. Cogliatti SB, Schmid U, Schumacher U, et al. Primary B-cell gastric lymphoma: a clinicopathological study of 145 patients. Gastroenterology 1991; 101:1159.
  22. White WL, Ferry JA, Harris NL, Grove AS Jr. Ocular adnexal lymphoma. A clinicopathologic study with identification of lymphomas of mucosa-associated lymphoid tissue type. Ophthalmology 1995; 102:1994.
  23. Rosado MF, Byrne GE Jr, Ding F, et al. Ocular adnexal lymphoma: a clinicopathologic study of a large cohort of patients with no evidence for an association with Chlamydia psittaci. Blood 2006; 107:467.
  24. Koss MN. Pulmonary lymphoid disorders. Semin Diagn Pathol 1995; 12:158.
  25. Borie R, Wislez M, Thabut G, et al. Clinical characteristics and prognostic factors of pulmonary MALT lymphoma. Eur Respir J 2009; 34:1408.
  26. Al-Saleem T, Al-Mondhiry H. Immunoproliferative small intestinal disease (IPSID): a model for mature B-cell neoplasms. Blood 2005; 105:2274.
  27. Zucca E, Conconi A, Pedrinis E, et al. Nongastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Blood 2003; 101:2489.
  28. Tsang RW, Gospodarowicz MK, Pintilie M, et al. Stage I and II MALT lymphoma: results of treatment with radiotherapy. Int J Radiat Oncol Biol Phys 2001; 50:1258.
  29. Iwamoto FM, DeAngelis LM, Abrey LE. Primary dural lymphomas: a clinicopathologic study of treatment and outcome in eight patients. Neurology 2006; 66:1763.
  30. Tu PH, Giannini C, Judkins AR, et al. Clinicopathologic and genetic profile of intracranial marginal zone lymphoma: a primary low-grade CNS lymphoma that mimics meningioma. J Clin Oncol 2005; 23:5718.
  31. George AC, Ozsahin M, Janzer R, et al. Primary intracranial dural lymphoma of mucosa-associated lymphoid tissue (MALT) type: report of one case and review of the literature. Bull Cancer 2005; 92:E51.
  32. Welsh JS, Howard A, Hong HY, et al. Synchronous bilateral breast mucosa-associated lymphoid tissue lymphomas addressed with primary radiation therapy. Am J Clin Oncol 2006; 29:634.
  33. Ikeda J, Morii E, Yamauchi A, et al. Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type developing in gonarthritis deformans. J Clin Oncol 2007; 25:4310.
  34. Servitje O, Gallardo F, Estrach T, et al. Primary cutaneous marginal zone B-cell lymphoma: a clinical, histopathological, immunophenotypic and molecular genetic study of 22 cases. Br J Dermatol 2002; 147:1147.
  35. Ferry JA, Fung CY, Zukerberg L, et al. Lymphoma of the ocular adnexa: A study of 353 cases. Am J Surg Pathol 2007; 31:170.
  36. Stefanovic A, Lossos IS. Extranodal marginal zone lymphoma of the ocular adnexa. Blood 2009; 114:501.
  37. Troch M, Formanek M, Streubel B, et al. Clinicopathological aspects of mucosa-associated lymphoid tissue (MALT) lymphoma of the parotid gland: a retrospective single-center analysis of 28 cases. Head Neck 2011; 33:763.
  38. Vazquez A, Khan MN, Sanghvi S, et al. Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue of the salivary glands: a population-based study from 1994 to 2009. Head Neck 2015; 37:18.
  39. Jackson AE, Mian M, Kalpadakis C, et al. Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue of the Salivary Glands: A Multicenter, International Experience of 248 Patients (IELSG 41). Oncologist 2015; 20:1149.
  40. Teckie S, Qi S, Chelius M, et al. Long-term outcome of 487 patients with early-stage extra-nodal marginal zone lymphoma. Ann Oncol 2017; 28:1064.
  41. Koch P, del Valle F, Berdel WE, et al. Primary gastrointestinal non-Hodgkin's lymphoma: I. Anatomic and histologic distribution, clinical features, and survival data of 371 patients registered in the German Multicenter Study GIT NHL 01/92. J Clin Oncol 2001; 19:3861.
  42. Wang T, Gui W, Shen Q. Primary gastrointestinal non-Hodgkin's lymphoma: clinicopathological and prognostic analysis. Med Oncol 2010; 27:661.
  43. Imai H, Sunaga N, Kaira K, et al. Clinicopathological features of patients with bronchial-associated lymphoid tissue lymphoma. Intern Med 2009; 48:301.
  44. Wenzel C, Fiebiger W, Dieckmann K, et al. Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue of the head and neck area: high rate of disease recurrence following local therapy. Cancer 2003; 97:2236.
  45. Thieblemont C, Berger F, Dumontet C, et al. Mucosa-associated lymphoid tissue lymphoma is a disseminated disease in one third of 158 patients analyzed. Blood 2000; 95:802.
  46. Dabaja BS, Ha CS, Wilder RB, et al. Importance of esophagogastroduodenoscopy in the evaluation of non-gastrointestinal mucosa-associated lymphoid tissue lymphoma. Cancer J 2003; 9:321.
  47. Liao Z, Ha CS, McLaughlin P, et al. Mucosa-associated lymphoid tissue lymphoma with initial supradiaphragmatic presentation: natural history and patterns of disease progression. Int J Radiat Oncol Biol Phys 2000; 48:399.
  48. Raderer M, Wöhrer S, Streubel B, et al. Assessment of disease dissemination in gastric compared with extragastric mucosa-associated lymphoid tissue lymphoma using extensive staging: a single-center experience. J Clin Oncol 2006; 24:3136.
  49. Wöhrer S, Streubel B, Bartsch R, et al. Monoclonal immunoglobulin production is a frequent event in patients with mucosa-associated lymphoid tissue lymphoma. Clin Cancer Res 2004; 10:7179.
  50. Asatiani E, Cohen P, Ozdemirli M, et al. Monoclonal gammopathy in extranodal marginal zone lymphoma (ENMZL) correlates with advanced disease and bone marrow involvement. Am J Hematol 2004; 77:144.
  51. Ambrosetti A, Zanotti R, Pattaro C, et al. Most cases of primary salivary mucosa-associated lymphoid tissue lymphoma are associated either with Sjoegren syndrome or hepatitis C virus infection. Br J Haematol 2004; 126:43.
  52. Ramos-Casals M, la Civita L, de Vita S, et al. Characterization of B cell lymphoma in patients with Sjögren's syndrome and hepatitis C virus infection. Arthritis Rheum 2007; 57:161.
  53. Ekström Smedby K, Vajdic CM, Falster M, et al. Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium. Blood 2008; 111:4029.
  54. Husain A, Roberts D, Pro B, et al. Meta-analyses of the association between Chlamydia psittaci and ocular adnexal lymphoma and the response of ocular adnexal lymphoma to antibiotics. Cancer 2007; 110:809.
  55. Ferreri AJ, Dolcetti R, Dognini GP, et al. Chlamydophila psittaci is viable and infectious in the conjunctiva and peripheral blood of patients with ocular adnexal lymphoma: results of a single-center prospective case-control study. Int J Cancer 2008; 123:1089.
  56. Chanudet E, Adam P, Nicholson AG, et al. Chlamydiae and Mycoplasma infections in pulmonary MALT lymphoma. Br J Cancer 2007; 97:949.
  57. Matthews JM, Moreno LI, Dennis J, et al. Ocular Adnexal Lymphoma: no evidence for bacterial DNA associated with lymphoma pathogenesis. Br J Haematol 2008; 142:246.
  58. Ferreri AJ, Guidoboni M, Ponzoni M, et al. Evidence for an association between Chlamydia psittaci and ocular adnexal lymphomas. J Natl Cancer Inst 2004; 96:586.
  59. Ponzoni M, Ferreri AJ, Guidoboni M, et al. Chlamydia infection and lymphomas: association beyond ocular adnexal lymphomas highlighted by multiple detection methods. Clin Cancer Res 2008; 14:5794.
  60. Ferreri AJ, Ponzoni M, Guidoboni M, et al. Regression of ocular adnexal lymphoma after Chlamydia psittaci-eradicating antibiotic therapy. J Clin Oncol 2005; 23:5067.
  61. Ferreri AJ, Ponzoni M, Guidoboni M, et al. Bacteria-eradicating therapy with doxycycline in ocular adnexal MALT lymphoma: a multicenter prospective trial. J Natl Cancer Inst 2006; 98:1375.
  62. Govi S, Dognini GP, Licata G, et al. Six-month oral clarithromycin regimen is safe and active in extranodal marginal zone B-cell lymphomas: final results of a single-centre phase II trial. Br J Haematol 2010; 150:226.
  63. Ferreri AJ, Govi S, Pasini E, et al. Chlamydophila psittaci eradication with doxycycline as first-line targeted therapy for ocular adnexae lymphoma: final results of an international phase II trial. J Clin Oncol 2012; 30:2988.
  64. Vargas RL, Fallone E, Felgar RE, et al. Is there an association between ocular adnexal lymphoma and infection with Chlamydia psittaci? The University of Rochester experience. Leuk Res 2006; 30:547.
  65. Daibata M, Nemoto Y, Togitani K, et al. Absence of Chlamydia psittaci in ocular adnexal lymphoma from Japanese patients. Br J Haematol 2006; 132:651.
  66. Zucca E, Bertoni F. Chlamydia or not Chlamydia, that is the question: which is the microorganism associated with MALT lymphomas of the ocular adnexa? J Natl Cancer Inst 2006; 98:1348.
  67. Gracia E, Froesch P, Mazzucchelli L, et al. Low prevalence of Chlamydia psittaci in ocular adnexal lymphomas from Cuban patients. Leuk Lymphoma 2007; 48:104.
  68. Isaacson PG. Gastrointestinal lymphoma. Hum Pathol 1994; 25:1020.
  69. Ben-Ayed F, Halphen M, Najjar T, et al. Treatment of alpha chain disease. Results of a prospective study in 21 Tunisian patients by the Tunisian-French intestinal Lymphoma Study Group. Cancer 1989; 63:1251.
  70. Lecuit M, Abachin E, Martin A, et al. Immunoproliferative small intestinal disease associated with Campylobacter jejuni. N Engl J Med 2004; 350:239.
  71. Adam P, Czapiewski P, Colak S, et al. Prevalence of Achromobacter xylosoxidans in pulmonary mucosa-associated lymphoid tissue lymphoma in different regions of Europe. Br J Haematol 2014; 164:804.
  72. Swerdlow A, Campo E, Harris NL, et al. World Health Organization Classification of Tumours of Hematopoietic and Lymphoid Tissue, International Agency for Research on Cancer Press, Lyon 2008.
  73. Zukerberg LR, Medeiros LJ, Ferry JA, Harris NL. Diffuse low-grade B-cell lymphomas. Four clinically distinct subtypes defined by a combination of morphologic and immunophenotypic features. Am J Clin Pathol 1993; 100:373.
  74. Schmid C, Kirkham N, Diss T, Isaacson PG. Splenic marginal zone cell lymphoma. Am J Surg Pathol 1992; 16:455.
  75. Isaacson P, Wright DH. Malignant lymphoma of mucosa-associated lymphoid tissue. A distinctive type of B-cell lymphoma. Cancer 1983; 52:1410.
  76. Du M, Diss TC, Xu C, et al. Ongoing mutation in MALT lymphoma immunoglobulin gene suggests that antigen stimulation plays a role in the clonal expansion. Leukemia 1996; 10:1190.
  77. Qin Y, Greiner A, Trunk MJ, et al. Somatic hypermutation in low-grade mucosa-associated lymphoid tissue-type B-cell lymphoma. Blood 1995; 86:3528.
  78. Bahler DW, Miklos JA, Swerdlow SH. Ongoing Ig gene hypermutation in salivary gland mucosa-associated lymphoid tissue-type lymphomas. Blood 1997; 89:3335.
  79. Pan L, Diss TC, Cunningham D, Isaacson PG. The bcl-2 gene in primary B cell lymphoma of mucosa-associated lymphoid tissue (MALT). Am J Pathol 1989; 135:7.
  80. Wotherspoon AC, Finn TM, Isaacson PG. Trisomy 3 in low-grade B-cell lymphomas of mucosa-associated lymphoid tissue. Blood 1995; 85:2000.
  81. Ott G, Katzenberger T, Greiner A, et al. The t(11;18)(q21;q21) chromosome translocation is a frequent and specific aberration in low-grade but not high-grade malignant non-Hodgkin's lymphomas of the mucosa-associated lymphoid tissue (MALT-) type. Cancer Res 1997; 57:3944.
  82. Auer IA, Gascoyne RD, Connors JM, et al. t(11;18)(q21;q21) is the most common translocation in MALT lymphomas. Ann Oncol 1997; 8:979.
  83. Rinaldi A, Mian M, Chigrinova E, et al. Genome-wide DNA profiling of marginal zone lymphomas identifies subtype-specific lesions with an impact on the clinical outcome. Blood 2011; 117:1595.
  84. Panayiotidis P, Kotsi P. Genetics of small lymphocyte disorders. Semin Hematol 1999; 36:171.
  85. Mateo M, Mollejo M, Villuendas R, et al. 7q31-32 allelic loss is a frequent finding in splenic marginal zone lymphoma. Am J Pathol 1999; 154:1583.
  86. Troussard X, Mauvieux L, Radford-Weiss I, et al. Genetic analysis of splenic lymphoma with villous lymphocytes: a Groupe Français d'Hématologie Cellulaire (GFHC) study. Br J Haematol 1998; 101:712.
  87. Streubel B, Lamprecht A, Dierlamm J, et al. T(14;18)(q32;q21) involving IGH and MALT1 is a frequent chromosomal aberration in MALT lymphoma. Blood 2003; 101:2335.
  88. Dierlamm J, Baens M, Stefanova-Ouzounova M, et al. Detection of t(11;18)(q21;q21) by interphase fluorescence in situ hybridization using API2 and MLT specific probes. Blood 2000; 96:2215.
  89. Schreuder MI, Hoeve MA, Hebeda KM, et al. Mutual exclusion of t(11;18)(q21;q21) and numerical chromosomal aberrations in the development of different types of primary gastric lymphomas. Br J Haematol 2003; 123:590.
  90. Du MQ, Peng H, Liu H, et al. BCL10 gene mutation in lymphoma. Blood 2000; 95:3885.
  91. Alpen B, Neubauer A, Dierlamm J, et al. Translocation t(11;18) absent in early gastric marginal zone B-cell lymphoma of MALT type responding to eradication of Helicobacter pylori infection. Blood 2000; 95:4014.
  92. Liu H, Ruskon-Fourmestraux A, Lavergne-Slove A, et al. Resistance of t(11;18) positive gastric mucosa-associated lymphoid tissue lymphoma to Helicobacter pylori eradication therapy. Lancet 2001; 357:39.
  93. Liu H, Ye H, Dogan A, et al. T(11;18)(q21;q21) is associated with advanced mucosa-associated lymphoid tissue lymphoma that expresses nuclear BCL10. Blood 2001; 98:1182.
  94. Starostik P, Patzner J, Greiner A, et al. Gastric marginal zone B-cell lymphomas of MALT type develop along 2 distinct pathogenetic pathways. Blood 2002; 99:3.
  95. Du MQ, Isaccson PG. Gastric MALT lymphoma: from aetiology to treatment. Lancet Oncol 2002; 3:97.
  96. Taji S, Nomura K, Matsumoto Y, et al. Trisomy 3 may predict a poor response of gastric MALT lymphoma to Helicobacter pylori eradication therapy. World J Gastroenterol 2005; 11:89.
  97. Liu H, Ye H, Ruskone-Fourmestraux A, et al. T(11;18) is a marker for all stage gastric MALT lymphomas that will not respond to H. pylori eradication. Gastroenterology 2002; 122:1286.
  98. Lévy M, Copie-Bergman C, Gameiro C, et al. 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 Oncol 2005; 23:5061.
  99. Ye H, Liu H, Raderer M, et al. High incidence of t(11;18)(q21;q21) in Helicobacter pylori-negative gastric MALT lymphoma. Blood 2003; 101:2547.
  100. Chang KJ, Katz KD, Durbin TE, et al. Endoscopic ultrasound-guided fine-needle aspiration. Gastrointest Endosc 1994; 40:694.
  101. Wiersema MJ, Kochman ML, Cramer HM, et al. Endosonography-guided real-time fine-needle aspiration biopsy. Gastrointest Endosc 1994; 40:700.
  102. Vilmann P, Hancke S, Henriksen FW, Jacobsen GK. Endoscopic ultrasonography-guided fine-needle aspiration biopsy of lesions in the upper gastrointestinal tract. Gastrointest Endosc 1995; 41:230.
  103. Suekane H, Iida M, Kuwano Y, et al. Diagnosis of primary early gastric lymphoma. Usefulness of endoscopic mucosal resection for histologic evaluation. Cancer 1993; 71:1207.
  104. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Swerdlow SH, Campo E, Harris NL, et al. (Eds), IARC Press, Lyon 2008.
  105. Harris NL, Jaffe ES, Diebold J, et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol 1999; 17:3835.
  106. Harris NL, Jaffe ES, Diebold J, et al. The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November, 1997. Ann Oncol 1999; 10:1419.
  107. Harris NL, Jaffe ES, Diebold J, et al. The World Health Organization classification of neoplastic diseases of the haematopoietic and lymphoid tissues: Report of the Clinical Advisory Committee Meeting, Airlie House, Virginia, November 1997. Histopathology 2000; 36:69.
  108. Barth TF, Döhner H, Werner CA, et al. Characteristic pattern of chromosomal gains and losses in primary large B-cell lymphomas of the gastrointestinal tract. Blood 1998; 91:4321.