Herpes virus type 8-negative primary effusion lymphoma associated with PAX-5 gene rearrangement and hepatitis C virus

At present, there is no case report of HHV8^- primary effusion lymphoma (PEL) with t(9; 14) (pl3;q32) involving both PAX-5 and immunoglobulin heavy chain gene rearrangement, which is a rare translocation in B-cell non- Hodgkin's lymphoma, in an HIV^- patient. We examined an HIV-seronegative 63- year-old Japanese man with hepatitis C virus-associated liver cirrhosis and hepatocellular carcinoma manifesting peritoneal lymphomatous effusion without tumor mass at any body site. The lymphoma cells were examined twice by light microscopy, immunohistochemistry, three-color flow cytometry, cytogenetics, and molecular analyses. The nuclear morphology of lymphoma cells was similar to that of large noncleaved cells, although the lymphoma cell size was a little smaller that of the usual large-cell lymphoma. Immunophenotyping of lymphoma cells in the ascitic fluid revealed a mature peripheral B-cell phenotype (CD5^- CD10^- CD19⁺ CD20⁺ CD22⁺ Ig G⁺ λ⁺). Cytogenetics showed a clonal population: 45,X,-Y, der(2) t(2;6)(q31 ;p21.3), t(4;8)(q21 ;q 11.2), der(6) t(2;6)(q31;p21.3) add(6)(q15), t(9;14)(p13;q32.3) [10]/47, idem, +der(6) t(2;6), +16 [10]. Southern blot analysis revealed rearranged fragments with a probe for immunoglobulin heavy chain, some of which were a size similar to those with a PAX-5 gene probe. Polymorphism, not rearrangement, of the c-MYC gene, was also found. HHV8 and the Epstein-Barr virus were not detected by polymerase chain reaction. This case is the first report of an HHV8^- PEL with t(9;14) involving a PAX-5 gene rearrangement in an HIV-seronegative patient. This primary effusion lymphoma manifested spontaneous regression without any therapy. These findings suggest that there may be an additional subcategory of primary effusion lymphoma that is not associated with HHV8 nor c-MYC(R) but is pathogenetically associated with the PAX-5 gene or hepatitis C virus.