History and exam

Key diagnostic factors

common

presence of risk factors

Key factors include Epstein-Barr virus infection, positive family history, and young adults from higher socio-economic class.

lymphadenopathy

Persistent lymphadenopathy, typically painless and most commonly involving the cervical and/or supraclavicular nodal chain, is the most common presenting symptom of HL.

Mediastinal lymphadenopathy is common and is often asymptomatic. Occasionally, shortness of breath and/or cough may be present.

Axillary and inguinal lymphadenopathy is less common.

Other diagnostic factors

uncommon

unexplained fevers

History of recurrent, unexplained fevers, ≥38°C (≥100.4°F). One of the three B symptoms that occur in up to 30% of patients with HL, usually with advanced disease or other adverse risk factors.[4][5]

night sweats

History of drenching night sweats, necessitating change of bedclothes, is one of the three B symptoms that occur in up to 30% of patients with HL, usually with advanced disease or other adverse risk factors.[4][5]

weight loss

Unexplained weight loss of >10% of baseline weight in the preceding 6 months is one of the three B symptoms that occur in up to 30% of patients with HL, usually with advanced disease or other adverse risk factors.[4][5]

dyspnoea

Mediastinal lymphadenopathy is common but is often asymptomatic. Extensive mediastinal lymphadenopathy can compress the major airways causing dyspnoea.

cough

Extensive mediastinal lymphadenopathy can cause a dry cough.

chest pain

Extensive mediastinal lymphadenopathy can cause a vague chest discomfort.

superior vena cava syndrome (SVCS)

Extensive mediastinal lymphadenopathy can compress the superior vena cava which can result in SVCS.

Symptoms of SVCS include dyspnoea, cough, orthopnoea, facial and upper extremity oedema, and dilated neck veins.

abdominal pain

Extensive abdominal lymphadenopathy can result in abdominal pain.

pruritus

Approximately 10% of patients present with either localised or generalised pruritus.

Originally, but no longer, considered a B symptom. Several studies have demonstrated that pruritus is of no prognostic significance.[39]

alcohol-induced pain at involved sites

While rare, pain at sites of lymphadenopathy after drinking alcohol is a distinct and striking symptom characteristic of HL.

hepatomegaly and/or splenomegaly

May be present in advanced disease.

tonsillar enlargement

May be indicative of involvement of the tonsillar lymphoid tissue.

Risk factors

strong

age 20-34 years and >55 years

Peak incidence occurs at ages 20-34 years.[7] 

Data indicate a bimodal distribution of age at diagnosis, with an initial peak at ages 15-35 years followed by a more modest peak among those >55 years.​[6][7]​​​[8]

history of Epstein-Barr virus (EBV) infection

EBV antigens are found in 20% to 40% of Reed-Sternberg cells.[9][10] Antibodies against EBV antigens are more likely to be elevated several years prior to the diagnosis of HL than in healthy controls.[24] Infectious mononucleosis, of which EBV is the causative agent, is a risk factor for developing EBV-positive HL.[11] The vast majority of patients who contract EBV do not develop HL.

EBV-positive HL is more commonly of mixed cellularity histology, and it is predominantly reported in men and children in lower-income settings.[8][25]

In populations with European ancestry, 60% to 70% of patients have EBV-negative nodular sclerosis HL.[26]

family history of Hodgkin's lymphoma

There is evidence of a familial predisposition to HL, but this is uncommon (approximately 5% of cases are believed to be familial).[12][13][14]

If a monozygotic twin is diagnosed with HL, the risk of the second twin developing HL is nearly 100 times greater than that of the general population.[15] The risk among dizygotic twins is lower (approximately 7 times greater than the general population).[16]

First-degree relatives of patients with HL are approximately 3 times more likely to develop the disease than the general population.[17][18]

young adults from higher socio-economic class

Young adults from higher socio-economic classes are at greater risk of developing HL than their peers from lower socio-economic classes, especially with nodular sclerosis sub-type.[26][27]

Additionally, among young adults, the risk of developing HL seems to decrease with increasing birth order and increasing sibship size.[28] It is postulated that these associations are secondary to delayed exposure to infectious agents. These trends are not appreciated in children and older adults who develop HL.

weak

human leukocyte antigen (HLA) types

Numerous HLA types have been associated with an increased risk of HL.[29][30] These associations have been present in both sporadic and familial cases. The relative magnitude of the effect has been modest.

Lack of HLA class II expression has been associated with an adverse prognosis, independent of other known prognostic factors.[31]

Jewish ancestry

Jewish ancestry is associated with an increased risk of developing HL, even after adjusting for socio-economic status.[32]

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