Abstract
Expression of T-cell markers, generally investigated for immunophenotyping of T-cell lymphomas, is also observed in several types of B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL). We previously reported that CD5 expression in DLBCL is an inferior prognostic factor in the era of rituximab. However, data regarding the frequencies, histological relevance, and prognostic importance of T-cell markers other than CD5 are currently unavailable. In the present study, we comprehensively evaluated the expression of T-cell markers (CD2, CD3, CD4, CD5, CD7, and CD8) in 501 B-cell lymphomas, including 225 DLBCLs, by flow cytometry and subsequent immunohistochemistry. T-cell markers other than CD5, such as CD2, CD4, CD7, and CD8, were expressed in 27 (5%) patients, and notably, all of these cases were classified as large B-cell lymphoma subtypes: 25 DLBCLs and 2 intravascular large B-cell lymphomas. CD5 and other T-cell markers were expressed in 15% (31/225) and 10% (25/225) of DLBCL cases, respectively. Five of them co-expressed CD5 and other T-cell markers. Retrospectively analyzing the prognostic relevance of T-cell markers in 169 patients with primary DLBCL treated with rituximab-based chemotherapy, we showed that only CD5 was a strong predictor of poor survival. This study provides information about the occurrence of T-cell markers other than CD5 in B-cell lymphomas, their frequent histological subtypes, and their prognostic significance in DLBCL. CD5 was reconfirmed as a negative prognostic marker in DLBCL patients receiving rituximab-inclusive chemotherapy, whereas T-cell markers other than CD5 were found to have no impact on clinicopathological and survival analyses.
Highlights
Lymphocytes are generally subdivided into B, T, and natural killer cells, depending on their lineage markers: CD19, CD20, CD22, and immunoglobulins for B cells; CD2, CD3, CD4, CD5, CD7, and CD8 for T cells; and CD56 for natural killer cells
Of the 501 mature B-cell lymphoma cases analyzed, 92 cases were positive for T-cell marker(s), including diffuse large B-cell lymphoma (DLBCL)-not otherwise specified (DLBCL) (51/225, 23%), mantle cell lymphomas (MCLs) (17/17, 100%), CLL/SLL (13/13, 100%), marginal zone lymphoma (MZL) (4/81, 5%; 2 extranodal, 2 nodal), intravascular large B-cell lymphoma (IVLBCL) (2/2, 100%), follicular lymphoma (FL) (1/134, 0.7%), and low-grade B-cell lymphoma unclassifiable (4/19, 21%) cases
T-cell markers other than CD5 (CD8, CD7, CD2, and CD4) were found in 27/501 (5%) cases, all of which were histologically categorized as large B-cell lymphomas: 25 DLBCL, including one case accompanied by FL grade 3B, and 2 IVLBCL cases (Figure 1 and Table 2)
Summary
Lymphocytes are generally subdivided into B, T, and natural killer cells, depending on their lineage markers: CD19, CD20, CD22, and immunoglobulins for B cells; CD2, CD3, CD4, CD5, CD7, and CD8 for T cells; and CD56 for natural killer cells. Lymphoma cells, which are the neoplastic counterparts of lymphocytes, usually retain the lineage marker expression pattern of their normal counterparts. Lymphomas are subclassified according to the expression pattern of their markers. In some lymphomas, aberrant expression of lineage markers is observed. In B-cell neoplasms, CD5 is usually expressed in chronic/small lymphocytic lymphomas (CLLs/SLLs) and mantle cell lymphomas (MCLs), for which the normal counterparts are considered to be CD5-positive B cells. Other B-cell lymphomas may sometimes express CD5 aberrantly. 10% of the diffuse large B-cell lymphomas (DLBCLs) express CD5 [2, 3], and such cases comprise an immunohistochemical subgroup of DLBCL, according to the 2008 WHO classification [4]. CD5-positive DLBCL has been well studied, and some researchers claim that it has a worse prognosis than CD5negative DLBCL [2, 3]
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