Introduction

Hodgkin lymphoma (HL) is a malignant lymphoma characterized by the presence of mononucleated Hodgkin and multinucleated Reed-Sternberg (HRS) cells in the classical variant (cHL), while lymphocytic and histiocytic (L&H) cells are pathognomonic for the nodular lymphocyte-predominant HL (NLP-HL). In the majority of cases, HRS cells are most likely derived from preapoptotic germinal-center B-cells, but have lost most of the B-cell-typical genes, while L&H cells are reported to originate from antigen-selected germinal center B-cells and are characterized by the expression of multiple B-cell markers. Many questions concerning the pathogenesis of HL are still unanswered. Multiple signaling pathways and transcription factors show deregulated activity in HRS cells, including the NF-κB-, Jak-Stat- and PI3k-pathway, and signaling molecules such as Notch-1, which are physiologically not activated in B-cells. Additionally, the interaction of HRS cells with the surrounding inflammatory cells, the microenvironment, seems to play an important role in HRS cell growth and survival.

The prognosis of affected patients with HL depends on stage of disease and other clinical risk factors. The development of stage- and risk-adapted treatment regimens based on modern polychemotherapy and radio-therapy has improved the outcome dramatically over the past few decades. Current strategies aim at reducing therapy-associated complications while maintaining high cure rates. The increasing knowledge on the biology of HL offers the opportunity to develop targeted treatment approaches.