Detection of occult low-grade B-cell non-Hodgkin's lymphoma in patients with chronic hepatitis C infection and mixed cryoglobulinemia

Hepatitis C virus (HCV) is both hepatotropic and lymphotropic and has been shown to be associated with the benign lymphoproliferative disorder, mixed cryoglobulinemia (MC). Preliminary studies suggest that there may be an ass ociation between chronic hepatitis C, MC, and non-Hodgkin's lymphoma (NHL). The aim of this study was to determine whether patients with chronic HCV a nd MC have occult bone marrow NHL. Sixteen patients with chronic HCV and cl inically active MC underwent bone marrow biopsy and aspiration. Flow cytome try was performed looking for abnormal B-cell lineage. Molecular genetic st udies were performed to identify B-cell monoclonality, Nine of 16 patients (56%) had abnormal marrow morphology, 7 (44%) were interpreted as suspiciou s for lymphoma, and 2 (13%) as consistent with lymphoma. Flow cytometry on 13 patients identified 5 (39%) with increased B-cell populations. Molecular analysis on 13 patients identified 3 (23%) with monoclonal proliferation o f the B-cell lineage. All 13 patients tested for Epstein-Barr virus were ne gative by polymerase chain reaction (PCR). Four of 16 patients (25%) had ma rrow morphology and evidence of a monoclonal B-cell population by flow cyto metry and/or molecular studies, consistent with B-cell NHL. These findings confirm the presence of lymphoproliferative disorders in patients with chro nic HCV and MC, Some of these disorders meet the morphological and molecula r criteria for the diagnosis of malignant lymphoma.