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Pathobiology of diffuse large B cell lymphoma and primary mediastinal large B cell lymphoma

Jennifer R Brown, MD, PhD
Arnold S Freedman, MD
Jon C Aster, MD
Section Editor
Andrew Lister, MD, FRCP, FRCPath, FRCR
Deputy Editor
Alan G Rosmarin, MD


Diffuse large B cell lymphoma (DLBCL) is the most common histologic subtype of non-Hodgkin lymphoma (NHL), accounting for approximately 25 percent of adult NHL cases. (See "Classification of the hematopoietic neoplasms".)

The molecular pathogenesis of DLBCL is a complex, multistep process that ultimately results in the transformation and expansion of a malignant clone of germinal or post-germinal B cell origin. While some steps in this pathway have been elucidated, many remain unknown. The best-characterized oncogenic events are acquired genetic lesions (eg, rearrangements of BCL-6, BCL-2, and MYC), many of which are also seen in other NHL variants. This may reflect in part the not uncommon evolution of low-grade lymphoma into DLBCL. (See "Epidemiology, clinical manifestations, pathologic features, and diagnosis of diffuse large B cell lymphoma" and "Histologic transformation of follicular lymphoma" and "Pathobiology and treatment of Richter's transformation in chronic lymphocytic leukemia/small lymphocytic lymphoma".)

The following sections will describe genetic changes, aberrant gene and protein expression, and other alterations that are thought to play a role in the development of DLBCL. It is increasingly appreciated that the diagnostic category of "DLBCL" is heterogeneous in terms of morphology, genetics, and biologic behavior. The 2016 World Health Organization classification of lymphoid neoplasms recommends that immunohistochemistry and/or gene expression profiling be used to subclassify “typical” DLBCL into tumors of germinal center and non-germinal center origin, in recognition that these two classes of tumors have different prognoses with current therapies [1]. Most of the non-germinal center tumors fall into a specific category, termed the activated B cell (ABC) type, so named based on a resemblance in terms of gene expression to normal activated B cells, whereas others into an unclassifiable category. In addition, a number of clinicopathologic entities are recognized that are sufficiently distinct to be considered separate diagnostic and/or therapeutic categories:

T cell rich large B cell lymphoma. (See "Epidemiology, clinical manifestations, pathologic features, and diagnosis of diffuse large B cell lymphoma" and "Initial treatment of advanced stage diffuse large B cell lymphoma".)

Primary diffuse large B cell lymphoma of the mediastinum, also called primary mediastinal large B cell lymphoma. (See "Primary mediastinal large B cell lymphoma".)


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Literature review current through: Sep 2016. | This topic last updated: Apr 26, 2016.
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