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Childhood Hodgkin Lymphoma Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Cellular Classification and Biologic Correlates

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.[3]

The hallmark of classic Hodgkin lymphoma is the Reed-Sternberg cell,[4] 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.[4]
  • The malignant Reed-Sternberg cell comprises only about 1% of the abundant reactive cellular infiltrate of lymphocytes, macrophages, granulocytes, and eosinophils in involved specimens.[4]
  • 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.[8]
  • Reed-Sternberg cells show constitutive activation of the nuclear factor kappa B pathway, which may prevent apoptosis and provide a survival advantage.[8]

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:

  • Lymphocyte-rich classical Hodgkin lymphoma.
  • Nodular sclerosis Hodgkin lymphoma.
  • Mixed-cellularity Hodgkin lymphoma.
  • Lymphocyte-depleted Hodgkin lymphoma.

These subtypes are defined according to the number of Reed-Sternberg cells, characteristics of the inflammatory milieu, and the presence or absence of fibrosis.

Characteristics of the histological subtypes of classical Hodgkin lymphoma include the following:

  • Lymphocyte-rich classical Hodgkin lymphoma may have a nodular appearance, but immunophenotypic analysis allows distinction between this form of Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma.[11] Lymphocyte-rich classical Hodgkin lymphoma cells express CD15 and CD30, while nodular lymphocyte-predominant Hodgkin lymphoma almost never expresses CD15.
  • Nodular sclerosis Hodgkin lymphoma histology accounts for approximately 80% of Hodgkin lymphoma cases in older children and adolescents but only 55% of cases in younger children in the United States.[12] This subtype is distinguished by the presence of collagenous bands that divide the lymph node into nodules, which often contain an Reed-Sternberg cell variant called the lacunar cell. Some pathologists subdivide nodular sclerosis into two subgroups (NS-1 and NS-2) on the basis of the number of Reed-Sternberg cells present. Transforming growth factor-beta may be responsible for the fibrosis in the nodular sclerosis Hodgkin lymphoma subtype.

    A study of over 600 patients with nodular sclerosis Hodgkin lymphoma from three different university hospitals in the United States showed that two haplotypes in the HLA class II region were identified, which correlated with 70% increased risk of developing nodular sclerosis Hodgkin lymphoma.[13] Another haplotype was associated with a 60% decreased risk. It is hypothesized that these haplotypes result in atypical immune responses that lead to Hodgkin lymphoma.

  • Mixed-cellularity Hodgkin lymphoma is more common in young children than in adolescents and adults, with mixed-cellularity Hodgkin lymphoma accounting for approximately 20% of cases in children younger than 10 years, but only approximately 9% of older children and adolescents aged 10 to 19 years in the United States.[12] Reed-Sternberg cells are frequent in a background of abundant normal reactive cells (lymphocytes, plasma cells, eosinophils, and histiocytes). Interleukin-5 may be responsible for the eosinophilia in mixed-cellularity Hodgkin lymphoma. This subtype can be confused with non-Hodgkin lymphoma.
  • Lymphocyte-depleted Hodgkin lymphoma is rare in children. It is common in adult patients with human immunodeficiency virus. This subtype is characterized by the presence of numerous large, bizarre malignant cells, many Reed-Sternberg cells, and few lymphocytes. Diffuse fibrosis and necrosis are common. Many cases previously diagnosed as lymphocyte-depleted Hodgkin lymphoma are now recognized as diffuse large B-cell lymphoma, anaplastic large-cell lymphoma, or nodular sclerosis classical Hodgkin lymphoma with lymphocyte depletion.[14]

WebMD Public Information from the National Cancer Institute

Last Updated: February 25, 2014
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.
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