Hodgkin Lymphoma


Hodgkin lymphoma (HL) is a neoplasm of the lymphatic system representing one of the common cancers in young adults; characterized by a low number of malignant cells deriving from B lymphocytes and an extensive inflammatory microenvironment


  • Historical background:
    • Described first in 1832 by Thomas Hodgkin about a series of six patients with clinical findings different from those with tuberculosis, syphilis, and inflammation
    • German pathologist Carl Sternberg (1898) and American pathologist Dorothy Reed (1902) independently provided accounts of the giant “Reed-Sternberg” (RS) cells—the microscopic hallmarks of Hodgkin disease.
    • Initially treated with herbs, surgery, and arsenic in the 19th century; noted to shrink upon exposure to x-rays in the beginning of the 20th century. Chemotherapy instituted as first-line treatment in the early 1970s.
  • Subtypes:
    • Two subtypes:
      • Classical HL (cHL)—95% of cases; includes nodular sclerosing, mixed cellularity, lymphocyte rich, and lymphocyte depleted
      • Nodular lymphocyte predominant HL (NLPHL)—5% of cases


  • Incidence: 2 to 3 per 100,000 per year
  • 11% of all lymphoid malignancies
  • Has a bimodal age distribution—between 20 and 40 years and a second peak at around 55 years; typically diagnosed at age 20 to 34 years with median age 39 years at diagnosis given decreasing bimodal age distribution
  • 1.3:1 male-to-female ratio

Etiology and Pathophysiology

  • cHL is a B-cell lymphoma of germinal center origin that has lost its B-cell phenotype.
  • RS cells harbor clonal rearrangements of hypermutated, class-switched immunoglobulin genes resulting in nonfunctional immunoglobulin genes lacking the expression of the cell surface B-cell receptor. In a healthy B cell, this should lead to apoptosis; however, in HL, these cells appear to be “rescued” from apoptosis by additional oncogenic events.
  • NLPHL lacks typical RS cells but has lymphocytic and histiocytic cells, characterized by larger cells with folded multilobulated nuclei (“popcorn cells” or LP cells)—show a nucleus with multiple nucleoli that are basophilic and smaller than RS cells.
  • Genome-wide association studies identified 19p13.3 at intron 2 of TCF3.


  • First-degree relative: 3 to 9 times risk
  • Siblings of younger patients: 7 times risk
  • Weak correlation between familial HL and HLA class I regions containing HLA-A1, HLA-B5, HLA-B8, HLA-B18 alleles

Risk Factors

  • HIV: Increased risk of HL in patients who are HIV positive
  • Epstein-Barr virus (EBV): detected in nearly 45% of patients with HL
  • Genetic predisposition: significantly increased risk in identical twins indicating role of genetics in HL

General Prevention

Avoid exposure to chemicals such as pesticides, herbicides, and benzene.

Commonly Associated Conditions

HIV infection

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