Approach Considerations
Staging mucosa-associated lymphoid tissue 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.
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.
MALTomas are almost always negative for CD10, CD5, and CD23, but 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. In a study of 33 patients with biopsy-proven MALToma, PET/CT identified only 42% of cases of early-stage disease but yielded positive results in 100% of patients with stage III-IV MALToma. [22] PET/CT is also less likely to detect gastric MALTomas.
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.
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]
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.
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Stage IE – Lymphoma is present in only 1 area or organ outside the lymph nodes
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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
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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
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Stage IV – Lymphoma is widespread to several organs, with or without lymph node involvement
The International Extranodal Lymphoma Study Group (IELSG) has published a simplified MALT prognostic index (MALT-IPI) that was constructed using three individual features with the greatest prognostic significance for event-free survival (EFS) [23] :
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Age ≥70 years
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Ann Arbor stage III or IV
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Elevated lactate dehydrogenase level
The MALT-IPI identifies 3 groups based on the presence of those features:
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Low risk (0 factors present)
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Intermediate risk (1 factor present)
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High risk (2 or 3 factors present)
The 5-year EFS rates in the low-, intermediate-, and high-risk groups were found to be 70%, 56%, and 29%, respectively. The MALT-lymphoma International Prognostic Index (MALT-IPI) also significantly discriminated patients with different progression-free, overall, and cause-specific survival, and the prognostic utility was retained in gastric and nongastric lymphomas. [23, 24]
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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.
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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.
