Mucosa-Associated Lymphoid Tissue Workup
- Author: Sara J Grethlein, MD; Chief Editor: Emmanuel C Besa, MD more...
Staging mucosa-associated lymphoid tissue (MALT) lymphomas (MALTomas) can be a challenge (see Staging). Imaging studies (eg, barium contrast studies, computed tomography [CT], magnetic resonance imaging [MRI], and positron-emission tomography [PET]) are not helpful for visualizing normal MALT, but they may be useful in diagnosing and staging MALTomas.
Endoscopy may be helpful. Bone marrow aspiration and biopsy findings can signal bone marrow involvement. Histologically, MALT is characterized by large amounts of immune-competent cells in the lamina propria of the mucosal layer of many organs.
A complete blood count (CBC) 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 resembling that of marginal-zone lymphomas.
Although MALTomas are almost always negative for CD10, CD5, and CD23, they do express CD20. They also express surface immunoglobulin that is restricted to a single 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).
Barium Contrast, CT, MRI, and PET
Barium contrast studies of the upper gastrointestinal (GI) tract, small bowel, or colon may demonstrate the presence of masses or infiltration of the bowel wall in MALT. However, the results from these studies are often nonspecific and may be insensitive.
CT and 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 MALT.
PET-CT is becoming more widely accepted as useful in the management of MALTomas. Gastric disease is less likely to be detected by this imaging modality. In one case series, PET-CT identified only 42% of cases of early MALT but yielded positive results in 100% of stage III-IV patients.
Endoscopy may reveal mucosal rigidity and hyperplasia in patients with MALTomas. The diagnosis requires a biopsy. Endoscopic ultrasonography can be performed for GI 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.
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 GI, genitourinary (GU), and respiratory mucosae contains an outer, dense-staining region that contains small T cells (dark zone) and a lighter-staining region that contains large cells (B cells and plasma cells).
Together, these areas constitute the germinal center, consisting of a mesh of dendritic follicular cells (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; pseudostratified and ciliated columnar epithelia are 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 characteristic is a diffuse infiltrate that invades epithelial structures and disrupts epithelium, causing 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 CD19 and CD20 and monotypic surface immunoglobulin (usually immunoglobulin M [IgM] without immunoglobulin D [IgD]). The CD23 marker (negative in almost all MALTomas) helps distinguish 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– H pylori 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 the staging of other non-Hodgkin lymphomas (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 or the spleen
Stage IV – Lymphoma is widespread to several organs, with or without lymph node involvement
Johnson RM, Brown EJ. Cell-mediated immunity in host defense against infectious diseases. Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Disease. 5th ed. Philadelphia, Pa: Churchill Livingstone; 2000. 131-4.
Greer JP, Macon WR, McCurley TL. Non-Hodgkin lymphoma. Lee GR, Foerster J, Lukens J, et al, eds. Wintrobe's Clinical Hematology. 10th ed. Baltimore, Md: Lippincott, Williams & Wilkins; 1999. 2471-3.
Bufo P. Academic lesson; 1999. The MALTomas.
Santacroce L. Academic lesson; 1997. Anatomy, physiology and surgical pathophysiology of the MALT.
Beagley KW, Elson CO. Cells and cytokines in mucosal immunity and inflammation. Gastroenterol Clin North Am. 1992 Jun. 21(2):347-66. [Medline].
Featherstone C. M cells: portals to the mucosal immune system. Lancet. 1997 Oct 25. 350(9086):1230. [Medline].
Hamzaoui N, Pringault E. Interaction of microorganisms, epithelium, and lymphoid cells of the mucosa-associated lymphoid tissue. Ann N Y Acad Sci. 1998 Nov 17. 859:65-74. [Medline].
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. 1999 Mar 15. 162(6):3428-36. [Medline]. [Full Text].
Delves PJ, Roitt IM. The immune system. First of two parts. N Engl J Med. 2000 Jul 6. 343(1):37-49. [Medline].
Delves PJ, Roitt IM. The immune system. Second of two parts. N Engl J Med. 2000 Jul 13. 343(2):108-17. [Medline].
Chin YH, Cai JP, Hieselaar T. Lymphocyte migration into mucosal lymphoid tissues: mechanism and modulation. Immunol Res. 1991. 10(3-4):271-8. [Medline].
Keren DF. Intestinal mucosal immune defense mechanisms. Am J Surg Pathol. 1988. 12 suppl 1:100-5. [Medline].
Rosebeck S, Lucas PC, McAllister-Lucas LM. Protease activity of the API2-MALT1 fusion oncoprotein in MALT lymphoma development and treatment. Future Oncol. 2011 May. 7(5):613-7. [Medline]. [Full Text].
Chen T, Cen L, Xiao R, Yang JH, Jiang NK, Lu XZ, et al. [Prognostic value of t(11; 18) (q21; q21) for gastric mucosa-associated lymphoid tissue lymphoma]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2012 Apr. 29(2):181-3. [Medline].
Perry C, Herishanu Y, Metzer U, et al. Diagnostic accuracy of PET/CT in patients with extranodal marginal zone MALT lymphoma. Eur J Haematol. 2007 Sep. 79(3):205-9. [Medline].
Fischbach W, Schramm S, Goebeler E. Outcome and quality of life favour a conservative treatment of patients with primary gastric lymphoma. Z Gastroenterol. 2011 Apr. 49(4):430-5. [Medline].
Chen Y, Inobe J, Marks R, et al. Peripheral deletion of antigen-reactive T cells in oral tolerance. Nature. 1995 Jul 13. 376(6536):177-80. [Medline].
Bachert C, Möller P. [The tonsils as MALT (mucosa-associated lymphoid tissue) of the nasal mucosa] [German]. Laryngorhinootologie. 1990 Oct. 69(10):515-20. [Medline].
Kracke A, Hiller AS, Tschernig T, et al. Larynx-associated lymphoid tissue (LALT) in young children. Anat Rec. 1997 Jul. 248(3):413-20. [Medline].
Lugton I. Mucosa-associated lymphoid tissues as sites for uptake, carriage and excretion of tubercle bacilli and other pathogenic mycobacteria. Immunol Cell Biol. 1999 Aug. 77(4):364-72. [Medline].
Ferreri AJ, Assanelli A, Crocchiolo R, et al. Therapeutic management of ocular adnexal MALT lymphoma. Expert Opin Pharmacother. 2007 Jun. 8(8):1073-83. [Medline].
Wündisch T, Dieckhoff P, Greene B, Thiede C, Wilhelm C, Stolte M, et al. Second Cancers and Residual Disease in Patients Treated for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma by Helicobacter pyloriEradication and Followed for 10 Years. Gastroenterology. 2012 Jun 27. [Medline].
Choi YJ, Lee DH, Kim JY, Kwon JE, Kim JY, Jo HJ, et al. Low Grade Gastric Mucosa-associated Lymphoid Tissue Lymphoma: Clinicopathological Factors Associated with Helicobacter pylori Eradication and Tumor Regression. Clin Endosc. 2011 Dec. 44(2):101-8. [Medline]. [Full Text].
Amiot A, Lévy M, Copie-Bergman C, Dupuis J, Szablewski V, Le Baleur Y, et al. Rituximab, alkylating agents or combination therapy for gastric mucosa-associated lymphoid tissue lymphoma: a monocentric non-randomised observational study. Aliment Pharmacol Ther. 2014 Mar. 39(6):619-28. [Medline].
Zucca E, Conconi A, Laszlo D, López-Guillermo A, Bouabdallah R, Coiffier B, et al. 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. 2013 Feb 10. 31(5):565-72. [Medline].