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Although Hodgkin's disease (HD) has been a subject of much investigation, fundamental questions remain unanswered regarding its lineage and clonality. The authors used a polymerase chain reaction (PCR) technique to investigate whether clonal Variable-Diversity-Joining recombination of the immunoglobulin heavy (IgH) chain gene, a phenomenon that characterizes clonal B-cell proliferations, exists in nodular sclerosing (NSHD) and mixed cellularity (MCHD) Hodgkin's disease (so-called "classical" Hodgkin's disease). The isolation of DNA from paraffin-embedded tissue sections allowed for direct correlation of PCR results with the cell populations that were analyzed. Thirty-two cases were studied. These included 12 cases in which the Reed-Sternberg (RS) cells expressed the B-cell antigen, CD20, and 10 cases that were classified as syncytial variant of NSHD (3 CD20+, 7 B-cell antigen negative). Overall, clonal patterns of VDJ PCR products were found in 14 of 32 (44%) cases. These clonal patterns were identified in 7 of 12 (58%) cases of CD20+ classical HD and in 7 of 20 (35%) cases of B-antigen-negative classical HD. Clonal patterns were found in 3 of 10 cases of syncytial variant of NSHD, including 2 of 3 (67%) CD20+ cases and 1 of 7 (14%) B-cell antigen-negative cases. The results of this study provide support that a subset of HD represents a clonal B-cell neoplasm, and indicate that clonal IgH VDJ sequences are more frequently found in CD20+ HD.
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