Essential differences in oncogene involvement between primary nodal and extranodal large cell lymphoma

Large cell lymphomas (LCLs) are heterogeneous in morphology, clinical presentation, and behavior. We studied 52 de novo LCLs of B-cell type for rearrangements of the bcl-2 and c-myc oncogenes by Southern blot analysis and related these data to the primary site of presentation, stage, and cytomorphology. Thirteen tumors had comigrating rearrangements of JH and bcl-2, indicative of a t(14;18). Far more primary nodal lymphomas than extranodal lymphomas carried a t(14;18) (40% v less than 5%). Additionally, almost all lymphomas with a t(14;18) versus 41% of the tumors without a bcl-2 rearrangement presented with lymphadenopathy. c-myc rearrangements were seen in 35% of the extranodal lymphomas and 5% of the nodal lymphomas. No differences were observed in bone marrow involvement and staging according to Ann Arbor. bcl-2 rearrangements were found in 50% of the LCLs with cleaved nuclei, whereas c-myc rearrangements were relatively frequent (25%) in the noncleaved subtype. Our data support the hypothesis that primary nodal and extranodal lymphomas have a different genetic origin.