BCL6 gene rearrangement and protein expression are associated with large cell presentation of extranodal marginal zone B‐cell lymphoma of mucosa‐associated lymphoid tissue

Abstract

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is an indolent B-cell lymphoma, which is often localized in the stomach. It is characterized by typical morphology, immunology, cytogenetics and expression profile. The coexistence of a large B-cell lymphoma and a MALT lymphoma in the gastrointestinal tract is defined as a composite lymphoma (ComL) and, as we have previously shown, is almost always the consequence of secondary transformation of MALT lymphoma. Here, we have analyzed a panel of seven MALT lymphomas, seven ComL and thirteen large cell variants of marginal zone B-cell lymphomas (MZBL) using FISH for the detection of rearrangements of IGH, MALT1, BCL6, BCL10 and FOXP1 and immunohistochemistry for Bcl6, Bcl10 and FoxP1. Translocations involving IGH were found in 10/27 lymphomas including two cases with IGH-BCL6 fusion and one with IGH-BCL10 fusion; in 7/10 cases, the translocation partner was not identified. Bcl10 and FoxP1 protein expression was heterogeneous throughout the series. Genetic rearrangements of BCL6 and Bcl6 protein expression were found almost exclusively in the large cell components of the ComL and the large cell extranodal MZBL (p 5 0.2093 and p 5 0.0261, respectively). These findings suggest Bcl6 as a marker for transformation of MALT lymphoma.A large variety of B-cell lymphomas can primarily arise extranodally involving organs with constitutive or acquired lymphoid tissue. Among them, marginal zone B-cell lymphoma (MZBL) is the only entity occurring more frequently in organs than in lymph nodes, hence it deserves a separate place in the current WHO lymphoma classification, 1 i.e. extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) (ICD-O 9699/3). While the large cell variant of MZBL in the lymph node is a canonized, albeit rare, lymphoma variant, the current WHO classification does not apply this term when it comes to name the large cell component of extranodal MZBL in composite lymphoma (ComL) of MALT. Actually, the WHO describes this situation as ''diffuse large B-cell lymphoma (DLBCL) in the presence of accompanying MALT lymphoma''. The result of clonal progression of MALT lymphoma is, according to WHO, also to be called DLBCL: ''Transformation of MALT lymphoma to DLBCL may occur''. 1 This nomenclature reflects the fact that, on histomorphological and immunohistochemical grounds, the large cell component arising in MZBL is still poorly defined. While lymphomas like B-lymphocytic leukemia/lymphoma, mantle cell lymphomas and Burkitt lymphoma can be diagnosed easily in extranodal sites using morphology, immunohistochemistry and cytogenetics, this task is very difficult concerning the heterogeneous group of aggressive B-cell lymphomas. This is regrettable since clinical studies show that the DLBCL of the MALT has a far better cure rate than nodal DLBCL. 2,3 For example, in over half of the cases, regression of gastric DLBCL in an early localized stage occurs following Helicobacter pylori-eradication. 4 The ...

Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma

“…NOTCH2 mutations link BN2 to marginal-zone lymphoma, which is also responsive to ibrutinib. 27–29 BCL6 fusions, the second defining feature of BN2, are common in transformed marginal-zone lymphoma, 30 raising the possibility that BN2 arises from an occult marginal-zone lymphoma. N1 differs from BN2 genetically, phenotypically, and clinically, despite functional similarities between NOTCH1 and NOTCH2, suggesting a distinct pathogenesis.…”

Sensitive and Specific Immunohistochemical Diagnosis of Human Alveolar Echinococcosis with the Monoclonal Antibody Em2G11

“…The antibody is available on request from P. Deplazes at the Institute of Parasitology, University of Zurich, Switzerland. For immunohistochemistry, standard protocols were used [22]. Briefly, for antigen retrieval, the sections were heated in citrate buffer at pH 6 in a microwave oven for 20 minutes.…”

No evidence of IGH‐MALT1 translocation in the Ma‐1 cell line

“…Opinions regarding the presence of an IGH-BCL2 translocation in mucosa-associated lymphoid tissue (MALT) lymphoma are controversial, so Ma-1 is to be considered a lymphoma cell line not harboring the common genetic changes observed in MALT lymphoma. This all the more important, since the MALT concept including transformation in a blastic marginal zone B-cell lymphoma is expanding and in vitro work will have to focus on mechanisms involved including the use of cell lines stemming from this particular type of lymphoma (Barth et al, 2007;Flossbach et al, 2011Flossbach et al, , 2013 …”