Hodgkin Lymphoma

Hodgkin Lymphoma is a topic covered in the 5-Minute Clinical Consult.

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Historical background:

  • Described in 1832 by Thomas Hodgkin in “On some morbid appearance of the absorbent glands and spleen”
  • First neoplasm to be (i) defined by cytologic grounds based on presence of Reed-Sternberg (RS) cells, (ii) clinically staged neoplastic disease, and (iii) treated with chemotherapy and/or radiotherapy
  • Neoplastic RS cells of monoclonal lymphoid B-cell origin within inflammatory background of lymphocytes (T-helper type 2 and regulatory T cells), eosinophils, histiocytes, and plasma cells
  • Two subtypes: classic Hodgkin lymphoma (CHL, 95% of cases) and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL, 3–8% of cases)
    • NLPHL: B cells, neoplastic luteinizing hormone (LH) cells with multilobulated nuclei, small nucleoli, and popcorn-like appearance
    • CHL histologic subdivisions: nodular sclerosing (60%), mixed cellularity (30%), lymphocyte depleted (<10%), lymphocyte rich (<10%)
    • Frequency of lymph node involvement: cervical > mediastinal > axillary > paraaortic


  • Incidence: 2.6/100,000/year
  • Predominance: 8% of lymphoid malignancies
  • 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
Geriatric Considerations
Poorer prognosis if present at ≥60 years:
  • Less likely to tolerate intensive chemotherapy
  • Less likely to be included in clinical trial

Pediatric Considerations
Young females (<30 years of age) treated with thoracic radiation are at high risk for breast cancer, and early breast cancer screening is recommended.

Pregnancy Considerations
  • Abdominal ultrasonography to detect subdiaphragmatic disease
  • Treatment:
    • Delay until after delivery if asymptomatic and early stage.
    • ABVD safely used in 2nd and 3rd trimesters
    • Vinblastine monotherapy to control symptoms
    • 1st trimester: ABVD may or may not cause fetal malformations.

Approximately 8,500 new cases in the United States annually

Approximately 220,000 living with Hodgkin lymphoma in the United States as of 2015

Etiology and Pathophysiology

  • RS cells likely derived from germinal center B cells with mutations in immunoglobulin variable chain
  • Seasonal features and higher frequencies with Epstein-Barr virus (EBV) suggest environmental factors.
  • T-lymphocyte defects persist even after successful treatment.
  • Human leukocyte antigen (HLA) is strongly associated with increased risk.
  • EBV positivity associated with increased risk
  • 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

  • Immunodeficiency (inherited or acquired)
  • Autoimmune disorders
  • EBV
  • Seasonal factors

Commonly Associated Conditions


  • AIDS-defining illness
  • Predominantly mixed-cellularity or lymphocyte-depleted histologic subtypes
  • At diagnosis: widespread disease, extranodal involvement, systemic symptoms

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