The molecular pathology of classical Hodgkin lymphoma

Abstract

In 1832, Dr. Thomas Hodgkin reported the first cases with this malignancy, which came to be named Hodgkin's disease. The cells that are a hallmark of this disease, Hodgkin and Reed-Sternberg (HRS) cells, account for only 1% of those in tumor tissues, with the majority of cells in Hodgkin lymphoma being of various inflammatory types. Advances in molecular techniques have contributed to molecular biological analysis of HRS cells. Intriguingly, HRS cells are derived from germinal center B-cells, but have lost their B-cell gene-expression and co-express non-B-cell genes. Multiple signaling pathways, including the NFκB and JAK/STAT pathways, show deregulated activity in HRS cells, suggesting an important role for these pathways in the pathogenesis of Hodgkin lymphoma. This article describes the molecular pathological characteristics of HRS cells: 1) the cellular origin of HRS cells, 2) deregulated gene expression in HRS cells, 3) genetic alterations and 4) epigenetic alterations in HRS cells, 5) the lost B-cell phenotype of HRS cells, 6) the role of EBV in Hodgkin lymphoma pathogenesis, and 7) micro-environmental interactions between HRS and reactive cells.