The diffuse aggressive large B-cell lymphomas are a heterogeneous group of B-cell malignancies. Although many are readily recognized due to characteristic clinical and pathologic features, several problematic areas still exist in diagnosis of these lymphomas due to a variety of reasons that include imprecise or difficult-to-apply diagnostic criteria, gaps in our understanding of lymphoma biology, and limitations in technologies available in the clinical laboratory compared to the research laboratory. This may result in some degree of confusion in the pathology report, particularly if the issues are not clearly explained, leading to frustration or misinterpretation on the part of the reader. In this review, I will discuss the pathologic features of a subset of the WHO 2008 classification diffuse aggressive large B-cell lymphomas, focusing on areas in which difficulties exist in diagnosis and/or biomarker marker assessment. A deeper understanding of the issues and areas of uncertainty due to limitations in our knowledge about the biology of these diseases should lead to better communication between pathologists and clinicians.
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