Primary Hepatic Diffuse Large B-Cell Lymphoma in a Patient with Chronic Hepatitis C
Division of Clinical Pathology, University Hospital, Geneva, Switzerland.American Journal of Surgical Pathology (Impact Factor: 5.15). 10/1999; 23(9):1124-30. DOI: 10.1097/00000478-199909000-00017
Epidemiological and experimental data suggest that the hepatitis C virus infection might be associated with the development of distinct types of non-Hodgkin's lymphomas. Here, we report a case of a patient with chronic hepatitis C and type II mixed cryoglobulinemia, who developed a primary hepatic non-Hodgkin's B-cell lymphoma. A diffuse, large B-cell lymphoma was diagnosed based on morphological, immunophenotypical and molecular genetic findings. Hepatitis C virus replication, as evaluated by strand-specific reverse transcriptase-polymerase chain reaction, was detected in the nonneoplastic liver, but not in the lymphomatous tissue. High grade non-Hodgkin's lymphomas, although rare complications, have to be considered as part of the spectrum of hepatitis C virus-related hepatic lesions.
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ABSTRACT: In order to gain further insight into the mechanisms of calcium (Ca) homeostasis in hypercalciuria, we studied 32 lithiasic patients who were divided into three groups: normocalciuric patients (NC; n = 11), patients with absorptive hypercalciuria (AH; n = 12) and patients with renal hypercalciuria (RH; n = 9). The patients were investigated on 3 occasions: during a random diet, after a Ca-restricted diet and during a Ca tolerance test. The following determinations were made: Ca intake, Ca tubular reabsorption (Ca TR), plasma 1,25-dihydroxyvitamin D [1,25(OH)2D] and parathyroid hormone (PTH) levels, natriuresis and urinary protein-bound Gla. The latter was measured as a marker of urinary nephrocalcin excretion. Ca TR was decreased in hypercalciuric patients (HC). AH but not RH patients normalized their Ca TR during fasting. Plasma PTH and 1,25(OH)2D levels were similar in all the groups on the 3 occasions. Natriuresis was elevated in RH during the fasting period (p < 0.02 vs. AH). Compared with NC, protein-bound Gla urinary excretion rates (UER) were enhanced in AH after the Ca-restricted period (p < 0.02) and in RH during fasting (p < 0.02). In AH, a strong positive correlation was found between Ca TR and protein-bound Gla UER (r = 0.79, p = 0.002) following a Ca-restricted diet. In the HC group as a whole, fasting protein-bound Gla UER were correlated to plasma 1,25(OH)2D levels (r = 0.68, p < 0.001). In conclusion, the results suggest that PTH directly or indirectly through 1,25(OH)2D increases nephrocalcin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)Mineral and Electrolyte Metabolism 01/1993; 19(6):377-84.
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ABSTRACT: Like other hepatotropic viruses, hepatitis C virus (HCV) shares the property of inducing hepatocellular damage, possibly through induction of immune mechanisms that lead to hepatocellular necrosis. After infection of hepatocytes, and possibly other cells, humoral and cellular responses occur aimed at prevention of virus dissemination and elimination of infected cells. The early activated mechanisms include production of nonspecific and specific antibodies that represent the first-line of defense against invading foreign pathogens. As a consequence, circulating immune complexes are promptly formed, and antigen uptake and processing by specialized cells are enhanced. A major fraction of circulating immunoglobulins (Igs) are part of the spectrum of the so-called natural antibodies, which include anti-idiotypic antibodies and molecules with rheumatoid factor (RF) activity. They mainly belong to the IgM class, are polyclonal, and have no intrinsic pathogenetic potential. In 20-30% of HCV-infected patients, RFs share characteristics of high affinity molecules, are monoclonal in nature, and result in the production of cold-precipitating immune complexes and mixed cryoglobulinemia. It has been shown that anti-idiotypic antibodies and polyclonal and monoclonal RF molecules have the same cross-reactive idiotype, called WA, suggesting that their production is highly restricted. This strongly indicates that they arise from stimulation with the same antigen, likely HCV. It has also been speculated that B-1 (CD5+) and B-2 (CD5-) B-cell subsets, which use a limited number of VH germline genes, underlie the production of low-affinity polyclonal and high-affinity monoclonal antibodies, respectively. The persistent production of monoclonal RF molecules implies the existence of a further mechanism capable of restricting the reactivity and reflects a distinct selection of a cell population that can be maintained throughout life because they are continuously exposed to antigen pressure. Either polyclonal or monoclonal profiles of B-cell expansion are demonstrable in the liver of most HCV-infected patients. The occurrence of B-cell clonal expansion is strictly related to intrahepatic production of RF molecules, and this suggests that liver is a microenvironment, other than lymphoid tissue, in which a germinal centerlike reaction is induced. The frequent detection of oligoclonal B-cell expansion may, indeed, represent a key pathobiologic feature that sustains nonmalignant B-cell lymphoproliferation. The preferential expansion of one clone would in turn lead to a monoclonal pattern that could favor stochastic oncogenic events. It can be postulated that HCV is the stimulus not only for the apparent benign lymphoproliferative process underlying a wide spectrum of clinical features, but also for the progression to frank lymphoid malignancy in a subgroup of patients. Current data indicate a higher prevalence of overt B-cell non-Hodgkin's lymphoma in HCV-infected patients, especially in some geographic areas.Seminars in Liver Disease 02/2000; 20(2):143-57. DOI:10.1055/s-2000-9613 · 4.95 Impact Factor
Article: Hepatitis C and lymphoma[Show abstract] [Hide abstract]
ABSTRACT: Epidemiologic data presented in this review suggest the involvement of hepatitis C virus (HCV) in the patho- genesis of some histotypes of B-cell non-Hodgkin's lymphoma, in particular immunocytoma and lymphomas growing primarily in the liver and major salivary glands. Experimental data further support this hypothesis. Recent findings include demonstration that patients with hematologic malignancies can be treated safely with standard and high-dose chemotherapy even in the presence of HCV infection.Current Oncology Reports 04/2000; 2(2):172-5. DOI:10.1007/s11912-000-0090-0 · 2.89 Impact Factor
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