Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content +++ DEFINITION ++ Diffuse large B-cell lymphomas (DLBCLs) are a heterogeneous group of aggressive lymphomas composed of sheets of large, transformed B cells that replace and efface normal lymph nodes and other affected tissues. DLBCLs can arise de novo or may transform from a low-grade lymphoma, such as small lymphocytic lymphoma or follicular lymphoma. Table 61–1 lists the variants and subtypes of DLBCL. ++Table Graphic Jump LocationTABLE 61–1DIFFUSE LARGE B-CELL LYMPHOMA: VARIANTS AND SUBTYPESView Table||Download (.pdf) TABLE 61–1 DIFFUSE LARGE B-CELL LYMPHOMA: VARIANTS AND SUBTYPES Diffuse large B-cell lymphoma, NOS Germinal center B-cell type Activated B-cell type Related mature B-cell neoplasms T-cell/histiocyte-rich large B-cell lymphoma Primary DLBCL of the CNS Primary cutaneous DLBCL, leg typea EBV-positive DLBCL, NOS EBV-positive mucocutaneous ulcer DLBCL associated with chronic inflammation Lymphomatoid granulomatosis Primary mediastinal (thymic) large B-cell lymphoma Intravascular large B-cell lymphoma ALK-positive DLBCL Plasmablastic lymphoma Primary effusion lymphoma HHV8-positive DLBCL, NOS High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements High-grade B-cell lymphoma, NOS Borderline cases B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma aThis represents provisional entities or subtypes.ALK, anaplastic lymphoma kinase; BCL, B-cell lymphoma; CNS, central nervous system; DLBCL, diffuse large B-cell lymphoma; EBV, Epstein-Barr virus; HHV, human herpes virus; NOS, not otherwise specified. +++ EPIDEMIOLOGY ++ This is the most common B-cell lymphoid neoplasm in the United States and Europe and accounts for approximately 30% of all mature B-cell lymphomas. The standardized incidence rate ranges between 4 and 7 per 100,000 per year in Western countries. Median age at diagnosis is approximately 65 years. +++ ETIOLOGY AND PATHOGENESIS ++ This molecularly heterogeneous disease is associated with multiple complex chromosomal translocations, copy number changes, recurrent mutations, and abnormalities of gene expression. DLBCL is derived from B cells that have undergone somatic mutation in the immunoglobulin (Ig) genes. BCL6 gene rearrangements may be specific for DLBCL. — Approximately 40% of cases in immunocompetent persons and approximately 20% of human immunodeficiency virus (HIV)-related cases display BCL6 rearrangements. — BCL6 protein is a repressor of transcription. — BCL6 overexpression prevents apoptosis. Approximately 30% of patients have the t(14;18) translocation involving BCL2 and the Ig heavy chain gene. — The presence of p53 mutation in combination with BCL2 suggests that the tumor is derived from a transformation of a prior follicular lymphoma. c-MYC is rearranged in approximately 10% of cases. — Rearrangements of c-MYC together with BCL2 or, less commonly, BCL6 are referred to as double-hit lymphomas (DHLs). — High-level expression of MYC and BCL2 proteins is often referred to as double-expressor lymphomas (DELs). Fluorescence in situ hybridization (FISH) studies to detect translocations of BCL2, BCL6, and c-MYC are increasingly part of standard diagnostic procedures. Aberrant somatic mutation occurs in most cases. In one large study, 98 candidate cancer genes were identified with an average of 17 genetic changes per ... Your Access profile is currently affiliated with [InstitutionA] and is in the process of switching affiliations to [InstitutionB]. Please select how you would like to proceed. Keep the current affiliation with [InstitutionA] and continue with the Access profile sign in process Switch affiliation to [InstitutionB] and continue with the Access profile sign in process Get Free Access Through Your Institution Learn how to see if your library subscribes to McGraw Hill Medical products. Subscribe: Institutional or Individual Sign In Error: Incorrect UserName or Password Username Error: Please enter User Name Password Error: Please enter Password Sign in Forgot Password? Forgot Username? Download the Access App: iOS | Android Sign in via OpenAthens Sign in via Shibboleth You already have access! Please proceed to your institution's subscription. Create a free profile for additional features.