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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 61–1 lists the variants and subtypes of DLBCL.



  • Most common B-cell lymphoid neoplasm in the United States and Europe and accounts for approximately 28 percent 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.


  • Molecularly heterogeneous disease with multiple complex chromosomal translocations and genetic abnormalities as 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 percent of cases in immunocompetent persons and approximately 20 percent of HIV-related cases display BCL6 rearrangements.

    — BCL6 protein mediates the specific binding of several transcription factors to DNA.

  • Approximately 30 percent 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 percent of cases and targets multiple loci (e.g., 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.

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

    — Primary mediastinal B-cell lymphoma: might arise from thymic B cells.



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