Hodgkin disease immunopathogenesis: long-standing questions, recent answers, further directions

Over the last decade, research into Hodgkin disease pathogenesis has progressed at an ever increasing pace. In the present Review, we address the issue of origin and clonality of Hodgkin and Reed-Sternberg (HRS) cells and their variants and present the compelling available evidence in favour of B-cell derivation. Emphasis is given to the global transcriptional de-regulation of HRS precursor cells, which prevents them from executing their B-cell developmental program and leads to loss of phenotypic B-cell identity; as suggested by recent experimental data, Epstein–Barr virus infection could be crucially implicated in this process.