Marginal zone B-cell lymphomas comprise three distinct
clinicopathologic entities with variable clinical presentations,
namely, the extranodal marginal zone lymphomas also known as mucosa-associated
lymphatic tissue (MALT) lymphoma, the nodal marginal zone lymphoma,
and the splenic marginal zone lymphoma. The extranodal type is the
most common, accounting for approximately 7.5 percent of all cases
of non-Hodgkin lymphoma.
The marginal zone B cells usually have small- to
medium-size, irregular nuclei with dispersed chromatin, and inconspicuous
nucleoli, resembling centrocytes and express surface immunoglobulins,
pan-B antigens (CD19, CD20, and CD79a) and marginal zone-associated
antigens (CD35 and CD21), but lack CD5, CD10, CD23, and cyclin D1
expression. Recurrent karyotype abnormalities have been described.
All marginal zone lymphoma types present gains of chromosomes 3
and 18 at a higher frequency in comparison with other B-cell lymphomas.
Rearrangements and deletions affecting chromosome 7q are most common
in primary splenic lymphoma. In extranodal marginal zone lymphoma,
three disparate translocations [t(11;18)(q21;q21), t(1;14)(p22;q32),
and t(14;18)(q32;q21)], despite involving different genes, appear
to affect the same signalling pathway, resulting in the activation
of nuclear factor-kappa B (NF-κB), a transcription
factor with a central role in immunity, inflammation, and apoptosis.
These translocations are not present in splenic and nodal marginal
zone lymphomas. Deletions or mutations of the tumor necrosis factor-α–induced
protein 3 gene (TNFAIP3, A20, a negative regulator of the NF-κ B
pathway) on chromosome 6q was described in all subtypes of marginal zone
lymphoma and are likely to represent another pathogenetic mechanism
that can lead to NF-κB activation. The
most common site of MALT lymphoma is the stomach, although primary
involvement may occur at many other sites, including small intestine,
lung, salivary gland, thyroid, skin, and other tissues. Most MALT
lymphomas arise at sites normally devoid of lymphoid tissue, often
preceded by a chronic inflammatory condition (infections or autoimmune
disorders), such as Sjögren syndrome, Hashimoto thyroiditis,
or, in the case of gastric MALT lymphoma, infection with Helicobacter
pylori. Other infectious agents may have a pathogenetic
role (Borrelia burgdorferi in cutaneous localizations, Chlamydophila
psittaci in the ocular adnexa, and Campylobacter
jejuni in the small intestine). Hepatitis C virus is associated
with a subset of nodal and splenic marginal zone lymphomas. Appropriate
antibiotic therapy eradicating H. pylori infection
can lead to the regression of gastric MALT lymphoma in approximately
75 percent of cases. Patients who do not respond to antibiotic therapy
may be considered for involved-field radiotherapy. Chemotherapy
and immunotherapy with rituximab can be effective in patients with
disseminated disease. Patients with splenic or nodal marginal zone
lymphoma and hepatitis C virus infection may achieve a lymphoma remission
after treatment of viral infection. Once hepatitis C virus infection
is ruled out, most patients with nodal or splenic lymphoma can be
managed initially with a wait-and-see policy. When treatment is
needed, splenectomy is the treatment of choice for the splenic lymphomas.
Chemotherapy may be considered for patient who have contraindication
to splenectomy and for those with nodal marginal zone lymphoma.
Alkylating agents and purine analogues have been reported ...