Multi-neoplastic potentials including metachronous clonally unrelated nodal T-follicular helper cell lymphomas in clonal haematopoiesis.

Abstract

Nodal T-follicular helper cell lymphoma-angioimmunoblastic type (nTFHL-AI) commonly develops from a background of clonal haematopoiesis through stepwise acquisition of genetic changes with early genetic events (TET2 and DNMT3A mutations) in haematopoietic stem cells, and late changes (RHOA, IDH2, VAV1, PLCG1 and CD28 mutation/translocation) specifically in the lymphoma cells. There is growing evidence demonstrating multiple neoplastic potential of clonal haematopoiesis, as shown by early report of metachronous nTFHL-AI and myeloid neoplasm,1 and more recent studies from us and others that delineate parallel evolution of nTFHL-AI and other B [nodal marginal zone lymphoma (NMZL) like] and T-cell lymphomas (CD8+ cytotoxic peripheral T-cell lymphoma).2,3 We have now investigated a further follow up biopsy of “relapsed” nTFHL from the previous case with metachronous nTFHL-AI and NMZL-like lesion,2 and discovered that the relapsed nTFHL was not clonally related to the original nTFHL-AI, and harboured a different lymphoma specific mutation albeit sharing the same TET2 and DNMT3A mutations associated with clonal haematopoiesis.