Background: Follicular helper T-cell cell lymphomas (TFHL) may exhibit complex clonal evolution.
Case Presentation: A 48-year-old woman was diagnosed in 2012 with a TFHL, angioimmunoblastic-type. The disease course was indolent, with spontaneous remissions, allowing a watch-and-wait approach. Between 2017 and early 2018, two self-limited lymphadenopathy flares occurred, with biopsies confirming persistence of the TFHL.
In November 2018, she developed fever, elevated LDH, and a positive plasma EBV PCR (3.4 log). PET-CT showed diffuse lymphadenopathy, pulmonary and hepatic nodules, and nasopharyngeal involvement. A lymph node biopsy revealed a nodal EBV-positive T/NK-cell lymphoma (CD8⁺/CD30⁻, TFH⁻ phenotype), stage IV, aaIPI 2.
Molecular profiling detected TET2 and RHOA G17V mutations (VAF 7–12%) in all prior TFHL samples but were absent in the T/NK-cell lymphoma biopsy. IDH2 R172K was present only in the 2012 sample. T-cell clonality demonstrated an identical clone in the 2012, 2017 and early 2018 biopsies and a distinct clone in the final specimen.
Four cycles of an asparaginase-based chemotherapy (Dec 2018–Mar 2019) followed by autologous stem cell transplantation (May 2019) achieved complete response. She remains in complete remission to date.
Conclusion: This case allows the discussion of indolent form of TFHL, with possible watch-and-wait approach, the clonal evolution of TFHL, the emergence of a clonally unrelated primary nodal EBV+ T/NK-cell lymphoma, and discussion about the management of this new entity. It also highlights the complexity of peripheral T-cell lymphomas and the importance of prolonged follow-up integrating molecular data.
