Immunophenotypic and genomic landscape of Richter transformation diffuse large B-cell lymphoma

Siba El Hussein, L. Jeffrey Medeiros, Kirill A. Lyapichev, Hong Fang, Fatima Zahra Jelloul, Warren Fiskus, Jiansong Chen, Peng Wei, Ellen Schlette, Jie Xu, Shaoying Li, Rashmi Kanagal-Shamanna, Hong Yang, Zhenya Tang, Beenu Thakral, Sanam Loghavi, Nitin Jain, Philip A. Thompson, Alessandra Ferrajoli, William G. WierdaElias Jabbour, Keyur P. Patel, Bouthaina S. Dabaja, Kapil N. Bhalla, Joseph D. Khoury

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)514-524
Number of pages11
Issue number4
StatePublished - Jun 2023


  • Richter transformation
  • chronic lymphocytic leukaemia
  • diffuse large B-cell lymphoma
  • immunophenotype
  • leukaemia
  • next generation sequencing

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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