Non-Hodgkin lymphoma (NHL) is a heterogeneous cancer encompassing several dozen distinct clinicopathologic diseases. The incidence of NHL appears to be rising independent of the aging of the population, and NHL currently ranks as the fifth most common cancer in both men and women with 71,380 new cases in 2007 and nearly 20,000 estimated deaths. Diffuse large B-cell lymphoma (DLBCL), accounting for approximately one-third of all new cases, is both the most common histologic subtype of NHL and the prototype of aggressive lymphomas.
There are several histologic variants and clinical subtypes of DLBCL that are recognized (Figure 16.1). Histologic variants include immunoblastic, centroblastic, and anaplastic morphologies, whereas distinct clinical subtypes have included primary mediastinal large B-cell lymphoma (PMBL), intravascular large B-cell lymphoma, and primary effusion lymphoma, among others. The latter two entities occur primarily in immunocompromised hosts and are associated with human herpesvirus 8. The histologic heterogeneity of DLBCL is complicated by the recent identification of molecular heterogeneity discovered by gene expression profiling, and is discussed in more detail below with an emphasis on its prognostic potential.
In general, DLBCL is a chemosensitive disease with a substantial portion of patients achieving cure with frontline chemoimmunotherapy. Unfortunately, many patients continue to relapse and are in need of further treatment. Patients with chemosensitive disease at relapse can achieve long-term disease control with autologous stem cell transplant, but others will succumb to DLBCL. Patients with refractory disease, those who relapse following transplant, and those who are not candidates for transplantation have no true curative options and most will ultimately die of lymphoma.