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Mucosa-Associated Lymphoid Tissue Workup

  • Author: Sara J Grethlein, MD; Chief Editor: Emmanuel C Besa, MD  more...
 
Updated: Dec 09, 2014
 

Approach Considerations

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.

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Laboratory Studies

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).

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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.[18]

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Other Studies

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.

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Histologic Findings

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]

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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
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Contributor Information and Disclosures
Author

Sara J Grethlein, MD Associate Dean for Undergraduate Medical Education, Indiana University School of Medicine

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

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, 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 Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Acknowledgements

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.

Jose A Perez Jr, MD, MBA, MSEd Residency Director, Internal Medicine Residency Program, Vice Chair of Education, 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.

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

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Low magnification micrograph of a lymphoepithelial lesion of the gastrointestinal tract in the setting of a primary gastrointestinal tract lymphoma. H&E stain. Colonic biopsy (descending colon). Lymphoepithelial lesions are strongly associated with mucosa-associated lymphoid tissue lymphomas (MALT lymphomas); however, they may appear in other types of lymphomas.
High magnification micrograph of a lymphoepithelial lesion of the gastrointestinal tract in the setting of a primary gastrointestinal tract lymphoma. H&E stain. Colonic biopsy (descending colon). Lymphoepithelial lesions are strongly associated with mucosa-associated lymphoid tissue lymphomas (MALT lymphomas); however, they may appear in other types of lymphomas.
 
 
 
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