Aetiology
MALT lymphomas are commonly associated with autoimmune disease and chronic infection.[14][15][16][17]
Gastric MALT lymphoma is strongly associated with chronic Helicobacter pylori infection (detected in up to 90% of cases).
Salivary/parotid gland MALT lymphoma is associated with Sjögren's syndrome, lymphoepithelial sialadenitis, and hepatitis C virus infection.
Thyroid MALT lymphoma is associated with Hashimoto's thyroiditis.
Lung MALT lymphoma is associated with:
Sjögren's syndrome, systemic lupus erythematosus, common variable immunodeficiency syndrome, and
infection with H pylori, Achromobacter xylosoxidans, HIV, and hepatitis C virus.
Ocular adnexa MALT lymphoma is associated with Chlamydia psittaci infection and hepatitis C virus infection.
Skin/cutaneous MALT lymphoma is associated with Borrelia burgdorferi infection.
Intestinal MALT lymphoma (including immunoproliferative small intestinal disease) is associated with Campylobacter jejuni infection.
Liver MALT lymphoma is associated with hepatitis C virus infection and H pylori infection.
Pathophysiology
MALT lymphomas develop at extranodal sites that do not have organised lymphoid tissue. The first stage in the pathophysiology of MALT lymphoma is the acquisition of lymphoid tissue at an extranodal site, usually due to an autoimmune disease or chronic infection.[18][19][20]
It is thought that B cells at the extranodal site undergo malignant transformation due to chronic antigen stimulation and the acquisition and accumulation of genetic abnormalities.[18][19][20]
Neoplastic B cells infiltrate the marginal zone (the area around a reactive lymphoid follicle) and later into the surrounding mucosa.[21] Infiltration of neoplastic cells in the epithelial tissue results in lymphoepithelial lesions.[5]
MALT lymphoma may undergo high-grade histological transformation to diffuse large B-cell lymphoma. This is characterised by an increase in the number of transformed blasts, which can eventually lead to complete effacement of the original MALT lymphoma.[22]
Genetic abnormalities associated with MALT lymphoma
The following cytogenetic abnormalities have been identified in MALT lymphoma:[18][23][24]
t(11;18)(q21;q21)/BIRC3::MALT1; the most common translocation, identified in 10% to 50% of gastric and lung MALT lymphomas
t(14;18)(q32;q21)/IGH::MALT1; identified in 5% to 20% of MALT lymphomas (mainly liver, skin, lung, ocular adnexa)
t(3;14)(p14;q32)/IGH::FOXP1; identified in 10% of MALT lymphomas (mainly thyroid, ocular adnexa, skin)
t(1;14)(p22;q32)/IGH::BCL10; identified in 1% to 2% of MALT lymphomas (mainly gastric and lung)
The t(11;18) translocation has clinical significance because there is a high incidence of t(11;18) in H pylori-negative gastric MALT lymphoma patients. Patients with the t(11;18) translocation are less likely to respond to H pylori eradication therapy, and are more likely to present with advanced-stage disease associated with aberrant expression of nuclear BCL10.[25][26][27][28] Patients with t(11;18) are, however, less likely to undergo histological transformation to aggressive lymphomas (because they are unlikely to develop secondary chromosomal abnormalities).[29]
Genetic mutations identified in MALT lymphoma include: TNFAIP3, CREBBP, KMT2C, TET2, SPEN, KMT2D, LRP1B, PRDM1, EP300, TNFRSF14, NOTCH1/NOTCH2, and B2M.[24] These mutations can affect chromatin remodelling or cell-signalling pathways, which may contribute to the pathogenesis of MALT lymphoma.
[Figure caption and citation for the preceding image starts]: Infiltrate of lymphoid cells in the lung, confirming their B-cell origin (CD20 staining, ×200)From the collections of Dr R. Joshi and Dr C. McNamara; used with permission [Citation ends].
[Figure caption and citation for the preceding image starts]: Lung MALT lymphoma: residual respiratory epithelium has been distorted by infiltrating lymphocytes; the lymphoepithelial lesion (cytokeratin staining, ×200)From the collections of Dr R. Joshi and Dr C. McNamara; used with permission [Citation ends].
Classification
The 5th edition of the World Health Organization classification of haematolymphoid tumours: lymphoid neoplasms[3]
Extranodal marginal zone lymphoma of MALT is a mature B-cell neoplasm.
The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee[2]
Extranodal marginal zone lymphoma of MALT is a mature B-cell neoplasm.
Clinical classification
Indolent (low-grade) B-cell lymphoma.
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