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

Abstract

Mantle cell lymphoma is a mature lymphoid neoplasm characterized by the t(11;14)(q13;q32) and cyclin D1 overexpression. SOX11 is a transcription factor commonly overexpressed in these tumors but absent in most other mature B-cell lymphomas whose function is not well understood. Experimental studies have shown that silencing of SOX11 in mantle cell lymphoma cells promotes the shift from a mature B cell into an early plasmacytic differentiation phenotype, suggesting that SOX11 may contribute to tumor development by blocking the B-cell differentiation program. The relationship between SOX11 expression and terminal B-cell differentiation in primary mantle cell lymphoma and its relationship to the plasmacytic differentiation observed in occasional cases is not known. In this study we have investigated the terminal B-cell differentiation phenotype in 60 mantle cell lymphomas, 41 SOX11-positive and 19 SOX11-negative. Monotypic plasma cells and lymphoid cells with plasmacytic differentiation expressing cyclin D1 were observed in 7 (37%) SOX11-negative but in none of 41 SOX11-positive mantle cell lymphomas (Po0.001). Intense cytoplasmic expression of a restricted immunoglobulin light chain was significantly more frequent in SOX11-negative than -positive tumors (58 vs 13%) (P = 0.001). Similarly, BLIMP1 and XBP1 expression was also significantly more frequent in SOX11-negative than in -positive cases (83 vs 34% and 75 vs 11%, respectively) (P = 0.001). However, no differences in the expression of IRF4/MUM1 were observed among these subtypes of mantle cell lymphoma. In conclusion, these results indicate that SOX11-negative mantle cell lymphoma may be a particular subtype of this tumor characterized by more frequent morphological and immunophenotypic terminal B-cell differentiation features that may be facilitated by the absence of SOX11 transcription factor.

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

“…7c). These findings are concordant with a recent larger study (which included case 89), showing that plasma cell and terminal B cell differentiation in MCL mainly occur in SOX11-negative tumors [39]. …”

“…The three cases presented in the workshop, together with those previously published, illustrate how easily these MCLs can be confused with other SBLs with plasmacytic differentiation, particularly those that are CD5 negative and have a paraprotein [8, 39, 59]. However, the clinical presentation with generalized lymphadenopathy, and extranodal involvement, splenomegaly, and leukemic expression in some of the cases, may suggest the diagnosis of MCL that can be confirmed by demonstrating cyclin D1 expression.…”

“…In addition, although the t(11;14) is found in both MCL and a minority of myelomas, it is more critical in defining entities than MYD88 mutations which are present in a much broader spectrum of B cell lymphoid neoplasms. The other two MCLs with plasmacytic differentiation in the workshop, as well as six additional recently published cases, lacked MYD88 mutation, in addition to more than 100 other MCLs investigated for this mutation [39]. Another differential diagnosis when there is marked plasmacytic differentiation is PCM with t(11,14).…”

Patient-derived xenografts of low-grade B-cell lymphomas demonstrate roles of the tumor microenvironment

“…MZL, mantle cell lymphomas, and even FLs may be associated in patients with significant numbers of plasma cells that are derived from the neoplastic B cells. [14][15][16] In the case of MZL, these plasma cell accumulations may be so marked that the neoplasm mimics a plasmacytoma or creates an amyloidoma. More subtle accumulations of clonal plasma cells occur in MZLs arising at mucosal sites: the clonal plasma cells are enriched at the most superficial sites, visually suggesting that the environment is modulating either the differentiation of the tumor cells or that cells with plasmacytic differentiation preferentially traffic to specific locations.…”

The role of targeted treatment in mantle cell lymphoma: is transplant dead or alive?

“…The role of targeted treatment in mantle cell lymphoma haematologica | 2016; 101(2) need immediate treatment (the clinically defined "indolent MCL", potentially identified by the lack of SOX11 expression), [95][96][97] and others benefit from very long remissions after ASCT, it is reasonable to challenge the value of intensified treatment in these patients in order to avoid unnecessary toxicities. In this context, the recent improvements in induction schemes, 34,98 as well as the very promising data on rituximab maintenance, 41 even after ASCT, 42 strongly suggest a more sustained PFS, especially in younger patients.…”