- Clinical science
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 (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.
- 2–3/100 000 per year 
- Subtype variance with age (see “Pathology” below)
- Young adults: nodular sclerosing HL
- Elderly adults: mixed-cellularity HL
Age: bimodal distribution 
- 1st peak: 25–30 years
- 2nd peak: 50–70 years
Sex: ♂ > ♀ 
- Male predominance, especially in pediatric cases
- Exception: ♀ = ♂ in nodular sclerosing HL (most common type)
Epidemiological data refers to the US, unless otherwise specified.
- Cervical lymph nodes (in ∼ 60–70% of patients) > axillary lymph nodes (in ∼ 25–35% of patients) > inguinal lymph nodes (in ∼ 8–15% of patients) 
- Involvement of a single group of lymph nodes
- Contiguous pattern of lymph node spread
- Mediastinal mass → chest pain, dry cough, and shortness of breath
- Splenomegaly or hepatomegaly may occur if the spleen or liver are involved.
- B symptoms 
- Pel-Ebstein fever: Intermittent fever with periods of high temperature for 1–2 weeks, followed by afebrile periods for 1–2 weeks. Relatively rare but very specific for HL.
- Alcohol-induced pain: Pain in involved lymph nodes after ingestion of alcohol. Relatively rare but highly specific for HL.
- Pruritus (focal or generalized)
|Cotswolds modified Ann Arbor system (based on the original Ann Arbor staging system) |
|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|
- Complete blood count
- Serum chemistry
- Obligatory diagnostic step
Lymph node excision
- Reed-Sternberg cells (RSCs)
- Hodgkin cells: mononuclear, malignant B lymphocytes
- Inflammatory background containing the following cell types in varying numbers: lymphocytes, neutrophils, eosinophils, macrophages/histiocytes, plasma cells, and fibroblasts
- Granuloma formation
Reed-Sternberg cells are bi(2)nucleate with CD15/CD30 positivity. To recall the cell markers, remember that 2 x 15 = 30.
- Chest x-ray or CT-scan: detection and measurement of masses and enlarged lymph nodes in chest, abdomen, and pelvis
- Bone scintigraphy or PET-CT: performed before treatment to assess disease spread
|Histological classification of Hodgkin lymphoma (WHO)|
|Classical Hodgkin lymphoma (95%)||Nodular sclerosing classical HL (NSHL)|| || || |
|Mixed-cellularity classical HL (MCHL)|| |
|Lymphocyte-rich classical HL (LRHL)|| || |
|Lymphocyte-depleted classical HL (LDHL)|| || || |
|Lymphocyte predominant Hodgkin lymphoma (5%)||Nodular lymphocyte predominant HL (NLPHL)|| || |
Hodgin vs Non-Hodgkin lymphoma
|Feature||Hodgkin lymphoma||Non-Hodgkin lymphoma|
|Age distribution|| || |
|Lymph node involvement|| || |
| || |
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.
|Size|| || || |
|Consistency|| || |
|Tender/nontender|| || || |
|Fixation|| || || |
- Non-Hodgkin lymphomas, Hodgkin lymphomas
- Other hematopoietic malignancies (e.g. CML, ALL)
- Solid tumors
The differential diagnoses listed here are not exhaustive.
- Early stage (I and II): combination of chemotherapy and radiation therapy
- Advanced stage (III and IV and often II with bulky disease): combination chemotherapy with radiation therapy in select cases
- Primary refractory or relapsed disease: trial of alternative chemotherapy or consideration of high-dose chemotherapy and autologous stem cell transplantation
Independent of stage, treatment is typically initiated with curative intent!
- Good prognosis
- Prognosis is largely determined by disease stage (i.e., lower stage has a better prognosis)
- ∼ 10–20% of patients will develop secondary malignancies (especially lung cancer; related to radiation therapy and chemotherapy) 
- Unfavorable factors for Hodgkin lymphoma (relevant when selecting a treatment regimen)
International Prognostic Score (IPS): evaluation of prognosis in patients with advanced disease (for each factor present, the patient receives one point)
- IPS factors
- IPS categories: Based on the calculated IPS, patients can be categorized as follows:
- Good prognosis (IPS 0–1)
- Fair prognosis (IPS 2–3)
- Poor prognosis (IPS 4–7)