Chapter 61: Diffuse Large B-Cell Lymphoma

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 61–1 lists the variants and subtypes of DLBCL.

TABLE 61–1DIFFUSE LARGE B-CELL LYMPHOMA: VARIANTS AND SUBTYPES

TABLE 61–1 DIFFUSE LARGE B-CELL LYMPHOMA: VARIANTS AND SUBTYPES

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
Diffuse large B-cell lymphoma subtypes
1. T-cell/histiocyte-rich large B-cell lymphoma
2. Primary DLBCL of the CNS
3. Primary cutaneous DLBCL, leg type
4. EBV-positive DLBCL of the elderly
Other lymphomas of large B cells
1. Primary mediastinal (thymic) large B-cell lymphoma
2. Intravascular large B-cell lymphoma
3. DLBCL associated with chronic inflammation
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
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.

Source: Williams Hematology, 8th ed, Chap. 100, Table 100–1, p. 1548.

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.