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PubMed1988

Differential adherence of epithelium overlying gut-associated lymphoid tissue. An ultrastructural study.

The relative adherence of follicle associated and nonfollicle associated epithelial cells in intestinal lymphoid tissues was compared morphologically. Incubation of Peyer's patches and appendix with hyaluronidase resulted in detachment of M cells and other epithelial cells overlying lymphoid follicle surfaces but not of villus or colonic epithelial cells. Enzymatic treatment of intestinal lymphoid tissues produced superficial erosions of follicle epithelium which exposed a porous and fenestrated basal lamina. After enzymatic treatment, detached M cell-containing follicle epithelium was characterized by intracellular vacuoles, widening of intercellular spaces, cell rounding, disappearance of microvilli, and loss of M cell-lymphocyte associations. Enzymatic treatment was responsible for removal of follicle epithelium, since Peyer's patches and appendix tissues incubated with medium alone did not exhibit appreciable epithelial detachment. These results, showing that the adherence of epithelial cells overlying intestinal lymphoid follicles is more labile than that of villus and colonic epithelial cells, may be of pathophysiologic significance in follicle ulcerative processes.

Animals↗
PubMed2005

TuJ1 (class III beta-tubulin) expression suggests dynamic redistribution of follicular dendritic cells in lymphoid tissue.

Follicular dendritic cells (FDCs) play central roles in the B cell survival, proliferation, and differentiation into memory cells. Here, we show that TuJ1 (class III beta-tubulin) is expressed strongly in FDCs of human lymphoid tissue. TuJ1 has been a marker of neurons in the central and peripheral nervous systems from the early stage of neural differentiation. FDCs expressed TuJ1 protein diffusely in both light and dark zones of germinal centers in all human lymphoid tissues. In contrast, CD21 expression was relatively concentrated to the light zone, suggesting that TuJ1 was a marker for FDCs with broader spectrum than CD21. In addition to the germinal center, there were single TuJ1-expressing cells scattered in the mantle zone, blurring the border of the FDC network. In human tonsils, single scattered TuJ1-positive cells were also present in the crypt epithelium, suggesting a dynamic redistribution of FDCs among the antigen-rich epithelium, mantle zone, and germinal center. Such migration of FDCs could reflect a way of direct transport of various antigens carried on their surface to the germinal center, and a basis for the polarity of lymphoid follicles toward the epithelium in mucosa-associated lymphoid tissues. HK cells, cultured FDCs, also expressed TuJ1. The expression of TuJ1 by FDCs suggests that they may share certain biological characteristics of the neural system.

Blotting, Western↗
PubMed1994

Mucosa-associated lymphoid tissue lymphoma of the lung with cold-reacting autoantibody-mediated hemolytic anemia.

Mucosa-associated lymphoid tissue lymphoma (MALT-oma) of the lung is a rare low-grade B cell lymphoma arising from bronchus-associated lymphoid tissue. This report concerns a 39-year-old woman with bilateral diffuse alveolar consolidations and cold-reacting autoantibody-mediated hemolytic anemia. Open-lung biopsy showed angulated lymphoid cells with lymphoepithelial lesions. Immunocytochemistry revealed that the lymphoid cells were positive for CD19, CD20, and IgM (lambda), which was consistent with immunophenotype of MALToma. The serum immunoelectrophoresis demonstrated IgM (lambda) monoclonal gammopathy. The association of cold-reacting auto-antibody-mediated hemolytic anemia with MALToma, to our knowledge, has never been reported before in the English language.

Adult↗
PubMed1984

Conjunctival-associated lymphoid tissue: evidence for a role in the secretory immune system.

A specialized lymphoid tissue in rabbit conjunctiva was studied by various histologic and immunologic techniques and compared with similar structures along other mucosal surfaces. The flattened conjunctival lymphoepithelium overlying the lymphoid follicles was devoid of goblet cells. This lack of goblet cells is characteristic of epithelium overlying similar lymphoid collections in gut and bronchus. The lymphoid follicles demonstrated neither intra- nor extracellular immunoglobulin, and the lymphocytes in these follicles were composed of B-cells and T-cells, when studied by various immunologic techniques. A high proportion of these lymphocytes showed surface immunoglobulin A (IgA), and a high proportion of IgA precursors were determined by pokeweed mitogen (PWM) stimulation in 4-day cultures. The morphologic and immunologic results are similar to those obtained from gut and bronchus, tissues known to disseminate lymphoid cells to other mucosal sites already committed to antigen and IgA isotype. It is speculated that conjunctival associated lymphoid tissue of rabbit is part of a generalized system of secretory immunity capable of sampling conjunctival applied antigen, and then disseminating cells committed to IgA antibody production to other mucosal sites.

Animals↗
PubMed1996

A study of accessory cells in the acquired lymphoid tissue of helicobacter gastritis.

This paper presents a description of the patterns of distribution of accessory cells in helicobacter gastritis and low-grade gastric MALT lymphomas. The use of gastric resection specimens afforded abundant, well-orientated lymphoid tissue. Fifteen cases were selected from patients with MALT lymphomas, three with gastritis alone, and six histologically normal controls. A panel of antibodies working in paraffin-embedded tissue, identifying differing accessory cells, was used. These comprised antibodies to HLA class II (WR18), acid cysteine proteinase inhibitor (ACPI), CD68 (PGM1), Factor XIIIa, S100 protein, CD23 (BU38), CD106 (V-CAM1), CD55 (BRIC 128), and CD21 (1F8). CD68-positive macrophages in the gastritis cases were abundant in the superficial mucosa. Factor XIIIa also identified dendritic cells at deeper sites but these were absent from both the acquired and the neoplastic lymphoid tissue. Antibodies to both S100 protein and ACPI stained dendritic cells localized to areas within and adjacent to the lymphoid tissue only. S100 protein-positive cells were concentrated in close contact with glandular epithelium immediately above the germinal centres, while ACPI-positive dendritic cells were identified, especially around the more blastic reactive follicles, in the intervening space between the germinal centres and the overlying epithelium. Similar patterns of organization were also seen in the areas of mucosal lymphoma. The follicular dendritic markers revealed overlapping but distinct sub-populations within the germinal centres which appeared to alter depending on the activity of the germinal centres. While both ACPI and CD55 stained the germinal centre dendritic reticulum cell networks only, CD21 and CD106 also stained the mantle dendritic cells. The proportion staining with CD23, which stains dendritic reticulum cells within the centrocyte-rich areas of the germinal centres only, was greatest in the more quiescent germinal centres. Similar patterns of staining were also seen in germinal centres within the gastric MALT lymphomas. It is proposed that the sub-populations of dendritic cells staining with S100 protein and ACPI may facilitate helicobacter antigen delivery to the germinal centres. The follicular dendritic cells then promote a sustained B-cell response to the luminal pathogen.

Antigen Presentation↗
PubMed1996

Replication error phenotype and p53 gene mutation in lymphomas of mucosa-associated lymphoid tissue.

Low grade mucosa-associated lymphoid tissue (MALT) lymphomas commonly arise from a background of chronic inflammatory lesions and can transform into high grade tumors at a late stage. Because chronic inflammation is closely associated with genetic instability, which is one of the mechanisms leading to activation of oncogenes and inactivation of tumor suppressor genes, it is possible that genetic instability plays an important role in MALT lymphomagenesis. In this study, we have examined the frequency of replication error (RER+) phenotype, a newly defined manifestation of genetic instability, and its relationship to p53 mutations in 40 MALT lymphomas (16 high grade and 24 low grade). RER+ phenotype was detected in 21/40 (52.5%) MALT lymphomas (12/24, 50% in low grade; 9/16, 56.2% in high grade). Five of seven reactive lymphoid infiltrates adjacent to tumors also showed one microsatellite alteration, four of which were identified in the corresponding lymphoma lesions in the same patient. In five RER+ high grade lymphomas with low grade lesions, homogeneous and heterogeneous microsatellite alterations were observed between the two components. The same 40 cases were investigated for p53 gene mutations at exons 5 to 8 by PCR-SSCP and direct sequencing. p53 point mutations were found in 11 (27.5%) of the 40 cases. These mutations were statistically related to RER+ phenotype (P < 0.05). Our results demonstrate that the RER+ phenotype is a common genetic feature of MALT lymphomas. Genetic instability occurs throughout the spectrum of the lymphoma development and may be related to the accumulation of genetic aberrations such as p53 mutations. The observation of identical microsatellite alterations between the adjacent lymphoid infiltrates and their corresponding lymphomas provides genetic evidence for evolutionary link of the two lesions. The homogeneous and heterogeneous microsatellite alterations observed between low and high grade components indicate their clonal lineage and genetic diversity.

Base Sequence↗
PubMed1981

Stages of B cell differentiation in human lymphoid tissue.

Monoclonal antibodies reactive with B cell-specific differentiation and other antigens were used to investigate stages of B cell maturation in human lymphoid tissue, using an immunoperoxidase technique on frozen tissue sections. Lymphoid follicles, which represent the major anatomic compartment of B cells, demonstrated cellular antigenic expressions that appear to reflect differentiation of B cells. The majority of cells in the primary follicles and the mantle zones of secondary follicles expressed surface antigens similar to those of circulating B cells, namely IgM, IgD, Ia, B1, and B2. In contrast, the germinal center cells of secondary follicles stained for IgM, IgG, B1, B2, and Ia antigens, but not for IgD, and furthermore, acquired the T10 antigen. The germinal centers stained much more intensely than mantle zones with anti-B2, whereas no such striking difference in the staining intensity was observed with anti B1. Plasma cells, which represent the end stage of B cell differentiation, showed intense cytoplasmic staining with the anti-T10 antibody. The results indicate that the generation of germinal center cells in primary lymphoid follicles involves phenotype changes that correspond largely to those previously observed after both antigenic and mitogenic activation of B lymphocytes.

Antigens, Surface↗
PubMed1992

[Immunohistochemistry of bovine lymphoid tissue: neutralization of the non-specific reactivities of serum anti-immunoglobulins by bovine serum].

In lymphoid tissue, the presence of high amounts of free proteins and immunoglobulins frequently leads to the observation of non-specific reactivities during immunohistochemical reactions. The types of anti-immunoglobulin sera utilized in these immunohistochemical reactions may be capable of identifying immunoglobulins secreted or harboured by the tissue cells under study, leading to non-specific marking. Incubation of these antisera with serum from the species in which the lymphoid tissue is studied neutralizes the non-specific reactivities connected with the presence of tissue immunoglobulins.

Animals↗
PubMed2001

Induction of intestinal rotavirus-specific antibodies in respiratory, but not gut, lymphoid tissues following mucosal immunization of mice with inactivated rotavirus.

Intranasal (i.n.), but not oral, immunization of mice with inactivated rotavirus induces protection against challenge. To understand the mechanisms by which i.n. immunization with inactivated rotavirus evokes protective immunity, we examined the site of rotavirus-specific B cell activation and the origins of intestinal IgA-secreting B cells following i.n. inoculation of mice with inactivated rhesus rotavirus. We found that (1) i.n., but not oral, inoculation induced partial protection after challenge; (2) i.n., but not oral, inoculation induced production of rotavirus-specific IgM, IgA, and IgG by intestinal lymphoid tissues; and (3) after i.n. inoculation, nasal-associated lymphoid tissues (NALT) and bronchial lymph nodes (BLN) were the sites of initial production of rotavirus-specific antibodies. These studies indicate that after inoculation with inactivated rotavirus, virus-specific effector B cells may be more easily activated in respiratory, compared to intestinal, lymphoid tissues. Additional studies are needed to determine if these observations are due to fundamental differences in the microenvironment of NALT and BLN compared to Peyer's patches or are a function of the anatomic differences between the respiratory and the gastrointestinal tracts.

Administration, Intranasal↗
PubMed1996

B cell clonality in gastric lymphoid tissues of patients with Sjögren's syndrome.

OBJECTIVE: To determine the prevalence of mucosa associated lymphoid tissue (MALT) in the stomach and of a possible antigen driven proliferation, in patients with Sjögren's syndrome (SS). METHODS: Twenty one patients with primary SS and 80 dyspeptic controls underwent upper endoscopy. Lymphoid tissue and Helicobacter pylori were assessed by histopathological analysis. Epstein-Barr virus (EBV) or human herpes virus-6 (HHV-6) genome were studied by polymerase chain reaction (PCR) DNA amplification. Two PCR VDJ procedures were used to detect immunoglobulin heavy chain (IgH) gene rearrangement. RESULTS: Organised MALT was found in 33.3% of the patients, compared with 21.5% of the controls (NS). H pylori infection was seen in 71% of patients and 63% of controls. Genomic EBV or HHV-6 was found in a minor portion of SS gastric tissues. B cell expansion was detected in nine of the 21 patients. Infectious agents in the stomach might have contributed to B cell clonality only in 55.5% of the cases. No strict relationship was found between lymphoid follicles and clonality. CONCLUSION: Lymphoid accumulation in the gastric mucosa is common in Sjögren's syndrome, but full evidence for an antigen driven B cell expansion could not be demonstrated. Only a portion of those with clonal B cell expansion had evidence of an infectious agent. Other unknown infectious agents or factors related to the underlying disease (autoantigen) and its tissue environment may have a further role as possible causes of B clonal expansion in the gastric mucosa.

Adult↗
PubMed1996

Development of bronchus-associated lymphoid tissue in goats.

Development of bronchus-associated lymphoid tissue (BALT) was studied in clinically healthy and diseased Assam local goats. Animals were sacrificed before term as well as at different postnatal periods to screen lung sections for the presence of BALT. In a retrospective study sections prepared from pneumonic lungs were examined for any alteration of BALT. No BALT-like structure was found in neonatal goats. Bronchial lymphoid structures appeared in half of the animals from 1 month of age onward. The frequency of the BALT/4.5 cm2 of lung section ranged from one to two in 1-month-old and three to six in 1-year-old goats. In pneumonic lungs BALT became hyperplastic, and the size was also increased. The incidence of BALT was increased in lungs with fibrotic pneumonia. The number of BALT/section was high (five to eight/4.5-cm2 area) in mesenchymal cell proliferation. The present study shows that BALT did not develop in prenatal periods. But in the presence of potent antigens lymphoid aggregates appeared in the bronchial lamina propria of normal and diseased lungs.

Animals↗
PubMed2004

Fludarabine-containing chemotherapy as frontline treatment of nongastrointestinal mucosa-associated lymphoid tissue lymphoma.

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphoma is a specific clinicopathologic entity with gastric and nongastrointestinal site involvement. The authors reported the clinical outcome of patients with Stage IE nongastrointestinal MALT lymphoma treated with a frontline fludarabine-containing regimen or with a regimen containing cyclophosphamide, vincristine, and prednisone (CVP). METHODS: Between 1998 and 2001, 31 patients with Stage IE disease were referred to the Seràgnoli Institute of Hematology and Medical Oncology at the University of Bologna (Bologna, Italy). Presenting sites included periorbital soft tissue (n = 8), lung (n = 5), skin (n = 5), salivary glands (n = 5), lacrimal glands (n = 5), and thyroid (n = 3). Twenty patients were treated with fludarabine and mitoxantrone (FM), and 11 were treated with the CVP regimen. The median follow-up was 3 years. RESULTS: All patients achieved complete responses (CR). Four patients, all treated with CVP, experienced disease recurrence and then achieved a second CR after FM salvage treatment. No tumor recurrence was observed in patients with thyroid, lacrimal gland, or pulmonary lymphoma. The projected 5-year overall survival and disease-free survival rates were 100% and 85%, respectively. CONCLUSIONS: The fludarabine-containing FM regimen provided a relatively effective frontline (or salvage) treatment option for patients with nongastrointestinal Stage IE MALT lymphoma and probably was superior to CVP in terms of efficacy.

Adult↗
PubMed1999

CT appearances of mucosa-associated lymphoid tissue (MALT) lymphoma.

Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade lymphoma that differs from high-grade non-Hodgkin lymphoma both clinically and histologically. The CT appearances of MALT lymphoma are described. Of 40 patients referred with biopsy-proven MALT lymphoma, only seven had not had gastrectomy or chemotherapy prior to CT examination. The CT scans of these seven cases were analysed for the degree and extent of gastric wall thickening, enlargement of abdominal and extra-abdominal lymph nodes, and presence of extra-nodal disease. In all patients the stomach was distended with oral contrast medium and scans performed at narrow collimation, after intravenous administration of 20 mg hyoscine butylbromide. In six patients focal thickening of the gastric wall was 1 cm or less. One patient had thickening of over 4 cm. There was no enlargement of abdominal or extra-abdominal lymph nodes or extension to adjacent organs. Thus on CT, at presentation, MALT lymphoma results in minimal gastric wall thickening, unlike high-grade non-Hodgkin lymphoma, which typically causes bulky gastric disease, nodal enlargement and extension into adjacent organs. CT is therefore of limited value in monitoring response to treatment. With disease greater than minimal thickening, transformation to a higher grade should be considered.

Adult↗
PubMed1999

Eradication of Helicobacter pylori infection did not lead to cure of duodenal mucosa-associated lymphoid tissue lymphoma.

Duodenal mucosa-associated lymphoid tissue (MALT) lymphoma is very rare, and little is known about its clinical course or association with Helicobacter pylori infection. This report describes the case of a 76-year-old man with a polypoid mass in the duodenal bulb, diagnosed as low-grade MALT lymphoma. H. pylori infection in the duodenal mucosa was confirmed by histology with silver stain. Endoscopic examination showed that the gross lesion regressed after the eradication of H. pylori despite its histopathologic persistence. Ten months later, however, cervical and intraperitoneal lymphadenopathy and bone marrow involvement was observed, and the pathologic diagnosis of the cervical lymph node was identical with that of the duodenal lesion.

Aged↗
PubMed2002

Monoclonal gammopathy of undetermined significance predisposing to Helicobacter pylori-related gastric mucosa-associated lymphoid tissue lymphoma.

Gastric mucosa-associated lymphoid tissue (MALT)-associated B-cell proliferation may range from benign to malignant, and Helicobacter pylori is the only identified critical antigenic stimulus to the development of gastric MALT. Monoclonal gammopathy of undetermined significance (MGUS) is characterized by B-cell hyper-activation and clonal expansion and is know to predispose to B-cell malignancies. We report a patient with MGUS and H. pylori infection in whom we noted the progression of gastritis to acquired gastric MALT and gastric MALT to MALT lymphoma during a 3-year follow-up.

Causality↗
PubMedDate not supplied

Importance of esophagogastroduodenoscopy in the evaluation of non-gastrointestinal mucosa-associated lymphoid tissue lymphoma.

PURPOSE: Mucosa-associated lymphoid tissue (MALT) lymphoma is an extranodal low-grade B-cell lymphoma that most commonly presents in the gastrointestinal (GI) tract. However, it can present in non-GI primary sites. This study was conducted to determine the incidence of gastric involvement in non-GI presentation of MALT lymphoma. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 36 consecutive patients who presented with non-GI MALT lymphoma and had EGD as a part of the initial staging work-up between 1992 and 2001. RESULTS: The median age was 62 years (range, 27-82); 27 were female patients. The frequency of the primary site was; salivary gland/parotid gland (N = 14), ocular adnexa (N = 7), lung (N = 3), oral cavity (N = 3), skin (N = 3), thyroid (N = 2), nasopharynx (N = 2), larynx (N = 1), breast (N = 1). Twelve patients were found to have gastric involvement; 2 additional patients progressed in the stomach 5 and 6 months later, respectively. DISCUSSION: Routine evaluation of the stomach should be a part of the initial staging work-up of non-GI MALT lymphoma.

Adult↗
PubMed2001

Immunoglobulin G1 antibody response to Helicobacter pylori heat shock protein 60 is closely associated with low-grade gastric mucosa-associated lymphoid tissue lymphoma.

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is related to Helicobacter pylori infection. Specifically, it has been pointed out that pathogenesis of MALT lymphoma involves the 60-kDa heat shock protein (hsp60). To investigate humoral immune responses to the H. pylori hsp60 in patients with gastroduodenal diseases and patients with MALT lymphoma, the hsp60 of H. pylori was expressed with a glutathione S-transferase fusion protein and was purified (recombinant hsp60). Sera were obtained from H. pylori-positive patients with gastroduodenal diseases (MALT lymphoma, n = 13; gastric ulcer, n = 20; duodenal ulcer, n = 20; gastritis, n = 20) and from H. pylori-negative healthy volunteers (n = 9). Sera from patients with MALT lymphoma were also obtained at two times: before and after eradication therapy. Antibodies to hsp60 and H. pylori were assessed by enzyme-linked immunosorbent assay. The levels of immunoglobulin G (IgG) antibodies to the hsp60 of H. pylori-positive patients with gastroduodenal diseases were significantly elevated compared to those in the controls. The levels of IgG1 antibodies to hsp60 were elevated and correlated with the levels of anti-H. pylori antibodies in patients with MALT lymphoma. Humarol immunity against hsp60 may be important and relevant to gastroduodenal diseases induced by H. pylori infection.

Adult↗
PubMed2004

Monoclonal immunoglobulin production is a frequent event in patients with mucosa-associated lymphoid tissue lymphoma.

PURPOSE: Mucosa-associated lymphoid tissue (MALT) lymphoma comprises 7% of all newly diagnosed non-Hodgkin's lymphomas and is therefore among the most common lymphoma entities. Monoclonal gammopathy due to production of a monoclonal immunoglobulin by lymphoma cells is a well-known phenomenon associated with various types of B-cell non-Hodgkin's lymphomas. The objective of the present study was to evaluate the incidence and clinical relevance of paraprotein (PP) production in patients with MALT lymphoma. EXPERIMENTAL DESIGN: Fifty two patients were prospectively evaluated with regard to differentiation of the MALT lymphoma cells, t(11;18) translocation, monoclonal immunoglobulin production, Helicobacter pylori (HP) status, stage, treatment, and clinical outcome. RESULTS: Nineteen of 52 MALT lymphoma patients (36%) had PP (8 IgMkappa, 6 IgGkappa, 4 IgMlambda, and 1 IgAkappa). The histologic feature of plasmacytic differentiation correlated significantly with the production of PP (P = 0.001). No correlation was found between PP and clinical stage, HP status, and t(11;18) status. PP was, however, negatively associated with response to eradication of HP in gastric MALT lymphoma, and PP levels declined significantly in patients responding to chemotherapy or radiation. Importantly, both immunofixation and serum electrophoresis have to be performed to detect low PP levels. CONCLUSIONS: In conclusion, PP levels may probably be used as a potential prognostic tool for response to HP eradication, and serial measurements may also allow for noninvasive assessment of response to radiation or chemotherapy in patients with MALT lymphoma.

Adult↗