High-Grade B-Cell Lymphomas with Concurrent MYC and BCL2 Abnormalities Other Than Translocations Behave Similarly to MYC/BCL2 Double Hit Lymphomas
Shaoying Li, Adam Seegmiller, PEI Lin, L Jeffrey Medeiros. Vanderbilt University, Nashville, TN; MD Anderson Cancer Center, Houston, TX
Background: High-grade B-cell lymphomas with IGH-BCL2 and MYC rearrangement, known as MYC/BCL2 double hit lymphomas (DHL), are clinically aggressive with a poor prognosis. Some high-grade B-cell lymphomas have concurrent abnormalities of MYC and BCL2 other than coexistent translocations. Little is known about them designated here as atypical MYC/BCL2 DHL.
Design: We studied 20 cases of atypical MYC/BCL2 DHL from 2006 to 2012 confirmed by fluorescence in situ hybridization (n=20) and also by karyotype (n=6), including cases with BCL2 rearrangement (RA) and multiple copies (MC) of MYC (n=14), MYC RA and MC of BCL2 (n=3), and no RA but MC of both MYC and BCL2 (n=3). They were compared to 48 typical MYC/BCL2 DHL. Patient survival was analyzed using the Kaplan-Meier method and compared using the log-rank test.
Results: The study group included 9 men and 11 women, with a median age of 52 years (range, 18-80). Sixteen (80%) patients presented de novo and 4 had a history of low-grade follicular lymphoma (FL). Nine (45%) patients had two or more extranodal sites of disease. Bone marrow involvement was observed in 6/12 (50%) case assessed. At diagnosis, 11/14 (79%) patients with available data had an elevated serum LDH level. Using the 2008 WHO system, the lymphomas were classified as: 11 diffuse large B-cell lymphoma (DLBCL), 7 B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma, and 2 high-grade FL with focal DLBCL. CD10, BCL6, and BCL2 were expressed in 15/19 (79%), 9/10 (90%), and 13/13 (100%) cases, respectively. Cytogenetic analysis showed a complex karyotype in all 6 cases analyzed. Each patient was treated with chemotherapy including R-CHOP (n=8) or more aggressive regimens (n=12). The clinicopathologic features of the atypical MYC/BCL2 DHL cases were very similar to the 48 typical MYC/BCL2 DHLs. In particular, the median overall survival was similarly poor (12.2 months in atypical vs 18.6 months in typical MYC/BCL2 DHL, P=0.58).
Conclusions: Patients with atypical MYC/BCL2 DHL demonstrate similar clinicopathologic features to those with MYC/BCL2 DHL and have a similar poor prognosis. The results suggest that abnormalities of MYC and BCL2 other than concurrent translocations have similar biologic effects, and the category of MYC/BCL2 DHL should be expanded to include cases of high-grade B-cell lymphoma with concurrent genetic abnormalities of MYC and BCL2 other than translocations.
Monday, March 4, 2013 1:15 PM
Proffered Papers: Section C, Monday Afternoon