Chronic lymphocytic leukemia/small lymphocytic lymphoma: another neoplasm related to the B-cell follicle?

Abstract

Although there has been increased attention paid to the critical nature of nodal involvement in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), the B-cell compartment it is most closely related to and its relationship to the follicle remain uncertain. A clinicopathologic investigation of 60 extramedullary biopsies of LEF1+ CLL/SLL, including 29 cases with perifollicular/follicular (PF/F) growth, was therefore performed. A subset of PF/F cases demonstrated inner mantle zone preservation or intra-mantle zone growth. All PF/F and 16/31 other cases contained CD21+ follicular dendritic cells. No cytogenetic, IGHV mutational or gene usage differences were seen between PF/F and diffuse cases. PF/F cases were more often kappa positive (p<0.03) and had fewer involved nodal sites (p=0.0004). These findings suggest that at least a subset of bona fide CLL/SLL is related to the follicle, most likely the outer mantle zone, and that at least a subset of the diffuse cases may represent "later" disease.

The many faces of small B cell lymphomas with plasmacytic differentiation and the contribution of MYD88 testing

“…In the past, some CLLs/SLLs were classified as “lymphoplasmacytoid” lymphoma in the Kiel classification because of this (as opposed to LPL which had frank plasma cells). Cytoplasmic immunoglobulin can be documented in paraffin-embedded sections in the majority of CLLs/SLLs, and proliferation centers characteristically are IRF4/MUM1+ [51]. PRDM1/BLIMP-1 is present in plasma cell neoplasms, LPL, and a significant number of diffuse large B cell lymphomas (DLBCLs), with weak reactivity reported in 15 % of CLLs/SLLs [11].…”

Follicular colonization in chronic lymphocytic leukemia/small lymphocytic lymphoma (comment on “Small lymphocytic lymphoma mimicking primary cutaneous marginal zone lymphoma with colonization of germinal center follicles”)

“…We previously postulated that at least a subset of CLL/SLL is related to the follicle, most likely the outer mantle zone. 4 All of these findings further highlight the point made by LeBlanc et al 1 namely, the importance of ancillary studies in the accurate diagnosis and classification of lymphoid neoplasms whether in the skin or at other sites.…”

“…2 Furthermore, as explained and illustrated in subsequent publications, some CLL/SLL have a perifollicular growth pattern that can also lead to confusion with marginal zone lymphomas. 3,4 Others can have a very follicular growth pattern, sometimes clearly associated with follicular colonization with underlying follicular dendritic cell meshworks. 4 This may even lead to confusion with a follicular lymphoma.…”

“…3,4 Others can have a very follicular growth pattern, sometimes clearly associated with follicular colonization with underlying follicular dendritic cell meshworks. 4 This may even lead to confusion with a follicular lymphoma. We previously postulated that at least a subset of CLL/SLL is related to the follicle, most likely the outer mantle zone.…”

Chronic lymphocytic leukemia and mantle cell lymphoma: crossroads of genetic and microenvironment interactions

“…45,46 These crucial interactions mainly occur in the proliferation centers of lymph nodes infiltrated by CLL that contain a loose meshwork of follicular dendritic cells (FDCs), a variable number of T cells, and other stromal cells (Figure 3). [46][47][48] Bone marrow also provides a supportive microenvironment although less structurally organized. Tumor cells in proliferation centers become larger and have increased expression of downstream targets of the BCR signaling, NF-kB activation, cytokines, and antiapoptotic and proliferation-related markers.…”