Follicular Lymphoma Grade 3: Review and Updates

Follicular lymphoma (FL), Grade 3, is recognized as a distinct entity in the World Health Organization classification of lymphoma. It is further classified into Grade 3a and Grade 3b depending on the Bernard cell counting system and percentage of centroblasts. Grade 3 has molecular and genetic characteristics that distinguish it from other grades of FL. There is confusion and misunderstanding about the natural history and clinical course of Grade 3a and 3b because some studies indicate them as having indolent behavior and others describe more aggressive biology. The purpose of this article is to understand the concept of Grade 3 FL, especially the fundamental differences between Grade 3a and Grade 3b FL. Grade 3 FL is still an evolving subclass in FL and the practicing physician should understand the aggressive nature of Grade 3b, which typically requires timely attention, compared with Grade 3a. Grade 3a FL has more indolent characteristics but can possibly progress to Grade 3b and/or transform to diffuse large B-cell lymphoma at a future time. Nevertheless, large prospective studies are missing for an optimal evidence-based management approach for patients with Grade 3 FL at this time.