Department of Pathology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen.
Department of Pathology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong Province, China.
Am J Surg Pathol. 2020 Dec;44(12):1602-1611. doi: 10.1097/PAS.0000000000001577.
Double-hit/triple-hit lymphomas (DH/THLs) are high-grade B-cell lymphomas with MYC and BCL2 rearrangements and/or BCL6 rearrangements, which have poor outcomes after standard chemoimmunotherapy. This retrospective study analyzed 51 patients (range, 19 to 82 y) diagnosed from 2016 to 2019 and treated for DH/THL (n=34 MYC/BCL6 DHL, n=14 MYC/BCL2 DHL, n=3 THL) at one institution in South China. Extranodal lesions occurred in 32 patients (62.7%), more frequently in MYC/BCL6 DHL (22/34, 64.7%) than in MYC/BCL2 DHL (7/14, 50%). The most common extranodal sites were the stomach (8/32, 25.0%) and intestine (5/32, 15.6%). Most patients (33/45, 73.3%) presented with Ann Arbor stage III/IV. Interestingly, 14.3% (4/28) of MYC/BCL6 DHL tumors showed diffuse, medium-intensity CD30 expression. Epstein-Barr virus-encoded RNA was positive in 3 cases, all MYC/BCL6 DHL. Among 48 patients (94.1%) with follow-up data, 18 (37.5%) died owing to the disease, and the median survival was 5.5 months. Germinal center B cells were observed more frequently in MYC/BCL2 DHL (14/14, 100.0%) than in MYC/BCL6 DHL (15/34, 44.1%; P<0.001). Bone marrow involvement tended to lower overall survival (OS) (P=0.033). No association was observed between stage, B symptoms, lactate dehydrogenase levels, and central nervous system involvement and OS. A total of 25 patients (25/47, 53.2%) with previous hepatitis B virus (HBV) infections had significantly poorer OS (P=0.014). Chronic HBV infection was positively correlated with MYC/BCL6 DHL (r=0.317, P=0.030). Compared with DH/THL in western countries, the disease in South China has distinct characteristics with a higher prevalence of MYC/BCL6 DHL. We speculate that HBV is important in DH/THL tumorigenesis. These findings might provide clues for novel treatment strategies.
双打击/三打击淋巴瘤（DH/THL）是一种高级别 B 细胞淋巴瘤，具有 MYC 和 BCL2 重排和/或 BCL6 重排，在接受标准化疗免疫治疗后预后较差。本回顾性研究分析了 2016 年至 2019 年在华南地区一家机构诊断并治疗的 51 例（年龄 19 至 82 岁）DH/THL 患者（n=34 MYC/BCL6 DHL，n=14 MYC/BCL2 DHL，n=3 THL）。32 例患者（62.7%）存在结外病变，MYC/BCL6 DHL（22/34，64.7%）比 MYC/BCL2 DHL（7/14，50%）更常见。最常见的结外部位是胃（8/32，25.0%）和肠（5/32，15.6%）。大多数患者（33/45，73.3%）表现为安阿伯分期 III/IV 期。有趣的是，14.3%（4/28）的 MYC/BCL6 DHL 肿瘤表现为弥漫性、中等强度的 CD30 表达。3 例 EBV 编码 RNA 阳性，均为 MYC/BCL6 DHL。在有随访数据的 48 例患者（94.1%）中，18 例（37.5%）因疾病死亡，中位生存期为 5.5 个月。生发中心 B 细胞在 MYC/BCL2 DHL 中更常见（14/14，100.0%），而在 MYC/BCL6 DHL 中则较少见（15/34，44.1%；P<0.001）。骨髓受累与总生存期（OS）降低有关（P=0.033）。分期、B 症状、乳酸脱氢酶水平和中枢神经系统受累与 OS 之间无相关性。25 例（25/47，53.2%）有既往乙型肝炎病毒（HBV）感染的患者 OS 明显较差（P=0.014）。慢性 HBV 感染与 MYC/BCL6 DHL 呈正相关（r=0.317，P=0.030）。与西方国家的 DH/THL 相比，中国南方的这种疾病具有明显的特征，MYC/BCL6 DHL 更为常见。我们推测 HBV 在 DH/THL 肿瘤发生中起重要作用。这些发现可能为新的治疗策略提供线索。
