In the Revised European American
Lymphoma (REAL) classification, several subtypes of
high-grade lymphomas were combined in the entity
diffuse large cell lymphoma (DLL). In the present study, a total of 19 cases of DLL (10 cases of centroblastic
lymphoma, 5 cases of mediastinal
B cell lymphoma, 2 cases of immunoblastic
lymphoma, 1 case of T cell-rich B
lymphoma and one case of large cell anaplastic
lymphoma) were analyzed for somatically mutated
immunoglobulin V region genes. Somatic mutations are acquired in the course of the germinal center (GC) reaction and are thus found in GC B cells and their descendants, i.e. memory B cells. The V gene sequences revealed that the
tumor cells of all five subtypes of DLL harbored mutated V region genes and are thus derived from
antigen-experienced (post) GC B cells. This indicates that from the point of view of the stage of development of the
tumor precursor, the combination of those five subtypes to one entity, i.e. DLL, seems reasonable. In some cases, an unusually high frequency of somatic mutations was detected. This may indicate that DLL are derived from GC B cells, which, due to transforming events, stayed in the GC for prolonged periods of time, thereby accumulating a high load of somatic mutation. An analysis of the mutation pattern suggests that the
tumor clone or its precursor were selected for antibody expression while acquiring somatic mutations. The latter observation discriminates DLL from classical
Hodgkin's disease, where we recently also observed a high load of somatic mutation within rearranged V region genes, but a frequent occurrence of crippling mutations.