title: Splenic large B-cell lymphoma in patients with hepatitis C virus infection.
abstract: Hepatitis virus infection, especially type C (hepatitis C virus [HCV]), has been suggested to be one of the important pathogenetic factors for low- and high-grade B-cell lymphoma, including splenic marginal zone lymphoma (SMZL), in southern Europe. Here, we analyzed the incidences of HCV and hepatitis B virus (HBV) infections, and the clinicopathologic features in 29 cases of splenic diffuse large B-cell lymphoma (DLBCL), 10 SMZL, 3 splenic mantle cell lymphoma, 1 hairy cell leukemia, 13 B-chronic lymphocytic leukemia, and 12 hepatosplenic T-cell and natural killer cell lymphoma. Fifteen (51.7%) splenic DLBCL cases were HCV antibody-positive, and another 6 (20.7%) had the HBsAg. The incidence of each was significantly (P < .01) higher than those of HCV (9.3%) and HBV (1.9%) infections in 54 node-based DLBCL cases. Four examined HCV-positive DLBCL cases showed no type II cryoglobulinemia. HCV RNA was detected in fresh tumor tissues from 6 of 7 examined DLBCL cases, and HBV DNA was present in another 2, as evaluated by real-time polymerase chain reaction. Immunohistologically, tumor cells in 5 of 7 examined DLBCL cases showed intracytoplasmic reactions for HCV NS3 and E2 proteins and the viral receptor CD81. Of 6 cases, 2 showed an intranuclear reaction for the HBV surface protein. By Southern blot analysis, no rearrangement of the Bcl2 gene was detected in the tumor tissue of 7 HCV-positive DLBCL cases. For the other types of malignant lymphoma, 1 case each of SMZL (10%) and hepatosplenic T-cell and natural killer cell lymphoma (8.3%) showed HCV infection. In conclusion, persistent human hepatitis virus infections, especially HCV, may play an important role in the tumorigenesis of splenic DLBCL in Japan.
authors.affiliation: Department of Pathology, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan. m-take@fukuoka-u.ac.jp
authors.forename: Morishige
authors.initials: M
authors.lastname: Takeshita
authors.forename: Hironori
authors.initials: H
authors.lastname: Sakai
authors.forename: Seiichi
authors.initials: S
authors.lastname: Okamura
authors.forename: Yumi
authors.initials: Y
authors.lastname: Oshiro
authors.forename: Koichi
authors.initials: K
authors.lastname: Higaki
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakashima
authors.forename: Naokuni
authors.initials: N
authors.lastname: Uike
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yamamoto
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kinjo
authors.forename: Fujio
authors.initials: F
authors.lastname: Matsubara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015139:Blotting, Southern; D004279:DNA, Viral / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D019254:Genes, bcl-2 / Q000235:genetics; D016174:Hepacivirus; D006509:Hepatitis B / Q000453:epidemiology; D006515:Hepatitis B virus; D006526:Hepatitis C / Q000453:epidemiology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007938:Leukemia / Q000821:virology; D008223:Lymphoma / Q000821:virology; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000473:pathology / Q000821:virology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009858:Oncogenic Viruses; D015995:Prevalence; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013160:Splenic Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology*; D014157:Transcription Factors / Q000235:genetics; D014412:Tumor Virus Infections / Q000453:epidemiology*
chemical_list: D004279:DNA, Viral; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors