Diffuse Large B-cell Lymphoma (DLBCL)

At a Glance

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of B-cell lymphomas with a diffuse pattern of growth, composed of large cells with open/vesicular nuclear chromatin, and a nuclear size at least double the size of a normal lymphocyte nucleus or equal or greater to a normal histiocyte nucleus. DLBCL is one of the most common lymphoid neoplasms (30% of B-cell lymphomas) and occurs mainly in older patients. It can occur, however, at any age, including in the pediatric age group. The DLBCL designation encompasses several subtypes. These include T-cell/histiocyte rich large B-cell lymphoma, primary DLBCL of the CNS, primary cutaneous DLBCL, leg type, and EBV positive DLBCL of the elderly.

DLBCL can also arise as a transformation/progression of lower grade B-cell lymphoma, such as chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular lymphoma, marginal zone lymphoma, or nodular lymphocyte predominant Hodgkin lymphoma. There are other types of large B-cell lymphomas. However, they have received their own separate category in the 2002 World Health Organization (WHO) classification. The overall 5-year survival rate in DLBCL is 46%. There have been attempts to identify prognostic groups based on gene expression profiling, which did divide DLBCL into "germinal center like" and "activated B-cell like" subgroups, with a subsequent identification of immunohistochemical markers, such as CD10, BCL-6(germinal center markers), MUM-1 (activated B-cell/plasma-cell markers), and BCL-2.

By WHO criteria, the use of immunohistochemical panels to assign prognostic groups does not currently have a role in clinical practice. However, this is a somewhat controversial topic among hematopathologists and clinicians.


The pathologic diagnosis will typically include at least a CD20 immunohistochemistry stain as a quite specific marker of the cell lineage and the target of rituximab therapy. For cases with medium-size cells, a cyclin D1 may be performed to exclude a blastoid variant of mantle cell lymphoma. Some pathologists add a Ki-67 staying to assess the proliferation fraction. Fresh tissue for flow cytometry may not always be available, particularly in instances in which the diagnosis was unexpected. Flow cytometry, when available, does not always detect the neoplastic cells due to fragility/loss of the large neoplastic cells during processing. When diagnostic, it will detect a population of larger lymphocytes, with clonal immunoglobulin light chain expression or sometimes without detectable surface immunoglobulin. Flow cytometry may be helpful in detecting and characterizing a low-grade component in a staging bone marrow biopsy by providing evidence of monoclonality when only limited involvement is present.


Most patients will undergo a staging bone marrow biopsy with flow cytometry. The percentage of bone marrow involvement by large cell lymphoma at presentation is rather low, at 10-30%. A low-grade complement, such as follicular lymphoma, may be found in the marrow at the time of the staging bone marrow examination. Serum lactate dehydrogenase (LDH) levels are also part of the International Prognostic Index, which also includes the amount of extranodal involvement, age, performance status, and stage.


Ki-67 immunohistochemical staining identifies those lymphomas with a very high proliferation rates. Conventional cytogenetic analysis is not indicated routinely. However, fluorescence in situ hybridization (FISH) performed on sections of the paraffin embedded tissue is increasingly used to detect specific translocations in cases morphologically more aggressive and that have a high proliferation index. The most common cytogenetic abnormality in DLBCL (up to 30% of cases) is a translocation involving the BCL6 at 3q27, which has been found by some studies, but not others, associated with a better prognosis. The follicular lymphoma associated translocation of the BCL2 and immunoglobulin heavy chain loci t(14;18) (q32;q21) is detected in 20-30% of cases. Rearrangements of the myc oncogene at 8q24, including the Burkett lymphoma characteristic translocation t(8;14) (q24;q32), are detected in approximately 10% of cases and have adverse prognostic significance.

Particularly aggressive cases likely poorly responsive or resistant to therapy are identified by the presence of BCL2 and myc translocations ("double hit" lymphomas), rarely with an added BCL6 translocation ("triple hit" lymphomas). These lymphomas, if composed of small- to medium-size cells likely fall into a newly created category of B cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma.


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