SOX11 Is Useful To Differentiate Cyclin D1+ Diffuse Large B-Cell Lymphoma from Mantle Cell Lymphoma
Shih-Chuan Hsiao, Inma Ribera, Hongtao Ye, Hongxiang Liu, Sheng-Tsung Chang, Elias Campo, Shih-Sung Chuang. St. Martin de Porres Hospital, Chia-Yi, Taiwan; University of Barcelona, Barcelona, Spain; University College London, London, United Kingdom; University of Cambridge, Cambridge, United Kingdom; Chi-Mei Medical Center, Tainan, Taiwan
Background: Cyclin D1 expression is characteristic of mantle cell lymphoma (MCL) and is very rare in diffuse large B-cell lymphoma (DLBCL). Differential diagnosis between cyclin D1+ DLBCL from MCL could be a challenge.
Design: We encountered an index case of cyclin D1+ DLBCL from consultation service and subsequently conducted a retrospective study of DLBCL from 2005 to 2010 using immunohistochemistry for cyclin D1 and SOX11 and fluorescence in situ hybridization (FISH).
Results: Two (1.1%) of 180 in-house DLBCLs expressed cyclin D1. We identified a pleomorphic MCL initially mis-diagnosed as DLBCL through this retrospective approach. The prevalence of cyclin D1 expression among DLBCL including consultation cases was 1.5% (3 of 206). Of the 1 male and 2 females with cyclin D1+ DLBCL, 2 were 78 years old and 1, 43. The 2 former tumors showed focal necrosis and the third, focal starry-sky pattern. Histologically, 2 were immunoblastic and 1, anaplastic. All 3 cyclin D1+ DLBCLs shared the same post-germinal center phenotype (CD10- bcl-6+ MUM1+) and were negative for SOX11 and EBV (by in situ hybridization), excluding DLBCL of the elderly. FISH assay showed absence of CCND1 break in all 3 cases; and interestingly, the case with a focal starry-sky pattern revealed rearrangements involving BCL6, MYC and IGH loci, indicating a double-hit lymphoma. All 3 patients were with high-stage disease and high performance status scores. Two died of disease progression shortly and the third patient with double-hit lymphoma was in complete remission after immunochemotherapy. In the same study period, there were 22 MCLs, all expressing cyclin D1. Of the 19 evaluable cases, 17 (89%) expressed SOX11, a frequency statistically different from cyclin D1+ DLBCLs (p = 0.006, Fisher's exact test). The initially mis-diagnosed pleomorphic MCL was positive for CCND1 translocation.
Conclusions: We showed a low prevalence of cyclin D1 expression in DLBCLs and fully characterized the clinicopathological features of 3 cyclin D1+ DLBCL cases including a double-hit lymphoma, which has never been reported to be associated with cyclin D1 expression. In diagnostic practice, cases suspicious for DLBCL should be routinely stained for cyclin D1; and if positive, additional SOX11 staining is useful in differentiating cyclin D1+ DLBCL from MCL, particularly for the pleomorphic variant.
Monday, March 19, 2012 1:00 PM
Poster Session II # 196, Monday Afternoon