Screening Strategy for Detecting Double-Hit Lymphoma in a Resource-Limited Setting.

Abstract

Aim: High-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements [double-hit lymphomas (DHL)] are aggressive lymphomas. Current literature recommends fluorescent in-situ hybridization analysis (FISH) in all cases of diffuse large B-cell lymphoma (DLBCL) to identify cases of DHL. However, this approach is not feasible in a resource-limited setting. We analyzed cases of de novo high-grade B-cell non-Hodgkin lymphoma using histomorphology, immunohistochemistry and FISH to identify which cases need to undergo FISH testing in a resource-limited setting.

Materials and methods: Cases of de novo high-grade B-cell non-Hodgkin lymphoma that included DLBCL, not otherwise specified and B-cell lymphoma unclassifiable (BCLU) with features intermediate between DLBCL and Burkitt lymphoma diagnosed over a period of 5 years were analyzed by Hans algorithm, MYC, BCL2, and Ki67. MYC, BCL2, and BCL6 break apart FISH was tested in selected cases.

Results: One hundred and nine cases were obtained, of which 102 had DLBCL morphology and 7 had BCLU/blastoid morphology. BCL2 expression was noted in 48 cases (44%), MYC in 33 cases (30.3%) and MYC/BCL2 co-expression in 24 cases (22%). FISH testing could be done in 42 consecutive cases, of which 5 cases had MYC and BCL2 co-rearrangement (11.9%) (double-hit) and 2 cases showed rearrangement for only MYC (4.7%) (single-hit). Single-hit lymphoma/DHL showed significant independent positive correlation with BCLU/blastoid morphology, CD10 expression, germinal center B-cell phenotype, and MYC/BCL2 co-expression. The sensitivity and specificity of each parameters include BCLU/blastoid morphology (42% vs. 94%), CD10 positive (50% vs. 88%), germinal center B-cell phenotype (57% vs. 82%), MYC/BCL2 co-expression (85% vs. 80%). Selected candidates for FISH (any one of the above parameters) using this strategy showed a sensitivity and specificity of 100% and 68%, respectively (P=0.001).

Conclusion: We propose a highly sensitive screening strategy for detection of MYC/BCL2 rearrangement in high-grade B-cell lymphoma in a resource-limited setting (pending validation in a larger cohort).