Cutaneous Marginal Zone Lymphomas Have Distinctive Features and Include 2 Subsets

Abstract

Cutaneous marginal zone lymphomas (CMZL) were segregated in the WHO/EORTC consensus classification but grouped with other MALT lymphomas in the subsequent WHO classification. It has been suggested, however, that CMZL have distinctive features and might include 2 subsets. To address these issues, the clinicopathologic, phenotypic and, when possible, genotypic features of 29 CMZL with plasmacytic differentiation were assessed. The monotypic plasma cells had class-switched heavy chain expression in 22 cases, technically inadequate staining in 1 case (included with class-switched cases for analysis) and 6 were IgM. The class-switched cases had a predominance of T cells in 22 out of 23 cases with a CD4:CD8>1 in 15 out of 16 cases, usually showed nodules and scattered small B cells often with IgD apparently nonneoplastic follicles, lacked CXCR3 B-cell expression, never showed a totally diffuse growth pattern, often had prominent mast cells, and lacked known extracutaneous involvement. The IgM cases showed a predominance of B cells in 5 out of 6 (P=0.0003), a diffuse proliferation of CD20 B cells in all (P<0.0001), CXCR3+ B cells in 2 out of 5 (P<0.04), and extracutaneous disease in 3 out of 6 (P<0.008). CD21 usually disrupted follicular dendritic meshworks were seen in 9 out of 12 class-switched and 5 out of 5 IgM cases. CD123 plasmacytoid dendritic cells, PD1+ T follicular helper cells, CD25 or FOXP3+ regulatory T cells, and TIA1/granzyme B cytotoxic cells were never numerous. Only 1 out of 14 tested cases showed a low-level clonal/oligoclonal T cell receptor γ gene rearrangement. These findings support the presence of 2 types of cutaneous MALT lymphomas with the class-switched cases being the most distinctive but still sharing significant features with MALT lymphomas from other sites, specifically an extranodal extramedullary CD5-, CD10- indolent small B cell lymphoma with plasmacytic differentiation, frequent benign follicular structures, and not fulfilling the criteria for any other well-defined lymphoma.

Primary cutaneous marginal zone lymphomas with plasmacytic differentiation show frequent IgG4 expression

“…In contrast, there is good evidence that a high number of FOXP3-positive regulatory T cells in hematological malignancies suppresses tumor growth by various mechanisms, thus showing an inverse correlation with outcome. 33,34 The decreased number of regulatory T cells in IgM-positive primary cutaneous marginal zone lymphomas compared with the other primary cutaneous marginal zone lymphomas in our series might therefore contribute to the inferior clinical outcome of IgM-positive primary cutaneous marginal zone lymphomas that has been suggested in the report by Edinger et al 7 Although the number of IgM-positive primary cutaneous marginal zone lymphomas was low in our cohort, all four patients with available clinical data in this group showed a higher tendency toward relapses (data not shown).…”

“…Whereas primary cutaneous marginal zone lymphomas exhibit a preferential expression of IgA and IgG, noncutaneous marginal zone lymphomas display a predominant IgM expression. 7,9 Recent studies suggest two major biological subsets within primary cutaneous marginal zone lymphomas, namely one subset that expresses class-switched immunoglobulins (IgA, IgG, and IgE), whereas the other, rarer subtype expresses nonclass-switched immunoglobulins (IgM). 7,9 This subdivision appears to correlate with profound differences in the composition of the microenvironment and cytokine/chemokine profiles.…”

“…7,9 Recent studies suggest two major biological subsets within primary cutaneous marginal zone lymphomas, namely one subset that expresses class-switched immunoglobulins (IgA, IgG, and IgE), whereas the other, rarer subtype expresses nonclass-switched immunoglobulins (IgM). 7,9 This subdivision appears to correlate with profound differences in the composition of the microenvironment and cytokine/chemokine profiles. Specifically, the IgM-positive group develops in a preferential Th1 cytokine background and shows increased levels of CXCR3 expression, analogous to the scenario in most of the noncutaneous marginal zone lymphomas.…”

“…1 In primary cutaneous marginal zone lymphomas with plasmacytic differentiation, monoclonal immunoglobulin light chain expression (k and l) as well as immunoglobulin heavy chain expression (IgA, IgE, IgG, and IgM) can be typically visualized by immunohistochemistry. Interestingly, primary cutaneous marginal zone lymphomas preferentially express IgG, IgA, or IgE, in contrast to noncutaneous marginal zone lymphomas that predominantly express IgM, [6][7][8][9] suggesting specific pathogenetic features for primary cutaneous marginal zone lymphomas. This concept is supported on the genetic basis, as translocations involving API2 and BCL10 that have been described to play a role in the pathogenesis of marginal zone lymphomas in general are virtually absent in primary cutaneous marginal zone lymphomas, whereas the translocation t(14;18) involving MALT1 appears to be quite common.…”

Early lymphoid lesions: conceptual, diagnostic and clinical challenges

“…However, in contrast to MZL in most other sites, the cells show evidence of class switching, and express IgG rather than IgM. 83 MALT-lymphoma associated translocations have not been described. 81,84,85 but clonality can usually be shown by PCR.…”