Description

• 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 lymphoma.
  • 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 with the introduction of two different regimen—MOPP (mechlorethamine, vincristine [Oncovin], procarbazine, prednisone) and ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and dacarbazine); noted to have 80–90% remission rates
• Subtypes:
  • Two subtypes:
    • Classical Hodgkin lymphoma (cHL)—95% of cases; includes nodular sclerosing, mixed cellularity, lymphocyte rich, and lymphocyte depleted
    • Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)—5% of cases

Epidemiology

• Incidence: 2 to 3 per 100,000 per year
• Predominance: 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.

Genetics

• 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% patients with HL
• Genetic predisposition: significantly increased risk in identical twins indicating role of genetics in HL