An extra-nodal lymphoma of small B lymphoid cells including marginal zone (centrocyte-like) cells, monocytoid-like cells, small lymphocytes and scattered immunoblast and centrocyte-like cells. Some cases show plasma-cell differentiation. The infiltrate is seen in the marginal zone of B-cell follicles and in the interfollicular areas. There is infiltration of epithelia to form lymphoepithelial lesions.
7-8% of all B-cell lymphomas and 50% of gastric lymphomas.
The development of MALT lymphoma is commonly preceded by a history of chronic inflammation / autoimmune disease:
Chronic gastritis associated with Helicobacter pylori, which is thought to be pathogenic in the stomach. Eradication of the organisms has been reported to result in regression of MALT lymphoma after histologically and molecular confirmation of the diagnosis2. The organisms progressively disappear as the lymphoma develops. Helicobacter pylori has also been implicated in the salivary gland4.
Sjögren syndrome / lymphoepithelial sialadenitis; 4-7% of patients will develop lymphoma, a 44-fold increase in risk. 85% of these lymphomas are MALT lymphomas.
Hashimoto thyroiditis; 05-1.5% of patients will develop lymphoma, a 70-fold increased risk of thyroid lymphoma and a threefold overall increased risk of lymphoma.
Borrelia burgdorferi skin infection associated with cutaneous marginal zone B-cell lymphoma
Persistent infection with Chlamydia psittaci has been implicated in ocular adnexal lymphoma: regression has been reported after antibiotic therapy13.
gastrointestinal tract; 50%
other sites include thymus9, conjunctiva, Waldeyer's ring, thymus, trachea, gallbladder and urinary bladder. Morphologically similar lymphomas have also been described in the testis, kidney, prostate, liver and dura mater1.
The neoplastic cells are first found in a marginal zone distribution, external to an intact mantle zone. Eventually there is interfollicular expansion and the follicles are overrun. The neoplastic cells have small to medium sized slightly irregular nuclei and relatively abundant cytoplasm, resembling centrocytes. With a larger amount of cytoplasm, they resemble monocytes and discrete aggregates of monocytoid cells are seen in a perisinusoidal distribution. Plasma cell differentiation occurs in one third of gastric cases and is usual in thyroid MALT lymphoma and IPSID. There are limited numbers of large blastic cells.
Lymphoepithelial lesions are characteristic. Colonisation of non-neoplastic follicles may give a resemblance to follicular lymphoma. Nodal involvement in gastric MALT lymphoma shows various patterns .
Variants
alpha chain disease (aCHD, immunoproliferative small intestinal disease, IPSID, Mediterranean abdominal lymphoma): defective alpha heavy chains are secreted. This is a disease of young adults (second and third decades), affecting the gastrointestinal tract and resulting in constitutional symptoms, malabsorption, hypocalcaemia and diarrhoea. Initially, it may be reversible with antibiotics, but progresses to high grade lymphoma. It is associated with poor hygiene and frequent intestinal infections. Recently, Campylobacter jejuni has been specifically implicated in the aetiology11,12. It usually involves the small intestine and mesenteric node: rare respiratory tract cases have been described. The lamina propria of the intestine is infiltrated by a mixture of plasma cells and small lymphocytes. Marginal zone B-cells may form lymphoepithelial lesions. Villous atrophy may occur.
Cytogenetics
60% show trisomy 3.
25-50% of cases show t(11;18)(q21;q21), resulting in API2-MALT1 fusion. API2 is a member of the IAP (inhibitor of apoptosis) gene family. The fusion product may have increased API2 activity. The frequency of this fusion gene seems to vary with the anatomic site of MALT lymphomas, being found in 21 of 51 pulmonary MALT lymphomas, where it correlated with the absence of any underlying autoimmune disease8. However, it is rare in cutaneous MALT lymphoma7 and at those sites, thyroid, salivary gland and thymus9, where autoimmune disease plays an important role in lymphomagenesis.
t(1;14)(p22;q32) results in in a variety of truncation mutations of bcl-10 and may confer anti-apoptotic functions on bcl-10. Aberrant bcl-10 expression (with or without the t(1;14)(p22;q32) translocation) occurs in the nucleus and is associated with failure of gastric lymphomas to respond to the eradication of H. pylori5 and more advanced stage3. Both the API2-MALT1 fusion product and the mutated bcl-10 may activate NF-kB, a transcription factor for several survival-related genes7.
t(14;18)(q32;q21) juxtaposes the immunoglobulin heavy chain gene and MALT1. This translocation and t(11;18)(q21;q21) appear to be mutually exclusive. The mutation was found in 12 of 66 MALT lymphomas and appears to be associated with certain anatomic sites, being found in MALT lymphoma of liver (4 of 4), skin (3 of 11), ocular adnexa (3 of 8), and salivary gland (2 of 11), but did not occur in MALT lymphomas of the stomach (n = 10), intestine (n = 9), lung (n = 7), thyroid (n = 4), or breast (n = 2)10.
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IgM |
positive |
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IgA |
less often positive |
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IgG |
less often positive |
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light chains |
positive except in IPSID |
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may be aberrant nuclear positivity; 28/533 |
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negative |
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negative |
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variably negative or weakly positive |
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positive |
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positive |
a marginal zone cell-associated antigen |
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negative |
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positive |
a marginal zone cell-associated antigen |
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variable |
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positive |
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Reactive processes. Demonstration of light chain restriction may be helpful to establish a diagnosis of MALT lymphoma. Assessment of clonality may be necessary. In the stomach, a grading system has been devised:
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Score |
Diagnosis |
features in lamina propria |
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0 |
normal |
scattered plasma cells but no lymphoid follicles |
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1 |
chronic active gastritis |
small clusters of lymphocytes but no lymphoid follicles and no lymphoepithelial lesions |
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2 |
chronic active gastritis with florid lymphoid follicle formation |
lymphoid follicles with surrounding mantle zone and plasma cells but no lymphoepithelial lesions |
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3 |
suspicious lymphoid infiltrate, probably reactive |
lymphoid follicles surrounded by small lymphocytes that diffusely infiltrate the lamina propria and occasionally the epithelium |
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4 |
suspicious lymphoid infiltrate, probably lymphoma |
lymphoid follicles surrounded by marginal zone cells that diffusely infiltrate the lamina propria and into the epithelium in small groups
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5 |
MALT lymphoma |
a dense infiltrate of marginal zone cells with prominent lymphoepithelial lesions |
follicular lymphoma may be emulated when follicles are heavily colonised. Follicular lymphoma is CD10+.
mantle cell lymphoma; CD5+, cyclinD1+
diffuse large B-cell lymphoma. MALT lymphoma may progress to a high grade lymphoma but the term "high-grade MALT lymphoma" should not be used. It does, however, seem reasonable to record "MALT lymphoma with a minor (less than 20% of the entire tumour) large B-cell lymphoma" or "large B-cell lymphoma with MALT lymphoma" as appropriate: in one series of gastric lymphomas, none of the 18 patients in the former category recurred, while 2 of 14 in the latter category recurred, of whom one died6. The presence of a large B-cell component also correlated with lymph node involvement6.
World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.
3 Liu, H., H. Ye, et al. (2001). "T(11;18)(q21;q21) is associated with advanced mucosa-associated lymphoid tissue lymphoma that expresses nuclear BCL10." Blood 98(4): 1182-7, first published in abstract, Liu T et al. t(11;18)(q21;q21) is associated with more advanced MALT lymphoma that expresses nuclear bcl-10. J Pathol 2001:193(suppl):2A.
12 Parsonnet J,Isaacson PG Bacterial infection and MALT lymphoma. N Engl J Med 2004; 350:213-5
This page last revised 12.8.2006.
©SMUHT/PW Bishop