Born with two faces: sequential DLBCL, NOS and TFHL-AI with TET2 mutation – a case report

Diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) and nodal T follicular helper cell lymphoma, angioimmunoblastic type (TFHL-AI) share significant histopathological and pathogenetic similarities. However, the mechanisms underlying these overlaps remain insufficiently explored in the literature. We report the case of a 74-year-old man who initially presented with progressive sore throat and was diagnosed with DLBCL, NOS based on a tonsillar biopsy. He achieved complete remission following six cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, vindesine, liposomal doxorubicin, and dexamethasone). However, the patient was lost to follow-up. About two years later, he re-presented with generalized pruritus and lymphadenopathy. A cervical lymph node biopsy confirmed TFHL-AI. He received four cycles of the histone deacetylase inhibitor (HDACi) chidamide combined with COEP chemotherapy (cyclophosphamide, vindesine, etoposide, and prednisone), resulting in a partial remission. However, the disease subsequently progressed, and the patient passed away six months later, with a total overall survival of 35months. Next-generation sequencing (NGS) of biopsy specimens from both lymphoma types revealed shared <i>TET2</i> mutations. These findings suggest that <i>TET2</i> mutations may drive clonal evolution and reprogram the tumor microenvironment, potentially facilitating divergent evolution from a common mutated precursor or the sequential development of distinct lymphoid neoplasms. This case highlights the diagnostic and therapeutic challenges of TFHL-AI following DLBCL, NOS. Although the prognosis is generally poor, treatment combining HDAC inhibitors such as chidamide with chemotherapy may offer therapeutic potential. Further studies are needed to clarify the molecular mechanisms underlying such lymphoid evolution and to guide optimal management.