Abstract：
Several reports of concurrent MYC, BCL2, BCL6, and CCND1 rearrangements in high-grade B-cell lymphoma (HGBL) have been recently described. Herein, we aimed to delineate the scope of this entity through a review of HGBL with a \"quadruple-hit\" genetic profile identified at our institution. We performed a retrospective review (2015-2023) at our institution of B-cell lymphoma (BCL) cases that were evaluated with concurrent MYC, BCL2, and BCL6 break-apart and IGH::MYC and IGH::CCND1 dual-color dual-fusion fluorescence in situ hybridization studies. Of 203 cases meeting inclusion criteria, 2 (1%) with a quadruple-hit genetic profile were identified. Case 1 represented a 59-year-old female with widespread lymphadenopathy and a diagnosis of HGBL who exhibited primary refractoriness to dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) chemotherapy. Case 2 represented a 58-year-old male with mediastinal and abdominal lymphadenopathy and a diagnosis of large BCL who died from disease after 1 cycle of DA-EPOCH-R chemotherapy. Similarly, a literature review of 7 previously reported cases of HGBL with a quadruple-hit profile also demonstrated aggressive disease behavior. Our study adds 2 new cases to the rarely encountered quadruple-hit HGBL, and a brief meta-analysis of the 9 available cases indicates aggressive disease behavior conferred by this constellation of genetic events.
摘要：
并发MYC的几份报告，最近已经描述了高级B细胞淋巴瘤（HGBL）中的BCL2，BCL6和CCND1重排。在这里，我们的目的是通过对HGBL进行审查来划定该实体的范围，该HGBL具有我们机构确定的“四重命中”遗传特征。我们在我们的B细胞淋巴瘤（BCL）病例机构进行了回顾性审查（2015-2023），并同时进行了MYC评估，BCL2和BCL6分裂和IGH::MYC和IGH::CCND1双色双融合荧光原位杂交研究。在203个符合纳入标准的案例中，2（1％）具有四重打击的遗传特征。病例1代表一名59岁女性，患有广泛的淋巴结病，诊断为HGBL，对剂量调整的依托泊苷表现出原发性难治性，泼尼松,长春新碱,环磷酰胺,阿霉素,和利妥昔单抗（DA-EPOCH-R）化疗。病例2代表一名58岁男性，患有纵隔和腹部淋巴结病，诊断为大型BCL，在1个周期的DA-EPOCH-R化疗后死于疾病。同样，对先前报道的7例具有4次感染特征的HGBL病例的文献综述也证明了侵袭性疾病行为.我们的研究在罕见的四重重击HGBL中增加了2例新病例，对9个可用病例的简短荟萃分析表明，这种遗传事件引起的侵袭性疾病行为。
