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  • 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.



  • 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.


  • 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 ...

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