伴MYC、BCL2、BCL6基因重排的DLBCL/HGBL临床病理学特征分析

魏晶; 何雅琪; 薛田; 柏乾明; 水若鸿; 陆洪芬; 李小秋; 于宝华

doi:10.19401/j.cnki.1007-3639.2023.09.001

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伴MYC、BCL2、BCL6基因重排的DLBCL/HGBL临床病理学特征分析

论著 | 更新时间：2025-12-31

- 伴MYC、BCL2、BCL6基因重排的DLBCL/HGBL临床病理学特征分析
- Clinicopathological analysis of DLBCL/HGBL with MYC, BCL2 and BCL6 gene rearrangement
- 中国癌症杂志 2023年33卷第9期页码：809-817
- 作者机构：
  
  复旦大学附属肿瘤医院病理科，复旦大学上海医学院肿瘤学系，上海 200032
- 作者简介：
  
  [ "魏晶（ORCID: 0009-0008-9307-3255），学士。" ]
  于宝华（ORCID: 0000-0003-4433-4136），博士，主任医师。
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2023.09.001
  中图分类号： R733.4
- 收稿：2023-03-26，
  
  修回：2023-07-03，
  
  纸质出版：2023-09-30
- 稿件说明：
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魏晶, 何雅琪, 薛田, 等. 伴MYC、BCL2、BCL6基因重排的DLBCL/HGBL临床病理学特征分析[J]. 中国癌症杂志, 2023,33(9):809-817.

Jing WEI, Yaqi HE, Tian XUE, et al. Clinicopathological analysis of DLBCL/HGBL with MYC, BCL2 and BCL6 gene rearrangement[J]. China Oncology, 2023, 33(9): 809-817.
魏晶, 何雅琪, 薛田, 等. 伴MYC、BCL2、BCL6基因重排的DLBCL/HGBL临床病理学特征分析[J]. 中国癌症杂志, 2023,33(9):809-817. DOI： 10.19401/j.cnki.1007-3639.2023.09.001.

Jing WEI, Yaqi HE, Tian XUE, et al. Clinicopathological analysis of DLBCL/HGBL with MYC, BCL2 and BCL6 gene rearrangement[J]. China Oncology, 2023, 33(9): 809-817. DOI： 10.19401/j.cnki.1007-3639.2023.09.001.

摘要

背景与目的：

伴

MYC

、

BCL

2和

BCL

6基因重排的弥漫性大B细胞淋巴瘤/高级别B细胞淋巴瘤（diffuse large B-cell lymphoma/high-grade B-cell lymphoma，DLBCL/HGBL）又称三重打击淋巴瘤（triple-hit lymphoma，THL），其发病率低且文献报道较少，人们对其缺乏充分认识。本研究旨在探讨THL的临床病理学特征及患者预后。

方法：

收集复旦大学附属肿瘤医院病理科2016年6月—2021年12月诊断的THL病例10例，回顾性分析其临床特征，采用H-E染色观察其组织病理学特征，采用免疫组织化学法分析其免疫表型，采用荧光原位杂交（fluorescence

in situ

hybridization，FISH）法检测

MYC

、

BCL

2和

BCL

6基因重排，采用EB病毒编码RNA（Epstein-Barr virus-encoded RNA，EBER）原位杂交法检测判断EB病毒的感染状态。

结果：

10例THL患者中，男性4例，女性6例。中位年龄54岁（43~80岁）。其中2例发生在淋巴结，6例发生在结外器官，其余2例结内外均受累。临床分期Ⅲ/Ⅳ期4例（40%），Ⅰ/Ⅱ期6例（60%）。40%（4/10）的患者国际预后指数（international prognostic index，IPI）评分≥3分。50%（4/8）的患者有骨髓侵犯。2例（20%）有B症状。40%（4/10）的患者有乙肝病毒既往感染史。显微镜下观察5例呈非特指DLBCL（DLBCL

not otherwise specified，DLBCL-NOS）形态，2例兼具DLBCL与伯基特淋巴瘤特征，1例呈母细胞样形态，其余2例因组织挤压严重无法准确分类。免疫组织化学染色显示，80%为生发中心B细胞（germinal center B-cell，GCB）型，20%为非GCB（non-GCB）型；78%（7/9）为MYC/BCL2双表达，BCL6阳性率为80%，Ki-67增殖指数均≥80%。FISH检测显示，10例均同时有

MYC

、

BCL

2和

BCL

6基因重排。EBER原位杂交均呈阴性。除1例手术切除病灶后未化疗外，9例均接受系统治疗。10例患者的总生存期为2.0 ~ 55.5个月，中位总生存期为16.8个月。1年总生存率为68.6%，其中Ⅰ/Ⅱ期患者的1年总生存率100%，Ⅲ/Ⅳ期患者为25%。

结论：

THL好发于中老年人，以结外器官受累更常见，是一组形态学表现多样、以GCB型为主并常伴有MYC/BCL2双表达的侵袭性B细胞淋巴瘤。本研究患者中临床分期Ⅰ/Ⅱ期占多数且预后较好，因此及早甄别THL对于及时干预、改善预后具有重要临床意义。

Abstract

Background and purpose:

Diffuse large B-cell lymphoma/high-grade B-cell lymphoma (DLBCL/HGBL) with gene rearrangement of

MYC

BCL

2 and

BCL

also known as triple-hit lymphoma (THL)

has a low incidence and relevant literature is limited. Thus comprehensive and sufficient understanding is lacking. The purpose of this study was to explore the clinicopathological features and prognosis of this rare disease.

Methods:

Ten cases of THL diagnosed in Department of Pathology

Fudan University Shanghai Cancer Center from June 2016 to December 2021 were collected. Clinical features were analyzed retrospectively. Histopathological features were observed using H-E stain. Immunophenotype was analyzed by immunohistochemistry. The rearrangement of

MYC

BCL

2 and

BCL

6 genes was detected by fluorescence

in situ

hybridization (FISH)

and Epstein-Barr virus (EBV) infection was detected by

in situ

hybridization using EBV-encoded RNA (EBER).

Results:

Of the 10 cases

4 cases were male and 6 cases were female. The median age was 54 years (43-80 years). Two cases occurred in lymph nodes

6 cases involved extranodal organs

and both lymph nodes and extranodal organs were involved in the other 2 cases. There were 4 cases (40%) with clinical stage Ⅲ/Ⅳ disease and 6 cases (60%) with clinical stage Ⅰ/Ⅱ disease. 40% (4/10) patients had international prognostic index (IPI) score ≥3. 50% (4/8) patients had bone marrow invasion. Two (20%) cases had B symptoms. 40% (4/10) patients had a history of hepatitis B virus infection. Five cases had the morphology of DLBCL

not otherwise specified (DLBCL-NOS); Two cases showed morphological features intermediate both DLBCL and Burkitt lymphoma; One case had a blastoid cytomorphology

and the other 2 cases failed to be classified accurately because of serious crushing artifacts of the tissue. Immunophenotypically

80% of the cases were of germinal center B-cell (GCB) type and 20% were of non-GCB type. MYC/BCL2 double expression accounted for 78% (7/9)

BCL6 positivity was found in 80% of t

he total cases

and the Ki-67 proliferation index was ≥80% in all cases. FISH showed that all 10 cases had

MYC

BCL

2 and

BCL

6 gene translocation rearrangement. EBV infection was consistently absent. All except one case received systemic treatment. The overall survival was 2.0-55.5 months (median

16.8 months)

and 1-year overall survival rate was 68.6%. The 1-year overall survival rates of patients with stage Ⅰ/Ⅱ disease and stage Ⅲ/Ⅳ disease were 100% and 25% respectively.

Conclusion:

THL mainly affects middle-aged and elderly patients

which occured more frequently in extranodal organs

and it is characterized by GCB immunophenotype and MYC/BCL2 double expression. A considerable number of patients have a clinical stage of Ⅰ/Ⅱ disease and a better prognosis in the current series

indicating that early identification of THL is of great importance for timely intervention and improving the prognosis.

关键词

Keywords

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