DETECTION OF IDENTICAL HODGKIN-REED STERNBERG CELL-SPECIFIC IMMUNOGLOBULIN GENE REARRANGEMENTS IN A PATIENT WITH HODGKINS-DISEASE OF MIXED CELLULARITY SUBTYPE AT PRIMARY DIAGNOSIS AND IN RELAPSE 2 AND A HALF YEARS LATER

Background: The malignant nature of Hodgkin-Reed Sternberg (H-RS) cell s has been questioned due to their scarcity in lymphoma tissues. Recen tly, using micromanipulation of H-RS cells and single cell PCR evidenc e was obtained that H-RS cells represent a clonal B-cell population. I n these studies H-RS cells were isolated from each one lymph node for a given case. In classical Hodgkin's disease (HD) it thus could not be ruled out that H-RS cell clonality reflected a locally restricted clo nal proliferation. We analysed biopsy specimens from a patient sufferi ng from HD for the presence of clonally related H-RS cells at primary diagnosis and during relapse of the disease. Materials and methods. In 1994 the H-RS cell line L1236 was generated from the peripheral blood of a patient suffering from a disseminating relapse of HD of mixed ce llularity subtype. The patient had relapsed despite intensive treatmen t including high dose chemotherapy and autologous bone marrow transpla ntation. The clonal identity of this cell line with H-RS cells in situ was proven by amplifying identical Ig gene rearrangements of the: cel l line as well as of single H-RS cells picked from the patients bone m arrow. Primers covering the CDR3 region were chosen from the H-RS cell specific VHI gene rearrangement to detect H-RS cells of the identical clone by amplifying the rearranged VHI genes in tissue samples obtain ed during disseminating relapsing disease and at primary diagnosis of HD in 1991. Results. The H-RS cell specific DNA sequence was detected in all affected tissues analysed including the cervical lymph node whi ch has been exstirpated at primary diagnosis. Conclusion: This finding indicates the existence of a clonal H-RS cell population during the f irst manifestation of HD and persistence and dissemination of this clo ne despite aggressive treatment. Thus, in the described case the malig nant nature of H-RS cells defined by dissemination and recurrence of t he identical H-RS cell clone in relapsing disease is proven.