Hodgkin/Reed-Sternberg cells and Hodgkin's disease in patients with B-cellchronic lymphocytic leukaemia: an immunohistological, molecular and clinical study of four cases suggesting a heterogeneous pathogenetic background

We report the immunohistological, molecular and clinical findings in four p atients affected by B-cell chronic lymphocytic leukaemia (CLL) who develope d "Richter's syndrome with Hodgkin's disease (HD) features" or "CLL with Ho dgkin's transformation", all characterised by the presence of typical Hodgk in / Reed-Sternberg (H/RS) cells in lymph node biopsies. In three cases the nodal involvement by CLL was demonstrated both by the presence of a predom inant background of CD5/CD19/CD23+ small lymphocytes and an IgH monoclonal rearrangement revealed by PCR analysis. Conversely, in the remaining case t here was neither immunohistological nor molecular evidence of lymph node in volvement by CLL, In all four cases H/RS cells were Epstein-Barr virus (EBV ) latent membrane protein (LMP-1) positive. These findings suggest that the presence of H/RS cells in the first three patients, who had CLL/HD nodal i nvolvement, might be related to transformation or clonal evolution of CLL c ells in H/RS cells, which is in keeping with use of the term "CLL with Hodg kin's transformation". In the fourth case a de novo HD may be postulated, r epresenting a second malignancy presumably not clonally related to CLL. In all cases a key pathogenetic role of EBV is suggested by the expression of LMP-1 in H/RS cells. Our findings indicate that the presence of typical H/R S cells in lymph node biopsies in CLL patients may reflect a heterogeneous pathogenetic background. The different clinico-pathologic settings should b e taken into consideration because of their possible implications for patie nts' treatment and prognosis.