Summary
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.
Key words
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Article info
Publication history
Published online: March 16, 2023
Accepted:
December 14,
2022
Received in revised form:
December 4,
2022
Received:
September 17,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.
