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Keywords:

  • hepatitis C virus;
  • interferon;
  • primary splenic marginal zone lymphoma;
  • bone marrow biopsy;
  • immunohistochemistry

We read with interest the recent report by Audoin et al (2003) in which they describe the different patterns of bone marrow involvement in 58 patients with primary splenic marginal zone lymphoma. Seven different patterns of infiltrates were recognized. Immunohistochemistry demonstrated the expression of B cell-associated antigens, and a monotypic lymphoplasmacytic cell component was evident in 40% of cases with a serum M component and autoimmune disorders.

Successive biopsies carried out after splenectomy showed a progression to more extensive lesions, whereas a slight decrease in infiltrates was observed after chemotherapy. However, Audoin et al (2003) did not indicate how many of their patients, if any, was hepatitis C virus (HCV) positive. Studies in Italy, Southern California and Japan have reported a high prevalence (9–32%) of chronic HCV infection among patients with B-cell non-Hodgkin's lymphoma (Zuckerman et al, 1997). HCV infections are most frequently encountered in patients with lymphoplasmacytoid lymphoma, marginal-zone lymphomas and diffuse primary hepatosplenic large B-cell lymphomas (Rasul et al, 1999). Other epidemiological studies, however, did not find a statistically significant association between HCV and non-Hodgkin's lymphoma (Germanidis et al, 1999). The beneficial effects of interferon-alpha in HCV-positive splenic lymphoma were reported by Hermine et al (2002) in nine patients enrolled from several French Centres. In this study, seven patients obtained a complete haematological remission and HCV-RNA negative status after treatment with interferon. The two non-responders were treated with interferon plus ribavinine and obtained one complete haematological remission and one partial remission. Unfortunately in this study, examination of the bone marrow was not required for the assessment of haematological response. We selected one case each of splenic marginal zone lymphoma and HCV infection treated with interferon-alpha 2b alone (3 MU subcutaneously three times a week for 6 months) after splenectomy from our patient cohort. Bone marrow biopsy specimens showed interstitial and nodular infiltrates readily identified by immunohistochemistry with an anti-CD20 antibody (Fig 1), associated with intravascular involvement in both bone marrow biopsies. After antiviral therapy for 6 months, these two patients had a negative HCV by reverse transcriptase polymerase chain reaction, which was maintained for 9 months after treatment with interferon. Their complete blood counts returned to normal, as did the spleen size; the bone marrow biopsy showed the disappearance of infiltrates after therapy. In HCV-positive patients, an antiviral therapy may be an alternative to splenectomy, chemotherapy, or both. Epidemiological studies are warranted in larger groups of patients with splenic marginal zone lymphoma, as they may benefit from antiviral therapy.

image

Figure 1. Nodular infiltrate. The aggregates consist of CD20-positive B cells. Original magnification ×40.

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References

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  2. References
  • Audoin, J., Le Tourneau, A., Molina, T., Camilleri-Broët, S., Adida, C., Compera, E., Benattar, L., Delmer, A., Devidas, A., Rio, B. & Diebold, J. (2003) Patterns of bone marrow involvement in 58 patients presenting primary splenic marginal zone lymphoma with or without circulating villous lymphocytes. British Journal of Haematology, 122, 404412.
  • Germanidis, G., Haioun, C., Pourquier J., Gaulard, P., Pawlotsky, J.M., Dhumeaux, D. & Reyes, F. (1999) Hepatitis C virus infection in patients with overt B-cell non-Hodgkin's lymphoma in a French Center. Blood, 93, 17781779.
  • Hermine O., Lefrère, F., Bronowicki J.P., Mariette, X., Jondeau, K., Eclache-Sandreau, V., Delmas, B., Valensi, F., Cacoub, P., Brechot, C., Varet, B. & Troussard, X. (2002) Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection. The New England Journal of Medicine, 347, 8994.
  • Rasul, I., Shepherd, F.A., Kamel-Ried, S., Krajden, M., Pantalony, D. & Heathcote, E.J. (1999) Detection of occult low-grade B-Cell non Hodgkin's lymphoma in patient with chronic hepatitis C virus infection and mixed cryoglobulinemia. Hepatology, 29, 543547.
  • Zuckerman, E., Zuckerman, T., Levine, A.M, Douer, D., Gutekunst, K., Mizokami, M., Qian, D.G., Velankar, M., Nathwani, B.N. & Fong, T.L. (1997) Hepatitis C virus infection in patients with B-cell non-Hodgkin lymphoma. Annals of Internal Medicine, 127, 423428.