Mucosa-Associated Lymphoid Tissue Treatment & Management

  • Author: Sara J Grethlein, MD; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Dec 6, 2011
 

Medical Care

MALTomas have been reclassified as extranodal marginal-zone lymphomas of mucosa-associated lymphoid tissue (MALT)-type.[14] Management is different for gastric and nongastric MALTomas.

Nongastric MALTomas are most common in the head and neck,[16, 17, 18] lung,[19] and orbit.[15, 20] These nongastric MALTomas are not associated with H. pylori and are treated using standard modalities that include radiation, chemotherapy, and monoclonal antibodies. In general, patients with stage IE-II disease can be treated with locoregional radiation therapy and/or surgery.

Patients whose condition subsequently recur, as well as patients with stage III/IV disease at presentation, are treated with regimens typically used for follicular lymphoma (ie, rituximab, CVP [chlorambucil, vincristine, prednisone], fludarabine, FND [fludarabine, mitoxantrone, dexamethasone], etc). However patients who have nongastric MALToma that is 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, and prednisone]).

Gastric MALTomas are the most common and well-studied MALTomas. These neoplasms are intimately associated with H. pylori, with the organism present in more than 90% of pathologic specimens of MALTomas.

  • Proton pump inhibitors (PPIs) and antibiotics
    • Treatment with a PPI and antibiotics to eradicate H. pylori is the most important modality used in the therapy of gastric MALTomas, resulting in regression in up to 75% of cases of the low-grade form and some, but a minority, of the intermediate-grade forms of MALToma.
    • Treatment with a combination of amoxicillin, clarithromycin, and PPIs results in eradication rates of 90%. An alternate regimen of metronidazole, clarithromycin, and PPIs achieves the same result.
    • The presence of t(11;18)(q21;q21) translocations has been shown to predict a poor response to therapy.
    • Because most gastric MALTomas are of a low grade, they may remain localized and may not progress for several years.
    • 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.
    • In cases in which no initial response to anti-Helicobacter therapy is observed, an alternative regimen is recommended for use during the second course of treatment.
    • Locally advanced disease that has infiltrated the muscularis mucosa, serosa, or perigastric lymph nodes has a significantly lower response rate.
    • Patients who have 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 treatment used has been the chemotherapy used for low-grade NHLs.
    • Several traditional monotherapy regimens have been used for MALTomas, including chlorambucil, cyclophosphamide, or fludarabine. In addition, standard combination regimens such as CHOP (cyclophosphamide, Adriamycin [hydroxydaunomycin], Oncovin [vincristine], and prednisone) 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.
      • In cases in which antibiotic regimens fail, chemotherapy should be used, although it 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 in other NHLs.
      • A small, nonrandomized study evaluated single agents (chlorambucil and cyclophosphamide) in the treatment of low-grade gastric MALTomas. Complete remissions were achieved in 75% of patients.
      • Rituximab, an anti-CD20 monoclonal antibody, has been reported to achieve remissions in patients with gastric MALTomas whose conditions were either not responsive to anti– H. pylori therapy or who were not infected with H. pylori.
    • The large-cell, intermediate-grade forms of MALToma require standard chemotherapy similar to that used in 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 whose cases antibiotic treatment has failed.
    • Treatment with radiation therapy has achieved long-term remissions (≥ 8 y in one series) in selected patients with gastric MALToma.
    • The optimal dose, patient characteristics, and role in the treatment armamentarium for gastric MALToma are not well delineated, but the dose generally recommended is in the range of 3000-3600 cGy.
    • Radiotherapy may be very effective for orbital soft-tissue MALTomas.
    • Caution is warranted in patients with tumor infiltration into the serosa; successful treatment may lead to gastric perforation, requiring immediate surgical intervention.
    • Secondary malignancies may occur in a small fraction of patients with gastric MALToma treated with radiation.
Next

Surgical Care

  • Surgery has an important, although limited, role in the treatment of gastric MALTomas. The morbidity associated with a partial or total gastrectomy is considerable, and, in most cases, neither is necessary. The efficacy of antibiotics, chemotherapy, and monoclonal antibody therapy has dramatically reduced the need for these procedures. Similarly, debulking is only rarely performed.
  • Surgery for nongastrointestinal MALToma is predominantly used for excisional biopsy of the lungs or orbital soft tissue. The presence of microscopic disease in other sites and the efficacy of other treatment modalities have made surgical therapy an adjunctive rather than curative component of treatment.
Previous
Next

Consultations

A gastroenterologist is an integral member of the treatment team for follow-up of the results of therapy for gastric MALTomas.

Previous
Next

Diet

No special diet is required for patients with MALTomas.

Previous
Proceed to Medication
 
 
Contributor Information and Disclosures
Author

Sara J Grethlein, MD  Senior Attending Physician, Cancer Treatment Center, Bassett Healthcare Network

Sara J Grethlein, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Clinical Oncology, and American Society of Hematology

Disclosure: Nothing to disclose.

Coauthor(s)

Jose A Perez Jr, MD, MBA, MSEd  Consulting Staff, Department of Medicine, Methodist Hospital; Associate Professor of Clinical Medicine, Weill Cornell Medical College

Jose A Perez Jr, MD, MBA, MSEd is a member of the following medical societies: American College of Physician Executives, American College of Physicians, Society of General Internal Medicine, and Society of Hospital Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Karen Seiter, MD  Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, and American Society of Hematology

Disclosure: Novartis Honoraria Speaking and teaching; Novartis Consulting fee Speaking and teaching; Eisai Honoraria Speaking and teaching; Celgene Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Troy H Guthrie, Jr, MD  Director of Cancer Institute, Baptist Medical Center

Troy H Guthrie, Jr, MD is a member of the following medical societies: American Federation for Medical Research, American Medical Association, American Society of Hematology, Florida Medical Association, Medical Association of Georgia, and Southern Medical Association

Disclosure: Nothing to disclose.

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

References

  1. Johnson RM, Brown EJ. Cell-mediated immunity in host defense against infectious diseases. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Disease. 5th ed. Philadelphia, Pa: Churchill Livingstone; 2000:131-4.

  2. Greer JP, Macon WR, McCurley TL. Non-Hodgkin lymphoma. In: Lee GR, Foerster J, Lukens J, et al, eds. Wintrobe's Clinical Hematology. 10th ed. Baltimore, Md: Lippincott, Williams & Wilkins; 1999:2471-3.

  3. Bufo P. The MALTomas. Academic lesson; 1999.

  4. Santacroce L. Anatomy, physiology and surgical pathophysiology of the MALT. Academic lesson; 1997.

  5. Beagley KW, Elson CO. Cells and cytokines in mucosal immunity and inflammation. Gastroenterol Clin North Am. Jun 1992;21(2):347-66. [Medline].

  6. Featherstone C. M cells: portals to the mucosal immune system. Lancet. Oct 25 1997;350(9086):1230. [Medline].

  7. Hamzaoui N, Pringault E. Interaction of microorganisms, epithelium, and lymphoid cells of the mucosa-associated lymphoid tissue. Ann N Y Acad Sci. Nov 17 1998;859:65-74. [Medline].

  8. Dubois B, Barthélémy C, Durand I, et al. Toward a role of dendritic cells in the germinal center reaction: triggering of B cell proliferation and isotype switching. J Immunol. Mar 15 1999;162(6):3428-36. [Medline]. [Full Text].

  9. Delves PJ, Roitt IM. The immune system. First of two parts. N Engl J Med. Jul 6 2000;343(1):37-49. [Medline].

  10. Delves PJ, Roitt IM. The immune system. Second of two parts. N Engl J Med. Jul 13 2000;343(2):108-17. [Medline].

  11. Chin YH, Cai JP, Hieselaar T. Lymphocyte migration into mucosal lymphoid tissues: mechanism and modulation. Immunol Res. 1991;10(3-4):271-8. [Medline].

  12. Keren DF. Intestinal mucosal immune defense mechanisms. Am J Surg Pathol. 1988;12 suppl 1:100-5. [Medline].

  13. Rosebeck S, Lucas PC, McAllister-Lucas LM. Protease activity of the API2-MALT1 fusion oncoprotein in MALT lymphoma development and treatment. Future Oncol. May 2011;7(5):613-7. [Medline]. [Full Text].

  14. Cavalli F, Isaacson PG, Gascoyne RD, Zucca E. MALT Lymphomas. Hematology Am Soc Hematol Educ Program. 2001;241-58. [Medline]. [Full Text].

  15. Perry C, Herishanu Y, Metzer U, et al. Diagnostic accuracy of PET/CT in patients with extranodal marginal zone MALT lymphoma. Eur J Haematol. Sep 2007;79(3):205-9. [Medline].

  16. Chen Y, Inobe J, Marks R, et al. Peripheral deletion of antigen-reactive T cells in oral tolerance. Nature. Jul 13 1995;376(6536):177-80. [Medline].

  17. Bachert C, Möller P. [The tonsils as MALT (mucosa-associated lymphoid tissue) of the nasal mucosa] [German]. Laryngorhinootologie. Oct 1990;69(10):515-20. [Medline].

  18. Kracke A, Hiller AS, Tschernig T, et al. Larynx-associated lymphoid tissue (LALT) in young children. Anat Rec. Jul 1997;248(3):413-20. [Medline].

  19. Lugton I. Mucosa-associated lymphoid tissues as sites for uptake, carriage and excretion of tubercle bacilli and other pathogenic mycobacteria. Immunol Cell Biol. Aug 1999;77(4):364-72. [Medline].

  20. Ferreri AJ, Assanelli A, Crocchiolo R, et al. Therapeutic management of ocular adnexal MALT lymphoma. Expert Opin Pharmacother. Jun 2007;8(8):1073-83. [Medline].

  21. Fung CY, Grossbard ML, Linggood RM, et al. Mucosa-associated lymphoid tissue lymphoma of the stomach: long term outcome after local treatment. Cancer. Jan 1 1999;85(1):9-17. [Medline]. [Full Text].

  22. Babcock GJ, Thorley-Lawson DA. Tonsillar memory B cells, latently infected with Epstein-Barr virus, express the restricted pattern of latent genes previously found only in Epstein-Barr virus-associated tumors. Proc Natl Acad Sci U S A. Oct 24 2000;97(22):12250-5. [Medline]. [Full Text].

  23. Brandtzaeg P, Sollid LM, Bjerke K, et al. Interactions of lymphoid cells with the epithelial environment. Monogr Allergy. 1988;24:51-9. [Medline].

  24. Dürkop H, Anagnostopoulos I, Bulfone-Paus S, Stein H. Expression of several members of the TNF-ligand and receptor family on tonsillar lymphoid B cells. Br J Haematol. Sep 1997;98(4):863-8. [Medline].

  25. Fasano A. Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation. Living life on the edge of the wall. Am J Pathol. Oct 2 2008;epub ahead of print. [Medline].

  26. González-Fernández A, Gilmore D, Milstein C. Age-related decrease in the proportion of germinal center B cells from mouse Peyer's patches is accompanied by an accumulation of somatic mutations in their immunoglobulin genes. Eur J Immunol. Nov 1994;24(11):2918-21. [Medline].

  27. Greiner A, Knörr C, Seeberger H, Schultz A, Müller-Hermelink HK. Tumor biology of mucosa-associated lymphoid tissue lymphomas. Recent Results Cancer Res. 2000;156:19-26. [Medline].

  28. Hammel P, Haioun C, Chaumette MT, et al. Efficacy of single-agent chemotherapy in low-grade B-cell mucosa-associated lymphoid tissue lymphoma with prominent gastric expression. J Clin Oncol. Oct 1995;13(10):2524-9. [Medline].

  29. Harris A, Misiewicz JJ. ABC of the upper gastrointestinal tract. Management of Helicobacter pylori infection. BMJ. Nov 3 2001;323(7320):1047-50. [Medline]. [Full Text].

  30. Harris NL, Isaacson PG. What are the criteria for distinguishing MALT from non-MALT lymphoma at extranodal sites?. Am J Clin Pathol. Jan 1999;111(1 suppl 1):S126-32. [Medline].

  31. Hein WR. Organization of mucosal lymphoid tissue. Curr Top Microbiol Immunol. 1999;236:1-15. [Medline].

  32. Husson H, Lugli SM, Ghia P, et al. Functional effects of TNF and lymphotoxin alpha1beta2 on FDC-like cells. Cell Immunol. Aug 1 2000;203(2):134-43. [Medline].

  33. Isaacson PG. Extranodal lymphomas: the MALT concept. Verh Dtsch Ges Pathol. 1992;76:14-23. [Medline].

  34. Iwasaki A, Kelsall BL. Localization of distinct Peyer's patch dendritic cell subsets and their recruitment by chemokines macrophage inflammatory protein (MIP)-3alpha, MIP-3beta, and secondary lymphoid organ chemokine. J Exp Med. Apr 17 2000;191(8):1381-94. [Medline]. [Full Text].

  35. Jain SL, Michael JG. The influence of antigen digestion on orally induced immunity and tolerance. Adv Exp Med Biol. 1995;371B:1245-50. [Medline].

  36. Kuo SH, Yeh PY, et al. Overexpression of B cell-activating factor of TNF family (BAFF) is associated with Helicobacter pylori-independent growth of gastric diffuse large B-cell lymphoma with histologic evidence of MALT lymphoma. Blood. Oct 1 2008;112(7):2927-34. [Medline].

  37. Köhne G, Schneider T, Zeitz M. Special features of the intestinal lymphocytic system. Baillieres Clin Gastroenterol. Sep 1996;10(3):427-42. [Medline].

  38. Langkamp-Henken B, Glezer JA, Kudsk KA. Immunologic structure and function of the gastrointestinal tract. Nutr Clin Pract. Jun 1992;7(3):100-8. [Medline].

  39. Liu YJ, Barthélémy C, de Bouteiller O, et al. Memory B cells from human tonsils colonize mucosal epithelium and directly present antigen to T cells by rapid up-regulation of B7-1 and B7-2. Immunity. Mar 1995;2(3):239-48. [Medline]. [Full Text].

  40. López-González MA, Sánchez B, Mata F, Delgado F. Tonsillar lymphocyte subsets in recurrent acute tonsillitis and tonsillar hypertrophy. Int J Pediatr Otorhinolaryngol. Feb 1998;43(1):33-9. [Medline].

  41. Miki H, Kobayashi S, Harada H, et al. Early stage gastric MALT lymphoma with high-grade component cured by Helicobacter pylori eradication. J Gastroenterol. Feb 2001;36(2):121-4. [Medline].

  42. Moretó M, Pérez-Bosque A. Dietary plasma proteins, the intestinal immune system and the barrier functions of the intestinal mucosa. J Anim Sci. Sep 26 2008;epub ahead of print. [Medline].

  43. Mosby. Schoefer J, Nissen D, eds. Mosby's GenRx 2001: A Comprehensive Reference for Generic and Brand Prescription Drugs. St. Louis, Mo: Mosby-Year Book; 2001.

  44. Owen RL. Mid-life crisis for M cells. Gut. Jan 1998;42(1):11-2. [Medline]. [Full Text].

  45. Pabst R. Lymphocyte migration to the gut: oversimplifications and controversial aspects. Immunol Res. 1991;10(3-4):279-81. [Medline].

  46. Patrick MK, Gall DG. Protein intolerance and immunocyte and enterocyte interaction. Pediatr Clin North Am. Feb 1988;35(1):17-34. [Medline].

  47. Richards JW Jr. Cryptic tonsillitis. J Fam Pract. Nov 1996;43(5):502. [Medline].

  48. Rothkötter HJ, Geist M, Fritz FJ, Pabst R. Age-dependence of lymphocyte production in Peyer's patch follicles in contrast to the other Peyer's patch compartments and the thymus. Adv Exp Med Biol. 1988;237:81-5. [Medline].

  49. Sierro F, Pringault E, Assman PS, Kraehenbuhl JP, Debard N. Transient expression of M-cell phenotype by enterocyte-like cells of the follicle-associated epithelium of mouse Peyer's patches. Gastroenterology. Sep 2000;119(3):734-43. [Medline].

  50. Syrjänen S, Syrjänen K, Horsmanheimo M. Structure and function of salivary glands in psoriatics. Arch Dermatol Res. 1982;274(3-4):295-301. [Medline].

  51. Yamamoto M, Rennert P, McGhee JR, et al. Alternate mucosal immune system: organized Peyer's patches are not required for IgA responses in the gastrointestinal tract. J Immunol. May 15 2000;164(10):5184-91. [Medline]. [Full Text].

  52. Zinzani PL, Magagnoli M, Galieni P, et al. Nongastrointestinal low-grade mucosa-associated lymphoid tissue lymphoma: analysis of 75 patients. J Clin Oncol. Apr 1999;17(4):1254. [Medline]. [Full Text].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.