RESULTS: Here we report 16 cases of EBV+ DHL/THL from screening 846 cases of DHL/THL and obtaining additional EBV+ cases through multi-institutional collaboration: 8 MYC/BCL2 DHL, 6 MYC/BCL6 DHL, and 2 THL. There were 8 men and 8 women with a median age of 65 years (range, 32-86). Two patients had a history of follicular lymphoma and one had AIDS. Nine of 14 patients had an International Prognostic Index of ≥3. Half of the cases showed high-grade/Burkitt-like morphology and the other half diffuse large B-cell lymphoma morphology. By immunohistochemistry, the lymphoma cells were positive for MYC (n=14/16), BCL2 (n=12/16), BCL6 (n=14/16), CD10 (n=13/16), and MUM1 (n=6/14). By Hans algorithm, 13 cases were classified as GCB and 3 as non-GCB. The lymphomas frequently showed an EBV latency type I with a median EBV-encoded small RNAs of 80% positive cells (range, 20-100%). After a median follow-up of 36.3 months (range, 2.0-41.6), 7 patients died with a median survival of 15.4 months (range, 3.4-47.3) after diagnosis of EBV+ DHL/THL. Five of 6 patients with MYC/BCL6 DHL were alive including 4 in complete remission. In contrast, only 4/10 patients with MYC/BCL2 DHL or THL were alive including 2 in complete remission. The median survival in patients with MYC/BCL6 DHL was unreached and was 21.6 months in patients with MYC/BCL2 DHL or THL.
CONCLUSIONS: EBV infection in DHL/THL is rare (~1.5%). Cases of EBV+ DHL/THL are largely similar to their EBV-negative counterparts clinicopathologically. Our findings expand the spectrum of EBV+ B-cell lymphomas currently recognized in the WHO classification and suggest differences between EBV+ MYC/BCL2 and MYC/BCL6 DHL that may have therapeutic implications.
结果:在这里,我们报告了16例EBV+DHL/THL,从846例DHL/THL的筛查和通过多机构合作获得额外的EBV+病例:8MYC/BCL2DHL,6MYC/BCL6DHL,2THL有8名男性和8名女性,中位年龄为65岁(范围,32-86).两名患者有滤泡性淋巴瘤病史,一名患有AIDS。14例患者中有9例的国际预后指数≥3。一半病例表现为高级别/Burkitt样形态,另一半为弥漫性大B细胞淋巴瘤形态。通过免疫组织化学,淋巴瘤细胞MYC阳性(n=14/16),BCL2(n=12/16),BCL6(n=14/16),CD10(n=13/16),和MUM1(n=6/14)。根据汉斯算法,13例分为GCB,3例为非GCB。淋巴瘤经常显示EBV潜伏期I型,EBV编码的小RNA中位数为80%阳性细胞(范围,20-100%)。经过36.3个月的中位随访(范围,2.0-41.6),7例患者死亡,中位生存期为15.4个月(范围,3.4-47.3)诊断为EBVDHL/THL后。6例MYC/BCL6DHL患者中有5例存活,其中4例完全缓解。相比之下,只有4/10的MYC/BCL2DHL或THL患者存活,其中2例完全缓解。MYC/BCL6DHL患者的中位生存期未达到,MYC/BCL2DHL或THL患者的中位生存期为21.6个月。
结论:EBV感染在DHL/THL中是罕见的(~1.5%)。EBVDHL/THL病例在临床病理上与EBV阴性的病例在很大程度上相似。我们的发现扩大了目前在WHO分类中认可的EBVB细胞淋巴瘤的范围,并表明EBVMYC/BCL2和MYC/BCL6DHL之间的差异可能具有治疗意义。