eMedicine Specialties > Hematology > Stem Cells and Disorders

Mucosa-Associated Lymphoid Tissue: Differential Diagnoses & Workup

Author: Sara J Grethlein, MD, Associate Dean for Graduate Medical Education, Professor, Department of Internal Medicine, Division of Hematology and Oncology, State University of New York Upstate Medical University
Coauthor(s): Jose A Perez Jr, MD, MSEd, MBA, Consulting Physician, Department of Internal Medicine, Residency Director, Vice Chair of Education Department of Medicine, The Methodist Hospital, Houston; Associate Professor of Clinical Medicine, Weill Cornell Medical College
Contributor Information and Disclosures

Updated: Oct 14, 2008

Differential Diagnoses

Helicobacter Pylori Infection
Lymphoma, B-Cell
Lymphoma, Diffuse Large Cell
Lymphoma, Non-Hodgkin

Other Problems to Be Considered

Extranodal lymphoma
Gastric lymphoma
Low-grade NHL

Workup

Laboratory Studies

  • Complete blood cell (CBC) counts and blood chemistries may provide important information about the tissues and organs affected by MALTomas.
  • Immunologic phenotyping of circulating lymphocytes, bone marrow lymphocytes, or biopsy specimens of MALTomas can be determined by flow cytometric analysis.
    • MALTomas have an immunophenotype that is similar to marginal-zone lymphomas.
    • MALTomas are almost always negative for CD10, CD5, and CD23, but they do express CD20. They also express surface immunoglobulin that is restricted to one type of light chain (kappa or lambda) and, often, both CD21 and CD35. Low-grade MALTomas are usually positive for BCL2, whereas intermediate-grade MALTomas are usually negative for BCL2.
  • Cytogenetic studies may show chromosomal abnormalities in the malignant cells of MALTomas. The most common abnormalities detected are trisomy 3, t(11;18), and, less frequently, t(1;4).

Imaging Studies

  • Staging MALTomas can be a challenge (see Staging). Imaging studies are not helpful for visualizing normal mucosa-associated lymphoid tissue (MALT), but they may be useful in diagnosing and staging MALTomas.
  • Barium contrast studies of the upper gastrointestinal tract, small bowel, or colon may demonstrate the presence of masses or infiltration of the bowel wall in mucosa-associated lymphoid tissue (MALT). However, the results from these studies are often nonspecific and may be insensitive.
  • Computed tomography (CT) scanning and magnetic resonance imaging (MRI) findings may help document the extent of the primary lesion and possible distant disease, but they cannot help differentiate malignant from benign lesions in mucosa-associated lymphoid tissue (MALT).
  • Positron-emission tomography (PET)/CT scans are becoming more widely accepted as useful in the management of MALToma. Gastric disease is less likely to be detected by this imaging modality. In one case series, only 42% of early mucosa-associated lymphoid tissue (MALT) was identified, but 100% of stage III-IV patients had positive studies.14

Procedures

  • Endoscopy may reveal mucosal rigidity and hyperplasia in patients with MALTomas. The diagnosis requires a biopsy. Endoscopic ultrasonography can be performed for gastrointestinal tract lesions, but its applicability is limited. H. pylori infection can also be detected in samples obtained via endoscopy.
  • Bone marrow aspiration and biopsy findings can show evidence of bone marrow involvement by the MALToma.

Histologic Findings

Mucosa-associated lymphoid tissue (MALT) is characterized by large amounts of immune-competent cells in the lamina propria of the mucosal layer of many organs.

Intercalated among the mucosal epithelial cells are the M cells, which have a membranous appearance and several external microfolds. Lymphoid tissue occupying the lamina propria of digestive, genitourinary, and respiratory mucosae contains an outer, dense-staining region that contains small T lymphocytes (dark zone) and a lighter-staining region that contains large cells (B lymphocytes and plasma cells). Together, these areas constitute the germinal center, consisting of a mesh of DFCs that support rapidly dividing B cells. The mantle zone surrounds the germinal center and contains small, resting B cells. Germinal centers also contain CD4+ T cells and macrophages.

In the ileum, the lamina propria may contain hundreds of aggregated nodules that form Peyer patches. In the tonsils, epithelium is distributed over lymphoid tissue. Small indentations in the tonsillar tissue form tonsillar crypts. Lymphoid tissue in the tonsils is dense and more nodular. Mucosal glands may be scattered among the surface epithelium of tonsillar tissue. Stratified squamous epithelium is seen in palatine and lingual tonsils, and pseudostratified and ciliated columnar epithelium is seen in the pharyngeal and tubaric tonsils, respectively.

MALTomas are B-cell lymphomas composed of small- to medium-sized lymphocytes that have irregular nuclear contours and abundant cytoplasm. Intermediate-grade MALTomas are distinguished from low-grade MALTomas by the presence of clusters or sheets of transformed blastlike cells with or without a background of low-grade MALToma. If no background of low-grade MALToma is present, the intermediate-grade form is morphologically indistinguishable from diffuse large B-cell lymphoma.

The unifying theme in MALTomas is the production of a diffuse infiltrate that invades epithelial structures and disrupts epithelium, resulting in a lymphoepithelial lesion. Reactive lymphoid follicles are present and become infiltrated and colonized by neoplastic lymphocytes. Thus, most MALTomas are low-grade B-cell lymphomas that express the B-cell antigens CD19 and CD20 and monotypic surface immunoglobulin (usually IgM without IgD). The CD23 marker, which is negative in almost all MALTomas, is useful for distinguishing MALTomas from mantle cell lymphomas.

Limited reports describe chromosomal anomalies that may have significant prognostic significance. The presence of trisomy 3 may indicate a low likelihood of response to anti-Helicobacter antibiotic therapy. The translocation t(11;18)(q21;q21) results in the API2-MALT1 fusion transcript, but it does not appear to have a negative prognostic impact.

Staging

The staging of MALTomas uses the same definitions as other NHLs; MALTomas are, by definition, extranodal in origin.

  • Stage IE: Lymphoma is present in only 1 area or organ outside the lymph nodes.
  • Stage IIE: Lymphoma is present in only 1 area or organ outside the lymph nodes and in the lymph nodes around it. Other lymph nodes on the same side of the diaphragm may also be involved.
  • Stage IIIE: Lymphoma is present on both sides of the diaphragm. It may also have spread to an area or organ near the lymph nodes and/or the spleen.
  • Stage IV: Lymphoma is widespread to several organs, with or without lymph node involvement.

More on Mucosa-Associated Lymphoid Tissue

Overview: Mucosa-Associated Lymphoid Tissue
Differential Diagnoses & Workup: Mucosa-Associated Lymphoid Tissue
Treatment & Medication: Mucosa-Associated Lymphoid Tissue
Follow-up: Mucosa-Associated Lymphoid Tissue
References
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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. Cavalli F, Isaacson PG, Gascoyne RD, Zucca E. MALT Lymphomas. Hematology Am Soc Hematol Educ Program. 2001;241-58. [Medline]. [Full Text].

  14. 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].

  15. 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].

  16. 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].

  17. 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].

  18. 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].

  19. 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].

  20. 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].

  21. 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].

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

  23. 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].

  24. 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].

  25. 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].

  26. 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].

  27. 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].

  28. 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].

  29. 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].

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

  31. 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].

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

  33. 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].

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

  35. 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].

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

  37. 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].

  38. 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].

  39. 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].

  40. 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].

  41. 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].

  42. 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.

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

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

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

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

  47. 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].

  48. 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].

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

  50. 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].

  51. 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].

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Further Reading

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Keywords

mucosa-associated lymphoid tissue, lymphoid tissue, MALToma, MALT lymphoma, MALT, marginal zone B-cell lymphoma, lymph node, mucus membrane, mucus, mucosal tissue, tonsils, Peyer patches, Peyer's patches, vermiform appendix, non-Hodgkin lymphoma, non-Hodgkin's lymphoma, NHL, lymphoma, malignancy, malignancies, cancer, Hashimoto thyroiditis, Hashimoto's thyroiditis, Crohn disease, Crohn's disease, celiac disease, Sjögren syndrome,
gut-associated lymphoid tissue, GALT, bronchial/tracheal-associated lymphoid tissue, BALT, nose-associated lymphoid tissue, NALT, vulvovaginal-associated lymphoid tissue, VALT, gastric MALT lymphoma, nongastric MALT lymphoma, gastric MALToma, nongastric MALToma, human mucosa

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Contributor Information and Disclosures

Author

Sara J Grethlein, MD, Associate Dean for Graduate Medical Education, Professor, Department of Internal Medicine, Division of Hematology and Oncology, State University of New York Upstate Medical University
Sara J Grethlein, MD is a member of the following medical societies: American Society of Hematology
Disclosure: Nothing to disclose.

Coauthor(s)

Jose A Perez Jr, MD, MSEd, MBA, Consulting Physician, Department of Internal Medicine, Residency Director, Vice Chair of Education Department of Medicine, The Methodist Hospital, Houston; Associate Professor of Clinical Medicine, Weill Cornell Medical College
Jose A Perez Jr, MD, MSEd, MBA is a member of the following medical societies: American College of Physician Executives, American College of Physicians, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Medical Editor

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; Schering Honoraria Speaking and teaching; Cephalon Honoraria Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

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.

CME Editor

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, 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 Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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