A practical approach to the modern diagnosis and classification of T- and NK-cell lymphomas

T- and NK-cell lymphomas are neoplasms derived from immature T cells (lymphoblastic lymphomas), or more commonly, from mature T and NK cells (peripheral T-cell lymphomas, PTCLs). PTCLs are rare but show marked biologic and clinical diversity. They are usually aggressive and may present in lymph nodes, blood, bone marrow or other organs. More than 30 T/NK-cell derived neoplastic entities are recognized in the International Consensus Classification and the classification of the World Health Organization (5th edition), both published in 2022, which integrate most recent knowledge in hematology, immunology, pathology and genetics. In both proposals, disease definition aims to integrate clinical features, etiology, implied cell of origin, morphology, phenotype and genetic features into biologically and clinically relevant clinico-pathologic entities. Cell derivation from innate immune cells, or specific functional subsets of CD4+ T cells like follicular helper T cells, are major determinants delineating entities. Accurate diagnosis of T/NK-cell lymphoma is essential for clinical management and mostly relies on tissue biopsies. Because the histologic presentation may be heterogeneous and overlaps with that of many benign lymphoid proliferations and B-cell lymphomas, the diagnosis is often challenging. Disease location, morphology and immunophenotyping remain the main features guiding the diagnosis, often complemented by genetic analysis including clonality and high-throughput sequencing mutational studies. This review provides a comprehensive overview of the classification and diagnosis of T-cell lymphoma in the context of current concepts and scientific knowledge.