ABSTRACT
Introduction 513 Definition 513 Epidemiology 514 Ontogeny 515 Pathology 515 Morphologic characteristics 515 Follicular lymphoma variants 517 Immunophenotype 519 Cytogenetic findings 519 Molecular genetics findings 520 Gene expression profiling 520
Transformation 521 Prognostic parameters 523 Clinical indices 523 Biologic indices 523 Pathogenesis 526 Genetic model 526 Immunologic model 527 Unifying model of pathogenesis 528 Key points 529 References 529
Follicular lymphoma (FL) represents the second most common subtype (22 percent) of non-Hodgkin lymphoma (NHL) after diffuse large B cell lymphoma (DLBCL), based on a large international NHL validation study.1 In North America, FL represents the most common histologic subtype, accounting for 32 percent of all NHLs.2 FL is imminently treatable, but most patients present with advanced stage disease and cannot be cured by conventional therapy. Follicular lymphoma is characterized by marked clinical heterogeneity, with median survivals in the range of 8-10 years, but with a wide range of outcomes. Some patients will survive in excess of 25 years, while 15-20 percent will die of transformed/aggressive FL within the first 3 years following diagnosis. Thus, the prevalence of FL is significant. The frequency of transformation is variably reported and generally portends a poor prognosis.3-11 Several recent single institution studies suggest that transformation occurs at a steady-state of approximately 3 percent per year and may possibly plateau at 15-17 years, suggesting that only half of the patients are at risk.11
