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1664 Part XI: Malignant Lymphoid Diseases Chapter 101: Marginal Zone B-cell Lymphomas 1665

survival- and proliferation-related genes in B cells during immune GENETIC ABERRATIONS
responses. The constitutive activation of this signalling pathway results Recurrent genomic lesions, including chromosomal translocations and
in uncontrolled B-cell proliferation and subsequent neoplastic transfor- unbalanced aberrations, can be detected in MALT lymphomas in up
mation of the involved tissue. to 40 percent of the cases, depending on the specific aberration. The
The longstanding antigenic stimulation explains how lymphoid t(11;18)(q21;q21) translocation is the most common structural chro-
infiltrates—or an acquired MALT—may appear in extranodal sites mosomal abnormality in MALT lymphoma, being demonstrated in
normally lacking MALT. The MALT that organizes in proximity to 15 to 40 percent of the cases, especially in gastric and lung MALT lym-
an epithelium receives stimuli from the epithelium itself (as occurs in phoma. Other chromosomal translocations include t(14;18)(q32;q21),
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autoimmune disorders) or from antigens entering the lymphoid tissue t(1;14)(p22;q32) and t(3;14)(p13;q32), all involving the immunoglob-
through the epithelium or via the afferent lymphatics (as during exoge- ulin heavy chain variable region (IGHV) gene on chromosome 14, and
nous infections). displaying a specific anatomic distribution (Table 101–1). The pres-
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Microbial species thought to be associated with MALT lymphoma ence of any of these chromosomal alterations correlates with a lack of
include: H. pylori and Helicobacter heilmannii, hepatitis C virus (HCV), any further genetic instability or chromosomal imbalances.
Campylobacter jejuni, Borrelia burgdorferi, and Chlamydia psittaci. Current knowledge of the genetic lesions seen in MALT lymphoma
These entities have been found to be related with the development of suggest a model of multistage development and progression from a
MALT lymphoma of the stomach, IPSID, cutaneous MALT lymphoma preneoplastic lesion to overt lymphoma. The accumulation of genetic
and orbital MALT lymphoma, respectively. H. pylori has been docu- abnormalities is associated with a loss of dependency from antigenic
4–7
mented as the etiologic agent in more than 90 percent of gastric MALT stimulation (with subsequent antibiotic resistance) and with possible
lymphoma, which arises from H. pylori–stimulated autoreactive B cells. histologic transformation.
8
H. pylori can be demonstrated by histology, polymerase chain reaction,
or urea breath test, and can be isolated and cultured. H. pylori appears
to be a fundamental factor for the development of the disease, and its CLINICAL FEATURES
elimination often induces a remission of the lymphoma by itself without EMZL mostly presents as Ann Arbor stage IE disease, which implies the
any other intervention, thus fulfilling all four of Koch’s postulates and sole involvement of the extranodal site of origin, with possible extension
establishing the microorganism as the main etiologic factor. However, of the disease to tributary lymph nodes in close proximity to the affected
because only a minority of patients with an overt H. pylori infection organ. Marrow and peripheral lymph node infiltration is uncommon,
develop the disease, it is obvious that the pathogenesis of gastric EMZL observed in less than 20 percent of the cases at presentation. The stomach
also depends on other, largely unknown factors, perhaps related to the is the most commonly involved organ, accounting for approximately one-
host, the environment, or the virulence of the infecting H. pylori strain. third of cases. Other typical presentations include the salivary glands, the
It has also been demonstrated that viable C. psittaci can be found orbits and the ocular adnexa, the thyroid, the lungs, the skin, the breasts,
not only in monocytes and macrophages infiltrating orbital MALT lym- the liver, and other gastrointestinal sites, apart from the stomach. Dis-
phoma, but also in patients’ blood and conjunctiva, raising the possibil- seminated disease can be documented in up to 25 percent of patients
ity of microbial eradication and disease remission by antibiotic therapy with gastric MALT lymphoma, although those with nongastrointestinal
with drugs such as doxycycline. 9 extranodal disease exhibit disseminated lymphoma in nearly half of the
Autoreactive B cells found in autoimmune diseases, such as those cases. Gastric MALT lymphoma is often multifocal, which may explain
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infiltrating the thyroid in Hashimoto thyroiditis, or the salivary glands the high rate of relapse in the gastric stump after surgical excision. Syn-
in Sjögren syndrome, organize progressively into a well-developed chronous involvement of gastrointestinal and extraintestinal sites is
MALT, mimicking lymphoproliferation and eventually evolving into detected in approximately 10 percent of cases.
an overt lymphoma. Patients with Sjögren syndrome have a 44-fold Systemic lymphoma-related symptoms are generally uncommon,
increased risk of developing lymphoma, and patients with Hashimoto and the clinical aspects and presenting symptoms generally correlate
thyroiditis have a 70-fold increased risk of thyroid lymphoma. 10,11 with the primary location of the disease.

TABLE 101–1. Common Genetic Lesions in Mucosa-Associated Lymphoid Tissue Lymphoma
Lesion Genes Frequency Sites
Stomach, lung
15–40%
t(11;18)(q21;q21)
BIRC3-MALT1
Translocations t(14;18)(q32;q21) IGHV-MALT1 20% Lung, skin, ocular adnexa, salivary gland
Stomach, lung
<5%
IGHV-BCL10
t(1;14)(p22;q32)
<5%
Unclear
IGHV-FOXP1
t(3;14)(p13;q32)
Gains +3; +3q 20–40% No differences in sites
No differences in sites
+18; +18q
20–40%
Losses −6q23 TNFAIP3 15–30% No differences in sites
BCL-10, B-cell CLL/lymphoma 10 gene; BIRC3, baculoviral IAP repeat-containing 3 gene; FOXP1, forkhead box P1 gene; IGHV, immunoglobulin
heavy-chain variable region gene; MALT1, mucosa-associated lymphoid tissue translocation gene 1; TNFAIP3, tumor necrosis factor-α–induced
protein 3 gene.

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