Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P=3.95 × 10(-15)) and HLA-B (rs2922994, P=2.43 × 10(-9)) in the HLA region significantly associated with MZL risk.
The diagnosis of Waldenström Macroglobulinaemia (WM)/lymphoplasmacytic lymphoma (LPL) remains one of exclusion because other B-cell lymphoproliferative disorders (B-LPD), such as marginal zone lymphoma (MZL), can fulfil similar criteria, including MYD88L265P mutation.
IGHV gene features and MYD88L265P mutation separate the three marginal zone lymphoma entities and Waldenström macroglobulinemia/lymphoplasmacytic lymphomas.
The most distinguishing features of LPL with respect to MZL were focal paratrabecular involvement (P < .001), the presence of lymphoplasmacytoid cells (P < .001) and Dutcher bodies (P < .001), increased numbers of mast cells (P < .001), and the MYD88L265P mutation (P < .001).
The immunophenotypic features and myeloid differentiation primary response gene (88) leucine to proline mutation data of LGBCL-NOS suggested that some cases present with characteristics similar to those of LPL or marginal zone lymphoma.
i) Besides +3 and 7q-, 13q14 deletion, total/partial +12, BCL6 rearrangement, and deletions at 6q21, 11q22-23, and 17p13.3 are relatively frequent events in MZBCL; ii) unlike in mantle cell lymphoma, 9p21 deletion occurred infrequently in MZBCL; iii) a switch into high grade histology is usually associated with complex chromosome defects, including 6q-, 11q-, +12, and 17p.
The most common scenario is transformation of follicular lymphoma to either diffuse large B-cell lymphoma or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 translocations; however, other indolent subtypes such as marginal zone lymphoma, lymphoplasmacytic lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia, or even nodular lymphocyte predominant Hodgkin lymphoma, can undergo similar histologic transformation.
First, 2 cases, one case of MALT lymphoma and another of aggressive marginal zone lymphoma (MZL) with t(14;18)(q32;q21), cytogenetically identical to the translocation involving BCL2, were shown by fluorescence in situ hybridization (FISH) to involve MALT1, which lies about 5 Mb centromeric of BCL2.
Two patients with FSCCL, 22 patients with DSCCL, and all of the patients with MZL had a phenotype of mantle zone (MZ) B-lymphocytes (SIgD+, Leu-1+, Leu-8+, positive alkaline phosphatase [ALPase+], and negative common acute lymphoblastic leukemia antigen [CALLA-]), and all the tested patients (2 patients with FSCCL, 13 patients with DSCCL, and 4 patients with MZL) had germlines of bcl-2 gene.
The translocation of chromosome 11, long arm, region 2, band 1, to chromosome 18, long arm, region 2, band 1 (t(11;18)(q21;q21)) represents a recurrent chromosomal abnormality in extranodal marginal zone B-cell lymphoma (MZBCL) of mucosa-associated lymphoid tissue (MALT) type and leads to a fusion of the apoptosis inhibitor-2 (API2) gene on chromosome 11 and the MALT lymphoma-associated translocation (MLT) gene on chromosome 18.