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

Abstract

Most follicular lymphomas (FLs) have a phenotype consistent with the origin from CD5-, CD10+, bcl-6+ follicular center cells and can progress to diffuse large B-cell lymphoma (DLBCL). CD5 is expressed in about 10% of DLBCLs, showing prognostic value, whereas expression is rare in FL. We present 6 cases with coexisting features of CD5+ FL and CD5+ DLBCL, supporting a follicular origin for some CD5+ DLBCLs. The follicular areas showed a meshwork of CD21+ follicular dendritic cells that were lacking in the DLBCL areas. All cases showed a clonal CD19+, CD20+, CD5+, and CD10+ population in both follicular and diffuse areas. Molecularly, 4 of 6 cases demonstrated immunoglobulin heavy chain rearrangements and 1 case, a bcl-2/immunoglobulin heavy chain gene rearrangement. Somatic hypermutations were high in all 4 cases, in keeping with their germinal center origin. Four of five patients died of disease within 42 months, consistent with the proposed prognostic value of CD5 expression in DLBCL. Our data describe an aggressive variant of CD5+ FL suggesting the follicular origin of some CD5+ DLBCLs.

Translocation (18;22)(q21;q11) in B-cell lymphomas: a report of 4 cases and review of the literature

“…In a study of 42 cases of B-cell lymphomas with coexpression of CD5 and CD10, 14 cases (33%) were classified as follicular lymphoma, underscoring the need to use other germinal center B-cell markers in immunophenotypically ambiguous cases [25]. CD5 expression can occur in DLBCL of follicle center origin with high somatic hypermutations and a more aggressive behavior [29]. Our case is the first to report dim CD5 expression in FL with a variant BCL-2 translocation.…”

CD5‐positive follicular lymphoma characterized by CD25, MUM1, low frequency of t(14;18) and poor prognosis

“…16 Some previous studies used bcl6 expression as follicular center B-cell markers in a definition of FL and exclusion from CLL/SLL or MCL. [9][10][11][12] Bcl6 expression was not adopted in diagnostic criteria in this study because cases of CLL/SLL with bcl6 expression have ever been described 17 and because neoplastic cells in FL could be negative for bcl6. 18 In this study, cases of CD5-positive FL had a higher frequency of MUM1 expression and a lower frequency of t(14;18)(q32;q21) compared with control cases.…”

“…However, an abnormal microenvironment around B-cells and neoplastic transformation of non-neoplastic B-cells with both CD5 and CD10 expression has been suggested. 12,[20][21][22][23][24][25][26] When non-neoplastic CD5-positive B-cells enter the germinal center from the mantle zone, they do not lose expression of CD5 in an abnormal follicular microenvironment. This includes downregulation of the cytokine network and interleukin (IL) −4, which suppresses expression of CD5 and inappropriate response of IL-2.…”

Immunophenotyping of mature B-cell non Hodgkin lymphoma involving bone marrow and peripheral blood: critical analysis and insights gained at a tertiary care cancer hospital

“…The coexpression of CD5 and CD10 is highly unusual because CD5 is expressed by a subpopulation of prefollicular mantle zone cells that lose CD5 as they differentiate into follicular cells and acquire CD10 [20]. Rarely CD5 has been expressed in conjunction with CD10 in cases with well-documented diagnoses of FL [41][42][43][44][45]. There were two cases of FL which were CD10 negative (7%).…”

“…Only one case expressed CD5. Newer WHO classification defines a separate entity of CD5 positive DLBCL [3,45,55].…”