Background-While a close association between gastric mucosa associated lymphoid tissue (MALT) lymphoma andHelicobacter pylori infection has been established, there are still cases which do not respond to H pylori eradication. Aims-To investigate the clinicopathological factors which may help predict the therapeutic eYcacy of H pylori eradication in gastric MALT lymphoma. Patients-Forty one patients with gastric MALT lymphoma, including low and high grade lesions. Methods-After endosonographic staging was determined, H pylori was eradicated in all patients, and the subsequent gastric pathological course was then investigated. Results-Complete regression of MALT lymphoma was observed in 29(71%) patients, partial regression in five (12%), and no regression in seven (17%). Twenty six (93%) of 28 MALT lymphomas restricted to the mucosa but only three (23%) of 13 lymphomas which invaded the deep portion of the submucosa or beyond completely regressed. Kaplan-Meier analysis for the probability of complete regression of MALT lymphoma revealed a significant diVerence between tumours restricted to the mucosa and those invading the submucosa deeply or beyond (p<0.05). Neither the presence of a high grade component, perigastric lymphadenopathy, nor clinical staging prior to eradication correlated with the probability of lymphoma regression. Conclusions-Assessment of deep submucosal invasion by endosonography is valuable for predicting the eYcacy of H pylori eradication in gastric MALT lymphoma. (Gut 2001;48:454-460)

The aim of our study was to clarify the association between immunoglobulin G(IgG) subclasses and the complement pathway in patients with idiopathic membranous nephropathy (MN). Immunofluorescence (IF) was performed in 16 MN patients and 20 controls using antibodies against IgG, IgA, IgM, C1q, C3c, C4d, IgG1, IgG2, IgG3, IgG4, mannose binding lectin (MBL), C4-binding protein (C4-bp), factor B, C5b-9, and CD59. MN was classified into two types, segmental MN (S-MN; six patients) and global MN (G-MN; ten patients), according to the distribution of IgG deposits along the glomerular capillary wall. No deposition of any antibody was found in the controls. IF revealed IgG1, IgG3, C1q, C3c, C4d, C4-bp, C5b-9, and CD59 deposits in patients with S-MN, whereas IgG1, IgG2, IgG3, IgG4, C3c, C4d, MBL, factor B, C4-bp, C5b-9, and CD59 deposits were detected in those with G-MN. There was a higher deposition of IG1, IgG2, and IgG4 in patients with G-MN than in those with S-MN, whereas the intensity of C1q deposits was higher in S-MN than in G-MN patients. In contrast, the intensity of factor B and MBL was higher in G-MN than in S-MN patients. This is the first report of S-MN patients showing complement activation of the classical pathway associated with IgG1 and IgG3 and G-MN patients showing complement activation of both the alternative and lectin pathways associated with IgG2 and IgG4.

CD10 and MUM1 are representative B cell differentiation markers. Follicular lymphoma (FL) is usually positive for CD10 and negative for MUM1. In this study, however, we compared 22 FLs with peculiar phenotype CD10 ؊ MUM1 ؉ with 119 typical CD10 ؉ MUM1 ؊ FLs. All CD10 ؊ MUM1 ؉ FL patients exhibited follicular structure with follicular dendritic meshwork, and a high rate of somatic hypermutation and ongoing mutation, similar to typical FL. However, CD10 ؊ MUM1 ؉ FLs were encountered frequently in the elderly compared with CD10 ؉ MUM1 ؊ typical FLs (67.0 versus 58.7 years, P < .01), showed high grade (grade 3A or 3B) morphology (91% versus 17%, P < .001), diffuse proliferation (59% vs 19%, P < .001), and lacked BCL2/IGH translocation (5% versus 92.5%, P < .001), which is the most characteristic aberration in FL, and 88% showed BCL6 gene abnormalities (translocation or amplification IntroductionFollicular lymphoma (FL) is the most prevalent form of low-grade B-cell lymphoma in adults. 1 Typically, FL cells express CD10, BCL2, and BCL6. CD10 is a marker for germinal center (GC) B cells, and thus its expression suggests that GC B cells are a normal counterpart of FL. 2 However, some reports, including our previous study, described the existence of CD10 Ϫ FL, especially in high-grade (grade 3) FL. [3][4][5][6] However, it is not clear whether CD10 negativity is just aberrant loss or whether it is meaningful, reflecting a specific differentiation stage and affecting clinical features. MUM1 (multiple myeloma oncogene 1)/IRF4 (interferon regulatory factor 4) is a lymphoid-specific member of the interferon regulatory factor family of transcription factors, 7-9 and it is a reliable marker of "late-stage GC" or "post-GC" B cells. 8 In this study, we clinicopathologically compared CD10 Ϫ MUM ϩ and "classical" CD10 ϩ MUM1 Ϫ FLs. Materials and methods Biologic materialTissue specimens were obtained from human lymph nodes filed at the Department of Pathology at Fukuoka University and Kurume University. The 147 FL patients have already been reported in our previous publication. 5 Paraffin-embedded tissues were available in almost all patients, while frozen tissues and cell suspensions were available in some patients. Histopathological diagnoses and grading were based on the new WHO classification and carried out by 4 pathologists (Y.G., K.K., M.K., and K.O.). 1 Clinical information was obtained by reviewing the tumor registry records and/or patients' medical charts. This study was approved by the Kurume University institutional review board (Kurume, Japan), and patients provided informed consent in accordance with the Declaration of Helsinki. ImmunohistochemistryParaffin sections from each sample were immunostained with monoclonal antibodies against CD10 (Novocastra, Newcastle, United Kingdom), Bcl2 (DAKO, Glostrup, Denmark), MUM1 (DAKO), CD21 (DAKO), CD138 (Novocastra), and Bcl6 (Novocastra) following the method described previously. 5 The following 2 categories were defined: negative (Ͻ 30% positively-stained tumor cells) and ...

Although lobular endocervical glandular hyperplasia (LEGH) was originally described as a distinct hyperplastic glandular lesion of the uterine cervix, recent studies have raised a question that LEGH may be a cancerous precursor of minimal deviation adenocarcinoma (MDA) and other mucinous adenocarcinomas (MACs) of the uterine cervix. In the present study, we studied LEGH, MDA, and MAC by using molecular-genetic and immunohistochemical methods for chromosomal imbalance, microsatellite instability, human papillomavirus (HPV) infection, and gastric pyloric-type mucin secretion to clarify their relationship. Comparative genomic hybridization revealed recurrent chromosomal imbalances, that is, gains of chromosome 3q and a loss of 1p, which were common to MDA and MAC, in 3 of 14 LEGHs analyzed (21%). LEGHs with chromosomal imbalances showed a degree of cellular atypia in the hyperplastic glandular epithelium. Dual-color fluorescence in situ hybridization confirmed a gain of chromosome 3 fragment in these cervical glandular lesions. HPV in situ hybridization revealed that high-risk HPV (types 16 and 18) was positive in over 80% of MACs, but negative in all LEGHs and MDAs examined. Microsatellite instability was rarely detected in these cervical glandular lesions. Our present study results demonstrated a molecular-genetic link between LEGH and cervical mucinous glandular malignancies including MDA and MAC, and are thought to support the hypothesis that a proportion of LEGHs are cancerous precursors of MDA and/or MAC.

Sixty-four cases of malignant lymphoma involving the liver were examined. Of these, 20 cases were histologically confirmed to be primary hepatic B-cell lymphoma. Twelve of these 20 cases were diffuse large B-cell lymphoma (DLBCL) and eight cases were mucosa-associated lymphoid tissue (MALT) lymphoma. Of the 12 cases of DLBCL, six were immunohistologically positive for CD10 and/or Bcl6 (indicating a germinal center phenotype), six were positive for Bcl2, and five were positive for CD25. Eight of the 12 DLBCL cases (66.7%) and two of the eight MALT lymphoma cases (25%) had serum anti-hepatitis C virus (HCV) antibodies and HCV RNA. The incidence of HCV infection was significantly higher in the hepatic DLBCL cases than in systemic intravascular large B-cell cases with liver involvement (one of 11 cases, 9.1%) and T/NK-cell lymphoma cases (one of 19 cases, 5.3%) (p < 0.01 for both). Two hepatic DLBCL cases (16.7%) had rheumatoid arthritis treated with methotrexate, and four MALT lymphoma cases (50%) had Sjögren’s syndrome, primary biliary cirrhosis, or autoimmune hepatitis; one case in each of these two groups was complicated by chronic HCV-seropositive hepatitis. Although primary hepatic lymphoma is rare, persistent inflammatory processes associated with HCV infection or autoimmune disease may play independent roles in the lymphomagenesis of hepatic B cells.