Hodgkin lymphoma is characterized by a variable number of characteristic multinucleated giant cells (Reed-Sternberg cells) or large mononuclear cell variants (lymphocytic and histiocytic cells) in a background of inflammatory cells consisting of small lymphocytes, histiocytes, epithelioid histiocytes, neutrophils, eosinophils, plasma cells, and fibroblasts. The inflammatory cells are present in different proportions depending on the histologic subtype. It has been conclusively shown that Reed-Sternberg cells and/or lymphocytic and histiocytic cells represent a clonal population. Almost all cases of Hodgkin lymphoma arise from germinal center B cells that cannot synthesize immunoglobulin.[1,2] The histologic features and clinical symptoms of Hodgkin lymphoma have been attributed to the numerous cytokines, chemokines, and products of the tumor necrosis factor receptors (TNF-R) family secreted by the Reed-Sternberg cells.
The hallmark of classic Hodgkin lymphoma is the Reed-Sternberg cell, which has the following features:
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The Reed-Sternberg cell is a binucleated or multinucleated giant cell with a bilobed nucleus and two large nucleoli that give a characteristic owl's eye appearance.
The malignant Reed-Sternberg cell comprises only about 1% of the abundant reactive cellular infiltrate of lymphocytes, macrophages, granulocytes, and eosinophils in involved specimens.
Reed-Sternberg cells almost always express CD30, and approximately 70% of patients express CD15. CD20 is expressed in approximately 6% to 10% of cases, and generally Reed-Sternberg cells do not express B-cell antigens such as CD45, CD19, and CD79A.[5,6,7]
Most cases of classic Hodgkin lymphoma are characterized by expression of TNF-Rs and their ligands, as well as an unbalanced production of Th2 cytokines and chemokines. Activation of TNF-R results in constitutive activation of nuclear factor kappa B.
Reed-Sternberg cells show constitutive activation of the nuclear factor kappa B pathway, which may prevent apoptosis and provide a survival advantage.
Hodgkin lymphoma can be divided into the following two broad pathologic classes:[9,10]
Classical Hodgkin lymphoma.
Nodular lymphocyte-predominant Hodgkin lymphoma.
Classical Hodgkin Lymphoma
Classical Hodgkin lymphoma is divided into the following four subtypes: