WITH this section we step gingerly into the territory of lymphomas
The large cells may be cleaved or round to oval. The most characteristic cell, called a "centroblast", has a large, open nucleus with several moderately prominent nucleoli that apply themselves to the nuclear membrane. About one-third of B-cell diffuse large cell lymphomas fail to produce surface immunoglobulin. Fortunately for the diagnostician, these are overt malignancies, so proving clonality is an academic issue.
As aggressive malignancies with a tendency to metastasize, the majority eventually demonstrate some extranodal component, including the gastrointestinal tract, testes, thyroid, skin, breast, central nervous system or bone. Although generally extra-nodal involvement is more common than in follicular lymphomas, the marrow is involved only about 10% of the time.
A majority of DLBCLs show expression of the bcl-6 protein, with some cases demonstrating a rearrangment of the BCL6 gene. About 20% of the cases have good evidence for a follicular center cell origin in the form of a t(14;18), BCL-2 rearrangement. Another soft indication of a follicular center cell origin (and perhaps transformation from a folliclar lymphoma) is the presence of small-cleaved cells interspersed among the large cells (images).
The WHO classification of DLBCLs takes note of several morphological variants:
The immunoblastic type includes many cases with very atypical cells. The prototypical immunoblast (image) is a large cell with reddish-blue ("amphophilic") cytoplasm and a large, oval, vesicular nucleus with a single, prominent, cherry-colored, central nucleolus. The patients' median age is 52 with a range from 10-81 years of age. One-half have extranodal disease including marrow involvement in 12%. They account for only 8% of all non-Hodgkin's lymphomas but a much higher proportion of AIDS-related lymphomas. Another clinical association is auto-immune disease.
Like diffuse large cell lymphomas, immunoblastic lymphomas are surface immunoglobulin negative one-third of the time. Their cytoplasm may, however, contain readily detectable amounts of immunoglobulin. Some studies, using the update Kiel Classification's definition of immunoblastic lymphoma (>90% immunoblasts), show a worse prognosis for this type.