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Hodgkin lymphoma (HL) is a haematological malignancy that arises from B lymphocytes in the lymphatic system.
In the United Kingdom, 2,100 people are diagnosed each year, with a peak incidence in young adults aged 20 – 34 years and in older adults aged over 70 years.
Overall, the prognosis is good with 75% of patients with HL surviving for ten years or more.
Prognosis is better in the younger population than in the older population. Younger patients under the age of 40-years-old have a five-year survival rate of 95% whereas older patients over the age of 70-years-old have a five-year survival rate of less than 50%.1,2
The lymphatic system is a network of tissues and organs that play a key role in the immune system. This network consists of lymph nodes, lymphatic vessels, lymphatic organs and lymphatic fluid.3
Lymphatic fluid contains a high number of lymphocytes and it is the mutation of these cells inside lymphoid tissues that results in a lymphoma.
Hodgkin lymphoma occurs when B lymphocytes, derived from the germinal centres of lymphoid tissues, mutate and lead to the presence of large, multi-nucleated giant cells called ‘Reed-Sternberg’ cells and large, mono-nucleated cells called malignant ‘Hodgkin cells’. 4,5
There are two main types of Hodgkin lymphoma (HL), classical Hodgkin lymphoma (which accounts for 95% of HL cases) and nodular lymphocyte-predominant Hodgkin lymphoma (which accounts for 5% of HL cases).
Classical Hodgkin lymphoma (cHL) is further subclassified into four types.
25% of cHL cases. Prevalent in patients with HIV and in developing countries. Splenic infiltration is seen in 30% of patients.
5% of cHL cases. Mediastinal mass is rare.
<1% of cHL cases. Prevalent in patients with HIV and in developing countries.
Nodular lymphocyte-predominant Hodgkin lymphoma is a more indolent disease with little in common with cHL. It is associated with a risk of transformation to a high grade (rapidly growing) non-Hodgkin lymphoma.7
The following risk factors are associated with an increased likelihood of developing HL:
Epstein-Barr virus (EBV): it is estimated that around 40% of Hodgkin lymphoma cases in the UK are related to EBV infection. However, most people who have glandular fever will not develop cancer as a result.3
Human immunodeficiency virus (HIV): it is estimated that the risk of developing Hodgkin lymphoma is 11 times higher than that of the general population
Immunosuppression: immunosuppressant drugs and certain autoimmune conditions such as rheumatoid arthritis increase the risk of developing HL
Previous history of non-Hodgkin lymphoma (NHL)
First-degree relative family history of Hodgkin lymphoma, non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukaemia (CLL)
The most common symptom of Hodgkin lymphoma (HL) is a painless, rubbery, enlarged lymph node/nodes, typically in the cervical or supraclavicular region.7
Other typical symptoms of Hodgkin lymphoma include:
B symptoms: fever >38°C, drenching night sweats and unintentional weight loss of >10% within the last 6 months. These symptoms affect 25% of patient with HL.
Chest discomfort +/- cough or dyspnoea: a mediastinal mass is present in 80% of patients with HL and may cause these symptoms8
Abdominal discomfort or pain: if abdominal lymphatic organs such as the liver or spleen have been affected
Alcohol-induced pain at nodal sites: this is a ‘classical’ textbook symptom of Hodgkin Lymphoma but not often seen
FBC: to investigate for leukaemia, infectious mononucleosis and other causes of lymphadenopathy
U&Es: to provide a baseline measurement before treatment
LFTs: reduced albumin levels are associated with a poorer prognosis
LDH: increased levels are associated with a poorer prognosis
ESR: increased levels are associated with a poorer prognosis
Tests to exclude differential diagnoses: for example, Monospot® test for infectious mononucleosis, sputum culture for TB, viral screen including HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) tests
Relevant imaging investigations include:
Chest X-ray: to assess for intrathoracic lymphadenopathy and mediastinal expansion
Contrast-enhanced CT neck, chest, abdomen and pelvis: usually performed when a patient first presents and is sometimes used for staging.
Positron emission tomography CT (PET-CT): now the gold-standard for staging in cHL, and is repeated during treatment to allow guided therapy according to response (aiming to minimise toxicity by reducing chemotherapy intensity when possible)
Lymph node excision biopsy is required for diagnosis and classification of HL type.
On light microscopy, the hallmark cell is the Reed-Sternberg cell which is a giant malignant multi-nucleated cell that is often referred to as being “owl-like”. A collection of non-malignant immune cells also surround the Reed-Sternberg cells.
Hodgkin cells are giant malignant mono-nucleated cells and tend to be present surrounding Reed-Sternberg cells.5
Using immunocytochemistry, CD15 and CD30 antigens are positively expressed on Reed-Sternberg cells.
A bone marrow biopsy is less frequently used as PET/CT can detect marrow involvement.7
Once Hodgkin lymphoma is diagnosed, the disease is staged to determine prognosis and guide treatment options. Staging is performing using the Ann Arbor staging system.8
The following table is a summarised version of the staging criteria; any more detail is beyond the scope of undergraduate learning.
Table 2. A summarised version of the Ann Arbor staging system.
Involvement of one lymph-node region or lymphoid structure (e.g. spleen or thymus).
Two or more lymph node regions on the same side of the diaphragm.
Lymph nodes on both sides of the diaphragm.
Involvement of extranodal site(s) beyond that designated E (see below).
Fever >38°C, drenching night sweats, weight loss of more than 10% over 6 months
Prior to treatment, patients usually undergo cardiac function testing, pulmonary function testing and reproductive counselling due to the potential side effects of chemotherapy and radiotherapy.
Due to the increased risk of opportunistic infections following chemotherapy, patients are also usually vaccinated with the following:8
Polyvalent pneumococcal vaccine
Meningococcal group C conjugate vaccine
Haemophilus influenzae type b vaccine
Early-stage disease (stage IA, IB, IIA) is usually treated with one or more cycles of combination chemotherapy plus radiotherapy.
Advanced stage (stage IIB or above) is usually treated with a more intensive chemotherapy course; often without radiotherapy unless a particularly large mass is present.
The most commonly used chemotherapy combination regimes in Hodgkin lymphoma are:
ABVD: Doxorubicin (used to be called Adriamycin®), Bleomycin, Vinblastine and Dacarbazine
Regardless of stage, relapsed disease is usually treated with high dose chemotherapy (HDCT) followed by autologous stem cell transplant (ASCT).
HDCT aims to eradicate all HL cancer cells, however, bone marrow stem cells are also destroyed during the process.
The re-transfusion of the patient’s own haematopoietic stem cells (salvaged prior to HDCT) aims to promote a quicker recovery of bone marrow function and reduce the duration period of profound immunosuppression in the patient.
The chemotherapeutic regime chosen for patients eligible for ASCT is based on individual patient factors.
If a patient cannot tolerate intensive HDCT and ASCT, then combination chemotherapy and radiotherapy is considered. A more intensive chemotherapy regimen than that used in the initial therapeutic plan is usually offered.
If a patient cannot tolerate the toxicities associated with more intensive regimens, palliative chemotherapy and/or radiotherapy is considered.
If a transfusion of blood products is required, patients with or treated for Hodgkin lymphoma (at any stage of the disease) must only receive irradiated blood products. This is a lifelong requirement.
Irradiated blood products are used to reduce the risk of transfusion-associated graft-versus-host disease.
Hodgkin lymphoma causes immunosuppression. The clonal expansion of B lymphocytes are abnormal and do not function properly. Patients are at a particularly higher risk of infection if there is bone marrow involvement.
Treatment-related complications may include:
Neutropenia: due to the effect of the chemotherapy on the bone marrow. Antibiotics are urgently required if patients are suspected to be neutropenic and have symptoms of infection or pyrexia (neutropenic sepsis). Patients can also be given granulocyte colony-stimulating factor (G-CSF) to stimulate the production of neutrophils which may reduce the duration of chemotherapy-induced neutropenia and therefore reduce the incidence of associated sepsis.
Secondary solid tumours: particularly in the lung, skin, breast and gastrointestinal tract1
Secondary leukaemias: especially acute myeloid leukaemia
Subfertility: patients should be counselled prior to treatment
Cardiovascular disease: secondary to adriamycin/doxorubicin
Lung fibrosis: secondary to bleomycin and presents months to years after treatment
Nausea and vomiting
Hodgkin lymphoma (HL) is a haematological malignancy that arises from B lymphocytes in the lymphatic system.
Hodgkin lymphoma is characterised by the presence of Reed-Sternberg cells which are derived from germinal centre B lymphocytes.
The main risk factor for Hodgkin lymphoma is previous EBV infection.
Hodgkin lymphoma classically presents with a painless, rubbery, enlarged lymph node +/- ’B symptoms’
The diagnosis is made by lymph node biopsy. PET-CT is used for staging in cHL.
Management of Hodgkin lymphoma is with combination chemotherapy (usually either ABVD or BEACOPP) plus radiotherapy in early-stage disease or a longer, more intensive course of chemotherapy in advanced-stage disease. High dose chemotherapy and autologous stem cell transplantation are considered in relapsed disease.
Complications include immunosuppression, low blood cell counts, secondary cancers, lung fibrosis, cardiovascular disease and subfertility.
Prognosis is good with a 75% ten-year survival rate.
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Dr Alex Langridge
Speciality Haematology Trainee (ST7)
Founder of Buku Medicine, a free app answering the commonest questions put to haematology, renal and endocrine specialties.
Dr Chris Jefferies
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National Cancer Institute. Image of Reed-Sternberg Cell. License: [Public Domain]. Available from: [LINK]
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