How immunologic and genetic biomarkers impact Hodgkin lymphoma classification, diagnosis, and management: a huge potential that yet needs to be exploited

“Ne è passata di acqua sotto i ponti.” It has been a long time since the diagnosis of Hodgkin lymphoma (HL) was exclusively based on the detection of typical Reed-Sternberg cells and the recognition of the characteristic morpho-histological background, as well as on the pathologist’s skill. The discovery of immunologic, molecular genetic and virologic biomarkers has provided an objective contribution to the diagnosis and a scientific basis for a modern classification of HL. Recent updates have clarified the nature of the so-called nodular lymphocyte predominant HL and its link to the T-cell/histiocyte-rich large B-cell lymphomas as well as its relationship with the lymphocyte-rich subset of classical HL (CHL). Molecular virology studies assessed a role for the Epstein-Barr virus in the pathogenesis of a fraction of CHL of the general population, and virtually in all cases of CHL occurring in people infected by HIV. Finally, immunologic and genetic findings corroborated the existence of grey zone lymphomas at the edges of CHL. Overall, these advances provided additional and useful information to address the treatment of patients affected by HL.