Classical Hodgkin Lymphoma And Nodular Lymphocyte Predominant Hodgkin Lymphoma

Hodgkin lymphoma (HL) is a rather unique neoplasm. In contrast to most other lymphomas, and indeed malignancies in general, the bulk of the infiltrate in tissues affected by HL is comprised of non-neoplastic T cells, B-cells, macrophages, eosinophils, neutrophils, and plasma cells, while the neoplastic cells are rare, accounting for only approximately 1% of the tumor mass. The neoplastic cells include the hallmark binucleated large Reed–Sternberg cells, and morphologic variants thereof, which are collectively referred to as Hodgkin/Reed–Sternberg (HRS) cells. Intricate bi-directional signaling between the neoplastic cells and this pleomorphic, reactive background is integral to the tumor’s pathobiology and clinical features, with an evaluation of the various neoplastic and reactive cells being central to contemporary diagnosis and classification. Another unusual feature is that whereas the cell of origin in other lymphomas can almost always be correlated with a specific stage of lymphoid maturation, HRS cells do not have a morphologically and immunophenotypically identifiable normal hematopoietic counterpart. In fact, the unusual but characteristic immunophenotype of HRS cells includes antigens typically found on a spectrum of cells, such as dendritic cells, granulocytes, monocytes, B-cells, and plasma cells., For these reasons (rarity of neoplastic cells within the tumor and confusing immunophenotype), determining the ontogeny of HRS cells had been technically challenging. Additional impediments to characterizing these cells included the presence of only several cell lines and no animal model.