Diffuse Large B-Cell Lymphomas with High Grade Morphologic Featues and/or MYC Translocations Lack Distinctive Clinicopathologic Features at Presentation: A SWOG S9704 Study
JR Cook, RR Tubbs, B Goldman, M Leblanc, L Rimsza, R Fisher, P Stiff. Cleveland Clinic, Cleveland; Fred Hutchinson Cancer Center, Seattle; Univ. of Arizona, Tuscon; Univ. of Rochester, Rochester; Loyola Univ., Chicago
Background: High grade morphologic (HGM) features (intermediate cell size, starry sky pattern) and MYC translocations are characteristic of Burkitt lymphoma (BL), but may also be seen in B-cell lymphomas that do not meet current BL criteria. The 2008 WHO classification introduced a new diagnostic category for unclassifiable B-cell lymphomas intermediate between diffuse large B-cell lymphoma (DLBCL) and BL. The spectrum of clinicopathologic features in non-Burkitt lymphomas with HGM and/or MYC translocations, however, remains unclear. We therefore examined 254 DLBCL patients enrolled on SWOG S9704, a phase 3 trial of advanced stage, High-Intermediate/High IPI non-Hodgkin lymphoma.
Design: Detailed histologic review of 354 eligible patients in S9704 identified 254 cases of DLBCL. Cases of BL (2008 criteria) were excluded. Clinical features and the presence or absence of HGM were reviewed in all cases. Immunohistochemical (IHC) staining for GC vs non-GC phenotype by the Hans algorithm (CD10, BCL6, MUM1) and FISH studies for MYC and/or BCL2 translocations (Abbot Molecular) were performed using whole sections (n= 44) or TMA (n= 73).
Results: HGM features were identified in 30/254 cases (12%). MYC translocations were identified in 8/24 (33%) and 8/45 (18%) cases with and without HGM, respectively. 11/14 (79%, 2 missing) MYC+ cases contained concurrent BCL2 FISH abnormalities, and 1 case was strongly BCL2 IHC+ without FISH abnormalities. 5/12 (42%) "double hit" lymphomas (MYC FISH+, BCL2 FISH/ IHC+) showed HGM. GC phenotype was noted in 13/27 (48%) of HGM cases, and in 10/14 (71%) of MYC+ cases. Cases with or without HGM and with or without MYC abnormalities showed no significant differences in age, gender, stage, IPI risk factors, IPI score or number of extranodal sites.
Conclusions: Cases of DLBCL with HGM and/or MYC translocations are heterogeneous. The possible prognostic significance of these findings will be assessed upon maturation of S9704 follow-up data. However, the lack of distinct clinicopathologic features at presentation, at least in this subset of advanced stage, high-intermediate/high IPI patients, suggests that cases of DLBCL with HGM and/or MYC translocations need not be considered a separate diagnostic category distinct from other DLBCL.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 180, Wednesday Morning