Pan-B antigens test positive. The immunophenotypic profile is CD10+, CD5-, sIg+ and the cell of origin is a germinal centre B-cell that has encountered the antigen.

This lymphoma accounts for 30-40% of all lymphomas occurring in the adult population in western countries. Its peak incidence is in the fifth and sixth decade.

The lymphoma is composed of a mixture of centrocytes and centroblasts with a follicular and diffuse pattern. Lymphoma grading by the number of large cells/centroblasts is recommended: three grades are recognized with incresing number of centroblasts.

Depending on age and stage at presentation it may vary from a "watch and wait" policy in initial stages to multiagent chemotherapy in advanced stages. Immunotherapy using chimeric anti-CD20 monoclonal antibody has an important role in combination with chemotherapy. Radioimmunotherapy has an important role in relapsed or refractory patients.

The majority of patients cannot be cured by chemotherapy and eventually relapse. Histologic switch into high grade lymphoma may occur. A positive impact on long term disease free survival and overall survival is likely to derive from the introduction of monoclonal antibodies in association with multiagent chemotherapy.

Approximately 60% of the patients presenting with limited disease are alive at 10 years. Patients in stages III and IV were reported to have a median survival in the 8-12 years range

Seventy-80% of the cases carry the t(14;18)(q32;q21) as the primary chromosome anomaly. Rare variant translocation t(2;18)(p11;q21) and t(18;22)(q21;q11) were described. Approximately 15% of the cases show a 3q27 break, half of which include the t(3;14)(q27;q32) and the variant translocations t(3;22)(q27;q11) and t(2;3)(p11;q27)

The incidence of 6q21 deletion and 17p13/p53 deletion (see below) by interphase FISH analysis may be around 60% and 20%, respectively

No fusion protein. The t(14;18) brings about the juxtaposition of BCL-2 with the Ig heavy chain joining segment, with consequent marked overexpression of the BCL2 protein product. The majority of breakpoints on 18q22 fall into two regions: the major breakpoint region (60-70% of the cases) and the minor cluster region (20-25% of the cases).
In those cases with 3q27/BCL6 involvement the breakpoints on 3q27 are usually located in a different region with respect to high grade diffuse large cell lymphoma. This region is located 245 and 285 kb 5¹ of BCL6 (alternative breakpoint cluster region)

BCL-2 overexpression prevents cell to die by apoptosis. BCL-2 forms heterodimers with BAX and the relative proportion of BCL-2 to BAX determines the functional activity of BCL-2. In vitro, BCL-2 constitutive expression has a definite role in sustaining cell growth, whereas in vivo, BCL-2 transgenes induce a pattern of polyclonal proliferation of mature B-cells.