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

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. Morpholog-ical evaluation and immunophenotyping, using immuno-histochemistry and/or multicolour flow cytometry, were performed. The results of conventional karyotyping, fluo-rescence 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 (77%) and MYC (46.3%). Most (51/65, 78.4%) cases had a non-germinal centre B-cell immunophenotype. MYC rear-rangement 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 immuno-phenotypic 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.

Automated summary

Integrated clinicopathological and molecular analyses were performed on 142 cases of RT-DLBCL. The study found that RT-DLBCL has distinctive morphological and immunophenotypic features, including immunoblastic morphology and common expression of CD5, MUM1, and LEF1. Cell-of-origin does not seem to have prognostic implications in RT-DLBCL.