Genetic and immunological features of immune deficiency and dysregulation-associated lymphoproliferations and lymphomas as a basis for classification

Immune deficiency and dysregulation-associated lymphoproliferative disorders and lymphomas (IDD-LPDs) encompass a heterogeneous clinical and pathological spectrum of disorders that range from indolent lymphoproliferations to aggressive lymphomas. They arise in a variety of clinical settings and are associated with oncogenic viruses such as the Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus/human herpes virus (KSHV/HHV8) in some, but not all, cases. The recognition of IDD-LPDs as distinct from LPDs in immune competent patients is essential to tailor clinical management options for affected patients. The 5th edition of the World Health Organisation classification has introduced an integrated classification of IDD-LPDs with the goal of standardising diagnoses among different settings to enhance clinical decision support. In parallel, new knowledge in the field, particularly surrounding the role of oncogenic viruses and the tumour microenvironment, has led to clearer understanding of the complex pathogenesis of IDD-LPDs and how these features can be precisely harnessed for therapeutic purposes. In this perspective, we highlight the need for multidisciplinary decision-making to augment patient care as well as key areas where evolving concepts offer challenges and opportunities for clinical management, research and future iterations of the classification.