Management of the Marginal Zone Lymphomas

  • Barbara Vannata
  • Anastasios Stathis
  • Emanuele ZuccaEmail author
Part of the Cancer Treatment and Research book series (CTAR, volume 165)


Marginal zone lymphomas (MZL) represent around 8 % of all non-Hodgkin lymphomas. During the last decades a number of studies have addressed the mechanisms underlying the disease development. Extranodal MZL lymphoma usually arises in mucosal sites where lymphocytes are not normally present from a background of either autoimmune processes, such as Hashimoto thyroiditis or Sjögren syndrome or chronic infectious conditions. In the context of a persistent antigenic stimulation, successive genetic abnormalities can progressively hit a B-cell clone among the reactive B-cells of the chronic inflammatory tissue and give rise to a MALT lymphoma. The best evidence of an etiopathogenetic link is available for the association between Helicobacter pylori-positive gastritis and gastric MALT lymphoma. Indeed, a successful eradication of this micro-organism with antibiotics can be followed by gastric MALT lymphoma regression in more than 2/3 of cases. Other microbial agents have been implicated in the pathogenesis of MZL arising in the skin (Borrelia burgdorferi), in the ocular adnexa (Chlamydophila psittaci), and in the small intestine (Campylobacter jejuni). The prevalence of hepatitis C virus (HCV) has also been reported higher in MZL patients (particularly of the splenic type) than in the control population, suggesting a possible causative role of the virus. In non-gastric MALT lymphoma and in splenic MZL the role of the antimicrobial therapy is, however, less clear. This review summarizes the recent advances in Marginal Zone Lymphomas, addressing the critical points in their diagnosis, staging and clinical management.


Marginal zone B-cell lymphoma Mucosa-Associated Lymphoid Tissue Extranodal lymphomas 


  1. 1.
    Swerdlow S, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al (eds) (2008) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC, LyonGoogle Scholar
  2. 2.
    Bertoni F, Coiffier B, Salles G, Stathis A, Traverse-Glehen A, Thieblemont C et al (2011) MALT lymphomas: pathogenesis can drive treatment. Oncology 25(12):1134–1142 47PubMedGoogle Scholar
  3. 3.
    Craig VJ, Arnold I, Gerke C, Huynh MQ, Wundisch T, Neubauer A et al (2010) Gastric MALT lymphoma B cells express polyreactive, somatically mutated immunoglobulins. Blood 115(3):581–591. doi: 10.1182/blood-2009-06-228015 PubMedGoogle Scholar
  4. 4.
    Roggero E, Zucca E, Mainetti C, Bertoni F, Valsangiacomo C, Pedrinis E et al (2000) Eradication of Borrelia burgdorferi infection in primary marginal zone B-cell lymphoma of the skin. Hum Pathol 31(2):263–268PubMedGoogle Scholar
  5. 5.
    Ferreri AJ, Guidoboni M, Ponzoni M, De Conciliis C, Dell’Oro S, Fleischhauer K et al (2004) Evidence for an association between chlamydia psittaci and ocular adnexal lymphomas. J Natl Cancer Inst 96(8):586–594PubMedGoogle Scholar
  6. 6.
    Ferreri AJ, Govi S, Pasini E, Mappa S, Bertoni F, Zaja F et al (2012) 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 30(24):2988–2994. doi: 10.1200/jco.2011.41.4466 PubMedGoogle Scholar
  7. 7.
    Ferreri AJM, Dolcetti R, Du MQ, Doglioni C, Giordano Resti A, Politi LS et al (2008) Ocular adnexal MALT lymphoma: an intriguing model for antigen-driven lymphomagenesis and microbial-targeted therapy. Ann Oncol 19(5):835–846. doi: 10.1093/annonc/mdm513 PubMedGoogle Scholar
  8. 8.
    Lecuit M, Abachin E, Martin A, Poyart C, Pochart P, Suarez F et al (2004) Immunoproliferative small intestinal disease associated with Campylobacter jejuni. N Engl J Med 350(3):239–248PubMedGoogle Scholar
  9. 9.
    Hermine O, Lefrere F, Bronowicki JP, Mariette X, Jondeau K, Eclache-Saudreau V et al (2002) Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection. N Engl J Med 347(2):89–94PubMedGoogle Scholar
  10. 10.
    Arcaini L, Paulli M, Boveri E, Vallisa D, Bernuzzi P, Orlandi E et al (2004) Splenic and nodal marginal zone lymphomas are indolent disorders at high hepatitis C virus seroprevalence with distinct presenting features but similar morphologic and phenotypic profiles. Cancer 100(1):107–115PubMedGoogle Scholar
  11. 11.
    Arcaini L, Burcheri S, Rossi A, Paulli M, Bruno R, Passamonti F et al (2007) Prevalence of HCV infection in nongastric marginal zone B-cell lymphoma of MALT. Ann Oncol 18(2):346–350. doi: 10.1093/annonc/mdl388 PubMedGoogle Scholar
  12. 12.
    Paulli M, Arcaini L, Lucioni M, Boveri E, Capello D, Passamonti F et al (2010) Subcutaneous ‘lipoma-like’ B-cell lymphoma associated with HCV infection: a new presentation of primary extranodal marginal zone B-cell lymphoma of MALT. Ann Oncol 21(6):1189–1195. doi: 10.1093/annonc/mdp454 PubMedGoogle Scholar
  13. 13.
    Ambrosetti A, Zanotti R, Pattaro C, Lenzi L, Chilosi M, Caramaschi P et al (2004) Most cases of primary salivary mucosa-associated lymphoid tissue lymphoma are associated either with Sjoegren syndrome or hepatitis C virus infection. Br J Haematol 126(1):43–49PubMedGoogle Scholar
  14. 14.
    Isaacson PG, Du MQ (2004) MALT lymphoma: from morphology to molecules. Nat Rev Cancer 4(8):644–653PubMedGoogle Scholar
  15. 15.
    Jost PJ, Ruland J (2007) Aberrant NF-kappaB signaling in lymphoma: mechanisms, consequences and therapeutic implications. Blood 109(7):2700–2707PubMedGoogle Scholar
  16. 16.
    Bertoni F, Zucca E (2006) Delving deeper into MALT lymphoma biology. J Clin Investig 116(1):22–26PubMedCentralPubMedGoogle Scholar
  17. 17.
    Langel FD, Jain NA, Rossman JS, Kingeter LM, Kashyap AK, Schaefer BC (2008) Multiple protein domains mediate interaction between Bcl10 and MALT1. J Biol Chem. doi: 10.1074/jbc.M800670200 PubMedCentralGoogle Scholar
  18. 18.
    Lucas PC, McAllister-Lucas LM, Nunez G (2004) NF-kappaB signaling in lymphocytes: a new cast of characters. J Cell Sci 117(Pt 1):31–39PubMedGoogle Scholar
  19. 19.
    Baens M, Fevery S, Sagaert X, Noels H, Hagens S, Broeckx V et al (2006) Selective expansion of marginal zone B cells in Emicro-API2-MALT1 mice is linked to enhanced IkappaB kinase gamma polyubiquitination. Cancer Res 66(10):5270–5277PubMedGoogle Scholar
  20. 20.
    Novak U, Rinaldi A, Kwee I, Murty VV, Nandula SV, Rancoita PMV et al. (2008) The NF-kB pathway component A20 (TNFAIP3) is commonly inactivated by DNA mutations and deletions in extranodal marginal zone B-cell lymphoma (EMZL). Ann Oncol abstract at the 10-ICMLGoogle Scholar
  21. 21.
    Kwee I, Rancoita PM, Rinaldi A, Ferreri AJ, Bhagat G, Gascoyne RD et al (2011) Genomic profiles of MALT lymphomas: variability across anatomical sites. Haematologica 96(7):1064–1066. doi: 10.3324/haematol.2011.040402 PubMedCentralPubMedGoogle Scholar
  22. 22.
    Zucca E, Copie-Bergman C, Ricardi U, Thieblemont C, Raderer M, Ladetto M (2013) Gastric marginal zone lymphoma of MALT type: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 24(6):vi144–vi148. doi: 10.1093/annonc/mdt343
  23. 23.
    Isaacson PG, Chott A, Nakamura S, Muller-Hermelink HK, Harris NL, Swerdlow S (2008) Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). In: Swerdlow S, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al (eds) WHO classification of tumours of haematopoietic and lymphoid tissues. IARC, Lyon, pp 214–217Google Scholar
  24. 24.
    Dreyling M, Thieblemont C, Gallamini A, Arcaini L, Campo E, Hermine O et al (2013) ESMO Consensus conferences: guidelines on malignant lymphoma. part 2: marginal zone lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma. Ann Oncol 24(4):857–877. doi: 10.1093/annonc/mds643 PubMedGoogle Scholar
  25. 25.
    Franco V, Florena AM, Iannitto E (2003) Splenic marginal zone lymphoma. Blood 101(7):2464–2472PubMedGoogle Scholar
  26. 26.
    Matutes E, Oscier D, Montalban C, Berger F, Callet-Bauchu E, Dogan A et al (2008) Splenic marginal zone lymphoma proposals for a revision of diagnostic, staging and therapeutic criteria. Leukemia 22(3):487–495PubMedGoogle Scholar
  27. 27.
    Zucca E, Conconi A, Pedrinis E, Cortelazzo S, Motta T, Gospodarowicz MK et al (2003) Nongastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Blood 101(7):2489–2495PubMedGoogle Scholar
  28. 28.
    de Boer JP, Hiddink RF, Raderer M, Antonini N, Aleman BMP, Boot H et al (2008) Dissemination patterns in non-gastric MALT lymphoma. Haematologica 93(2):201–206. doi: 10.3324/haematol.11835 PubMedGoogle Scholar
  29. 29.
    Thieblemont C, Coiffier B (2004) MALT lymphoma: sites of presentations, clinical features and staging procedures. In: Zucca E, Bertoni F (eds) MALT lymphomas. Landes Bioscience/Kluwer Academic, Georgetown, pp 60–80Google Scholar
  30. 30.
    Raderer M, Wohrer S, Streubel B, Troch M, Turetschek K, Jager U et al (2006) Assessment of disease dissemination in gastric compared with extragastric mucosa-associated lymphoid tissue lymphoma using extensive staging: a single-center experience. J Clin Oncol 24(19):3136–3141PubMedGoogle Scholar
  31. 31.
    Zucca E, Stathis A, Bertoni F (2014) The management of nongastric MALT lymphomas. Oncology 28(1):86–93PubMedGoogle Scholar
  32. 32.
    Thieblemont C, Davi F, Noguera ME, Briere J, Bertoni F, Zucca E et al (2012) Splenic marginal zone lymphoma: current knowledge and future directions. Oncology 26(2):194–202PubMedGoogle Scholar
  33. 33.
    Arcaini L, Merli M, Volpetti S, Rattotti S, Gotti M, Zaja F (2012) Indolent B-cell lymphomas associated with HCV infection: clinical and virological features and role of antiviral therapy. Clin dev immunol 2012:638185. doi: 10.1155/2012/638185 PubMedCentralPubMedGoogle Scholar
  34. 34.
    Arcaini L, Lazzarino M, Colombo N, Burcheri S, Boveri E, Paulli M et al (2006) Splenic marginal zone lymphoma: a prognostic model for clinical use. Blood 107(12):4643–4649. doi: 10.1182/blood-2005-11-4659 PubMedGoogle Scholar
  35. 35.
    Montalban C, Abraira V, Arcaini L, Domingo-Domenech E, Guisado-Vasco P, Iannitto E et al (2012) Risk stratification for Splenic Marginal Zone Lymphoma based on haemoglobin concentration, platelet count, high lactate dehydrogenase level and extrahilar lymphadenopathy: development and validation on 593 cases. Br J Haematol 159(2):164–171. doi: 10.1111/bjh.12011 PubMedGoogle Scholar
  36. 36.
    Angelopoulou MK, Kalpadakis C, Pangalis GA, Kyrtsonis MC, Vassilakopoulos TP (2014) Nodal marginal zone lymphoma. Leuk Lymphoma 55(6):1240–1250. doi: 10.3109/10428194.2013.840888 PubMedGoogle Scholar
  37. 37.
    van den Brand M, van Krieken JH (2013) Recognizing nodal marginal zone lymphoma: recent advances and pitfalls. A systematic review. Haematologica 98(7):1003–1013. doi: 10.3324/haematol.2012.083386 PubMedCentralPubMedGoogle Scholar
  38. 38.
    Traverse-Glehen A, Bertoni F, Thieblemont C, Zucca E, Coiffier B, Berger F et al (2012) Nodal marginal zone B-cell lymphoma: a diagnostic and therapeutic dilemma. Oncology 26(1):92–99 103-4PubMedGoogle Scholar
  39. 39.
    Kojima M, Inagaki H, Motoori T, Itoh H, Shimizu K, Tamaki Y et al (2007) Clinical implications of nodal marginal zone B-cell lymphoma among Japanese: study of 65 cases. Cancer Sci 98(1):44–49. doi: 10.1111/j.1349-7006.2006.00345.x PubMedGoogle Scholar
  40. 40.
    Camacho FI, Algara P, Mollejo M, Garcia JF, Montalban C, Martinez N et al (2003) Nodal marginal zone lymphoma: a heterogeneous tumor: a comprehensive analysis of a series of 27 cases. Am J Surg Pathol 27(6):762–771PubMedGoogle Scholar
  41. 41.
    Gachard N, Parrens M, Soubeyran I, Petit B, Marfak A, Rizzo D et al (2013) IGHV gene features and MYD88 L265P mutation separate the three marginal zone lymphoma entities and Waldenstrom macroglobulinemia/lymphoplasmacytic lymphomas. Leukemia 27(1):183–189. doi: 10.1038/leu.2012.257 PubMedGoogle Scholar
  42. 42.
    Oh SY, Ryoo BY, Kim WS, Kim K, Lee J, Kim HJ et al (2006) Nodal marginal zone B-cell lymphoma: analysis of 36 cases. Clinical presentation and treatment outcomes of nodal marginal zone B-cell lymphoma. Ann Hematol 85(11):781–786. doi: 10.1007/s00277-006-0160-y PubMedGoogle Scholar
  43. 43.
    Berger F, Felman P, Thieblemont C, Pradier T, Baseggio L, Bryon PA et al (2000) Non-MALT marginal zone B-cell lymphomas: a description of clinical presentation and outcome in 124 patients. Blood 95(6):1950–1956PubMedGoogle Scholar
  44. 44.
    Nathwani BN, Anderson JR, Armitage JO, Cavalli F, Diebold J, Drachenberg MR et al (1999) Marginal zone B-cell lymphoma: a clinical comparison of nodal and mucosa-associated lymphoid tissue types. Non-Hodgkin’s lymphoma classification project. J Clin Oncol 17(8):2486–2492PubMedGoogle Scholar
  45. 45.
    Treglia G, Zucca E, Sadeghi R, Cavalli F, Giovanella L, Ceriani L (2014) Detection rate of fluorine-18-fluorodeoxyglucose positron emission tomography in patients with marginal zone lymphoma of MALT type: a meta-analysis. Hematological oncology doi:  10.1002/hon.2152. [Epub ahead of print, July 22, 2014]
  46. 46.
    Wundisch T, Thiede C, Morgner A, Dempfle A, Gunther A, Liu H et al (2005) Long-term follow-up of gastric MALT lymphoma after Helicobacter pylori eradication. J Clin Oncol 23(31):8018–8024PubMedGoogle Scholar
  47. 47.
    Montalban C, Santon A, Redondo C, Garcia-Cosio M, Boixeda D, Vazquez-Sequeiros E et al (2005) Long-term persistence of molecular disease after histological remission in low-grade gastric MALT lymphoma treated with H. pylori eradication. Lack of association with translocation t(11;18): a 10-year updated follow-up of a prospective study. Ann Oncol 16(9):1539–1544PubMedGoogle Scholar
  48. 48.
    Kim JS, Chung SJ, Choi YS, Cheon JH, Kim CW, Kim SG et al (2007) Helicobacter pylori eradication for low-grade gastric mucosa-associated lymphoid tissue lymphoma is more successful in inducing remission in distal compared to proximal disease. Br J Cancer 96(9):1324–1328PubMedCentralPubMedGoogle Scholar
  49. 49.
    Stathis A, Chini C, Bertoni F, Proserpio I, Capella C, Mazzucchelli L et al (2009) Long-term outcome following Helicobacter pylori eradication in a retrospective study of 105 patients with localized gastric marginal zone B-cell lymphoma of MALT type. Ann Oncol 20(6):1086–1093. doi: 10.1093/annonc/mdn760 PubMedGoogle Scholar
  50. 50.
    Terai S, Iijima K, Kato K, Dairaku N, Suzuki T, Yoshida M et al (2008) Long-term outcomes of gastric mucosa-associated lymphoid tissue lymphomas after Helicobacter pylori eradication therapy. Tohoku J Exp Med 214(1):79–87PubMedGoogle Scholar
  51. 51.
    Andriani A, Miedico A, Tedeschi L, Patti C, Di Raimondo F, Leone M et al (2009) Management and long-term follow-up of early stage H. pylori-associated gastric MALT-lymphoma in clinical practice: an Italian, multicentre study. Dig Liver Dis 41(7):467–473. doi: 10.1016/j.dld.2008.09.009 (official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver)PubMedGoogle Scholar
  52. 52.
    Ruskone-Fourmestraux A, Fischbach W, Aleman BM, Boot H, Du MQ, Megraud F et al (2011) EGILS consensus report. Gastric extranodal marginal zone B-cell lymphoma of MALT. Gut 60(6):747–58. doi: 10.1136/gut.2010.224949
  53. 53.
    Copie-Bergman C, Wotherspoon AC, Capella C, Motta T, Pedrinis E, Pileri SA et al (2013) Gela histological scoring system for post-treatment biopsies of patients with gastric MALT lymphoma is feasible and reliable in routine practice. Br J Haematol 160(1):47–52. doi: 10.1111/bjh.12078 PubMedGoogle Scholar
  54. 54.
    Nakamura S, Sugiyama T, Matsumoto T, Iijima K, Ono S, Tajika M et al (2012) Long-term clinical outcome of gastric MALT lymphoma after eradication of Helicobacter pylori: a multicentre cohort follow-up study of 420 patients in Japan. Gut 61(4):507–513. doi: 10.1136/gutjnl-2011-300495 PubMedGoogle Scholar
  55. 55.
    Fischbach W, Goebeler ME, Ruskone-Fourmestraux A, Wundisch T, Neubauer A, Raderer M et al (2007) Most patients with minimal histological residuals of gastric MALT lymphoma after successful eradication of Helicobacter pylori can be managed safely by a watch and wait strategy: experience from a large international series. Gut 56(12):1685–1687PubMedCentralPubMedGoogle Scholar
  56. 56.
    Capelle LG, de Vries AC, Looman CW, Casparie MK, Boot H, Meijer GA et al (2008) Gastric MALT lymphoma: Epidemiology and high adenocarcinoma risk in a nation-wide study. Eur J Cancer 44(16):2470–2476. doi: 10.1016/j.ejca.2008.07.005 PubMedGoogle Scholar
  57. 57.
    Wundisch T, Dieckhoff P, Greene B, Thiede C, Wilhelm C, Stolte M et al (2012) Second cancers and residual disease in patients treated for gastric mucosa-associated lymphoid tissue lymphoma by Helicobacter pylori eradication and followed for 10 years. Gastroenterology 143(4):936–942. doi: 10.1053/j.gastro.2012.06.035 (quiz e13–e14)PubMedGoogle Scholar
  58. 58.
    Sackmann M, Morgner A, Rudolph B, Neubauer A, Thiede C, Schulz H et al (1997) Regression of gastric MALT lymphoma after eradication of Helicobacter pylori is predicted by endosonographic staging MALT Lymphoma study group. Gastroenterology 113(4):1087–1090PubMedGoogle Scholar
  59. 59.
    Nakamura S, Matsumoto T, Suekane H, Takeshita M, Hizawa K, Kawasaki M et al (2001) Predictive value of endoscopic ultrasonography for regression of gastric low grade and high grade MALT lymphomas after eradication of Helicobacter pylori. Gut 48(4):454–460PubMedCentralPubMedGoogle Scholar
  60. 60.
    Ruskone-Fourmestraux A, Lavergne A, Aegerter PH, Megraud F, Palazzo L, de Mascarel A et al (2001) Predictive factors for regression of gastric MALT lymphoma after anti- Helicobacter pylori treatment. Gut 48(3):297–303PubMedGoogle Scholar
  61. 61.
    Steinbach G, Ford R, Glober G, Sample D, Hagemeister FB, Lynch PM et al (1999) Antibiotic treatment of gastric lymphoma of mucosa-associated lymphoid tissue. An uncontrolled trial. Ann Intern Med 131(2):88–95PubMedGoogle Scholar
  62. 62.
    Liu H, Ye H, Ruskone-Fourmestraux A, De Jong D, Pileri S, Thiede C et al (2002) T(11;18) is a marker for all stage gastric MALT lymphomas that will not respond to H. pylori eradication. Gastroenterology 122(5):1286–1294PubMedGoogle Scholar
  63. 63.
    Neubauer A, Thiede C, Morgner A, Alpen B, Ritter M, Neubauer B et al (1997) Cure of Helicobacter pylori infection and duration of remission of low- grade gastric mucosa-associated lymphoid tissue lymphoma. J Natl Cancer Inst 89(18):1350–1355PubMedGoogle Scholar
  64. 64.
    Alpen B, Neubauer A, Dierlamm J, Marynen P, Thiede C, Bayerdorfer E et al (2000) Translocation t(11;18) absent in early gastric marginal zone B-cell lymphoma of MALT type responding to eradication of Helicobacter pylori infection. Blood 95(12):4014–4015PubMedGoogle Scholar
  65. 65.
    Kuo SH, Cheng AL, Lin CW, Hsu CH, Wu MS, Yeh KH et al (2011) t(11;18)(q21;q21) translocation as predictive marker for non-responsiveness to salvage thalidomide therapy in patients with marginal zone B-cell lymphoma with gastric involvement. Cancer Chemother Pharmacol 68(6):1387–1395. doi: 10.1007/s00280-011-1631-y PubMedGoogle Scholar
  66. 66.
    Levy M, Copie-Bergman C, Gameiro C, Chaumette MT, Delfau-Larue MH, Haioun C et al (2005) 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 23(22):5061–5066PubMedGoogle Scholar
  67. 67.
    Levy M, Copie-Bergman C, Molinier-Frenkel V, Riou A, Haioun C, Gaulard P et al (2010) Treatment of t(11;18)-positive gastric mucosa-associated lymphoid tissue lymphoma with rituximab and chlorambucil: clinical, histological, and molecular follow-up. Leuk Lymphoma 51(2):284–290. doi: 10.3109/10428190903431820 PubMedGoogle Scholar
  68. 68.
    Thieblemont C, Dumontet C, Bouafia F, Hequet O, Arnaud P, Espinouse D et al (2003) Outcome in relation to treatment modalities in 48 patients with localized gastric MALT lymphoma: a retrospective study of patients treated during 1976-2001. Leuk Lymphoma 44(2):257–262PubMedGoogle Scholar
  69. 69.
    Pinotti G, Zucca E, Roggero E, Pascarella A, Bertoni F, Savio A et al (1997) Clinical features, treatment and outcome in a series of 93 patients with low-grade gastric MALT lymphoma. Leuk Lymphoma 26(5–6):527–537PubMedGoogle Scholar
  70. 70.
    Yahalom J (2011) Patients with H pylori-independent MALT lymphoma are curable with radiotherapy. Oncology 25(12):1147–1149PubMedGoogle Scholar
  71. 71.
    Wirth A, Gospodarowicz M, Aleman BM, Bressel M, Ng A, Chao M et al (2013) Long-term outcome for gastric marginal zone lymphoma treated with radiotherapy: a retrospective, multi-centre, international extranodal Lymphoma study group study. Ann Oncol. doi: 10.1093/annonc/mds623 PubMedGoogle Scholar
  72. 72.
    Goda JS, Gospodarowicz M, Pintilie M, Wells W, Hodgson DC, Sun A et al (2010) Long-term outcome in localized extranodal mucosa-associated lymphoid tissue lymphomas treated with radiotherapy. Cancer 116(16):3815–3824. doi: 10.1002/cncr.25226 PubMedGoogle Scholar
  73. 73.
    Tsang RW, Gospodarowicz MK (2005) Radiation therapy for localized low-grade non-Hodgkin’s lymphomas. Hematol Oncol 23(1):10–17PubMedGoogle Scholar
  74. 74.
    Koch P, Probst A, Berdel WE, Willich NA, Reinartz G, Brockmann J et al (2005) Treatment results in localized primary gastric lymphoma: data of patients registered within the German multicenter study (GIT NHL 02/96). J Clin Oncol 23(28):7050–7059PubMedGoogle Scholar
  75. 75.
    Tsang RW, Gospodarowicz MK, Pintilie M, Wells W, Hodgson DC, Sun A et al (2003) Localized mucosa-associated lymphoid tissue lymphoma treated with radiation therapy has excellent clinical outcome. J Clin Oncol 21(22):4157–4164PubMedGoogle Scholar
  76. 76.
    Hitchcock S, Ng AK, Fisher DC, Silver B, Bernardo MP, Dorfman DM et al (2002) Treatment outcome of mucosa-associated lymphoid tissue/marginal zone non-Hodgkin’s lymphoma. Int J Radiat Oncol Biol Phys 52(4):1058–1066PubMedGoogle Scholar
  77. 77.
    Le QT, Eulau SM, George TI, Hildebrand R, Warnke RA, Donaldson SS et al (2002) Primary radiotherapy for localized orbital MALT lymphoma. Int J Radiat Oncol Biol Phys 52(3):657–663PubMedGoogle Scholar
  78. 78.
    Ansell SM, Grant CS, Habermann TM (1999) Primary thyroid lymphoma. Semin Oncol 26(3):316–323PubMedGoogle Scholar
  79. 79.
    Brogi E, Harris NL (1999) Lymphomas of the breast: pathology and clinical behavior. Semin Oncol 26(3):357–364PubMedGoogle Scholar
  80. 80.
    Agulnik M, Tsang R, Baker MA, Kazdan MS, Fernandes B (2001) Malignant lymphoma of mucosa-associated lymphoid tissue of the lacrimal gland: case report and review of literature. Am J Clin Oncol 24(1):67–70PubMedGoogle Scholar
  81. 81.
    Jhavar S, Agarwal JP, Naresh KN, Shrivastava SK, Borges AM, Dinshaw KA (2001) Primary extranodal mucosa associated lymphoid tissue (MALT) lymphoma of the prostate. Leuk Lymphoma 41(3–4):445–449PubMedGoogle Scholar
  82. 82.
    Suchy BH, Wolf SR (2000) Bilateral mucosa-associated lymphoid tissue lymphoma of the parotid gland. Arch Otolaryngol Head Neck Surg 126(2):224–226PubMedGoogle Scholar
  83. 83.
    Puri DR, Tereffe W, Yahalom J (2008) Low-dose and limited-volume radiotherapy alone for primary dural marginal zone lymphoma: treatment approach and review of published data. Int J Radiat Oncol Biol Phys 71(5):1425–1435. doi: 10.1016/j.ijrobp.2007.12.007 PubMedGoogle Scholar
  84. 84.
    Milgrom SA, Yahalom J (2013) Indolent non-Hodgkin lymphoma primarily involving the hard palate: outcome following radiotherapy. Leuk Lymphoma 54(6):1208–1211. doi: 10.3109/10428194.2012.741232 PubMedGoogle Scholar
  85. 85.
    NCCN National Comprehensive Cancer Network Guidelines (2013) V.2.2013—Non-Hodgkin’s lymphoma. Accessed 11 Nov 2013
  86. 86.
    Yahalom J (2001) MALT lymphomas: a radiation oncology viewpoint. Ann Hematol 80(3):B100–B105PubMedGoogle Scholar
  87. 87.
    Jager G, Hofler G, Linkesch W, Neumeister P (2004) Occurrence of a myelodysplastic syndrome (MDS) during first-line 2-chloro-deoxyadenosine (2-CDA) treatment of a low-grade gastrointestinal MALT lymphoma. Case report and review of the literature. Haematologica 89(4):ECR01Google Scholar
  88. 88.
    Zinzani PL, Stefoni V, Musuraca G, Tani M, Alinari L, Gabriele A et al (2004) Fludarabine-containing chemotherapy as frontline treatment of nongastrointestinal mucosa-associated lymphoid tissue lymphoma. Cancer 100(10):2190–2194PubMedGoogle Scholar
  89. 89.
    Conconi A, Martinelli G, Thieblemont C, Ferreri AJ, Devizzi L, Peccatori F et al (2003) Clinical activity of rituximab in extranodal marginal zone B-cell lymphoma of MALT type. Blood 102(8):2741–2745PubMedGoogle Scholar
  90. 90.
    Martinelli G, Laszlo D, Ferreri AJ, Pruneri G, Ponzoni M, Conconi A et al (2005) Clinical activity of rituximab in gastric marginal zone non-Hodgkin’s Lymphoma resistant to or not eligible for anti-helicobacter pylori therapy. J Clin Oncol 23(9):1979–1983PubMedGoogle Scholar
  91. 91.
    Zucca E, Conconi A, Martinelli G, Tucci A, Vitolo U, Russo E et al (2013) Chlorambucil plus rituximab produces better event-free and progression-free survival in comparison with chlorambucil or rituximab alone in extranodal marginal zone B-cell lymphoma (MALT lymphoma): results of the IELSG-19 study. Hematol Oncol 31(S1):97–98Google Scholar
  92. 92.
    Zucca E, Conconi A, Laszlo D, Lopez-Guillermo A, Bouabdallah R, Coiffier B et al (2013) Addition of rituximab to chlorambucil produces superior event-free survival in the treatment of patients with extranodal marginal-zone B-cell lymphoma: 5-year analysis of the IELSG-19 Randomized Study. J Clin Oncol 31(5):565–572. doi: 10.1200/JCO.2011.40.6272 PubMedGoogle Scholar
  93. 93.
    Salar A, Domingo-Domenech E, Panizo C, Nicolas C, Bargay J, A. M et al. (2013) Bendamustine plus rituximab in first line systemic treatment for extranodal MALT lymphoma: final results of phase II trial of the Spanish lymphoma study group (GELTAMO). Hematol oncol 31(S1):129–130Google Scholar
  94. 94.
    Brown JR, Friedberg JW, Feng Y, Scofield S, Phillips K, Dal Cin P et al (2009) A phase 2 study of concurrent fludarabine and rituximab for the treatment of marginal zone lymphomas. Br J Haematol 145(6):741–748. doi: 10.1111/j.1365-2141.2009.07677.x PubMedCentralPubMedGoogle Scholar
  95. 95.
    Thieblemont C (2005) Clinical presentation and management of marginal zone lymphomas. Hematology (Am Soc Hematol Educ Program) 2005:307–313Google Scholar
  96. 96.
    Kiesewetter B, Raderer M (2013) Antibiotic therapy in nongastrointestinal MALT lymphoma: a review of the literature. Blood 122(8):1350–1357. doi: 10.1182/blood-2013-02-486522 PubMedGoogle Scholar
  97. 97.
    van den Bosch J, Kropman RF, Blok P, Wijermans PW (2002) Disappearance of a mucosa-associated lymphoid tissue (MALT) lymphoma of the urinary bladder after treatment for Helicobacter pylori. Eur J Haematol 68(3):187–188PubMedGoogle Scholar
  98. 98.
    Raderer M, Pfeffel F, Pohl G, Mannhalter C, Valencak J, Chott A (2000) Regression of colonic low grade B cell lymphoma of the mucosa associated lymphoid tissue type after eradication of Helicobacter pylori. Gut 46(1):133–135PubMedCentralPubMedGoogle Scholar
  99. 99.
    Arima N, Tsudo M (2003) Extragastric mucosa-associated lymphoid tissue lymphoma showing the regression by Helicobacter pylori eradication therapy. Br J Haematol 120(5):790–792PubMedGoogle Scholar
  100. 100.
    Grunberger B, Wohrer S, Streubel B, Formanek M, Petkov V, Puespoek A et al (2006) Antibiotic treatment is not effective in patients infected with Helicobacter pylori suffering from extragastric MALT lymphoma. J Clin Oncol 24(9):1370–1375. doi: 10.1200/JCO.2005.02.9025 PubMedGoogle Scholar
  101. 101.
    Ferreri AJ, Ponzoni M, Guidoboni M, De Conciliis C, Giordano Resti A, Mazzi B et al. (2005) Regression of ocular adnexal lymphoma following Chlamydia psittaci-eradicating antibiotic therapy. J Clin Oncol 23:5067–5073Google Scholar
  102. 102.
    Ferreri AJ, Ponzoni M, Guidoboni M, Resti AG, Politi LS, Cortelazzo S et al (2006) Bacteria-eradicating therapy with doxycycline in ocular adnexal MALT lymphoma: a multicenter prospective trial. J Natl Cancer Inst 98(19):1375–1382PubMedGoogle Scholar
  103. 103.
    Kim TM, Kim KH, Lee MJ, Jeon YK, Lee SH, Kim DW et al (2010) First-line therapy with doxycycline in ocular adnexal mucosa-associated lymphoid tissue lymphoma: a retrospective analysis of clinical predictors. Cancer Sci 101(5):1199–1203. doi: 10.1111/j.1349-7006.2010.01502.x PubMedGoogle Scholar
  104. 104.
    Troch M, Kiesewetter B, Raderer M (2011) Recent developments in nongastric mucosa-associated Lymphoid Tissue Lymphoma. Curr Hematol Malignancy Rep. doi: 10.1007/s11899-011-0095-9 Google Scholar
  105. 105.
    Kalpadakis C, Pangalis GA, Vassilakopoulos TP, Sachanas S, Angelopoulou MK (2014) Treatment of splenic marginal zone lymphoma: should splenectomy be abandoned? Leuk Lymphoma 55(7):1463–1470. doi: 10.3109/10428194.2013.845884 PubMedGoogle Scholar
  106. 106.
    Bennett M, Schechter GP (2010) Treatment of splenic marginal zone lymphoma: splenectomy versus rituximab. Semin Hematol 47(2):143–147. doi: 10.1053/j.seminhematol.2010.01.004 PubMedGoogle Scholar
  107. 107.
    Else M, Marin-Niebla A, de la Cruz F, Batty P, Rios E, Dearden CE et al (2012) Rituximab, used alone or in combination, is superior to other treatment modalities in splenic marginal zone lymphoma. Br J Haematol 159(3):322–328. doi: 10.1111/bjh.12036 PubMedGoogle Scholar
  108. 108.
    Kalpadakis C, Pangalis GA, Angelopoulou MK, Sachanas S, Kontopidou FN, Yiakoumis X et al (2013) Treatment of splenic marginal zone lymphoma with rituximab monotherapy: progress report and comparison with splenectomy. Oncologist 18(2):190–197. doi: 10.1634/theoncologist.2012-0251 PubMedCentralPubMedGoogle Scholar
  109. 109.
    Olszewski AJ, Ali S (2014) Comparative outcomes of rituximab-based systemic therapy and splenectomy in splenic marginal zone lymphoma. Ann Hematol 93(3):449–458. doi: 10.1007/s00277-013-1900-4 PubMedGoogle Scholar
  110. 110.
    Vallisa D, Bernuzzi P, Arcaini L, Sacchi S, Callea V, Marasca R et al (2005) 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 Oncol 23(3):468–473PubMedGoogle Scholar
  111. 111.
    Arcaini L, Vallisa D, Rattotti S, Ferretti VV, Ferreri AJ, Bernuzzi P et al. (2014) Antiviral treatment in patients with indolent B-cell lymphomas associated with HCV infection: a study of the Fondazione Italiana Linfomi. Ann Oncol mdu166. doi: 10.1093/annonc/mdu166
  112. 112.
    Liang TJ, Ghany MG (2013) Current and future therapies for hepatitis C virus infection. N Engl J Med 368(20):1907–1917. doi: 10.1056/NEJMra1213651 PubMedCentralPubMedGoogle Scholar
  113. 113.
    Liang TJ, Ghany MG (2014) Therapy of hepatitis C–back to the future. N Engl J Med 370(21):2043–2047. doi: 10.1056/NEJMe1403619 PubMedGoogle Scholar
  114. 114.
    Arcaini L, Paulli M, Burcheri S, Rossi A, Spina M, Passamonti F et al (2007) Primary nodal marginal zone B-cell lymphoma: clinical features and prognostic assessment of a rare disease. Br J Haematol 136(2):301–304. doi: 10.1111/j.1365-2141.2006.06437.x PubMedGoogle Scholar
  115. 115.
    Traverse-Glehen A, Felman P, Callet-Bauchu E, Gazzo S, Baseggio L, Bryon PA et al (2006) A clinicopathological study of nodal marginal zone B-cell lymphoma. A report on 21 cases. Histopathology 48(2):162–173. doi: 10.1111/j.1365-2559.2005.02309.x PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Barbara Vannata
    • 1
  • Anastasios Stathis
    • 1
  • Emanuele Zucca
    • 1
    Email author
  1. 1.Lymphoma UnitOncology Institute of Southern SwitzerlandBellinzonaSwitzerland

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