Chapter 60: Diffuse Large B-Cell Lymphoma and Related Diseases

DEFINITION

• 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.

EPIDEMIOLOGY

• 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.

ETIOLOGY AND PATHOGENESIS

• 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 60–2...