Clinicopathological and Chromosomal Analysis of Small Intestinal Malignant Lymphoma using Fluorescence in situ Hybridization on Paraffin-Embedded Tissue Sections.

<Background> Specific chromosomal translocations are closely associated with distinctive subtypes of non-Hodgkin’s lymphoma (NHL). However, in small intestinal malignant lymphoma, the frequency of specific chromosomal abnormalities and their relationship to clinicopathological features remain unclear. The aim of this study was to demonstrate the frequencies of the chromosomal translocations involving BCL1, BCL2, c-MYC, MALT1 and BCL6 genes by using fluorescence in situ hybridization directly on paraffin-embedded tissue sections (tissue-FISH) and to evaluate the relationship between clinical outcome and these chromosomal translocations in small intestinal malignant lymphoma.

<Materials and Methods> Twenty-five consecutive patients (22 men and 3 women; age ranging from 10 to 78 years old) diagnosed as having small intestinal malignant lymphoma between 1996 and 2003 were investigated in this study. Tissue-FISH was performed with LSI IGH/BCL1 (Vysis, CA), LSI IGH/BCL2 (Vysis, CA), LSI IGH/MYC (Vysis, CA), and LSI BCL6 (Vysis, CA) probes. API2/MALT1 rearrangement was detected using two YAC clones, y966e4 for 11q21 and y943b8 for 18q21, on paraffin-embedded tissue sections as described previously.

<Result> The primary tumor was located at the duodenum (12 cases, 40%), jejunum (4 cases, 16%), ileum (9 cases, 32%) duodenum to ileum (2 cases, 8%) and duodenum to jejunum (1 case, 4%). Histopathologically, 14 patients were diagnosed as having diffuse large B-cell lymphoma (DLBCL) (56%), 6 as marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) (24%), 3 as follicular lymphoma (FL) (12%) and 2 as mantle cell lymphoma (MCL) (8%). IGH/BCL2 translocation was detected in 3 out of 3 cases of FL (100%), and 3 out of 14 cases of DLBCL (21%), but none of MALT lymphoma. IGH/c-MYC translocation was detected in 1 out of 14 cases of DLBCL (7%). API2/MALT1 translocation was detected in 1 out of 6 cases of MALT lymphoma (17%), and 1 out of 14 cases of DLBCL (7%). IGH/BCL1 translocation was detected only in MCL (2 cases out of 2: 100%). BCL6 translocation was detected in 5 out of 14 cases of DLBCL (36%). As for survival time, DLBCL with either BCL6 or IGH/BCL2 translocation showed poorer prognosis than DLBCL without these translocations (5-year survival rate; 20% vs 65%).

<Conclusion> The current study disclosed that the duodenum was preferentially involved in small intestinal malignant lymphoma (40%). Cytogenetically, 13 out of 25 cases (52%) showed specific chromosomal abnormalities. In DLBCL, BCL6 translocation was detected in five cases, t(14;18) in two, t(8;14) and t(11;18) in one each, indicating that DLBCL is cytogenetically heterogeneous. DLBCL with either BCL6 or IGH/BCL2 translocation appeared to be progressive as shown by shorter survival time. The current study validated that tissue-FISH is a routine diagnostic tool for detecting specific chromosomal translocations in NHL.