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PubMed2004

Primary lymphoma of the breast: a case of marginal zone B-cell lymphoma.

A case of primary marginal zone B-cell lymphoma in an elderly female patient is presented. Primary breast lymphomas are rare, comprising less than 1 per cent of all breast malignancies. These tumors have no clinical, pathologic, or radiologic pathognomonic features to distinguish them from breast adenocarcinoma. The diagnosis is usually made with an excisional biopsy, and more extensive surgery should be avoided. Delivery of radiation therapy and chemotherapy is tailored according to the histologic grade, stage of disease, and overall patient condition. This report summarizes the current knowledge reflected in the literature.

Aged↗
PubMed2001

Molecular-cytogenetic comparison of mucosa-associated marginal zone B-cell lymphoma and large B-cell lymphoma arising in the gastro-intestinal tract.

Extranodal B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type may represent a model of lymphoma progression, because a small cell component frequently occurs in the large cell variants. We studied 52 extranodal B-cell lymphomas: 18 extranodal marginal zone B-cell lymphomas of MALT type (MZBL,MT), 7 MZBL,MT of the gastro-intestinal tract with a diffuse large B-cell component (giMZBLplusLBCL), and 27 diffuse large B-cell lymphomas of the gastro-intestinal tract without small cell component (giLBCL). Analytical techniques were comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). The translocation t(11;18) was found as the sole aberration in two MZBL,MT only. In contrast to this, t(11;18)-negative MZBL,MT were characterized by frequent gains on chromosome 3 and DNA amplifications on 2p13-p15. Furthermore, we found a clonal lymphoma progression from the small to the large cell component with accumulation of gains and losses of chromosomal material in the large cell component in giMZBLplusLBCL. Aberrations overlapping with MZBL,MT and giMZBLplusLBCL included losses on chromosome 13, amplifications of the REL proto-oncogene, or gains on chromosome 12. In addition, the large cell component revealed gains on 8q24, including amplifications of the MYC proto-oncogene, and losses on 2q. The giLBCL had frequent gains on chromosomes 12 and 9, as well as on 11q, and losses on 6q. We conclude that, based on the distinctive and partly overlapping patterns of genetic aberrations, MALT lymphomas can be divided into different genetic subgroups.

Chromosome Aberrations↗
PubMedDate not supplied

Primary cutaneous marginal zone B-cell lymphoma of MALT type in a child.

Marginal zone B-cell lymphoma (MZBCL) of mucosa-associated lymphoid tissue type is a peculiar variant of B-cell neoplasm showing distinct clinical and pathologic features. Its occurrence in children or adolescents is extremely uncommon. We describe the case of an 11-year-old boy who developed such a lymphomatous process involving primarily the skin. The tumor was characterized by a maturing plasma cell population that included immunoblasts, heavy-chain but not light-chain restriction suggestive of monoclonality, and a prevalent, focally granulomatous component of histiocytes. As an additional interesting feature, a trisomy 3 was demonstrated by fluorescence in situ hybridization analysis. The clinical, morphological, phenotypic, and genetic characteristics seen in our patient do not differ significantly from those described in primary cutaneous MZBCL occurring in adults.

Biomarkers, Tumor↗
PubMed2002

Treatment of splenic marginal zone B-cell lymphoma: an analysis of 81 patients.

Splenic marginal zone B-cell lymphoma (MZL), with or without villous lymphocytes, is an indolent lymphoma, presenting with massive splenomegaly, generally associated with bone marrow dissemination. In patients requiring therapy, splenectomy has been reported as the treatment of choice. We reviewed the cases of 81 patients with splenic MZL. Patients presented with stage IV disease at diagnosis in 95% of the cases. Autoimmune events (hemolytic anemia, immune thrombocytopenia, acquired coagulation disorders, positive Coomb's test) were observed in 16 patients, and a monoclonal (M) serum component was detected in 46% of the patients. Twenty patients did not receive any initial treatment at diagnosis. Splenectomy was proposed in 79% of the treated patients, with adjuvant chemotherapy in 47% of patients. Median survival was 10.5 years and was significantly shorter in the presence of an M component, an elevated b2-microglobulin level, leukocyte count > 20000/microL, and lymphocytes > 9000/microL. Disease progression was significantly more frequent in patients presenting an immunological event or an M component. Seventy percent of the patients had persistent involvement of bone marrow and/or peripheral blood after splenectomy. Disease progression was significantly more frequent in partial responders than in complete responders (P < 0.005), but overall survival, risk of histologic transformation, and risk of death from lymphoma were not different in the 2 groups. Moreover, patients with cytopenia at diagnosis treated by splenectomy alone rapidly recovered normal hematological parameters. We conclude that splenectomy is an efficient treatment for splenic MZL, but that it may be delayed until the occurrence of symptoms or cytopenia.

Adult↗
PubMed2003

Ocular immune privilege: the eye takes a dim but practical view of immunity and inflammation.

The delicate visual axis that makes precise vision possible is highly vulnerable to the destructive potential of immunogenic inflammation. Immune privilege of the eye is the experimental expression of the way in which evolution has coped with the countermanding threats to vision of ocular infections and ocular immunity and inflammation. Ocular immune privilege has five primary features that account for its existence: blood:ocular barriers, absent lymphatic drainage pathways, soluble immunomodulatory factors in aqueous humor, immunomodulatory ligands on the surface of ocular parenchymal cells, and indigenous, tolerance-promoting antigen-presenting cells (APCs). Three manifestations of ocular immune privilege that have received the most extensive study are the intraocular microenvironment, which is selectively anti-inflammatory and immunosuppressive; the prolonged acceptance of solid tissue and tumor allografts in the anterior chamber; and the induction of systemic tolerance to eye-derived antigens. Anterior chamber-associated immune deviation is known to arise when indigenous, ocular APCs capture eye-derived antigens and deliver them to the spleen where multicellular clusters of these cells, natural killer T cells, marginal zone B cells, and gammadelta T cells create an antigen-presentation environment that leads to CD4(+) and CD8(+) alpha/beta T cells, which as regulators, suppress induction and expression of T helper cell type 1 (Th1) and Th2 immune expression systems. The ways the eye influences local and systemic immune responses to ocular antigens and pathogens carry risks to and benefits for mammalian organisms. As loss of sight is a powerful, negative-selecting force, the benefits of ocular immune privilege outweigh the risks.

Antigen-Presenting Cells↗
PubMed2003

Primary cutaneous marginal zone B-cell lymphoma: a molecular and clinicopathologic study of 24 asian cases.

Cutaneous marginal zone B-cell lymphoma is a recently proposed entity and constitutes a cutaneous counterpart of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). Borrelia burgdorferi infection has been suggested as a possible causative agent in European cutaneous cases of marginal zone B-cell lymphoma, whereas API2-MALT1 fusion and BCL10 mutation are highly associated with MALT lymphoma. Aberrant nuclear BCL10 expression may be closely correlated with API2-MALT1 fusion in gastric and pulmonary MALT lymphomas. We examined 24 Asian cases of cutaneous marginal zone B-cell lymphoma for B. burgdorferi involvement, API2-MALT1 fusion, BCL10 cellular expression, and BCL10 mutation. Neither Borrelia DNA nor API2-MALT1 fusion transcript was detected. Nuclear BCL10 expression was evident in tumor cells of 11 of 24 cases, although BCL10 mutation was found in one case only. Clinicopathologically, nuclear BCL10 was more frequently expressed in macroscopically nodular lesions than in plaques or papules (p = 0.0031). These data suggest that 1) B. burgdorferi infection may not play an important role in developing cutaneous marginal zone B-cell lymphoma in Asian cases, 2) neither API2-MALT1 fusion nor BCL10 mutation is closely associated with the pathogenesis, 3) aberrant nuclear BCL10 may frequently be expressed in the absence of these genetic abnormalities, and 4) nuclear BCL10 expression may be clinically important because it was observed in locally aggressive tumors.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Analysis of mutations in immunoglobulin heavy chain variable region genes of microdissected marginal zone (MGZ) B cells suggests that the MGZ of human spleen is a reservoir of memory B cells.

The splenic marginal zone (MGZ), which surrounds the mantle zone (MTZ) in human splenic white pulp, contains a phenotypically and morphologically distinct population of B cells. The origin of MGZ B cells is uncertain. Whereas some experiments in rodents have suggested that they are a distinct cell lineage responsible for the immune response to T-independent type 2 antigens, others have suggested that they are memory B cells derived from a germinal center (GC) response. The progeny of a GC reaction is expected to have rearranged immunoglobulin (Ig) genes that are mutated. The distribution of mutations would be expected to reflect the selection of Ig by its affinity for antigen. We have analyzed rearranged Ig heavy chain variable region (VH) 6 and VH 4.21 genes in MGZ and MTZ B cells microdissected from frozen sections of human spleen to determine whether these genes have the properties of an affinity-selected memory B cell population. MTZ B cells contained germline Ig VH genes, confirming previous reports and providing an internal control for mutational analysis. MGZ B cells contained Ig VH genes that were mutated, showing that these cells had been subjected to a mutational mechanism characteristically active in the GC. The rearranged VH 6 genes showed patterns of mutation indicative of an antigen selection process, whereas the distribution of mutations in VH 4.21 genes was not characteristic of gene selection by conventional T-dependent antigen. Our studies provide the first evidence that the human splenic MGZ is a reservoir of memory B cells.

Adult↗
PubMed1999

Monocytoid B cells are distinct from splenic marginal zone cells and commonly derive from unmutated naive B cells and less frequently from postgerminal center B cells by polyclonal transformation.

Monocytoid B cells represent a morphologically conspicuous B-cell population that constantly occurs in Toxoplasma gondii-induced Piringer's lymphadenopathy. Although widely believed to be closely related to splenic marginal zone B cells, neither this relationship, nor the B-cell differentiation stage of monocytoid B cells, nor their cellular precursors have been established. We have therefore examined monocytoid B cells for their expression of B-cell differentiation markers and the Ig isotypes at the RNA and protein level as well as for rearranged Ig heavy chain (H) genes and somatic mutations within the variable (V) region. The results obtained were compared with the corresponding features of other B-cell populations. The monocytoid B cells displayed immunophenotypical differences to all other B-cell populations. IgM and IgD expression was absent from most monocytoid B cells at the RNA and protein levels. Unrelated (polyclonal) Ig rearrangements were found in 85 of the 95 cells studied. Seventy-four percent of the rearranged VH genes were devoid of somatic mutations, whereas the remaining 26% carried a low number of somatic mutations. The majority of these showed no significant signs of antigen selection. This finding in conjunction with the predominantly unrelated Ig gene rearrangements indicates that most monocytoid B cells arise not by clonal proliferation but by transformation of polyclonal B cells. The B cells undergoing a monocytoid B-cell transformation are in the majority (74%) naive B cells, and only a minority are (26%) non-antigen-selected postgerminal center B cells. Thus, our data show that monocytoid B cells represent a distinct B-cell subpopulation.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1986

Germinal centre formation and follicular antigen trapping in the spleen of lethally X-irradiated and reconstituted rats.

In this study, the relationship between germinal centre formation and the follicular trapping of immune complexes in the rat spleen was investigated. Lethally (9 Gy) X-irradiated rats were reconstituted with thoracic duct lymphocytes and subsequently challenged with sheep red blood cells to induce germinal centre formation. Rats were killed at daily intervals from 1 to 8 days after reconstitution and antigenic stimulation. Antigen trapping capacity during this interval was assessed by intravenous injection of HRP-anti-HRP immune complexes, 24 hr before killing of the animals. Germinal centre formation could be observed from Day 4 onwards. The follicular trapping capacity, which had been abolished by the X-irradiation, however, returned 2 days later (i.e. by Day 6). Apparently, in these experiments, early germinal centre formation could occur without an intact follicular trapping mechanism. It was, therefore, concluded that in this transfer system follicular immune complex trapping is not a prerequisite for the induction of de novo germinal centre formation. Previous studies have shown that both follicular dendritic cells and marginal zone B cells may play a role in the follicular antigen trapping mechanism. FDCs, as detectable with mAB MRC OX 2 in immunoperoxidase-stained frozen sections, were present in spleens at any time after irradiation and reconstitution; the impaired follicular trapping of HRP-anti-HRP immune complexes was therefore not due to an absence of FDCs. Marginal zone B cells, however, were almost absent until 5 days after reconstitution, as observed by immunohistochemical staining with anti-B cell mABs (HIS 14 and HIS 22) and a polyclonal anti-IgD antiserum. Our data suggest that regeneration of follicular antigen trapping capacity is dependent on the presence of marginal zone B cells.

Animals↗
PubMed2005

Homeostatic and functional analysis of mature B cells in lambda5-deficient mice.

The peripheral B-cell pool is in dynamic equilibrium and is controlled by a variety of factors. The rate of generation of B cells can influence both the composition and size of the peripheral B-cell compartment. Mice deficient for lambda5 gene expression have a block in early B-cell development leading to a markedly reduced number of peripheral B cells. To address the question of how this early developmental block influences the composition of the B-cell pool, we have analyzed mature B-cell subpopulations in lambda5-deficient mice. In analogy with other situations of B lymphopenia, the proportion was increased but not the absolute number of marginal-zone B cells, whereas those of follicular B cells were decreased. Immunohistology revealed that B-cell follicles were smaller in overall size and contained a prominent B-cell replete marginal zone. BrdU labelling kinetics showed slower turnover of follicular as well as of marginal-zone B cells. Functionally, lambda5(-/-) mice were able to mount not only primary but also secondary thymus-dependent as well as thymus-independent responses, albeit mostly at reduced levels.

Animals↗
PubMed2003

Massive hyperplasia of marginal zone B-cells with clear cytoplasm in the lymph node: a case report.

An enlarged axillary lymph node from a 63-year-old woman showed proliferating marginal zone B-cells arranged in a vague nodular pattern or in band-forming aggregates throughout the cortex. Marginal zone B-cells, which also infiltrated the adjacent fatty tissue, had round or slightly indented nuclei of medium size and a moderate amount of clear cytoplasm. Immunohistochemically, these cells were CD20+, CD79a+, Bcl-2+, sIgD-, CD5-, CD10-, CD21-, CD23-, CD45RO-, Bcl-6-, and cyclin D-. A portion of the cells were sIgM- and CD43-positive. The polytypic nature of these cells was demonstrated by immunohistochemistry and polymerase chain reaction. Systemic bacterial infection appears to be the cause of marginal zone B-cell hyperplasia. This unusual marginal zone B-cell hyperplasia should be differentiated from low-grade B cell lymphomas, and particularly from nodal marginal zone B-cell lymphomas.

Anti-Bacterial Agents↗
PubMed2000

Primary nodal marginal zone B-cell lymphoma arising from more than one clonal neoplastic population.

Primary nodal marginal zone B-cell lymphoma is an uncommon monoclonal B-cell lymphoproliferative disorder. We report a case of a 79-year-old woman who presented with generalized lymphadenopathy. Histologic and immunohistochemical examinations of biopsy sections from an axillary lymph node were consistent with nodal marginal zone B-cell lymphoma. Flow cytometry analysis showed 2 distinct clonal B-cell populations expressing lambda or kappa light chain restriction. Subsequently, genomic deoxyribonucleic acid (DNA) isolated from a paraffin-embedded lymph node section was analyzed for the presence of gene rearrangements. Polymerase chain reaction (PCR) analysis of immunoglobulin heavy chain genes revealed 3 rearranged DNA bands, confirming the presence of more than one clonal B-cell population. These immunophenotypic and genotypic findings have not been previously described in association with this type of lymphoma. To our knowledge, this represents the first reported case of biclonal nodal marginal zone B-cell lymphoma.

Aged↗
PubMed2005

Floral variant of follicular lymphoma containing marginal zone B-cell component. Report of two cases.

We here report two unusual cases of floral variant of follicular lymphoma containing marginal zone B-cells. Histologically, the neoplastic follicles consisted of three distinct layers. The inner layer was composed of neoplastic germinal centers exhibiting a floral design and the middle layer had unusually prominent mantle zones. The outer zone of neoplastic follicles was surrounded by a pale cuff of marginal zone B-cells. Immunohistological study demonstrated that both the germinal center and marginal zone component lay within the follicular dendritic cell network. The germinal center component was CD10+ and bcl-2+. However, a portion of the marginal zone component weakly expressed bcl-2 but not CD10. Nodal marginal zone B-cell lymphoma (NMZBL) occasionally possesses "floral" lymphoid follicles. Follicular lymphoma with marginal zone differentiation is a high-risk variant of follicular lymphoma. In diagnostic practice, the differential diagnosis between the floral variant of follicular lymphoma containing marginal zone B-cells and the "floral variant" of NMZBL is important.

Adult↗