Origin of the Hodgkin/Reed-Sternberg Cells in Chronic Lymphocytic Leukemia With “Hodgkin's Transformation”

Abstract

A lymphoma with the characteristic features of Hodgkin's disease (HD) occasionally develops in patients with B-cell chronic lymphocytic leukemia (CLL), and has been called Richter's syndrome with HD features. In such cases, large tumor cells have the morphological and immunophenotypic features of classical Hodgkin and Reed-Sternberg (H-RS) cells. However, it is not known whether the H-RS cells arise from transformation of the underlying CLL cells or from a different pathological process. We report herein a study of the clonal relationship between the CLL cells and the H-RS cells in three cases of Richter's syndrome with HD features by using a single cell assay. We isolated single CLL cells and H-RS cells from immunostained tissue sections by micromanipulation. The immunoglobulin heavy chain gene (IgH) complementarity determining region (CDR) III of each cell was amplified by the polymerase chain reaction (PCR). The products were then compared by gel electrophoresis and nucleotide sequencing. The IgH CDRIII sequences from the H-RS cells were identical to those from the CLL cells in two cases. In one case, the clonal relationship between the two types of cells could not be determined because PCR products could not be obtained from any of the H-RS cells. This study shows that the H-RS cells and the CLL cells belong to the same clonal population in some cases of Richter's syndrome with HD features. Furthermore, our findings indicate that mature B cells can undergo transformation to cells with the features of H-RS cells, in association with a cellular background typical of HD. This study also supports recent findings suggesting that the H-RS cells in classical HD are derived from transformed B cells.

Partially successful treatment of a patient with chronic lymphocytic leukemia and Hodgkin's disease: Case report and literature review

“…There were a total of 88 case reports [1, included in the study (males, 64; females, 21; unknown sex, 2). The majority of classifiable patients belonged to either group 1 or group 2; only 6 patients fit the criteria for group 3, including our case.…”

“…Studies on composite lymphomas involving HD have contributed significantly to our present understanding of the origin of RS cells. Ohno et al [1] studied immunoglobulin heavy-chain gene sequences from RS cells and found then to be identical to those of CLL in two cases of CLL with HD features. A recent study of clonal relationships in CLL and Hodgkin's disease [30] also supports the hypothesis that RSL cells in CLL are clonally related to CLL cells.…”

“…Richter's syndrome, the transformation of chronic lymphocytic leukemia (CLL) into a high-grade lymphoma, occurs in 3-10% of CLL patients. Usually, the high-grade component is a large-cell anaplastic non-Hodgkin's lymphoma and is considered to represent a blastic transformation of CLL cells [1]. Only rarely, CLL transforms into morphologically typical Hodgkin's disease (HD).…”

The Reed–Sternberg cell in classical Hodgkin's disease

“…We assessed the clonal relationship between the CLL and the HD-like lesion that developed in the same patient, by single cell analysis. 70 In two out of three cases, the CLL cells and H/RS cells had identical IgH rearrangements as demonstrated by identical sequences in the complementary determining region (CDR) III. Braü ninger and colleagues 71 studied two cases of classical HD, one occurring concurrently with a follicular lymphoma and the other one after a T-cell rich B-cell lymphoma.…”

Richter syndrome in B‐cell chronic lymphocytic leukemia

“…73 Third, Ohno et al examined the clonal relationship by single cell PCR of IgH gene of HRS cells in HL as RS and B-CLL cells, and demonstrated the same clonal origin of HRS cells and B-CLL cells. 76 Cases of HL unrelated to B-CLL have been reported. 77 Most HL occurring in patients with B-CLL are regarded as clonal evolution of B-CLL, whereas a small number of cases are de novo HL, representing a second malignancy presumably not clonally related to CLL.…”