Originally published as JCO Early Release 10.1200/JCO.2005.15.503 on August 29 2005

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Large Cleaved and Immunoblastic Lymphoma May Represent Two Distinct Clinicopathologic Entities Within the Group of Diffuse Large B-Cell Lymphomas

From the Department of Pathology, Ghent University Hospital, Ghent; Department of Morphology and Molecular Pathology, Department of Haematology, and the Center of Human Genetics, Catholic University of Leuven, Leuven, Belgium

Address reprint requests to Pascale De Paepe, MD, Department of Pathology, Ghent University Hospital, De Pintelaan 185, Blok A, 5th floor, B-9000 Ghent, Belgium; e-mail: pascale.depaepe{at}ugent.be

PURPOSE: The reliability of immunohistochemistry for subdividing diffuse large B-cell lymphomas (DLBCL) into germinal center B-cell-like (GCB) and non-GCB prognostic subgroups is debated. In this study we evaluated the prognostic significance of such subgrouping on a series of 153 DLBCL patients. Furthermore, we investigated whether both subgroups could comprise clinicopathologic entities recognized by their morphology and characterized by a distinct phenotype, specific genetic abnormalities, and clinical characteristics.

PATIENTS AND METHODS: All samples from patients were reviewed and morphologically subdivided into large cleaved, immunoblastic, and not otherwise specified DLBCL. GCB and non-GCB immunohistochemical profiles were established. The presence of chromosomal translocations involving BCL2, BCL6, and MYC and/or rearrangements of these genes was investigated.

RESULTS: Subdividing DLBCL with either a GCB or non-GCB immunophenotypic profile was not of prognostic significance. Nevertheless, CD10 expression was a predictor of favorable outcome, whereas high bcl-2 expression and BCL6 rearrangement were adverse predictors of disease-free survival. Interestingly, large cleaved DLBCL was clearly associated with a GCB immunophenotypic profile, CD10 expression, BCL2 rearrangement, age younger than 60 years, and low to low/intermediate International Prognostic Index risk, but was not of prognostic significance. In contrast, immunoblastic morphology was associated with a non-GCB profile and was a significant predictor of unfavorable DFS.

CONCLUSION: Subdividing DLBCL into subgroups based on their immunohistochemical profile was not of prognostic significance. Nevertheless, it allowed the additional characterization of two lymphoma subgroups previously recognized in the Working Formulation. Both correspond to two distinct clinicopathologic entities within the DLBCL.

Supported by Grant No. G.0362.01 from the Fund for Scientific Research (FWO) Flanders; G.V. is a research fellow of the Belgian Federation against Cancer; and G.V. is holder of the Roche Chair in Hematology.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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