API2-MALT1 Fusion Defines a Distinctive Clinicopathologic Subtype in Pulmonary Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue

Abstract

t(11;18)(q21;q21) is associated with mucosa-associated lymphoid tissue (MALT)-type lymphoma and results in API2-MALT1 fusion. However, its clinicopathologic significance remains unclarified. API2-MALT1 fusion is detected most frequently in MALT lymphomas primarily involving the lung. We therefore screened 51 cases of pulmonary MALT lymphoma for API2-MALT1 fusion, and studied its relationship with clinicopathologic factors including the immunohistochemical expression of BCL10, another MALT lymphoma-associated molecule. The API2-MALT1 fusion transcript was detected in 21 of 51 (41%) cases, and was correlated with the absence of any underlying autoimmune disease, and with a normal serum lactate dehydrogenase, a "typical" histology without marked plasmacytic differentiation or an increased number of large cells, and aberrant nuclear BCL10 expression. However, its prognostic impact was not identified in the limited follow-up (6 to 187 months, median 27). These data suggest that the API2-MALT1 fusion may be a causative gene abnormality unrelated to autoimmune disease. In addition, this alteration may define a homogeneous MALT lymphoma subtype that is clinically more indolent and histologically more "typical.

p16/INK4a gene methylation is a frequent finding in pulmonary MALT lymphomas at diagnosis

“…A precise microscopic observation revealed that 46 of 60 cases were 'typical' in histology. 1,25 However, seven cases showed an increased number of large cells (5%olarge cells o10%, without solid or sheet-like proliferations), and seven cases exhibited marked plasmacytoid differentiation (plasmacytoid tumor cells 490%). The mean age of MALT lymphoma patients was 62.1 years with a range of 31-94 years.…”

“…Some of the tumors in this series were included in our previous study. 25 Extraction of Genomic DNA and Total RNA On examination of tissue sections under a dissecting microscope, selected areas were retrieved using a serial H&E section as a guide. Genomic DNA and total RNA were extracted in digestion buffer containing proteinase K as previously described.…”

“…Genomic DNA and total RNA were extracted in digestion buffer containing proteinase K as previously described. 25,28 For all cases included in this study, monoclonality was confirmed by a polymerase chain reaction (PCR) clonality assay of the immunoglobulin heavy chain gene and/or immunohistochemistry for immunoglobulin light chains as previously described. 25 We also confirmed that all cases had a sufficient quality of RNA by reverse transcription (RT)-PCR for betaactin mRNA (190 base).…”

“…25,28 For all cases included in this study, monoclonality was confirmed by a polymerase chain reaction (PCR) clonality assay of the immunoglobulin heavy chain gene and/or immunohistochemistry for immunoglobulin light chains as previously described. 25 We also confirmed that all cases had a sufficient quality of RNA by reverse transcription (RT)-PCR for betaactin mRNA (190 base). 28 As normal controls, 12 lung and 14 lymph node specimens were used and these were obtained from carcinoma patients during surgery.…”

“…23 It should be noted that the involvement of API2-MALT1 fusion is particularly high (up to half of all cases) in pulmonary MALT lymphoma compared with MALT lymphomas at other sites, 24 and may define a distinctive clinicopathologic subgroup of pulmonary MALT lymphomas. 25 Therefore, pulmonary MALT lymphoma is a good model for study of lymphomagenesis. Like other lymphoid malignancies, the p16 gene silencing has been associated with tumor progression in MALT lymphoma.…”