9/
This rare lymphoma may require organ-aware treatment strategies and could benefit from targeted approaches like STAT3 inhibition.

🎓 Big thanks to all co-authors & funders!

8/
💡 What does this mean clinically?

prDLBCL is:
• Genomically distinct from nodal DLBCL
• Closely aligned with immune-privileged lymphomas
• Marked by deep immune evasion strategies

Implication: Better diagnostic distinction & CNS-risk stratification needed.

7/
📈 RNA-seq revealed transcriptional programs enriched in:
• Interferon response (α/γ)
• MYC target genes
• STAT1/3 and NF-κB target genes
→ This further supports immune evasion and stress-adapted survival.

6/
We also detected structural fusions like ETV6::IGH and ETV6::PAX5, adding to the uniqueness of prDLBCL biology.
This hints at transcriptional deregulation as an additional driver.

5/
Despite some overlap, prDLBCL isn’t just CNS/testicular DLBCL in the kidney.
Only 3 cases met MCD subtype criteria (LymphGen).
Most fell into EZB (32%) or remained unclassified.

4/
Mutational landscape:
• Frequent mutations in STAT3, MYD88, TNFAIP3, CDKN2A, PIM1, PRDM1
• Deregulated signaling: JAK/STAT, NF-κB, MYC targets
• Large 6q deletions (PRDM1, ARID1B) in ~50% of cases

3/
Key findings:
• MHC class I loss: 69%
• MHC class II disruption: 62%
• Biallelic CDKN2A deletions: 38%
→ These changes mimic CNS/testicular DLBCL more than nodal forms.

2/
🧬 prDLBCL tumors harbor hallmarks of immune-privileged large B-cell lymphoma (IP-LBCL)—despite arising in the kidney, an organ with no native lymphoid tissue.

Immune escape is a key theme here.

1/
prDLBCL is a rare and understudied variant of the most common lymphoma.
We profiled the largest cohort to date (n=30), using WES, RNA-seq & SCNA.
What we found may reshape how we think about renal lymphomas 👇

🧵8/
🔍 We hope this adds to the understanding of extranodal MZL biology—and highlights the need for organ-aware diagnostics in rare lymphomas.

🎓 Big thanks to all co-authors & funders!

🧵7/
💡 Conclusion: prMZL seems to be a renal-adapted version of MALT lymphoma, not a separate disease.
The microenvironment + conserved molecular features might drive this rare localization.

🧵6/
🧼 Using metagenomic screening (Kraken2), we found no infectious signature in prMZL.
Unlike other MALT lymphomas, there’s no H. pylori or Chlamydia link—at least in FFPE samples.

🧵5/
🧪 Comparison with published MZL datasets:
→ prMZL is genomically closer to MALT lymphomas than to nodal or splenic MZL.
But some known pathogen-linked mutations (e.g. TNFAIP3, TET2, FAS) were rare, hinting at unique renal tropism.

🧵4/
📈 Copy number profiling showed:
Amplifications at chr3q, 7, 12, 18
Losses at chr6 (TNFAIP3) & chr17 (TP53)
chr3 gains (incl. FOXP1, PIK3CA, NFKBIZ) were especially prominent—also seen in gastric and ocular MALT lymphomas.

🧵3/
📊 Top recurrent mutations in prMZL:
KMT2C (33%)
NOTCH1 (33%)
TSC1 (33%)
SPEN, ARID1B, BCOR (24-29%)

This suggests key roles for chromatin remodeling & NOTCH signaling in its pathogenesis.

🧵2/
🧬 Using whole-exome sequencing & copy number profiling, we show that prMZL isn’t just a “renal version” of MZL—it shares striking molecular features with extranodal MZL (MALT lymphomas).
But some mutations are distinct. 👀