Clinico-pathological characterization of hepatitis C virus-related B-cell non-Hodgkin’s lymphomas without symptomatic cryoglobulinemia

Abstract A pathogenetic role of the hepatitis C virus (HCV) has been hypothesized for a subset of B-cell non-Hodgkin's lymphomas (NHLs). However, the preliminary characterization of B-cell NHLs in HCV-infected individuals has been poorly addressed. In the present study, we report detailed information on 35 consecutive patients with overt B-cell NHL of recent onset and HCV infection; all patients referred to a single oncological center in Northeast Italy. Histopathologic evaluation was performed by a single reference hemopathologist, and the link with the two relevant autoimmune diseases predisposing to B-cell NHL and in which HCV has been implied, ie, “essential” mixed cryoglobulinemia (EMC) and Sjögren's syndrome, was investigated. Control groups included 122 consecutive HCV-negative patients with B-cell NHL and 464 consecutive histopathologic cases of B-cell NHL referred to the same center, as well as 127 consecutive patients with HCV infection and without lymphoma referred to a different center in the same geographical area. B-cell NHLs in HCV-infected patients frequently presented at onset (1) an extranodal localization with peculiar target organs of HCV infection (ie, the liver and major salivary glands) being significantly overrepresented; (2) a diffuse large cell histotype without any prior history of low-grade B-cell malignancy or bone marrow involvement; and (3) a weak association with a full-blown predisposing autoimmune disease, although serum autoimmune features were common and cryoglobulins were always present. Therefore, the HCV-related B-cell NHLs in this oncological series presented distinctive features compared with B-cell NHLs in HCV-negative patients, and they differed from bone marrow low-grade NHLs frequently diagnosed in HCV-positive patients with EMC. Such novel information may be relevant for future research aimed at clarifying the possible link between HCV infection, autoimmunity, nonmalignant B-cell lymphoproliferation, and overt B-cell malignancy.

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Characterization of Overt B-Cell Lymphomas in Patients With Hepatitis C Virus Infection

Blood ◽

10.1182/blood.v90.2.776.776_776_782 ◽

1997 ◽

Vol 90 (2) ◽

pp. 776-782 ◽

Cited By ~ 2

Author(s):

Salvatore De Vita ◽

Cosimo Sacco ◽

Domenico Sansonno ◽

Annunziata Gloghini ◽

Franco Dammacco ◽

...

Keyword(s):

Bone Marrow ◽

Hepatitis C Virus ◽

Hepatitis C ◽

B Cell ◽

Hcv Infection ◽

Low Grade ◽

B Cell Malignancy ◽

Hodgkin's Lymphomas ◽

Cell Malignancy

A pathogenetic role of the hepatitis C virus (HCV) has been hypothesized for a subset of B-cell non-Hodgkin's lymphomas (NHLs). However, the preliminary characterization of B-cell NHLs in HCV-infected individuals has been poorly addressed. In the present study, we report detailed information on 35 consecutive patients with overt B-cell NHL of recent onset and HCV infection; all patients referred to a single oncological center in Northeast Italy. Histopathologic evaluation was performed by a single reference hemopathologist, and the link with the two relevant autoimmune diseases predisposing to B-cell NHL and in which HCV has been implied, ie, “essential” mixed cryoglobulinemia (EMC) and Sjögren's syndrome, was investigated. Control groups included 122 consecutive HCV-negative patients with B-cell NHL and 464 consecutive histopathologic cases of B-cell NHL referred to the same center, as well as 127 consecutive patients with HCV infection and without lymphoma referred to a different center in the same geographical area. B-cell NHLs in HCV-infected patients frequently presented at onset (1) an extranodal localization with peculiar target organs of HCV infection (ie, the liver and major salivary glands) being significantly overrepresented; (2) a diffuse large cell histotype without any prior history of low-grade B-cell malignancy or bone marrow involvement; and (3) a weak association with a full-blown predisposing autoimmune disease, although serum autoimmune features were common and cryoglobulins were always present. Therefore, the HCV-related B-cell NHLs in this oncological series presented distinctive features compared with B-cell NHLs in HCV-negative patients, and they differed from bone marrow low-grade NHLs frequently diagnosed in HCV-positive patients with EMC. Such novel information may be relevant for future research aimed at clarifying the possible link between HCV infection, autoimmunity, nonmalignant B-cell lymphoproliferation, and overt B-cell malignancy.

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Mapping and characterization of B cell linear epitopes in the conservative regions of hepatitis C virus envelope glycoproteins

Journal of Viral Hepatitis ◽

10.1046/j.1365-2893.2002.00358.x ◽

2002 ◽

Vol 9 (3) ◽

pp. 174-182 ◽

Cited By ~ 13

Author(s):

L. V. Olenina ◽

L. I. Nikolaeva ◽

B. N. Sobolev ◽

N. P. Blokhina ◽

A. I. Archakov ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

B Cell ◽

Envelope Glycoproteins ◽

Virus Envelope ◽

Linear Epitopes

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Prevalence of hepatitis C virus infection in patients with lymphoproliferative disorders

Blood ◽

10.1182/blood.v87.10.4296.bloodjournal87104296 ◽

1996 ◽

Vol 87 (10) ◽

pp. 4296-4301 ◽

Cited By ~ 237

Author(s):

F Silvestri ◽

C Pipan ◽

G Barillari ◽

F Zaja ◽

R Fanin ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

B Cell ◽

Close Association ◽

Mixed Cryoglobulinemia ◽

Lymphoproliferative Disorders ◽

Hcv Infection ◽

Hcv Rna ◽

Hodgkin's Lymphomas ◽

Hcv Genotyping

It has been recently hypothesized that the hepatitis C virus (HCV) might be involved in the pathogenesis of malignant B-cell non-Hodgkin's lymphomas (NHL). On the basis of this observation we sought to determine the prevalence of HCV infection in the patients affected by B- cell NHL and extended our analysis to all the patients affected by lymphoproliferation disorders seen at our institution in the last 30 months. Five hundred and thirty-seven unselected, consecutive patients were studied. HCV infection was investigated through detection of anti- HCV antibodies and HCV-RNA. HCV genotyping was performed on HCV-RNA positive specimens. The risk of being infected by HCV was compared with that of the general population of our area. Among all lymphoproliferative disorders, the prevalence and the relative risk (RR) of being infected by HCV were increased only among B-cell NHL (9%; RR 3.24; p < .0001). Among these, a strong prevalence of HCV was found only in the subgroup of immunocytomas (30%; RR 10.27; P < .0001), while other histotypes were associated with it only occasionally. Because HCV- positive lymphomas clinically behave as essential mixed cryoglobulinemia (EMC), the close association between HCV infection and EMC is confirmed, and evidence is provided that the pathological substrate of EMC corresponds to the immunocytoma. HCV genomic sequences were found in 84% of patients analyzed. Viral genotypes were those more frequent in our area.

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Characterization of Antibodies Directed against the Immunoglobulin Light κ Chain Variable Chain Region (VK) of Hepatitis C Virus-Related Type-II Mixed Cryoglobulinemia and B-Cell Proliferations

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.2009.04677.x ◽

2009 ◽

Vol 1173 (1) ◽

pp. 152-160 ◽

Cited By ~ 10

Author(s):

Valli De Re ◽

Maria Paola Simula ◽

Alessandro Pavan ◽

Marica Garziera ◽

Dolores Marin ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

B Cell ◽

Mixed Cryoglobulinemia ◽

Type Ii ◽

Cell Proliferations

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Somatic Hypermutation, Clonal Diversity, and Preferential Expression of the VH 51p1/VL kv325 Immunoglobulin Gene Combination in Hepatitis C Virus–Associated Immunocytomas

Blood ◽

10.1182/blood.v91.7.2433 ◽

1998 ◽

Vol 91 (7) ◽

pp. 2433-2442 ◽

Cited By ~ 186

Author(s):

Martin Ivanovski ◽

Federico Silvestri ◽

Gabriele Pozzato ◽

Shubha Anand ◽

Cesare Mazzaro ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

B Cell ◽

Cell Population ◽

Clonal Evolution ◽

Gene Repertoire ◽

Immunoglobulin Gene ◽

Region Gene ◽

Antigen Stimulation ◽

Hodgkin's Lymphomas

Abstract A high prevalence of chronic hepatitis C virus (HCV) infection has recently been shown in a subset of B-cell non-Hodgkin's lymphomas, most of which belong to the lymphoplasmacytoid lymphoma/immunocytoma subtype and are characterized by the production of a monoclonal IgM cryoglobulin with rheumatoid factor activity. To better define the stage of differentiation of the malignant B cell and to investigate the role of chronic antigen stimulation in the pathogenesis of the HCV-associated immunocytomas, we analyzed the variable (V) region gene repertoire in 16 cases with this type of tumor. The lymphoma-derived V gene sequences were successfully determined in 8 cases; 5 of them expressed the 51p1 VH gene in combination with the kv325 VL gene. Moreover, a monoclonal 51p1-expressing B-cell population was detected in 4 of the remaining immunocytomas by an allele-specific Ig gene fingerprinting assay, indicating that HCV-associated immunocytomas represent clonal proliferations of a highly selected B-cell population. Somatic mutations and intraclonal diversity were observed in all of the lymphoma V genes, and clonally related IgM and IgG VH transcripts indicative of isotype switching were present in one case. These findings are consistent with an antigen-driven process and support a role for chronic antigen stimulation in the growth and clonal evolution of HCV-associated immunocytomas.

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