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Anaplastic Variant of Diffuse Large B-cell Lymphoma Displays Intricate Genetic Alterations and Distinct Biological Features

Li, Mingyang MD*; Liu, Yixiong MD*; Wang, Yingmei MD*; Chen, Gang MD; Chen, Qiongrong MD; Xiao, Hualiang MD§; Liu, Fang MD; Qi, Chubo MD; Yu, Zhou MD*; Li, Xia MD*; Fan, Linni MD*; Guo, Ying MD*; Yan, Qingguo MD*; Guo, Shuangping MD*; Wang, Zhe MD, PhD*

American Journal of Surgical Pathology: October 2017 - Volume 41 - Issue 10 - p 1322–1332
doi: 10.1097/PAS.0000000000000836
Original Articles

Anaplastic diffuse large B-cell lymphoma (A-DLBCL) is a rare morphologic variant characterized by the presence of polygonal, bizarre-shaped tumor cells. However, the clinicopathologic and genetic features of this variant are largely unknown. In this study, we investigated 35 cases of A-DLBCL with regard to their clinical, pathologic, and genetic characteristics. The age of the patients ranged from 23 to 89 years (median age, 62 y) with a male to female ratio of 23:12. Twenty-two of 26 (85%) patients had Ann Arbor stage III or IV disease, and 17/26 (65%) patients had a high-intermediate or high International Prognostic Index score. For the 24 patients treated with aggressive chemotherapy regimens, the median overall survival (OS) was 16 months, and the 2-year OS rate was 36%. Immunophenotypically, 30/35 (86%) cases had a non–germinal center B-cell immunophenotype. CD30 expression was present in 18/35 (51%) cases, and the p53 protein stain was positive in 28/35 (80%) cases. Fifteen of 35 (43%) cases expressed both BCL2 and MYC (double expressor). Twenty-nine of 32 (91%) cases tested positive for RELA, RELB, or c-Rel in the nucleus, indicating activation of the NFκB signaling pathway. Cytogenetically, 11/27 (41%) cases had concurrent MYC and BCL2 and/or BCL6 abnormalities (translocation or extra copy), including 5 cases with triple abnormalities. TP53 mutation was found in 17/30 (57%) cases, whereas the MYD88 L265P, CD79B, and CARD11 mutations were found in 7/35, 4/30, and 5/30 cases, respectively. We compared the A-DLBCL group with 50 patients with DLBCL without anaplastic features (common DLBCL). The OS of patients with A-DLBCL was significantly worse than that of patients with DLBCL without anaplastic features (P=0.004). Cases of A-DLBCL more often had a high International Prognostic Index score and a non–germinal center B-cell immunophenotype, more frequently expressed CD30 and p53, and more often had mutations of TP53 and concurrent abnormalities of MYC and BCL2 and/or BCL6 (P<0.05). In conclusion, A-DLBCL displays clinicopathologic features that distinguish it from ordinary DLBCL. Most patients follow an aggressive clinical course and have a poor outcome. Cases of A-DLBCL have a high frequency of TP53 mutation and genetic abnormalities of MYC, BCL2, and BCL6.

*State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi’an

Department of Pathology, Fujian Cancer Hospital, Fuzhou

Department of Pathology, Hubei Cancer Hospital, Wuhan

§Department of Pathology, Daping Hospital, Third Military Medical University, Chongqing

Department of Pathology, the First People’s Hospital of Foshan, Foshan, China

Conflicts of Interest and Source of Funding: Supported by grants from the National Natural Science Foundation of China (No. 81072103, 81272651 and 81570180). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Q.Y., S.G. and Z.W. contribute equally to this paper.

Correspondence: Zhe Wang, MD, PhD, State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road #169, Xi’an 710032, China (e-mail: zhwang@fmmu.edu.cn).

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