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Cellular Classification and Biologic Correlates

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    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]
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