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Pathologie und molekulare Pathologie des Hodgkin-Lymphoms

Pathology and molecular pathology of Hodgkin’s lymphoma

Der Onkologe Aims and scope

Zusammenfassung

Hodgkin-Lymphome (HL) umfassen das noduläre, lymphozytenprädominante Hodgkin-Lymphom und das klassische Hodgkin-Lymphom, die separate Entitäten darstellen. Auch in der neuen WHO-Klassifikation werden die klassischen Hodgkin-Lymphome in den nodulär-sklerosierenden Subtyp, den Mischtyp, den lymphozytenreichen und den lymphozytenarmen Subtyp unterteilt. Hodgkin-Reed-Sternberg- (HRS-)Zellen stellen die Tumorzellpopulation im klassischen Hodgkin-Lymphom dar, während LP-Zellen charakteristisch für das noduläre, lymphozytenprädominante Hodgkin-Lymphom sind. HRS-Zellen stammen wahrscheinlich von präapoptotischen Keimzentrum-B-Zellen ab, und auch die LP-Zellen zeigen zahlreiche Keimzentrummerkmale. HRS-Zellen zeichnen sich durch eine Herabregulation des B-Zell-Phänotyps und eine Aktivierung zahlreicher potenter Signaltransduktionswege aus. Dazu zählen die konstitutive NFκB-Aktivierung, die JAK/STAT- und PI3K-Kaskaden sowie eine gesteigerte Expression antiapoptotischer Moleküle. Mit der kürzlichen Entdeckung von inaktivierenden Mutationen im TNFAIP3-Gen (A20) in ca. 40% aller klassischen Hodgkin-Lymphome scheint die NFκB-Signalkaskade eine zentrale Stellung in der Pathogenese einzunehmen.

Abstract

Hodgkin’s lymphoma comprises nodular lymphocyte-predominant Hodgkin’s lymphoma and classical Hodgkin’s lymphoma which are considered to be separate disease entities. The new WHO classification maintains the previously recognized subtypes of classical Hodgkin’s lymphoma which include the nodular sclerosis subtype, the mixed cellularity subtype and the lymphocyte-rich and lymphocyte-depleted subtypes. The tumor cells in classical Hodgkin’s lymphoma are the Hodgkin-Reed-Sternberg (HRS) cells, whereas LP cells are characteristic for nodular lymphocyte-predominant Hodgkin’s lymphoma. HRS cells are probably derived from pre-apoptotic germinal center B cells and LP cells also show many features of germinal center derivation. HRS cells are characterized by downregulation of the B cell expression program and activation of several potent signaling pathways. These include constitutive activation of NFκB, JAK/STAT and PI3 K signaling cascades as well as an increased expression of anti-apoptotic molecules. The recent identification of inactivating mutations of the TNFAIP3 gene coding for A20 in approximately 40% of classical Hodgkin’s lymphoma seems to indicate a central role for the NFκB cascade in the pathogenesis of this neoplasm.

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Rosenwald, A., Küppers, R. Pathologie und molekulare Pathologie des Hodgkin-Lymphoms. Onkologe 16, 9–17 (2010). https://doi.org/10.1007/s00761-009-1771-4

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  • DOI: https://doi.org/10.1007/s00761-009-1771-4

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