The Unique Immunophenotype of “Double-Hit Lymphomas”.
Alexandra M Harrington, Horatiu Olteanu, Camellia Eshoa, Steven H Kroft. Medical College of Wisconsin, Milwaukee; Columbia St. Mary's Hospital, Milwaukee, WI
Background: “Double-hit lymphomas” (DHLs), characterized by MYC and BCL-2 rearrangements, are clinically aggressive neoplasms that should be distinguished from other types of aggressive B-cell lymphoma. A recent flow cytometry (FC) study found decreased CD20 expression associated with this lymphoma type but did not test the specificity of this finding. We therefore compared the FC immunophenotype (IP) of DHLs to cohorts of Burkitt lymphomas (BL) and CD10(+) diffuse large B cell lymphomas (DLBCL).
Design: We retrospectively analyzed FC specimens from tissue, blood (PB), marrow (BM), or body fluids from patients (pts) with DHL, BL, and CD10(+) DLBCL, using 4-color FC with the following antigens: CD5, CD10, CD19, CD20, CD22, CD23, CD38, FMC-7, kappa, and lambda. Neoplastic populations were compared to normal B cells when present and antigen expression was defined as >20% of tumor events exceeding an isotypic control threshold. DHLs were defined as mature B-cell neoplasms harboring MYC and BCL-2 rearrangements by FISH.
Results: We identified 9 DHL pts (6 females; 3 males, 48-85 y/o; 12 specimens-3 CSF, 3 tissue, 3 PB, 2 BM, 1 peritoneal fluid), 6 BL pts (5 males; 1 female, 22-67 y/o; 7 specimens-5 tissue, 1 BM, 1 PB) and 17 DLBCL pts (9 females; 8 males, 24-78 y/o; 17 tissue specimens). 3/9 DHLs represented transformations of follicular lymphomas. Immunophenotypic findings were similar across specimens in pts with multiple analyses. All cases examined were CD10(+). Dim CD19 expression was observed in 7/9 (78%) DHLs vs. 6/17 (35%) DLBCLS (p=0.097); dim CD20 expression was observed in 7/9 (78%) DHLs vs. 2/17 (12%) DLBCLs (p=0.002). All DHLs with dim CD19 also showed dim CD20; no DLBCLs showed dim expression of both antigens (p<0.001). No BLs showed dim CD19 or dim CD20. CD38 was brightly (+) in 8/8 DHLs (100%) compared to 6/6 BLs and 6/17 DLBCLs (35%; p=0.006). CD22 expression was diminished in 5/6 DHLs (83%). 2/9 DHLs were CD19(+)/CD20(+), with 1 case demonstrating bright expression of both antigens. Decreased CD20 expression was not attributable to rituximab effect in any patient.
Conclusions: DHLs have a unique IP, showing frequently decreased expression of both CD19 and CD20, expression of CD10, and increased CD38 expression, when compared to normal B cells. Our data confirms a recent study demonstrating decreased CD20 expression in DHLs, but also identifies concomitant decreased expression of CD19, a novel finding. The combination of dim CD19 and CD20 carries a specificity of 100% for the diagnosis of DHL amongst CD10(+) aggressive B cell lymphomas.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 216, Wednesday Afternoon