Abstract

Aberrant expression of CD5 has been reported in 5-10% of diffuse large B-cell lymphomas (DLBCLs). CD5+ DLBCL had been recognized as an aggressive immunophenotypic subgroup of DLBCL in the 2008 WHO classification of haematolymphoid neoplasm; however, it was eliminated from the list of subgroups of DLBCLs in the revised 2016 classification. Nevertheless, there is much controversy regarding the clinical significance of CD5 expression, and many researchers still assert that this subgroup exhibits an extremely unfavorable prognosis with frequent treatment failure. We retrospectively investigated 405 DLBCLs recruited from three university hospitals in Korea from 1997 to 2013. The clinical profile, immunophenotype, and chromosomal structural alterations of the BCL2 and MYC genes were compared according to CD5 expression. A total of 29 cases of de novo CD5+ DLBCL were identified out of 405 in our series (7.4%). Clinicopathologic correlation was performed in all 29 CD5+ DLBCLs and 166 CD5- DLBCLs which were eligible for full clinical review and further pathologic examination. Compared with CD5- counterparts, CD5+ DLBCLs showed female preponderance, frequent bone marrow involvement, higher lactate dehydrogenase level, advanced Ann Arbor stages and poorer prognosis (all p<0.05). Pathologically, the expression of CD5 positively correlated with that of BCL2, MYC and Ki-67 (all p<0.05). Coexpression of BCL2 and MYC, which is referred to as a double-expressor, was relatively more common in CD5+ DLBCL, whereas translocation or amplification of these genes was very rare. in conclusion, the expression of CD5 is an independent poor prognostic factor of DLBCLs, and this subgroup displays unique clinicopathologic features. Although the exact mechanism remains uncertain, consistent activation of BCL2 and MYC by alternative pathways other than chromosomal translocation may contribute to the pathogenesis.

Highlights

  • Pathologic diagnosis of malignant lymphoma is based on the application of immunohistochemistry (IHC) using lineage-specific surface markers such as CD3 or CD20

  • A total of 405 cases of diffuse large B-cell lymphomas (DLBCLs) were investigated for CD5 expression on tumor cells, and 30 cases of CD5+ DLBCLs, consisting of one case transformed from CLL and 29 de novo cases (29 of 405, 7.2%), were identified

  • We demonstrated that CD5 expression was associated with aggressive clinical features and poor survival in DLBCL

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Summary

Introduction

Pathologic diagnosis of malignant lymphoma is based on the application of immunohistochemistry (IHC) using lineage-specific surface markers such as CD3 or CD20. Aberrant expression of some T-cell markers, of which the most representative is CD5, has been well documented in a subset of B-cell neoplasms [1,2,3]. The expression of CD5 in diffuse large B-cell lymphoma (DLBCL) can be observed in Richter transformation of CLL but can be found in de novo DLBCLs. The expression of CD5 in diffuse large B-cell lymphoma (DLBCL) can be observed in Richter transformation of CLL but can be found in de novo DLBCLs Since it was first recognized in 1995 [2], many de novo CD5+ DLBCL cases have been documented, and the overall incidence comprises 5–10% of all DLBCLs [1, 5, 6]. To achieve optimal therapeutic responses, better understanding of pathogenic mechanisms and risk stratification are crucial

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