Low-Grade B-Cell Lymphomas With Plasmacytic Differentiation Lack PAX5 Gene Rearrangements

Abstract

The chromosomal translocation t(9;14)(p13;q32) has been reported in association with lymphoplasmacytic lymphoma (LPL). Although this translocation involving the paired homeobox-5 (PAX5) gene at chromosome band 9p13 and the immunoglobulin heavy chain (IgH) gene at 14q32 has been described in ϳ50% of LPL cases, the actual number of cases studied is quite small. Many of the initial cases associated with t(9;14)(p13;q32) were actually low-grade B-cell lymphomas with plasmacytic differentiation other than LPL. Thus, we analyzed a series of low-grade B-cell lymphomas for PAX5 gene rearrangements. We searched records from the Department of Pathology, Stanford University Medical Center for low-grade Bcell lymphomas, with an emphasis on plasmacytic differentiation, that had available paraffin blocks or frozen tissue. We identified 37 cases, including 13 LPL, 18 marginal zone lymphomas (nodal, extranodal, splenic, and ␣-heavy chain disease), and 6 small lymphocytic lymphomas. A novel dual-color breakapart bacterial artificial chromosome probe was designed to flank the PAX5 gene, spanning previously described PAX5 breakpoints, and samples were analyzed by interphase fluorescence in situ hybridization. All cases failed to demonstrate a PAX5 translocation, indicating that t(9;14)(p13;q32) and other PAX5 translocations are uncommon events in lowgrade B-cell lymphomas with plasmacytic differentiation. This study also confirms recent reports that found an absence of PAX5 rearrangements in LPL, suggesting the reassessment of PAX5 rearrangements in LPL. Recent studies 1-3 have called into question the association of t(9;14)(p13;q32) and lymphoplasmacytic lymphoma (LPL), both medullary (ie, Waldenströ m's macroglobulinemia) and extramedullary. Initially described in a CD30-positive diffuse large B-cell lymphoma cell line, 4 this translocation involves the paired homeobox-5 (PAX5) gene at 9p13 and the immunoglobulin heavy chain (IgH) gene at 14q32.5 After its initial characterization, further studies found the t(9;14)(p13;q32) associated with LPL.

Splenic marginal zone lymphoma proposals for a revision of diagnostic, staging and therapeutic criteria

“…54 Although early reports suggested the presence of t(9;14)(p13;q32) and other PAX5 translocations in a small number of B-cell lymphomas with plasmacytic differentiation, more recent reports have been unable to reproduce these findings. 55 Deletions of 7q, gains of 3q and intrasinusoidal infiltration are in favor of SMZL, while del6q is more in favor of LPL. Isolated del(6q) is more suggestive of LPL/Waldenstrom macroglobulinemia.…”

Molecular Characteristics of Mantle Cell Lymphoma Presenting With Clonal Plasma Cell Component

“…In lymphoplasmacytic lymphomas, the malignant clone shows a wide morphologic heterogeneity ranging from small B lymphocyte to PC, although little is known about its cell of origin 17. Among pre-GC deriving lymphomas, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)9,14,47 and MCL29,46 have also been described to occasionally show plasmacytic differentiation.…”

Epstein–Barr virus-positive diffuse large B-cell lymphoma carrying a t(9;14)(p13;q32) translocation

“…Two large series investigating the presence of t(9;14)(p13;q32) by FISH using combinations of PAX5-and Hematoxylin-and eosin-stained section corresponding to the middle is shown in the right IgH-specific probes failed to demonstrate the rearrangement in lymphoma tissues of LPL or low-grade B-cell lymphomas with plasmacytic differentiation [14,15]. On the other hand, the translocation has been identified in multiple myeloma, plasma cell leukemia, chronic lymphocytic leukemia, splenic marginal zone lymphoma, and post-transplantation DLBCL [16][17][18][19][20], indicating that t(9;14)(p13;q32) is not restricted to a specific tumor subtype and occurs in both immunocompetent and immunocompromised settings.…”