Background
Peripheral T-cell lymphomas (PTCLs) are heterogeneous neoplasms necessitating accurate sub-classification and molecular profiling for prognosis. Rare TP53-mutated TFH lymphomas are therapeutically challenging and often chemoresistant.
Case Presentation
A 49-year-old man presented November 2023 with cervical and axillary lymphadenopathy. Excisional biopsy showed peripheral T-cell lymphoma, NOS (CD2⁺ CD3⁺ CD4⁻ CD8⁻ CD5⁻ CD7⁻ CD30 dim, ALK⁻). Baseline PET-CT demonstrated widespread hypermetabolic adenopathy (SUVmax 11.8).
He received six cycles of brentuximab vedotin + CHP (Dec 2023 – Apr 2024). End-of-treatment PET showed Deauville 2, with a left supraclavicular node showing minimal improvement. No biopsy was performed before autologous SCT (BEAM, July 2024). PET-CT (Sept 2024) demonstrated recurrence. Repeat biopsy was reclassified as nodal TFH lymphoma, NOS (PD-1⁺ ICOS⁺ BCL6⁺ CD4⁻/CD8⁻, Ki-67 80%). Retrospective NGS (2023) revealed TP53 p.R196* (c.586C>T; VAF 53.3%) and SMARCA4 p.G883D (c.2648G>A; VAF 24.6%), indicating de novo pathogenic mutations. Repeat NGS (Oct 2024) showed clonal expansion (TP53 69%, SMARCA4 41.8%).
He subsequently received azacitidine + romidepsin, duvelisib + ruxolitinib, and valemetostat without durable response and is now being evaluated for CCR4-directed CAR T-cell therapy.
Discussion
Residual PET activity (Deauville 2) can mask active disease; pre-transplant biopsy may prevent false CMR assumptions.
TP53/SMARCA4 mutations predict poor autologous SCT outcomes; early allogeneic SCT or clinical trial enrollment should be considered.
cfDNA or NGS-based MRD tracking could refine post-induction risk assessment and guide transplant decisions.
Conclusion
Genomic profiling identified a high-risk TFH lymphoma with intrinsic TP53 mutation and clonal expansion, explaining early relapse and resistance. Integrating molecular diagnostics and MRD assessment initially may refine transplant strategies and improve outcomes.
