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

Abstract

We report the immunohistological, molecular and clinical findings in four patients affected by B-cell chronic lymphocytic leukaemia (CLL) who developed "Richter's syndrome with Hodgkin's disease (HD) features" or "CLL with Hodgkin's transformation", all characterised by the presence of typical Hodgkin/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 predominant background of CD5/CD19/CD23+ small lymphocytes and an IgH monoclonal rearrangement revealed by PCR analysis. Conversely, in the remaining case there was neither immunohistological nor molecular evidence of lymph node involvement 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 involvement, might be related to transformation or clonal evolution of CLL cells in H/RS cells, which is in keeping with use of the term "CLL with Hodgkin's transformation". In the fourth case a de novo HD may be postulated, representing 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/RS cells in lymph node biopsies in CLL patients may reflect a heterogeneous pathogenetic background. The different clinico-pathologic settings should be taken into consideration because of their possible implications for patients' treatment and prognosis.

Systemic eosinophilia with skin and pulmonary infiltrates in a patient with chronic lymphocytic leukemia: A case report

“…[6] In contrast, CLL with HvRT (type 1 and type 2) predominantly carry mutated IGHV genes, independent of a clonal relationship. [6,30,35] Thus, our case represents an unusual HvRT developing in the background of IGHV-unmutated CLL, which fits to the lack of clonal relationship of both components suggested by the results of fragment length comparison analysis of IGHV PCR products.…”

“…Molecular analyses provide evidence in many cases for separate clonal origins of both tumors supporting development of HL as a distinct second malignancy. [20,26,30,31] While different pathogenetic mechanisms are discussed in both types of transformation, only type 2 is considered as true Hodgkin transformation irrespective of clonal relationship with the underlying CLL cells. [6,20,[29][30][31][32] In our patient, morphological and immunohistochemical findings at autopsy showed classical HL, namely type 2 transformation.…”

Latent Membrane Protein 2A, a Viral B Cell Receptor Homologue, Induces CD5+ B-1 Cell Development

“…However, it is not known whether the H-RS cells arise from transformation of the underlying CLL cells or from a different pathological process. Nevertheless, in a few of these cases, NHL or H-RS-like cells carry similar somatic mutations when compared with CLL, demonstrating a clonal relationship of CLL with NHL (55,56) or H-RS-like cells (57)(58)(59)(60). Because our data reveal that LMP2A of EBV can skew B cells toward the development of a B-1-like lineage, it may be informative to examine whether EBV is involved in the etiology of CLL and its related diseases.…”

MDR-1 gene polymorphisms G2677T and C3435T in a case of Hodgkin’s variant of Richter’s syndrome

“…Major points of interest in CLL with Hodgkin's transformation were considered, such as the possible role of MDR-1 gene polymorphisms (14).…”