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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.
Stephanie Sasse, First Department of Internal Medicine, University Hospital, Cologne, 50924, Cologne, Germany,
Andreas Engert, First Department of Internal Medicine, University Hospital, Cologne 50924, Cologne, Germany,
Andrew Wotherspoon, Department of Histopathology, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK,
Andreas Rosenwald, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany,
German Ott, Institute of Pathology, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, 97080, Germany
Hodgkin's lymphoma (HL) is a malignant lymphoma. The classical variant (cHL) is characterized by the presence of mononucleated Hodgkin and multinucleated Reed–Sternberg (HRS) cells, while lymphocytic and histiocytic (L&H) cells (“popcorn cells”) are pathognomonic for nodular lymphocyte-predominant HL (NLPHL). After the first description of patients suffering from enlarged lymph nodes and spleen by Thomas Hodgkin in 1832, it took more than 150 years finally to prove the malignant character of these pathognomonic cells and to show their origin from a germinal-center B cell in the majority of cases. Many questions concerning the pathogenesis of Hodgkin's lymphoma are still unanswered; an important step in the pathogenesis of classical HL seems to be the constitutive activation of the NF-κB pathway.
The prognosis of patients with HL depends on the stage of disease and clinical risk factors. The development of stage- and risk-adapted treatment regimens based on modern polychemotherapy and radiotherapy has improved the outcome dramatically over the past few decades. Current strategies aim at reducing therapy-associated complications while maintaining high cure rates.
HL has an annual incidence of 2–3 per 100 000 in Europe and the USA, and accounts for approximately one-sixth of all lymphoma. Slightly more men than women are affected. In industrialized countries the onset of disease shows a bimodal distribution, with a first peak in the third decade and a second, much smaller, peak after the age of 60.
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