Immunoglobulin gene rearrangement analysis in composite Hodgkin disease and large B-cell lymphoma: Evidence for receptor revision of immunoglobulin heavy chain variable region genes in Hodgkin-Reed-Sternberg cells?

Immunoglobulin heavy chain gene (IgH) rearrangement was studied in a patient showing the occurrence of classical Hodgkin disease and large B-cell lymphoma (LBCL) in the same lymph node. The V_HD_HJ_H region was amplified by polymerase chain reaction, the template being the DNA extracted from single Hodgkin and Reed-Sternberg and LBCL cells, micro dissected on hematoxylin-eosin-stained sections by laser capture. A repeated V_H4D_H3J_H4 segment was found in Reed Sternberg cells, whereas a repeated V_H3D_H3J_H4 segment was observed in LBCL cells. Rearranged V_H genes carried somatic mutations in both populations, indicating a common germinal center cell origin. The IgH rearrangement found in clonally related Reed-Sternberg cells differed from the one of LBCL cells in the V_H region but showed the same J_H and D_H segments with no variation from the respective germline sequence. The D_H-J_H junction is the first immunoglobulin gene segment rearranged in precursor B cells. Because the possibility of secondary Ig gene rearrangement in peripheral lymphoid organs has recently been reported, in the patient described here Reed Sternberg and LBCL cells might originate from a common precursor in which secondary V_H replacement took place during the germinal center reaction, giving rise to two different clonally related lymphomas.