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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.

TABLE 60–1DIFFUSE LARGE B-CELL LYMPHOMA: VARIANTS AND SUBTYPES
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TABLE 60–1DIFFUSE LARGE B-CELL LYMPHOMA: VARIANTS AND SUBTYPES

  1. Diffuse large B-cell lymphoma, not otherwise specified (NOS)

    1. Common morphologic variants

      1. Centroblastic

      2. Immunoblastic

      3. Anaplastic

    2. Rare morphologic variants

    3. Molecular subgroups

      1. Germinal center B-cell–like

      2. Activated B-cell–like

    4. Immunohistochemical subgroups

      1. CD5-positive DLBCL

      2. Germinal center B-cell–like

      3. Nongerminal center B-cell–like

  2. Diffuse large B-cell lymphoma subtypes

    1. T-cell/histiocyte-rich large B-cell lymphoma

    2. DLBCL associated with chronic inflammation

    3. EBV-positive DLBCL of the elderly*

  3. Related mature B-cell neoplasms

    1. Primary mediastinal (thymic) large B-cell lymphoma

    2. Intravascular large B-cell lymphoma

    3. Primary cutaneous DBCL, leg type*

    4. Lymphomatoid granulomatosis

    5. ALK-positive DLBCL

    6. Plasmablastic lymphoma

    7. Large B-cell lymphoma arising in HHV8-associated multicentric Castleman disease

    8. Primary effusion lymphoma

  4. Borderline cases

    1. B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma*

    2. B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classic Hodgkin lymphoma

ALK, anaplastic lymphoma kinase; DLBCL, diffuse large B-cell lymphoma; EBV, Epstein-Barr virus; HHV, human herpes virus; NOS, not otherwise specified.

*These represent provisional entities or provisional subtypes of other neoplasms.

Source: Williams Hematology, 9th ed, Chap. 98, Table 98–1.

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 ...

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