Analysis of immunoglobulin VH genes in CD10‐positive diffuse large B‐cell lymphoma

Abstract

CD10, a proteolytic enzyme seen in germinal center cells and in the majority of follicular lymphomas, is occasionally expressed in diffuse large B-cell lymphomas (DLBCL). To clarify the origin and cellular characteristics of CD10-positive DLBCL, we analyzed 36 de novo cases of DLBCL for somatic mutations of the immunoglobulin heavy chain variable region (VH) genes and for their immunophenotypes. Expression greater than that of grade 2 Bcl-6 was observed in 11 of the 30 CD10-negative cases (37%) and in all six CD10-positive cases (100%; P < 0.05) without expression of CD5, CD23, cyclin D1, CD30 or CD138. The average mutation frequencies of the six CD10-positive and 30 CD10-negative DLBCL were 12.9 and 9.8%, respectively. The range of SM frequencies in CD10-positive DLBCL (9.52-18.06) was distinctly narrower than that observed for CD10-negative DLBCL (0.69-26.89). These findings seem to indicate that CD10-positive DLBCL, originating from germinal center B cells, is a genetically and immunophenotypically more homogeneous group than CD10-negative DLBCL. Furthermore, three extranodal lymphomas, in five of the six CD10-positive DLBCL, showed ongoing mutation, indicating that antigen-driven, high-affinity somatic mutation may play an important role in clonal expansion in CD10-positive DLBCL. All four extranodal cases of the six CD10-positive DLBCL showed ongoing mutation and/or bcl-2/JH rearrangement. This result suggests that the cell origin of extranodal CD10-positive DLBCL may be the same as that of follicular lymphomas.

Molecular, cytogenetic, and immunophenotypic characterization of follicular lymphoma grade 3B; a separate entity or part of the spectrum of diffuse large B-cell lymphoma or follicular lymphoma?

“…We found a higher percentage overexpression of CD10 in the t(14;18)-positive subset, which might be in accordance with previous findings that both CD10 and t(14;18) are typical FL markers and appear in low percentages in DLBCLs, in particular, in DLBCL with a germinal center cell expression pattern [8,17,19,22]. The initial diagnosis of most of the cases with overexpression of CD10 was primary FL grade 3B.…”

“…The nuclear phosphoprotein myc, located on chromosome 8q24, has been implicated as a potent regulator of cellular proliferation and may also play an important role in the transformation process of FL [15,16]. Most precursor B cells as well as a subset of follicular center cells express CD10 antigen, whereas other mature B cells, plasma cells, and B-cell lymphomas only occasionally do [17,18]. The immunophenotype of the malignant lymphocytes in FL suggests that they are derived from germinal center cells, and mostly, they do express CD10, although some grade III FLs are negative [19].…”

CD10 expression in diffuse large B-cell lymphomas does not influence survival

“…Xu et al [29] showed 75% sensitivity and 100% specificity of CD10 expression using immunohistochemistry compared with multi-parameter flow cytometry. CD10 positivity in DLBCL has been previously reported in several studies, varying from 16% to 43% [2,4,5,8,9,10,13,14,16,22,23,24,27,28,29]. However, the level of positivity in our study fit well with the largest and recent study [13] published using tissue microarray of 152 cases (28% of CD10 expression using a 30% threshold).…”

Follicular Origin of a Subset of CD5+ Diffuse Large B-Cell Lymphomas

“…16 The histogenesis of CD5+ DLBCL is controversial, and few data are available on the cytogenetic alteration or the somatic hypermutation of the immunoglobulin heavy chain (IgH) gene variable region (V H gene). [19][20][21] The lack of data regarding the histogenesis of CD5+ DLBCL and the description of a CD5+ variant of FL prompted us to search for the existence of DLBCL possibly derived from CD5+ FL. We present 6 cases of CD5+ DLBCL in which the derivation from germinal center cells or FL can be inferred based on morphologic aspects, immunophenotypic expression of follicle-associated antigens, and/or molecular biologic data.…”