Pathogenesis of Classical and Lymphocyte-Predominant Hodgkin Lymphoma

Hodgkin and Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (HL) and lymphocytic and histiocytic (L&H) cells in nodular lymphocyte-predominant HL (NLPHL) are derived from germinal-center B cells. HRS cells have, however, largely lost their 13 cell phenotype and aberrantly express markers and transcriptional regulators of other hematolymphoid cell types. Deregulation of multiple signaling pathways and downstream transcription factors, including receptor tyrosine kinases, nuclear factor-kappa B (NF-kappa B),and Janus kinase/signal transducer and activator of transcription (JAK/STAT), is a further hallmark of HRS cells. These cells harbor genetic lesions that contribute to or cause increases in the activity of transcription factors of the NF-kappa B and STAT families. HRS cells are found within a mixed reactive cellular infiltrate and interact with these nonmalignant cells in a complex fashion that appears to be essential for HRS cell survival and proliferation. Less is known about the pathogenesis of L&H cells in NLPHL, but increases in the activity of receptor tyrosine kinases, NF-kappa B, and JAK/STAT have also been detected.