伴有MYC、bcl-2和/或bcl-6重排的高级别B细胞淋巴瘤临床病理学特征

Clinicopathological features and prognosis of high-grade B-cell lymphoma with MYC and bcl-2 and/or bcl-6 rearrangements

目的探讨伴有MYC、bcl-2和/或bcl-6重排的高级别B细胞淋巴瘤(HGBL)的临床病理学特征。方法收集2017年1月至2020年9月上海交通大学医学院附属瑞金医院病理科经MYC、bcl-2和bcl-6基因荧光原位杂交(FISH)检测的大B细胞淋巴瘤1 138例。对诊断为伴有MYC、bcl-2和/或bcl-6重排的HGBL回顾性分析其临床特点、病理学特征、免疫表型及预后。结果在1 138例大B细胞淋巴瘤中, 共检出45例(4.0%)伴有MYC、bcl-2和/或bcl-6重排的HGBL, 其中6例HGBL伴有MYC、bcl-2和bcl-6重排, 14例伴有MYC和bcl-2重排, 25例伴有MYC和bcl-6重排。45例患者中男性29例, 女性16例, 发病年龄29~83岁。依据Hans分型, 伴有MYC、bcl-2和bcl-6重排的HGBL、伴有MYC和bcl-2重排的HGBL均为生发中心B细胞(GCB)型, 伴有MYC和bcl-6重排的HGBL包括GCB型(17/25, 68.0%)和非GCB型(8/25, 32.0%)。大部分病例显示Ki-67高增殖指数。临床表现Ann Arbor Ⅲ~Ⅳ期、国际预后指数(IPI)3~5分、血清乳酸脱氢酶(LDH)升高的患者均占半数以上, 部分患者伴有血浆β2微球蛋白水平升高、B症状、骨髓侵犯等临床特征。伴有MYC、bcl-2和bcl-6重排的HGBL和伴有MYC和bcl-6重排的HGBL, 这两组的IPI和LDH临床指标差异均有统计学意义(P<0.05)。与伴有MYC、bcl-2和bcl-6重排的HGBL相比, 伴有MYC和bcl-2或bcl-6重排的HGBL的骨髓侵犯发生率较低(P<0.05)。此外, 伴有MYC、bcl-2和/或bcl-6重排的HGBL任两组之间在预后方面差异无统计学意义(P>0.05)。结论伴有MYC、bcl-2和/或bcl-6重排的HGBL是一种少见的B细胞淋巴瘤类型, 其侵袭性强, 预后较差。诊断时需要结合临床特征、病理组织学、免疫组织化学和荧光原位杂交检测结果, 以减少漏诊和误诊。

Objective To investigate the clinicopathological characteristics and prognosis of high-grade B-cell lymphoma(HGBL)involving combined rearrangements of MYC,bcl-2 and bcl-6.Methods A total of 1138 cases of large B cell lymphoma(LBL)that were treated at the Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2017 to September 2020 were analyzed using fluorescence in situ hybridization(FISH)with probes against MYC,bcl-2 and bcl-6.The clinical and pathological data of the 45 patients with HGBL that had rearrangements of MYC and bcl-2 and/or bcl-6 were collected and retrospectively analyzed.Results Among the 1138 LBL,45(4.0%)cases had combined rearrangements of MYC,bcl-2 and/or bcl-6 that included 6 HGBL cases with MYC,bcl-2 and bcl-6 rearrangements,14 HGBL cases with MYC and bcl-2 rearrangements,and 25 HGBL cases with MYC and bcl-6 rearrangements.Of these 45 patients,29 patients were male,and 16 patients were female,aged 29 to 83 years.HGBL with MYC,bcl-2 and bcl-6 rearrangements and HGBL with MYC and bcl-2 rearrangement were reclassified as the germinal center B-cell(GCB)subtype using the Hans algorithm.HGBL with MYC and bcl-6 rearrangement were reclassified as the GCB subtype(68.0%)and the non-GCB subtype(32.0%).The vast majority of HGBL cases had a high Ki-67 proliferation index.Most HGBL patients had advanced stage disease with a high IPI score and an increased LDH level.Also,some patients had clinical features including elevated plasmaβ2-microglobulin levels,B symptoms,and bone marrow involvement.The IPI scores and LDH levels were significantly different between the HGBL cases with MYC,bcl-2 and bcl-6 rearrangements and the HGBL cases with MYC and bcl-6 rearrangements(P<0.05).Compared with the HGBL cases with MYC,bcl-2 and bcl-6 rearrangements,the HGBL cases with MYC and bcl-2 or bcl-6 rearrangements had a lower incidence of bone marrow involvement(P<0.05).There were no significant differences in the prognosis among HGBL cases with MYC,bcl-2 and bcl-6 rearrangements,the cases with MYC and bcl-2 rearrangements,and the cases with MYC and bcl-6 rearrangements(P>0.05).Conclusions HGBL with MYC,bcl-2 and/or bcl-6 rearrangements are rare types of B-cell lymphoma with high degree of malignancy and have a short overall survival.To reduce misdiagnosis and improve diagnostic accuracy,it is necessary to assess the patients′clinical features and conduct histopathological,immunohistochemical and FISH analyses.