CLONAL RELATIONSHIP BETWEEN LYMPHOCYTIC PREDOMINANCE HODGKINS-DISEASEAND CONCURRENT OR SUBSEQUENT LARGE-CELL LYMPHOMA OF B-LINEAGE

The occurrence of a large-cell lymphoma (LCL) concurrent with or subse quent to lymphocytic predominance Hodgkin's disease (LPHD) is well doc umented. Given the well-characterized B-cell nature of the Reed-Sternb erg cell variants in LPHD, there may be a clonal relationship between the LPHD and the associated B-cell LCL. In this study, we adapted a hi ghly sensitive, clonospecific assay to test whether the clone comprisi ng the LCL exists in the corresponding LPHD tumor. Nine cases meeting the histologic criteria of nodular LPHD and B-cell LCL were identified , reviewed, and studied. Initially, clonality of both lesions was asse ssed using consensus primers to conserved regions in the IgH variable (framework III) and joining region genes in a polymerase chain reactio n (PCR) assay. The PCR assay detected a clonal B-cell population in fi ve of the LCLs, whereas analysis of eight cases of LPHD did not detect a dominant clone, Clonal products from the LCL were then sequenced, a nd clonospecific oligonucleotides were designed from the unique nucleo tide sequence encoding the complementarity-determining region-ill. The se were then used as primers and/or probes in sensitive PCR-based assa ys on the corresponding LPHD tumors. In two cases, the clonospecific a ssay showed that the LPHD and LCL shared a common clone that was furth er confirmed by sequence analysis. This finding provides genotypic evi dence that, at least in some cases, the LCL represents a clonal progre ssion of LPHD. (C) 1995 by The American Society of Hematology.