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Diffuse Large B-cell Lymphoma

CLINICAL FEATURES

• Presents as a nodal or extranodal mass
• Usually rapid tumour growth
• May be associated with systemic symptoms

Secondary Diffuse Large B-cell Lymphoma

LABORATORY DIAGNOSIS

A) Morphology

• Infiltration and destruction of nodal or other tissues
• The infiltrate consists of large lymphoid cells. These may be of several morphological types:
  • Centroblasts
  • Immunoblasts
  • Anaplastic large B-cells
• The cells usually have the phenotype of a germinal centre or post-germinal centre B-cell.

Bone marrow trephine biopsy stained by Haematoxylin & Eosin	CD20 immunoperoxidase stain of lymph node section	Peripheral blood slide showing DLBCL cells

Lymph node section - H & E staining.	Peripheral blood slide showing DLBCL cells

B) Immunophenotype

• The immunophenotype of diffuse large B-cell lymphoma is variable indicting that this is heterogenous group of tumours.
• Some cases have a typical germinal centre cell phenotype identical to that seen in follicle centre lymphoma. Almost all transformed follicle centre lymphoma have this phenotype but it not certain whether all DLBCL with these features are in fact transformed tumors.
• Most of the remainder have a post germinal centre phenotype - absence of IgD and CD23. A significant number of tumours are sIg negative and a few express sIgG.
• Some DLBCL express CD5 but only a small number are related to CLL or Mantle Cell lymphoma.

CYTOGENETICS AND MOLECULAR GENETICS

• Around 25 % of DLBCL have a t(14;18). Most cases are nodal tumour. There is uncertainty as to how these relate to Follicle Centre lymphoma. Many DLBCL express bcl-2 in the absence of a translocation.
• Chromosomal rearrangements affecting the bcl-6 gene at 3q27 are seen in 30% of DLBCL and are more frequent in extranodal tumours. Bcl-6 is a key regulator of germinal centre formation and tumours of germinal centre origin express the protein without the translocation.
• The t(8;14) that results in deregulation of c-myc may occur in DLBCL as well as Burkitt's Lymphoma.
• Mutations and deletion of p53 are common in DLBCL but some tumours also over-express the wild type protein.

OUTCOME AND THERAPY

• The initial treatment for most patients is CHOP type combination chemotherapy.
• Radiotherapy may have a role in early stage or bulky disease.
• The role of High Dose therapy with stem cell support may improve the outcome for some patients but its role has not been fully defined.
• Using standard treatment about 45% of patients will be cured of their disease.
• In devising future clinical trials it is important to be able to identify this group of patients who are adequately treated with conventional therapy.

Prognostic Factors

• The International Prognostic Index (IPI) is a scoring system based on extent of disease, age and performance status. It identifies good and very poor prognostic groups but most patients are in the intermediate category, many of whom will be cured by CHOP.
• An extranodal origin may be a favourable prognostic factor although it is not clear whether this is independent of other variable. Precise definitions may be a problem.
• Cell variables that may be important in predicting outcome are bcl-2 expression, cell proliferation rate, p53 expression and mutation and bcl-6 rearrangements. A strategy is needed to incorporate important cellular prognostic factors into the IPI.

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