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

Abstract

The normal counterparts of mantle cell lymphoma (MCL) are naïve quiescent B-cells that have not been processed through the germinal center (GC). For this reason, while lymphomas arising from GC or post-GC B-cells often exhibit plasmacytic differentiation, MCL rarely presents with plasmacytic features. Seven cases of MCL with a monotypic plasma cell (PC) population were collected from six centers and studied by immunohistochemistry, FICTION (Fluorescence immunophenotyping and Interphase Cytogenetics as a Tool for the Investigation of Neoplasms), capillary gel electrophoresis, and restriction fragment length polymorphism of immunoglobulin heavy chain analysis (RFLP/IgH) of microdissections of each of the MCL and PC populations to assess their clonal relationship. Clinical presentation was rather unusual compared to typical MCL, with two cases arising from extranodal soft-tissues of the head. All MCL cases were morphologically and immunohistochemically typical, bearing the t(11;14)(q13;q32). In all cases PC populations were clonal. In 5 of the 7 cases, the MCL and PC clones showed identical restriction fragments, indicating a common clonal origin of the neoplastic populations. The two cases with clonal diversity denoted the coexistence of two different tumors in a composite lymphoma/plasma cell neoplasm. Our findings suggest that MCL can present with a PC component that is often clonally related to the lymphoma, representing a rare but unique biological variant of this tumor.

Plasma cell and terminal B-cell differentiation in mantle cell lymphoma mainly occur in the SOX11-negative subtype

“…In one of these cases, the clonal relationship between plasma cells and mantle cell lymphoma cells had been previously demonstrated by molecularly investigating the IGH rearrangement. 32 Interestingly, the seven cases with the plasma cell component were SOX11-negative, confirming the idea that the absence of this transcription factor may allow mantle cell lymphoma cells to progress in the terminal B-cell differentiation process.…”

“…[30][31][32]37 Most of these patients had nodal involvement but extranodal dissemination was also frequent. One previous case had a periorbital presentation as one of our patients.…”

“…However, in recent years, several studies have reported occasional tumors with clonally related monotypic plasma cells. [30][31][32]37 These cases are rare but have raised questions on the potential mechanisms Plasmacytic differentiation mantle cell lymphoma involved in their terminal B-cell. This process is normally regulated by the coordinated action of several transcription factors including PAX5, IRF4/ MUM1, BLIMP1, and XBP1.…”

“…One previous case had a periorbital presentation as one of our patients. 32 Three cases had a mantle zone growth pattern and most cases had been cytologically considered classical mantle cell lymphoma except one pleomorphic variant. One previous case had an intriguing clonally related plasmablastic differentiation in the transformation of a classical mantle cell lymphoma.…”

“…29 However, occasional mantle cell lymphomas with focal areas of plasma cell differentiation have been reported. [30][31][32] These studies have emphasized the presence of mature clonally related plasma cells in otherwise classical mantle cell lymphoma but the potential relationship to SOX11 expression is not known. On the other hand, the expression of transcription factors regulating the switch from mature B-cell to plasma cells such BLIMP1, IRF4/MUM1 and XBP1 have not been well investigated in these tumors.…”