弥漫性大B细胞淋巴瘤（RT-DLBCL）Richter转化的临床病理和分子分析受到限制。本研究组包括142名RT-DLBCL患者。通过免疫组织化学和/或多色流式细胞术进行形态学评价和免疫表型分析。分析传统核型分析、荧光原位杂交分析和采用下一代测序进行的突变分型。患者中，男性91人（64.1％），女性51人（35.9％），RT-DLBCL诊断时的年龄中位数为65.4岁（范围25.4-84.9岁）。发病前CLL的中位时间为49.5个月（范围0-330个月）。RT-DLBCL的大多数病例（97.2％）具有免疫母细胞（IB）形态，其余具有高级别的形态。最常表达的标志包括：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47例中检测到9例（19.1％）的MYC重排、在22例中检测到BCL2重排的5例（22.7％）和在15例中检测到BCL6重排的2例（13.3％）。与CLL相比，RT-DLBCL涉及的染色体6、17、21和22的改变更多。在RT-DLBCL中最常见的突变包括TP53（9/14，64.3％）、NOTCH1（4/14，28.6％）和ATM（3/14，21.4％）。在突变TP53的RT-DLBCL病例中，5/8（62.5％）发生了TP53拷贝数丢失，在其中，这种丢失在疾病的CLL阶段中在4/8（50％）的病例中检测到。生发中心B细胞（GCB）和非-GCB RT-DLBCL患者的总生存期（OS）没有显着差异。只有CD5的表达与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形态和CD5、MUM1和LEF1的常见表达。细胞起源似乎在RT-DLBCL中没有预后影响。版权所有© 2023年澳大利亚皇家病理学院。由Elsevier BV出版。保留所有权利。

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.Copyright © 2023 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.