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(H)D(H)J(H) region was amplified by polymerase chain reaction, the template being the DNA extracted from single Hodgkin and Reed-Sternberg and LBCL cells, microdissected on hematoxylin-eosin-stained sections by laser capture. A repeated V(H4)D(H3)J(H4) segment was found in Reed-Sternberg cells, whereas a repeated V(H3)D(H3)J(H4) segment was observed in LBCL cells. Rearranged VIA 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, replacement took place during the germinal center reaction, giving rise to two different clonally related lymphomas.