里氏转化型弥漫性大B细胞淋巴瘤的免疫表型和基因组特征
Immunophenotypic and genomic landscape of Richter transformation diffuse large B-cell lymphoma.
作者信息
El Hussein Siba, Medeiros L Jeffrey, Lyapichev Kirill A, Fang Hong, Jelloul Fatima Zahra, Fiskus Warren, Chen Jiansong, Wei Peng, Schlette Ellen, Xu Jie, Li Shaoying, Kanagal-Shamanna Rashmi, Yang Hong, Tang Zhenya, Thakral Beenu, Loghavi Sanam, Jain Nitin, Thompson Philip A, Ferrajoli Alessandra, Wierda William G, Jabbour Elias, Patel Keyur P, Dabaja Bouthaina S, Bhalla Kapil N, Khoury Joseph D
机构信息
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Pathology, University of Rochester Medical Center, Rochester, NY, USA.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
出版信息
Pathology. 2023 Jun;55(4):514-524. doi: 10.1016/j.pathol.2022.12.354. Epub 2023 Feb 25.
Integrated clinicopathological and molecular analyses of Richter transformation of diffuse large B-cell lymphoma subtype (RT-DLBCL) cases remain limited. This study group included 142 patients with RT-DLBCL. Morphological evaluation and immunophenotyping, using immunohistochemistry and/or multicolour flow cytometry, were performed. The results of conventional karyotyping, fluorescence in situ hybridisation analysis and mutation profiling performed using next generation sequencing were reviewed. Patients included 91 (64.1%) men and 51 (35.9%) women with a median age of 65.4 years (range 25.4-84.9 years) at the time of RT-DLBCL diagnosis. Patients had CLL for a median of 49.5 months (range 0-330 months) before onset of RT-DLBCL. Most cases (97.2%) of RT-DLBCL had immunoblastic (IB) morphology, the remainder had a high grade morphology. The most commonly expressed markers included: CD19 (100%), PAX5 (100%), BCL2 (97.5%), LEF1 (94.7%), CD22 (90.2%), CD5 (88.6%), CD20 (85.7%), CD38 (83.5%), MUM1 (83.3%), CD23 (77%) and MYC (46.3%). Most (51/65, 78.4%) cases had a non-germinal centre B-cell immunophenotype. MYC rearrangement was detected in 9/47 (19.1%) cases, BCL2 rearrangement was detected in 5/22 (22.7%) cases, and BCL6 rearrangement was detected in 2/15 (13.3%) cases. In comparison to CLL, RT-DLBCL had higher numbers of alterations involving chromosomes 6, 17, 21, and 22. The most common mutations detected in RT-DLBCL involved TP53 (9/14, 64.3%), NOTCH1 (4/14, 28.6%) and ATM (3/14, 21.4%). Among RT-DLBCL cases with mutant TP53, 5/8 (62.5%) had TP53 copy number loss, and among those, such loss was detected in the CLL phase of the disease in 4/8 (50%) cases. There was no significant difference in overall survival (OS) between patients with germinal centre B-cell (GCB) and non-GCB RT-DLBCL. Only CD5 expression correlated significantly with OS (HR=2.732; 95% CI 1.397-5.345; p=0.0374). RT-DLBCL has distinctive morphological and immunophenotypic features, characterised by IB morphology and common expression of CD5, MUM1 and LEF1. Cell-of-origin does not seem to have prognostic implications in RT-DLBCL.
弥漫性大B细胞淋巴瘤亚型里氏转化（RT-DLBCL）病例的综合临床病理和分子分析仍然有限。该研究组纳入了142例RT-DLBCL患者。进行了形态学评估以及使用免疫组织化学和/或多色流式细胞术的免疫表型分析。回顾了使用下一代测序进行的传统核型分析、荧光原位杂交分析和突变谱分析的结果。患者包括91名（64.1%）男性和51名（35.9%）女性，RT-DLBCL诊断时的中位年龄为65.4岁（范围25.4 - 84.9岁）。患者在RT-DLBCL发病前患慢性淋巴细胞白血病（CLL）的中位时间为49.5个月（范围0 - 330个月）。大多数RT-DLBCL病例（97.2%）具有免疫母细胞（IB）形态，其余病例具有高级别形态。最常表达的标志物包括：CD19（100%）、PAX5（100%）、BCL2（97.5%）、LEF1（94.7%）、CD22（90.2%）、CD5（88.6%）、CD20（85.7%）、CD38（83.5%）、MUM1（83.3%）、CD23（77%）和MYC（46.3%）。大多数（51/65，78.4%）病例具有非生发中心B细胞免疫表型。在9/47（19.1%）的病例中检测到MYC重排，在5/22（22.7%）的病例中检测到BCL2重排，在2/15（13.3%）的病例中检测到BCL6重排。与CLL相比，RT-DLBCL涉及6号、17号、21号和22号染色体的改变数量更多。在RT-DLBCL中检测到的最常见突变涉及TP53（9/14，64.3%）、NOTCH1（4/14，28.6%）和ATM（3/14，21.4%）。在TP53突变的RT-DLBCL病例中，5/8（62.5%）存在TP53拷贝数缺失，其中4/8（50%）的病例在疾病的CLL阶段检测到这种缺失。生发中心B细胞（GCB）和非GCB RT-DLBCL患者的总生存期（OS）没有显著差异。只有CD5表达与OS显著相关（HR = 2.732；95% CI 1.397 - 5.345；p = 0.0374）。RT-DLBCL具有独特的形态学和免疫表型特征，其特征为IB形态以及CD5、MUM1和LEF1的共同表达。起源细胞似乎对RT-DLBCL的预后没有影响。
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