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  • Diffuse large B-cell lymphomas (DLBCLs) are a heterogeneous group of aggressive lymphomas of large, transformed B cells.

  • DLBCLs can arise de novo or may transform from a low-grade lymphoma, such as small lymphocytic lymphoma or follicular lymphoma.

  • Table 60–1 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 28% of all mature B-cell lymphomas.

  • The most common presentation is in late middle-aged and older persons.

  • Median age at diagnosis is approximately 65 years.


  • This molecularly heterogeneous disease with multiple complex chromosomal translocations and genetic abnormalities is identified by cytogenetics and gene expression profiling.

  • Disease 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 mediates the specific binding of several transcription factors to DNA.

  • 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 denotes that the tumor is derived from a transformation of a prior follicular lymphoma.

  • Aberrant somatic mutation occurs in more than 50% of cases and targets multiple loci (eg, IGH, PIM1, MYC, RhoH/TTF [ARHH], PAX5, c-MYC).

  • Three molecular subtypes have been identified determined by gene expression profiling:

    — Germinal center B-like (GCB) arise from normal germinal center B cells (Table 60–2).

    — Activated B-cell–like (ABC) may arise from postgerminal center B cells that are arrested during plasmacytic differentiation (see Table ...

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