• Clinical science

Hodgkin lymphoma (Lymphogranulomatosis)


Hodgkin lymphoma (HL) is a malignant lymphoma that is typically of B-cell origin. The incidence of HL has a bimodal age distribution, with peaks in the 3rd and 6th–8th decades of life. The WHO classifies HL into two types: classical HL (CHL) and nodular lymphocyte-predominant HL (NLPHL). CHL is further divided into four subtypes, which are nodular sclerosis (most common), mixed cellularity, lymphocyte-depleted, and lymphocyte-rich CHL. Risk factors for developing HL include a history of infectious mononucleosis caused by the Epstein-Barr virus (EBV) and immunodeficiency (e.g., HIV infection). HL typically presents with painless cervical lymphadenopathy, fever, night sweats, and involuntary weight loss. Pel-Ebstein fevers (cyclical fever with periods of both high and normal temperature) and alcohol-induced pain at affected lymph nodes are less common but specific for HL. Suspicious lymph nodes are excised and definitive diagnosis is made via histological analysis, which characteristically reveals pathognomonic Reed‑Sternberg cells (malignant B-cells). The modified Ann Arbor classification (Cotswold staging system) is used to stage HL based on both the localization of the lymphoma with respect to the diaphragm and on the presence of systemic symptoms. Treatment is typically initiated with curative intent. In early stages, treatment is generally limited to involved-field radiation and chemotherapy. In later stages, when local radiation is often unsuccessful or not feasible due to tumor spread, polychemotherapy is the mainstay of treatment.


  • Incidence
    • 2–3/100 000 per year [1]
    • Subtype variance with age (see “Pathology” below)
      • Young adults: nodular sclerosing HL
      • Elderly adults: mixed-cellularity HL
  • Age: bimodal distribution [2]
    • 1st peak: 25–30 years
    • 2nd peak: 50–70 years
  • Sex: > [2]
    • Male predominance, especially in pediatric cases
    • Exception: = in nodular sclerosing HL (most common type)

Epidemiological data refers to the US, unless otherwise specified.


The exact causes are unknown, but several risk factors have been associated with HL.


Clinical features



Cotswolds modified Ann Arbor system (based on the original Ann Arbor staging system) [7][8]
Stage Description
I Involvement of 1 lymph node area (IN), or 1 extranodal (IE) focus
II Confined to one side of the diaphragm: Involvement of ≥ 2 (IIN) lymph node areas or extranodal foci (IIE)
III On both sides of the diaphragm: Involvement of ≥ 2 (IIIN) lymph node areas or extranodal foci (IIIE)
IV Disseminated spread into one or more extralymphatic organs independent of lymph node involvement

Additional modifiers

  • Primarily involved tissue: nodal (N) or extranodal (E)
  • Symptoms
  • Bulky disease (X)

Staging is based on the number of affected nodes, the presence or absence of B symptoms, and whether or not the disease is present on both sides of the diaphragm.


Diagnosis of HL is primarily based on medical history and clinical features (B symptoms, localization of lymph node involvement) and is confirmed with lymph node biopsy.

Blood tests


Reed-Sternberg cells are bi(2)nucleate with CD15/CD30 positivity. To recall the cell markers, remember that 2 x 15 = 30.




Histological classification of Hodgkin lymphoma (WHO)
Classification Subtype Characteristics Prognosis Pathology
Classical Hodgkin lymphoma (95%) Nodular sclerosing classical HL (NSHL)
  • Most common subtype (> 60%)
  • Localization: mostly mediastinal and cervical
  • Good
  • Nodules of Reed-Sternberg cells within lacunae, separated by collagenous tissue with sclerosing appearance (hence the name “nodular sclerosing”).
  • Lymphocyte rich.
Mixed-cellularity classical HL (MCHL)
  • Commonly found in immunocompromised patients (e.g., HIV-positive individuals)
  • Localization: mostly abdominal and splenic
  • Good (but slightly worse than NSHL)
Lymphocyte-rich classical HL (LRHL)
  • Rare
  • Localization: mostly cervical and axillary
  • Very good
Lymphocyte-depleted classical HL (LDHL)
  • Very rare (< 1%)
  • Commonly found in immunocompromised patients
  • Localization: mostly below the diaphragm
  • Poor
Lymphocyte predominant Hodgkin lymphoma (5%) Nodular lymphocyte predominant HL (NLPHL)
  • Rare (5%)
  • Very good (but slightly worse than LRHL)


Differential diagnoses

Hodgin vs Non-Hodgkin lymphoma

Feature Hodgkin lymphoma Non-Hodgkin lymphoma
Age distribution
  • Increases with age (peak > 50 years)
Lymph node involvement
  • Lymph node groups localized above the diaphragm
  • Contiguous spread
  • Extranodal involvement rare
  • Multiple lymph node groups
  • Noncontiguous spread
  • Extranodal involvement common


  • Good
  • Worse .

Differential diagnoses of lymphadenopathy

Examining lymph nodes can yield important diagnostic clues. Generalized lymphadenopathy is usually a sign of systemic illness, such as HIV, mycobacterial infection (e.g., tuberculosis), infectious mononucleosis, systemic lupus erythematodes, or serum sickness. Signs of malignancy include rapid growth, painlessness, hardness/coarseness, and being fixed to underlying or surrounding tissue. Most often, though, there is no discernible cause or pathology.

Feature Normal Infection Malignancy
  • < 1 cm
  • > 1 cm
  • > 1 cm
  • Soft
  • Hard (various malignancies)
  • Rubbery (typical of lymphoma)
  • Nontender
  • Tender
  • Nontender
  • Freely movable
  • May be fixed or freely movable
  • Fixed to the underlying tissue

Differential diagnosis of B symptoms

Differential diagnosis of granulomatous disease

The differential diagnoses listed here are not exhaustive.


Independent of stage, treatment is typically initiated with curative intent!