Evaluation of the association of nine Helicobacter pylori virulence factors with strains involved in low-grade gastric mucosa-associated lymphoid tissue lymphoma

Helicobacter pylori has been associated with the development of two malignant diseases: gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Although the cag pathogenicity island, especially the cagA gene, has been linked with adenocarcinoma, few data concerning H. pylori pathogenic factors involved in low-grade gastric MALT lymphoma are available. The goal of this study was to analyze the prevalence of and correlation between genes coding for seven H. pylori virulence factors (cagA, cagE, vacA, iceA, babA, hopQ, and oipA) and two novel adhesins (sabA and hopZ) by comparing a collection of 43 H. pylori strains isolated from patients with low-grade gastric MALT lymphoma to 39 strains isolated from age-matched patients with gastritis only. Our results show that taken individually, none of the nine genes tested can be considered associated with MALT strains and allow us to conclude that MALT pathogenesis is not linked with more proinflammatory H. pylori strains. We demonstrated that in patients infected with strains harboring the iceA1 allele, sabA functional status, and hopZ "off" status, the odds of developing a MALT lymphoma were 10 times higher. However, the low prevalence of such strains (10 of 43 MALT strains) renders this triple association a low-sensitivity marker for MALT strains. Our data confirmed that H. pylori virulence factors are correlated with one another. If the involvement of H. pylori in MALT lymphoma is well established, the pathomechanism by which gastric lymphoma occurs remains to be identified.     

Serum antibody responses to Helicobacter pylori and the cagA marker in patients with mucosa-associated lymphoid tissue lymphoma.

The lymphoma of the mucosa-associated lymphoid tissue (MALT) of the stomach has been linked to Helicobacter pylori infection, but the mechanisms involved in B-cell proliferation remain elusive. In a search for putative H. pylori-specific monoclonal immunoglobulin production, an H. pylori strain was isolated from 10 patients with MALT lymphoma and used to detect the specific serum antibody response to the homologous strain by immunoblotting. Moreover, the antigenicity of the different strains was compared by using each of the 10 sera. We found that the different strains induced highly variable patterns of systemic immunoglobulin G antibody response, although several bacterial antigens, such as the 60-kDa urease B, were often recognized by the different sera. The cagA marker was detected in the strains by PCR with specific primers and by dot blot analysis, and the CagA protein was found in the sera of 4 of the 10 patients by immunoblotting. In conclusion, MALT lymphoma patients, like other patients with H. pylori gastritis, exhibit a polymorphic systemic antibody response, despite an apparently similar antigenic profile. The CagA marker of pathogenicity is not associated with this disease.     

Immunoglobulin G antibody response to infection with coccoid forms of Helicobacter pylori

An increasing number of studies support a potential role for coccoid forms in Helicobacter pylori infection. Evidence for this was obtained through scanning microscopy, genetic analysis for virulence traits, examination of the presence and activity of key enzymes, and other methods. We studied the serum immunoglobulin G responses to coccoid H. pylori forms by enzyme-linked immunosorbent assay (ELISA) and immunoblotting and compared them with those of bacillary cells. Sera from a total of 295 infected individuals were studied; these included sera from 100 patients with duodenal ulcers, 98 patients with nonulcer dyspepsia, 11 patients with gastroduodenal cancer, and 86 asymptomatic individuals. Initially, we characterized and selected coccoid and bacillary antigenic preparations by one-dimensional (1-D) and 2-D gel electrophoresis and immunoblotting. Data showed that coccoid and bacillary preparations with comparable protein contents have similar patterns in 1-D and 2-D electrophoresis gels and antigenic recognition at blotting. These results revealed that coccoid and spiral antigens in ELISA can equally recognize specific antibodies to H. pylori in sera from infected individuals. The analysis of the spiral and coccoid preparations by Western blotting showed no major differences in antigen recognition. No specific bands or profiles associated with a single gastric condition were identified.     

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.     

Clonal evolution of gastric lymphoma of mucosa-associated lymphoid tissue type.

Development of multiple lesions is frequent in gastric lymphoma of mucosa-associated lymphoid tissue (MALT) type. Presence of clonal components in multiple lesions was examined on the resected samples from 18 cases by using PCR-based method for immunoglobulin heavy-chain gene rearrangement. There were two or more lesions in 10 cases, and 2 to 12 samples were obtained from each lesion. The remaining eight cases had a single large lesion, from which two to six samples were collected from separate areas from each other. A total of 86 samples were analyzed. Histologic findings in each sample were categorized as follows: proliferation of exclusively centrocyte-like cells (CCL), large cells, and combined CCL and large cells. Monoclonal or biclonal pattern (single or two bands) was observed in 42 samples, oligoclonal pattern (three or more bands) in 30, polyclonal (smear) in 11, and no products in 3. Large-cell-type lesions showed fewer bands than those with other histologic types, and 75% of cases with large-cell type had mono- or biclonal proliferation. Common clones were found among lesions in about 60% of cases. Especially in 4 cases including 2 cases with large-cell type, every lesion in the same case contained the common clones. These findings suggested that gastric MALT lymphoma started as multi- or oligoclonal proliferation of cells, in which separate lesions composed of different clones from each other. As disease advances, dominant clones appear in some lesion and disseminate to other lesions via homing properties of the proliferating B lymphocytes.     

Helicobacter pylori associated gastric diseases and lymphoid tissue hyperplasia in gastric antral mucosa

AIM: To investigate the relation between Helicobacter pylori associated gastroduodenal diseases and lymphoid tissue hyperplasia in the antral mucosa and to pursue its evolution after eradication of H pylori. METHODS: Gastric antral biopsy specimens were obtained from 438 patients with H pylori positive gastroduodenal diseases (185 chronic gastritis, 69 gastric ulcer, and 184 duodenal ulcer) and 50 H pylori negative healthy controls. Lymphoid follicles and aggregates were counted and other pathological features were scored according to the updated Sydney system for classification of chronic gastritis. After a course of anti-H pylori treatment, biopsy specimens were obtained at four to six weeks, 12 months, and 24 months in the chronic gastritis patient group. RESULTS: The total prevalence of lymphoid follicles and aggregates in the biopsies was 79.9% (350 of 438; 95% confidence intervals (CI), 0.76 to 0.84). The prevalence and density of lymphoid follicles and aggregates were significantly different in the various gastroduodenal diseases. The highest prevalence (89.9%; 95% CI, 0.83 to 0.97) and density (0.82) of lymphoid follicles and aggregates occurred in patients with gastric ulcers. The lowest prevalence of lymphoid follicles and aggregates was found in patients with chronic gastritis (74.6%; 95% CI, 0.68 to 0.81), and the lowest density of lymphoid follicles and aggregates (0.56) was seen in patients with duodenal ulcers. The prevalence and density of lymphoid follicles and aggregates correlated strongly with the activity and severity of gastric antral mucosal inflammation. The eradication of H pylori resulted in a decrease in the prevalence and density of lymphoid follicles and aggregates. CONCLUSION: The prevalence and density of lymphoid follicles and aggregates in gastric antral mucosal biopsies correlated closely with H pylori infection.     

Monoclonality in Helicobacter pylori-positive gastric biopsies: an early detection of mucosa-associated lymphoid tissue lymphoma

Mucosa-associated lymphoid tissue (MALT) is not present in healthy gastric mucosa, but it can develop in sites of long-persisting inflammation and is connected with the development of MALT lymphoma. A monoclonal lymphocyte population is one of the characteristics of such lymphomas. In this study we analyzed gastric biopsies (formalin fixed and paraffin embedded or frozen) in 93 patients with dyspepsia accompanied by Helicobacter pylori infection. We applied PCR and single-cell immunocytochemistry to detect the clonality of the gastric B-cell population. Immunocytochemistry performed on 33 frozen biopsies showed two samples with monoclonal pattern. PCR analysis of immunoglobulin heavy-chain (IgH) gene rearrangements revealed two monoclonal populations out of 161 biopsies from 60 patients. We conclude that PCR analysis was the most sensitive method, which gave us insight into the nature of the earliest stage of MALT lymphoma in gastric biopsies.     

Primary low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma with polypoid appearance. Polypoid gastric MALT lymphoma: A clinicopathologic study of eight cases

In the current study, we report eight cases with primary low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma endoscopically characterized by polypoid lesions in order to highlight their clinicopathologic significance. Four patients were male, their ages ranging from 40 to 78 years old. The resected specimens revealed a histology of low-grade MALT lymphoma characterized by dense lymphocytic infiltration predominantly in the submucosa and a relatively monotonous proliferation of centrocyte-like cells with reactive follicles and infrequent lymphoepithelial lesions. The tumor cells were of CD5-, CD10-, CD20+, BCL2+ and cycline D1- phenotype, and showed a monoclonal rearrangement of immunoglobulin heavy chain genes in the five of six cases examined. Interestingly, Helicobacter pylori (H. pylori) was detected in three (37.5%) of the eight patients, which was significantly lower than previous reports. Two of the H. pylori-positive cases initially underwent H. pylori eradication, but showed no change in their lymphomas after the cure of H. pylori infection. The clinicopathologic findings of the present cases appeared to closely resemble those of colorectal MALT lymphoma with a polypoid appearance and few association of H. pylori infection in their pathogenesis. These gastric polypoid cases may merit separate consideration because of the therapeutic problems they pose.     

Urease-associated heat shock protein of Helicobacter pylori.

Helicobacter pylori urease is an extracellular, cell-bound enzyme with a molecular weight of approximately 600,000 (600K enzyme) comprising six 66K and six 31K subunits. A 62K protein is closely associated with the H. pylori urease, both in crude preparations and after gel filtration; this protein can be removed from the urease by ion-exchange chromatography without inactivating the enzyme. We purified this urease-associated protein and determined its N-terminal amino acid sequence. The sequence is 80% homologous (identical plus conserved amino acid residues) to the Escherichia coli GroEL heat shock protein (HSP), 75% homologous to the human homolog, and 84% homologous to the HSP homolog found in species of Chlamydia. Thus, the 62K urease-associated protein of H. pylori belongs to the HSP60 family of stress proteins known as chaperonins. Evidently this protein, HSP62, participates in the extracellular assembly and/or protection of the urease against inactivation in the hostile environment of the stomach.     

Monocytoid B-cell lymphoma: morphological variants and relationship to low-grade B-cell lymphoma of the mucosa-associated lymphoid tissue

Twenty-eight cases of monocytoid B-cell lymphoma of lymph nodes and 16 lymph node metastases of primary gastric lymphomas, mostly low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type were investigated morphologically and immunohistochemically. Both groups showed the same morphological and immunohistochemical features: diagnostically important sites of infiltration were the sinuses and the marginal zones. The tumour cells were either medium-sized or small. The cytoplasm stained grey with Giemsa and was sometimes rather pale. In imprints the grey colour of the cytoplasm was a characteristic feature. The medium-sized cell type was more frequent; in one third of the cases it was combined with a prominent lymphoplasmacytic component from the same clone, and it resembled the monocytoid B-cells of the sinuses. The small cell type was less common, was not combined with a lymphoplasmacytic component and more closely resembled marginal zone cells. The difference was underlined by the negative reaction with the monoclonal antibody Ki-B3 in the small cell type, which, conversely, was positive in the medium-sized cell type and in the monocytoid B-cell reaction of the sinuses. Both of these cell types, however, showed a granular reaction with the new monoclonal antibody Ki-Mlp. The morphological and immunohistochemical parallels are arguments in favour of the assumption that monocytoid B-cell lymphoma is the nodal equivalent of low-grade B-cell lymphoma of MALT type. This is further supported by the fact that in nine of our 28 cases of monocytoid B-cell lymphoma, lymphomas were found simultaneously or subsequently in organs of the MALT. Monocytoid B-cell lymphoma must be differentiated from an infiltration that occurs in the form of clusters of monocytoid B-cells in other low-grade B-cell lymphomas, especially in immunocytoma with a high content of epithelioid cells.     

T-cell, antibody, and cytokine responses to homologs of the 60-kilodalton heat shock protein in Helicobacter pylori infection.

For Helicobacter pylori, the hsp60 heat shock protein encoded by hspB is being considered as a potential candidate for subunit vaccines. We investigated the humoral and cellular responses to H. pylori hsp60 and its cross-reactivity with the homologous Mycobacterium bovis p65 protein and autologous human hsp60 protein. H. pylori-infected persons had significantly higher levels than uninfected persons of serum immunoglobulin G antibodies recognizing H. pylori hsp60, but not M. bovis p65 or human hsp60, as determined by enzyme-linked immunosorbent assay. In contrast, immunoblotting demonstrated cross-reactivity of H. pylori hsp60 with human hsp60. T-cell recognition of H. pylori hsp60 was found in both infected and uninfected subjects, and there was no recognition of human hsp60. T cells from infected and uninfected subjects that had been activated in response to H. pylori hsp60 or M. bovis p65 were phenotypically similar but appeared to secrete different levels of gamma interferon and interleukin-10. These results demonstrate an apparent difference in the epitopes recognized by the T and B cells responding to H. pylori hsp60 in H. pylori-infected persons. In contrast to the T-cell responses, which were highly variable in all subjects and showed no recognition of autologous proteins, a specific B-cell response that may have cross-reactivity to human hsp60 is evident in some infected subjects.     

Immune response against a cross-reactive epitope on the heat shock protein 60 homologue of Helicobacter pylori

We previously established a monoclonal antibody (MAb), designated H9, which reacts with the heat shock protein 60 (HSP60) homologue of Helicobacter pylori as well as with other bacterial and human HSP60s. To determine the importance of a cross-reactive epitope on H. pylori HSP60 in H. pylori immunopathogenesis, we performed (i) mapping of an epitope on H. pylori HSP60 recognized by the H9 MAb, (ii) analysis of immunoglobulin G responses of patients with or without H. pylori infection to its epitope region, and (iii) studies of the protective effect of immunization with its epitope region on H. pylori infection in mice. The epitope recognized by the H9 MAb was mapped to the sequence of amino acids 189 to 203 (VEGMQFDRGYLSPYF) on the H. pylori HSP60 molecule. It was confirmed that the synthesized peptide designated pH9 was recognized by the H9 MAb. Enzyme-linked immunosorbent assay analysis showed that patients with H. pylori infection (n = 349) had significantly lower titers of pH9 antibody than did uninfected patients (n = 200) (P < 0.001), but this was not the case with purified H. pylori HSP60 recombinant Escherichia coli GroEL, or recombinant human HSP60. In C57BL/6 mice immunized with the pH9 peptide with Freund's complete adjuvant (FCA), the number of H. pylori organisms colonizing the stomach was significantly lower than that in mice immunized with pCont plus FCA (P < 0.0001) or FCA only (P < 0.005). The results suggest that the immune response to the cross-reactive epitope (pH9 region) on H. pylori HSP60 is unique and might be associated with protection against H. pylori infection.     

Clinical,histological and molecular follow-up of 60 patients with gastric marginal zone lymphoma of mucosa-associated lymphoid tissue

The persistence of gastric lymphoma after Helicobacter pylori eradication may be difficult to evidence on endoscopic and histological examination. The aims of the study were to evaluate the detection of monoclonal immunoglobulin H (IgH) gene rearrangement in endoscopically infiltrated and normal mucosa at diagnosis and during follow-up in order to determine its clinical and prognostic impact. We studied 60 gastric marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT), and IgH monoclonality was detected at diagnosis in 52 patients (87%). The endoscopically normal mucosa contained clonal lymphomatous cells in 69% of cases before remission. A complete histological remission (HR) was observed in 28 patients (47%). Among them, 23 were followed for molecular remission (MR). The median delay was 10 months to achieve HR and 18 months to achieve MR. Interestingly, patients with HR but not MR had a longer delay to achieve HR (21 months) (P=0.0006) and a more frequent clonal normal mucosa at diagnosis (88%) than patients with both HR and MR (10 months and 39%, respectively). The presence of monoclonal B cells at both infiltrated and normal sites may therefore identify patients with a longer delay to achieve complete response, suggesting that molecular dissemination may require therapeutic intensification.Part of this work was presented at the 2002 Annual Meeting of the United States and Canadian Academy of Pathology and published in abstract form (Mod Pathol 2002;15:126A).     

Localization of Helicobacter pylori urease and heat shock protein in human gastric biopsies.

Helicobacter pylori is a spiral, gram-negative bacterium which causes chronic gastritis and plays a critical role in peptic ulcer disease, gastric carcinoma, and gastric lymphoma. H. pylori expresses significant urease activity which is an essential virulence factor. Since a significant fraction of urease activity is located on the surface of the bacterium, the urease molecule is a logical choice as an antigen for a vaccine; currently recombinant urease apoenzyme is being tested as a vaccine in phase II clinical trials. We have recently demonstrated that urease and HspB (a homolog of the GroEL heat shock protein) become associated with the surface of H. pylori in vitro in a novel manner: these cytoplasmic proteins are released by bacterial autolysis and become adsorbed to the surface of intact bacteria, reflecting the unique characteristics of the outer membrane. To determine if similar mechanisms are operative in vivo, we determined the ultrastructural locations of urease and HspB within bacteria present in human gastric biopsies. Our results demonstrate that both urease and HspB are located within the cytoplasm of all bacteria examined in human gastric biopsies. Interestingly, a significant proportion of the bacteria examined also possessed variable amounts of surface-associated urease and HspB antigen (from 5 to 50% of the total antigenic material), indicating that in vivo, H. pylori has surface characteristics which enable it to adsorb cytoplasmic proteins. This is consistent with our altruistic autolysis model in which H. pylori uses genetically programmed bacterial autolysis to release urease and other cytoplasmic proteins which are subsequently adsorbed onto the surface of neighboring viable bacteria. These observations have important implications regarding pathogenesis and development of vaccines for H. pylori.     

原位杂交对胃粘膜相关组织淋巴瘤的免疫球蛋白轻链的检测

目的 评价mRNA原位杂交方法检测免疫球蛋白轻链限制性在胃粘膜相关组织淋巴瘤诊断中的应用价值。方法 用非同位素标记寡核苷酸mRNA探针原位杂交方法检测27例原发怀胃粘膜相关淋巴瘤和5例慢性胃炎,对其中的肿瘤细胞、淋巴细胞及浆细胞的免疫球蛋白κ和λ轻链的比例进行分析,以确定肿瘤细胞的轻链限制性及浆细胞的单克隆性。结果 27例原发性胃粘膜相关淋巴瘤中有10例出现轻链限制性（37％）,其中5例（5／9）为低度恶性病例,5例（5／18,28％）为高度恶性病例,单克隆性的浆细胞只在低度恶性病例中检出。慢性胃炎标本及肿瘤旁组织中未检测出轻链限制性。结论 mRNA原位杂交方法检测轻链限制性是诊断胃淋巴瘤的一个有用工具,低度恶性淋巴瘤中单克隆性浆细胞的存在,可作为诊断早期胃粘膜相关淋巴瘤的依据之一。     

Clinicopathologic study of primary gastric lymphoma of B cell phenotype with special reference to low-grade B cell lymphoma of mucosa-associated lymphoid tissue among the Japanese

Resection specimens from 83 patients with primary gastric lymphoma (PGL) of B cell phenotype at stage I_E and at stage II_E, according to the Ann Arbor classification were investigated. Histologically, these lymphomas could be divided into four types: Type I lesions (n=24) were entirely made up of MALT lymphoma; Type II lesions (n=13) were predominantly MALT lymphoma containing one to a few foci of high-grade B cell lymphoma; Type III lesions (n=22) consisted largely of high-grade lymphoma with small areas of low-grade MALT lymphoma; and Type IV lesions (n=24) were pure high-grade B cell lymphoma, mostly of the large cefi type. All patients had undergone primary gastric resection, and 14 received additional chemotherapy (n=12), or both chemotherapy and radiotherapy (n=2). The survival probability was significantly higher for Types I and II lymphomas than for Types III and IV tumors (P < 0.05 by the generalized Wilcoxon test). According to The General Rules for the Gastric Cancer Study by the Japanese Research Society for Gastric Cancer, the stage of disease showed a clear distinction between each of them (P < 0.01 by the generalized Wilcoxon test). This staging method seemed to serve well as a prognostic indicator. The histological typing of the PGL of the present series also seemed to correlate with the gross appearance, pathologic stage and prognosis. Furthermore, the expression of cyclin D1, bcl-2 and p53 protein, and PCNA was immunohistochemically investigated in 42 cases of the present series. Most of the low-grade PGL (Types I and II) had less than 60% PCNA-positive cells, whereas the high-grade PGL (Types III and IV) had more than 60% positive cells. In a study for cyclin D1 protein, no cases showed the nuclear staining pattern characteristic for mantle cell lymphoma, and the cytoplasmic staining frequently observed in the node-based large B cell lymphoma was seldom identified in the PGL. This discrepancy might suggest a lineage difference among the morphologically similar, but site-dierent, lymphomas. On the other hand, bcl-2 protein overexpression was almost equal in frequency between the gastric and node-based high-grade B cell lymphomas. This is in contrast to the reports from Western countries, in which the majority of high-grade gastric tumors were bcl-2 negative.     

Diffuse large B-cell lymphoma with anaplastic features and focal low-grade mucosa-associated lymphoid tissue lymphoma component of the stomach

We describe an 83-year-old man diagnosed as having diffuse, large B-cell lymphoma with anaplastic features and CD30 expression of the stomach. Focally, the tumor showed typical low-grade mucosa-associated lymphoid tissue lymphoma. We are not aware of a previous report on the transformation of low-grade gastric lymphoma of mucosa-associated lymphoid tissue type into an "anaplastic," large B-cell tumor.     

Identification and purification of a cpn60 heat shock protein homolog from Helicobacter pylori.

Helicobacter pylori is associated with gastritis and peptic ulcer disease in humans. We have identified a homolog of the chaperonin cpn60 family of heat shock proteins in H. pylori, referred to as Hp54K. Hp54K, purified from water-extractable H. pylori proteins, migrated as a single band at 54 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its native molecular mass was 740 kDa; thus, Hp54K apparently comprises a 14-mer. The N-terminal 33 residues of Hp54K exhibited 60.6, 57.6, 54.5, 54.5, 51.5, and 51.5% identity with corresponding sequences in the following cpn60 homologs: HtpB (Legionella pneumophila), P1 (human mitochondria), GroEL (Escherichia coli), BA60K (Brucella abortus), HypB (Chlamydia trachomatis), and the 65-kDa immunodominant protein of Mycobacterium bovis BCG, respectively. Hp54K was the only protein recognized in whole-cell preparations of H. pylori by immunoblotting using monospecific antisera against cpn60 homologs from L. pneumophila, E. coli, C. trachomatis, and M. bovis BCG. Antiserum against Hp54K recognized proteins with molecular masses of 50 to 60 kDa in a large number of gram-negative bacteria, consistent with the known highly conserved nature of cpn60 proteins. Hp54K is a major protein and is immunogenic in humans infected with H. pylori. Thus, Hp54K shares many similarities with known cpn60 homologs. On the basis of the proposed role of other cpn60 proteins in induction of chronic inflammation, immune cross-reactivity between Hp54K and gastric tissue may provide an important link between H. pylori infection and gastritis.     

The lymphoepithelial lesion of gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT): an ultrastructural study

Lymphoepithelial lesions are a characteristic feature of primary, gastric low-grade lymphomas of mucosa-associated lymphoid tissue (MALT). The lymphoepithelial lesions in 12 such lymphomas have been examined by electronmicroscopy and immunohistochemistry. The lymphocytes present in these lesions are neoplastic centrocyte-like (CCL) B-cells and are morphologically and immunophenotypically similar to those of the surrounding lymphoma. Once the CCL cells penetrate the gastric glands, there is marked structural distortion and disruption of the epithelial cells which leads to their ultimate death. The close association of the neoplastic CCL cells and epithelial cells suggests the presence of a factor, an antigen or other receptor, on the plasma membrane of the latter through which these effects are mediated.     

Primary pulmonary low-grade marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type with prominent hyalinosis. A case report

We report a case of primary pulmonary low-grade marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT)-type with prominent sclerosis, which morphologically resembled pulmonary hyalinizing granuloma (PHG) or inflammatory pseudotumor (IPT) of the lung. The patient, a 66-year-old Japanese female with a history of Sj?gren's syndrome and primary biliary cirrhosis, presented with a lower left lobe mass 6.8 cm in diameter. Histologically, the lesion is characterized by dense bundles of collagen with scattered plasma cells, mature small lymphocytes, and histiocytes among the collagen bundles. Only the peripheral area of the nodule contained dense lymphoplasmacytoid and histiocytoid infiltrates. A few centrocyte-like cells were obscured by the numerous plasma cells and plasmacytoid cells. In addition, lymphoepithelial lesions and colonalized lymphoid follicles were identified by immunohistochemistry alone. Although PHG and IPT are unlikely to be confused with pulmonary MALT-type lymphomas, the present case suggests that MALT-type lymphoma should be added to the list of differential diagnoses for PHG and IPT.