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PubMed1996

Carcinoma-like signet-ring cells in gastric mucosa-associated lymphoid tissue (MALT) lymphoma.

We noticed the presence of epithelial signet-ring cells (SRCs) in a proportion of primary gastric B-cell lymphomas, and in some endoscopic biopsies we found it difficult to decide whether they represented an associated carcinoma. To evaluate the frequency and nature of this phenomenon, we reviewed 108 stomachs resected for primary lymphoma, including 70 mucosa-associated lymphoid tissue (MALT) and 38 non-MALT lymphomas. We found SRCs, either isolated or grouped in clusters, in 26 of 70 MALT lymphomas. The SRCs were always localized in the superficial portion of the lamina propria and associated exclusively with lymphomatous areas. Isolated and scarce SRCs were also found in four of 22 cases of polyclonal atypical lymphoid hyperplasia. Our data suggests that SRCs occurring in gastric MALT lymphomas represent a particular type of LEL in which the foveolar cells disaggregated by the lymphomatous infiltration acquire a globoid, signet-ring appearance. These "foveolar" LELs are found in 37% of MALT lymphomas and are usually associated with the more classic and constant "neck" LELs, which are localized between the foveolae and mucopeptic glands. An awareness of the existence of the foveolar LEL may help avoid overdiagnosis of SRC carcinoma on gastric endoscopic biopsies.

Adult↗
PubMed1999

Primary nodal marginal zone lymphomas of splenic and MALT type.

The existence of primary nodal marginal zone lymphomas (MZL) is controversial, as is their relationship to putative extranodal counterparts. Most nodal lymphomas with monocytoid B cell/marginal zone differentiation exhibit the morphologic and immunophenotypical characteristics of extranodal MALT-lymphomas. Splenic marginal zone lymphoma (SMZL) is also of putative marginal zone derivation, but it differs immunophenotypically from MALT lymphoma. To clarify the relationship between nodal and extranodal MZLs and to investigate the possible existence of a nodal variant of SMZL, 36 MZL initially considered to be primary nodal neoplasms were examined. Other low-grade lymphomas with marginal zone differentiation were excluded (small lymphocytic lymphoma/chronic lymphocytic leukemia [SLL/CLL], follicular lymphoma, and mantle cell lymphoma). Six nodal MZLs showed morphologic and phenotypic characteristics similar to those of SMZL, whereas 30 tumors were more similar to MALT-type lymphomas. The six tumors with SMZL features showed a polymorphic infiltrate surrounding residual germinal centers with absent or very attenuated mantle cuffs. These lymphomas were IgD positive (6/6) but cyclin D1 (0/5), CD5 (0/6), and CD23 (0/6) negative. Five of these patients came for treatment in stage I or II. No patient manifested splenomegaly, peripheral blood, and/or bone marrow infiltration either at diagnosis or during follow-up. Lymph nodes from 30 patients with MALT-type features showed a perisinusoidal and perivascular infiltration of monocytoid/centrocytoid cells and residual germinal centers with a relatively well-preserved mantle cuff. The neoplastic cells were negative for IgD (0/17), cyclin D1 (0/8), and CD5 (0/12). Seven of 16 (44%) patients with a detailed history and clinical follow-up had evidence of extranodal lymphoma. These observations suggest that most nodal B cell lymphomas with marginal zone differentiation are of the MALT type and that they are frequently associated with an extranodal component. In addition, a primary nodal counterpart of splenic MZL also exists, and may occur in the absence of splenomegaly.

Adult↗
PubMed1999

Pathologic features of the gastric mucosa adjacent to primary MALT-lymphomas.

The frequency of reported cases of primary gastric mucosa-associated lymphoid tissue (MALT)-lymphoma is increasing worldwide. Helicobacter pylori plays a preponderant role in its pathogenesis. Gastric MALT-lymphoma arises from nonrecirculating centrocytelike cells located at the periphery of reactive lymphoid follicles, which are common in patients infected with this microorganism. Histopathologic features other than lymphoid follicles have not been well described. In this study the authors describe the morphologic changes in the gastric mucosa adjacent to MALT-lymphomas. From the files of the departments of pathology at the Instituto Nacional de Cancerologia and the Instituto Nacional de la Nutricion in Mexico City, primary gastric MALT-lymphomas were retrieved. Patients with hematoxylin-eosin-stained histologic sections, including the overt neoplasia and the neighboring gastric mucosa, were selected. Lymphoid follicles as well as intestinal metaplasia, atrophy, and eosinophils were evaluated as present or absent and graded as proposed by the Updated Sydney System for gastritis. Fifty-one patients were eligible for analysis. There were 35 low-grade and 16 high-grade primary MALT-lymphomas. Forty-seven patients (92.6%) showed reactive lymphoid follicles in the neighboring mucosa, 32 patients (69.5%) had intestinal metaplasia, and 26 patients (54.1%) demonstrated atrophy. In 41 patients (73.8%) there was an increased number of eosinophils. Our findings suggest that lymphoid follicles, intestinal metaplasia, atrophy, and eosinophils in an endoscopic biopsy are markers of both gastric lymphoma and carcinoma.

Adult↗
PubMed2001

Helicobacter pylori-associated gastric MALT lymphoma in liver transplant recipients.

BACKGROUND: Immunosuppressed transplant recipients are at increased risk of developing several forms of malignancy. The aim of this study is to report the clinical presentation, treatment, and outcome of four liver transplant recipients with Helicobacter pylori-associated gastric mucosae-associated lymphoid tissue (MALT) lymphoma. METHODS: The medical records of four liver transplant recipients with gastric MALT lymphoma were reviewed. In situ hybridization for Epstein-Barr-encoded ribonucleic acid was performed on formalin-fixed tissues. RESULTS: All four subjects presented with abdominal symptoms at a mean of 6.1 years posttransplant. Ulcerative lesions biopsied at endoscopy demonstrated early-stage gastric MALT lymphoma with associated Helicobacter pylori gastritis. In situ hybridization revealed no evidence of Epstein-Barr virus infection in examined tissues. Antibiotic eradication of Helicobacter pylori lead to disease remission in three subjects with a mean follow-up of 21 months, and one subject failed to respond to antibiotics and radiation therapy and died from metastatic gastric adenocarcinoma. CONCLUSIONS: Early-stage, low-grade gastric MALT lymphoma that was associated with Helicobacter pylori gastritis responded to antibiotic therapy with a sustained clinical remission in three of four treated subjects. If other studies confirm a higher than expected incidence of gastric MALT lymphoma in immunosuppressed transplant recipients with Helicobacter pylori infection, screening and treating Helicobacter pylori infection in selected transplant patients may prove beneficial.

Female↗
PubMed2002

High frequency of MALT lymphoma in a series of 14 cases of primary breast lymphoma.

This article reports the clinicopathologic and immunohistochemical findings of 14 cases fulfilling the criteria of Wiseman and Liao for primary lymphoma of the breast (PBL), with emphasis on the frequency of mucosa-associated lymphoid tissue (MALT) lymphomas. The tumors were reclassified according to the revised European-American classification of lymphoid neoplasms. Immunohistochemistry was used to assist in the classification and subtyping of PBL, to demonstrate lymphoepithelial lesions (LEL), and to assess estrogen/progesterone receptor expression. Nine tumors were classified as MALT lymphomas (seven low grade and two high grade), four as diffuse large cell lymphomas and one as follicle center lymphoma. Extensive lymphoid cell infiltration of mammary ducts and acini was also found in non-MALT lymphoma cases. None of the 14 cases expressed hormonal receptors. Primary lymphoma of the breast is a rare and morphologically heterogeneous entity. There is similarity on the clinicopathologic overall profile of the current series of patients and those previously reported, but we recorded a higher incidence of MALT lymphoma (64.3%). Immunohistochemistry is mandatory to identify "true" LEL because epithelial permeation by lymphoid cells can also be found in non MALT-type lymphomas.

Adult↗
PubMed2004

Immune response in Helicobacter pylori-induced low-grade gastric-mucosa-associated lymphoid tissue (MALT) lymphoma.

We have reported previously that heat-shock protein 60 kDa (hsp60) of Helicobacter pylori is an important antigen in the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. In order to investigate associations with host immune reactions and hsp60 antigen, CD40 ligand (CD40L) expression and cytokine production were analysed following stimulation with hsp60. To provide a clear antigen-driven immune response, peripheral blood mononuclear cells (PBMC) from patients with low-grade MALT lymphoma and gastritis and those from healthy volunteers were stimulated with recombinant H. pylori hsp60 and H. pylori cell lysate in the presence of cytokines (IL4 and granulocyte-macrophage colony-stimulating factor). mRNA expression was also analysed by a cDNA microarray containing 1100 genes. Expression of CD40L on PBMCs of patients with MALT lymphoma was increased by cytokines or by combination with stimulation with hsp60 antigens. The production of IL4 in PBMC cultures was increased in patients with MALT lymphoma; however, production of IFN-gamma was at low levels. DNA microarray analysis indicated increased levels of HLA-DR and integrin mRNAs. In cases of low-grade MALT lymphoma, adaptive immune responses against hsp60 may be enhanced by host factors, such as antigen presentation and T-cell activation, resulting in B-cell proliferation, which can be demonstrated during chronic H. pylori infection.

Adult↗
PubMed2000

Salivary gland MALT lymphoma associated with Helicobacter pylori infection in a patient with Sjögren's Syndrome.

We report a case of salivary gland MALT lymphoma in Sjögren's syndrome associated with localized H. pylori infection. A 76-year-old woman had a history of bilateral cheek masses for two years. Histologically, the parotid glands were invaded by numerous centrocyte-like cells to form lymphoepithelial lesions. The tumor cells showed immunohistological differentiation into B cells. Southern blotting demonstrated immunoglobulin gene rearrangement. These results indicated that the tumors were MALT lymphoma. H. pylori, as assessed by the urease test (CLO test; BML Ltd., Tokyo, Japan), was positive in the tumor specimen. After wide local excision of the tumors followed by radio therapy and oral administration of antibiotics and proton pump inhibitor, no evidence of recurrence was found during the 24-months of follow up. H. pylori infection in the salivary gland is rare, although the source of infection and transmission of H. pylori organisms has been thought to be the oral cavity. We discussed the association between H. pylori infection and salivary gland MALT lymphoma. The microorganism may play a role as an additional antigenic stimulus for the development of salivary gland MALT lymphoma as well as for the development of gastric MALT lymphoma. This means that H. pylori can play a role in lymphoma progression as booster of B cell lymphoproliferation.

Aged↗
PubMed2004

No evidence of a correlation between BCL10 expression and API2-MALT1 gene rearrangement in ocular adnexal MALT lymphoma.

In the present study, 62 cases of ocular adnexal lymphoproliferative disorders were reviewed clinicopathologically. Of them, 51 were extranodal marginal zone B-cell lymphoma (MALT lymphoma), five were diffuse large B-cell lymphoma (DLBCL), one was peripheral T-cell lymphoma, one was NK/T cell lymphoma, nasal type, and four were reactive lymphoid hyperplasia. These lymphoma cases showed a favorable clinical course and localized disease, except for the case of NK/T cell lymphoma, although 19 cases (32.8%) had a recurrence of disease. To clarify the correlation between BCL10 protein expression and API2-MALT1 gene rearrangement, the 51 cases of MALT lymphoma and 5 cases of DLBCL were analyzed by immunohistochemical and RT-PCR methods. Nuclear BCL10 expression was identified in 58% of MALT lymphoma cases, but not in any DLBCL cases. There was no evidence of a correlation between aberrant nuclear BCL10 expression and the clinical parameters examined in the present study. API2-MALT1 transcription was not demonstrated in either the MALT lymphoma cases or the DLBCL cases studied using a multiplex one-tube reverse transcriptase-PCR method. These findings indicate that the nuclear expression of BCL10 is unlikely to correlate with the API2-MALT1 fusion gene in ocular adnexal MALT lymphoma.

Adaptor Proteins, Signal Transducing↗
PubMed2006

A prospective analysis of low-grade gastric malt lymphoma after Helicobacter pylori eradication.

BACKGROUND: Primary gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is known to be successfully treated with anti-Helicobacter pylori (H. pylori) therapy alone. However, there are few reports on long-term results after eradication therapy. The aims of this study were to analyze the rate and the interval to reach complete remission (CR), and to assess the rate and the factors affecting recurrence of MALT lymphoma. MATERIALS AND METHODS: Between 1996 and 2003, a total of 90 H. pylori-infected patients with low-grade MALT lymphoma were included in this study. For initial staging, endoscopic ultrasonography, chest-abdomen-pelvis CT scans, and bone marrow examination were taken. All patients were made to take anti-H. pylori therapy for 14 days. Tumoral response was assessed by endoscopy every 3 months till CR and every 6 months after achieving CR. RESULTS: Among 90 treated patients, 85 (94.4%) reached CR. The median interval to CR was 3 months (range, 1-24). Seventy-nine (92.9%) patients were in CR at 12 months. Median follow-up period after CR was 45 months (range 15-109). Among 77 patients who were followed-up after CR, 8 (10.4%) patients were proved with recurrence of MALT lymphoma. Cumulative recurrence rate was 2.7, 11.5, and 12.2% at 1, 2, and 3 years. The presence of H. pylori was only a significant risk factor affecting recurrence. CONCLUSIONS: The status of H. pylori is the most important risk factor affecting recurrence. Therefore, adequate eradication regimen and accurate regular evaluation for H. pylori status are needed during follow up of primary gastric low-grade B-cell MALT lymphoma.

Adult↗
PubMed2006

Frequent and rapid progression of atrophy and intestinal metaplasia in gastric mucosa of patients with MALT lymphoma.

OBJECTIVES: Association of gastric mucosa-associated lymphoid tissue (MALT) low-grade lymphoma and adenocarcinoma has repeatedly been reported. The aim of this study was to evaluate the frequency and the spreading of atrophy and intestinal metaplasia in gastric mucosa of patients with gastric MALT lymphoma followed after conservative treatment. METHODS: Forty-five patients (mean age 45 +/- 2.1 yr) with gastric MALT lymphoma, treated by Helicobacter pylori eradication, chemotherapy with per os single alkylating agents, or both treatments have been followed by gastroscopy with biopsies in antrum and corpus at least once a year. Univariate and multivariate analysis evaluated the association between the appearance of atrophy and intestinal metaplasia in antrum or corpus and different factors related to patients, H. pylori status, lymphoma features, and treatment. In addition, histological aspects of gastric biopsies at the diagnosis period and at the end of follow-up were compared with those of two control groups of age-matched patients with H. pylori gastritis. RESULTS: At the diagnosis time, only intestinal metaplasia in corpus was more frequent in patients with gastric MALT lymphoma than in patients with nonulcer dyspepsia. Within median follow-up of 54.4 months (range 9-196), the percentage of patients with gastric atrophy and intestinal metaplasia increased significantly and became significantly higher than in age-matched nonulcer dyspepsia patients. Multivariate analysis showed significant association between corpus intestinal metaplasia and corpus atrophy, intestinal metaplasia in antrum, and duration of the follow-up. CONCLUSIONS: Conservative management of gastric MALT lymphoma including H. pylori eradication is associated with progression of gastric atrophy and intestinal metaplasia with frequent involvement of the corpus which is known to be a precancerous condition. These findings show that long-term endoscopic monitoring should be recommended in such patients.

Atrophy↗
PubMed1998

Detection of Helicobacter pylori associated antigen and heat shock protein 60 on follicular dendritic cells in the germinal centres of low grade B cell lymphoma of gastric mucosa associated lymphoid tissue (MALT).

AIMS: To investigate the localisation of Helicobacter pylori antigens and the expression of human heat shock proteins (HSP) in stomachs affected by MALT lymphoma. METHODS: Surgically resected stomachs from 24 patients with MALT lymphoma were immunostained with anti-H pylori rabbit antibodies (ORP-1 and ORP-2) and anti-human HSP60 mouse monoclonal antibodies (mAb) (LK-1 and LK-2). RESULTS: Follicular dendritic cells of germinal centres in the stomachs affected by MALT lymphoma were immunostained with anti-H pylori polyclonal antibodies and with anti-human HSP60 mAb, as were the epithelial cells. None of the lymph node samples reacted. CONCLUSIONS: Human HSP60, which cross reacts with anti-H pylori polyclonal antibodies, is often expressed on follicular dendritic cells in gastric MALT lymphoma tissues and may be aetiologically relevant to lymphomagenesis of MALT lymphoma.

Antigens, Bacterial↗
PubMed2006

Antibiotic treatment is not effective in patients infected with Helicobacter pylori suffering from extragastric MALT lymphoma.

PURPOSE: Apart from anecdotal reports implicating Helicobacter pylori (HP) in the development of extragastric mucosa associated lymphoid tissue (MALT) lymphoma, no large scale prospective studies have been performed on this topic. PATIENTS AND METHODS: A total of 77 patients with extragastric MALT lymphoma were prospectively studied. The presence or absence of HP was tested by histology, urease breath test, and serology. Patients were also tested for hepatitis A, B, and C and autoimmune conditions along with assessment of MALT lymphoma-specific genetic changes. RESULTS: Evidence for infection with HP was present in 35 of 77 patients (45%), and three of 75 patients tested (4%) were positive for hepatitis C and one for hepatitis B. All patients with HP-infection underwent eradication, 16 before initiation of further therapy. Apart from one patient with lymphoma involving parotid and colon, who achieved regression of the colonic lesions, none of these 16 patients showed regression of the lymphoma after a median follow-up of 14 months (range, 8 to 48+ months) before initiation of definitive treatment. No correlation between HP-status, localization, stage, autoimmune diseases, and genetic findings was seen. CONCLUSION: In our series, HP-eradication was ineffective for treatment of extragastric MALT lymphomas. This finding, along with an infection rate of 45%-as could also be expected in the general Austrian population-suggests that HP does not play a role in the development of these lymphomas. Antibiotic treatment targeting HP should, therefore, be discouraged in patients with extragastric MALT lymphomas.

Adult↗
PubMed2005

p27kip1 expression is inversely related to the grade of gastric MALT lymphoma.

BACKGROUND: Decreased or lost expression of the cyclin-dependent kinase inhibitor p27kip1 protein has been found to be a poor prognostic factor in many cancers, including gastric cancer. AIM: To evaluate p27kip1 expression in gastric mucosa-associated lymphoid tissue (MALT) and gastric B-cell lymphoma. METHODS: Fifty-two cases of gastric lymphoma, mean age 68.7 yr (range 23-90 yr), 11 of chronic Helicobacter pylori-associated gastritis, and 5 of normal gastric mucosa were studied. Patients were classified into two groups. Stage IE gastric lymphomas were defined as local gastric lymphoma of MALT and more advanced stages as advanced gastric lymphoma. Twenty-three patients diagnosed as stage IE, 13 of these were low-grade and 10 diffuse large B-cell lymphoma (DLBL). Twenty-nine patients were at stage IIE or above, 18 with low-grade and 11 with DLBL. Serial sections were evaluated by immunohistochemistry after staining with antibodies against p27/Kip1 and Ki-67. RESULTS: The proliferative index was higher in gastric DLBL than in low-grade MALT lymphomas, 57.1+/-31.2 vs 17.3+/-20.6 (p=0.0001). The mean p27kip1 expression score for high-grade patients was significantly lower compared with that of low-grade patients, 0.5+/-0.4 and 1.6+/-0.8, respectively (p=0.001). Comparative evaluation of p27kip1 expression in malignant lymphoid cells revealed that B cells of the localized gastric DLBL patients expressed the least p27kip1, 0.36+/-0.32. This value was lower than that of malignant lymphoid cells of patients with advanced DLBL, 0.64+/-0.53, advanced low-grade MALT lymphoma, 1.59+/-0.79, and localized low-grade MALT lymphoma, 1.59+/-0.84. In the multivariate model in which all p27kip1 variables were entered, the expression of p27kip1 in malignant lymphoid cells was inversely correlated with the grade of the lymphoma irrespective of the stage of the disease (p=0.0001), and significantly predicted grade: OR:0.07, 95% CI 0.07-0.31, p=0.0001. CONCLUSION: p27kip1 may be a putative distinct molecular marker to differentiate between low-grade and high-grade gastric lymphoma.

Adult↗
PubMed2001

Extranodal lymphoma of MALT-type: perspective at the beginning of the 21st century.

Extranodal lymphomas arising from mucosa associated lymphoid tissue (MALT) have become a focus of interest in recent years due to their unique pathological and clinical properties. The link between Helicobacter pylori and the development of gastric MALT-type lymphoma has revolutionized treatment options as up to 80% of patients with early gastric MALT-type lymphoma achieve complete remission of the tumor following eradication of H. pylori. As opposed to surgical intervention, which has been the preferred form of treatment in the past, organ conserving approaches are increasingly being applied, as both irradiation and chemotherapy have given excellent results. However, mature data from prospective, randomized studies taking into account the concept of MALT lymphoma as a distinct entity are still lacking in order to define the optimal approach to the management of MALT-type lymphoma.

Helicobacter pylori↗
PubMed2006

Relationship between malt qualities and beta-amylase activity and protein content as affected by timing of nitrogen fertilizer application.

The effects of different timing of N fertilizer application at the same rate on grain beta-amylase activity, protein concentration, weight and malt quality of barley were studied. Grain beta-amylase activity and protein concentration were significantly higher in treatments where all top-dressed N fertilizer was applied at booting stage only or equally applied at two-leaf stage and booting stage than in the treatment where all top-dressed N fertilizer was applied at two-leaf age stage only. On the other hand, grain weight and malt extract decreased with increased N application at booting stage. There were obvious differences between barley varieties and experimental years in the grain and malt quality response to the timing of N fertilizer application. It was found that grain protein concentration was significantly and positively correlated with beta-amylase activity, but significantly and negatively correlated with malt extract and Kolbach index. The effect of grain protein concentration on malt quality was predominant over the effect of grain beta-amylase activity.

Agriculture↗
PubMed2006

Genotypic and environmental variation in barley limit dextrinase activity and its relation to malt quality.

Variation in the limit dextrinase activity of barley malt, and the relationships between limit dextrinase activity and malt quality parameters were investigated using eight cultivars grown at seven diverse locations in China for two successive years. Limit dextrinase activity varied with genotype and location, with the levels ranging from 0.245 U/g to 0.980 U/g. The results showed that the variation in limit dextrinase activity was more attributable to the environment (location and year) than to the genotype. The response of limit dextrinase activity to the environment differed markedly among cultivars, and was reflected by large difference in coefficient of variation of cultivars across diverse locations. Regression analysis showed that limit dextrinase activity was negatively correlated with malt viscosity (r=-0.52, P<0.01), positively correlated with Kolbach index (r=0.38, P<0.01) and malt extract (r=0.30, P<0.05), but had no significant correlation with malt protein content and diastatic power.

Beer↗
PubMed2001

MALT lymphoma originating in breast and uvula.

A case of marginal zone B cell lymphoma of MALT type arising in the uvula and breast is reported. The patient, a 30-year-old woman who delivered a child and lactated in 1997, was suffering from Sjögren syndrome (SS). She was diagnosed with MALT lymphoma after a biopsy of the right breast and uvula. To investigate the relationship of the delivery, lactation and MALT lymphoma, we examined the immunohistochemical analysis of hormone receptors. As a result, lymphoid cells of the breast were stained with anti-progesterone receptor antibodies in the cytoplasm. Consequently, the MALT lymphoma of the uvula appeared to be associated with SS. Moreover, hormones such as progesterone may have influenced the breast involvement of MALT lymphoma in our case.

Adult↗
PubMedDate not supplied

Mucosa-associated lymphoid tissue (MALT) lymphoma combined with tuberculous enteritis at the same site in the jejunum.

Mucosa-associated lymphoid tissue (MALT) lymphoma is derived from the marginal zone B-cell compartment and can be found at a wide variety of extranodal sites, most frequently at the gastrointestinal site. Recent clinicopathologic studies suggest a relationship between MALT lymphoma and chronic inflammatory disorders, such as Helicobacter pylori infection in the stomach or autoimmune disorders, such as Sjögren's syndrome in the salivary glands. Primary gastrointestinal MALT lymphomas most commonly arise in the stomach and less often in the small and large intestine. Recently we experienced a case who had MALT lymphoma combined with tuberculous enteritis at the same site (jejunum) confirmed by exploratory laparotomy. We suspect that there may be some relationship between MALT lymphoma and chronic inflammatory process of mycobacterial tuberculous enteritis.

Disease-Free Survival↗