Diffuse large B cell lymphoma (DLBL) constitutes the greatest percentage of adult non-Hodgkin's lymphomas and represents a diverse spectrum of lymphoid neoplasms. Clinicopathologic, phenotypic and genotypic findings were correlated and compared for 63 DLBL cases to investigate whether they represent clinically relevant subtypes. They were all cyclin D1 negative and were phenotypically divided into three groups, ie group I (CD5 + type, n = 11), group II (CD5 − CD10 + type, n = 19), and group III (CD5 − CD10 − type, n = 33). Data were correlated by observing the respective gene rearrangement and expression of BCL2 and BCL6. In clinical aspects, the group I cases demonstrated a significantly inferior survival than those of the other two groups (log-rank test, P = 0.016). Although rearrangement of BCL2 and BCL6 did not show any inclination to a specific subgroup, the immunohistochemical detection of BCL2 was less frequent, at a statistically significant level (P = 0.011), in group II (50%) than in group I (82%) and III (82%) cases. This appears to confirm the unique aspect of the CD5 − CD10 + type DLBL, indicating a certain relationship with the normal germinal center cells which usually lack BCL2 expression. The BCL6 protein expression was detected in most of the present DLBL cases (92%) irrespective of this grouping. These data suggest that the phenotypic delineation by the detection of CD5 and CD10 will improve our understanding of DLBL and be helpful in a future subgrouping of DLBL.

To investigate the relationship between high serum levels of IgA and glomerular lesions, selective mating was performed in high serum IgA ddY mice, a murine model of spontaneously developing mesangioproliferative glomerulonephritis mimicking human IgA nephropathy. The selection and mating of high IgA ddY mice were accomplished when the mice were three to four months old. In the 12th generation of high IgA ddY (HIGA) mice, significantly higher levels of serum IgA from 10 age weeks to 60 weeks (P < 0.0002 to 0.0001) were observed in comparison with BALB/c mice. Relatively high proteinuria was observed at 40 weeks of age, although hematuria was consistently negative. Microscopic observations of renal tissue disclosed a marked glomerular mesangial matrix increase and a reduction of cell proliferation with age by both semiquantitative and morphometric analyses with moderate tubulointerstitial damage. These mesangial matrices were stained markedly by antisera for collagen type IV and by fibronectin, but not by collagen type I. Localization of TGF-beta protein was also detected in the mesangium of the HIGA mice. The positive mesangial IgA deposition was maintained consistently by this mating procedure and became more marked with age. Size analysis of IgA from ten pooled HIGA mice aged 50 to 60 weeks revealed dominant polymeric IgA in sera and dimeric IgA in glomerular eluates. Clonal analysis of serum IgA disclosed heterogeneous spectrotypes in a wide pH range (4.5 to 6.5), in contrast to very limited spectrotypes in the acidic pH range (4.5 to 5.2) of IgA in the glomerular eluates from these mice. The analyses of retroviral gp70 antigen involvement in the HIGA mice disclosed a significant increase of serum levels of gp70 anti-gp70 immune complexes with age, with no relationship to the severity of glomerular gp70 deposition. Northern blot analysis of renal tissue revealed markedly high mRNA expression of collagen type I, IV, fibronectin and TGF-beta even in 10-week-old HIGA mice in comparison with BALB/c mice. The expression became more significant in 60-week-old animals. The genetic background required to induce the expansion of IgA-producing B-cell clones is suggested to be closely related to the increased gene expression of TGF-beta, which induces enhanced glomerular extracellular matrix (especially fibronectin) accumulation in HIGA mice, being possibly mediated by the mesangial deposition of dimeric and highly acidic IgA. This newly established strain may provide a model for investigating the relationship between progressive glomerular sclerotic lesions and the induction of pathogenic IgA in human IgA nephropathy.

Chronic viral hepatitis B and C and non-alcoholic fatty liver disease (NAFLD) have been widely acknowledged to be the leading causes of liver cirrhosis and hepatocellular carcinoma. As anti-viral treatment progresses, the impact of NAFLD is increasing. NAFLD can coexist with chronic viral hepatitis and exacerbate its progression. Oxidative stress has been recognized as a chronic liver disease progression-related and cancer-initiating stress response. However, there are still many unresolved issues concerning oxidative stress, such as the correlation between the natural history of the disease and promising treatment protocols. Recent findings indicate that oxidative stress is also an anti-cancer response that is necessary to kill cancer cells. Oxidative stress might therefore be a cancer-initiating response that should be down regulated in the pre-cancerous stage in patients with risk factors for cancer, while it is an anti-cancer cell response that should not be down regulated in the post-cancerous stage, especially in patients using anti-cancer agents. Antioxidant nutrients should be administered carefully according to the patients’ disease status. In this review, we will highlight these paradoxical effects of oxidative stress in chronic liver diseases, pre- and post-carcinogenesis.

A 59‐year‐old woman with Sjögren's syndrome had an anterior mediastinal tumor. The tumor had epithelium‐lined thymic cysts. Histologically, centrocyte‐like (CCL) cells were present as clusters intermingling with small lymphocytes and plasma cells, invaded the epithelium, and formed characteristic lymphoepithelial lesions; the tumor was identified as malignant lymphoma arising in mucosa‐associated lymphoid tissue (MALT). Within the tumor, trapped Hassall's corpuscles were recognized. Immunohistochemical staining demonstrated monotypic cytoplasmic kappa light chains in a small portion of the CCL cells. Furthermore, Southern blot hybridization studies showed rearrangements of immunoglobulin heavy chain, immunoglobulin kappa light chain, and T‐cell receptor beta genes. The findings are consistent with thymic low‐grade B‐cell MALT lymphoma. Cancer 1992; 69:1347‐1355.