Hodgkin Lymphoma

Hodgkin Lymphoma

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Hodgkin lymphoma (HL) is a form of haematological malignancy that develops from B lymphocytes inside the lymphatic system.

In the United Kingdom, 2,100 people are diagnosed annually, with higher incidences in young adults aged 20–34 years and over 70 years.

75% of patients with HL have good prognoses, surviving for at least ten years. Prognosis is particularly positive in younger patients, with those under 40 years old having a 95% five-year survival rate, compared to those over 70 years old with a five-year survival rate of less than 50%.1,2


The lymphatic system is a network of tissues and organs that are important to the immune system. These include lymph nodes, lymphatic vessels, lymphatic organs, and lymphatic fluid.3

This system contains numerous lymphocytes, and the mutation of these cells within lymphoid tissues leads to lymphoma. Hodgkin lymphoma occurs when B lymphocytes derived from the germinal centres of lymphoid tissues mutate and cause the presence of large, multi-nucleated giant cells called ‘Reed-Sternberg’ cells, and large, mono-nucleated cells known as malignant ‘Hodgkin cells’.4,5


There are two main types of Hodgkin lymphoma (HL): classical Hodgkin lymphoma (which accounts for 95% of cases) and nodular lymphocyte-predominant Hodgkin lymphoma (which accounts for 5% of cases).

Classical Hodgkin lymphoma (cHL) is further classified into four types (see Table 1).

Classical Hodgkin Lymphoma Sub-Classification

The four types of classical Hodgkin lymphoma (cHL) are: nodular sclerosis, mixed cellularity, lymphocyte-rich and lymphocyte-depleted. Nodular lymphocyte-predominant Hodgkin lymphoma is a more indolent disease with little in common with cHL, however it is associated with a risk of transformation to a high grade (rapidly growing) non-Hodgkin lymphoma.

Risk Factors

Risk factors associated with an increased likelihood of developing HL include:

  • Epstein-Barr virus (EBV)
  • Human immunodeficiency virus (HIV)
  • Immunosuppression
  • Previous history of non-Hodgkin lymphoma (NHL)
  • First-degree relative family history of Hodgkin lymphoma, non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukaemia (CLL)
  • Cigarette smoking

Clinical Features


The most common symptom of Hodgkin lymphoma (HL) is a painless, rubbery, enlarged lymph node/nodes, typically in the cervical or supraclavicular region. 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, which affect 25% of patient with HL), chest discomfort +/- cough or dyspnoea, abdominal discomfort or pain, alcohol-induced pain at nodal sites, pruritis, malaise and fatigue.

Clinical Examination

All patients with suspected Hodkin lymphoma require a through lymphoreticular system examination. On examination, clinical findings in HL may include lymphadenopathy, hepatomegaly, splenomegaly, superior vena cava (SVC) syndrome, and paraneoplastic syndromes such as cerebellar degeneration, neuropathy or Guillain-Barré syndrome.

Differential Diagnoses

The clinical presentation of Hodgkin lymphoma is similar to several other conditions, including infectious mononucleosis, non-Hodgkin lymphoma, acquired immunodeficiency syndrome (AIDS), tuberculosis, sarcoidosis, leukaemia and Castleman's Disease.


Laboratory investigations

Relevant laboratory investigations include:

  • 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)

Specialist investigations

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. 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.


Once Hodgkin lymphoma is diagnosed, the disease is staged to determine prognosis and guide treatment options.


The Ann Arbor staging system is used to perform staging. The following is a summarized version of the criteria; more detail is beyond the scope of undergraduate learning.

Table 2. A summarized version of the Ann Arbor staging system.

  • Stage I: Involvement of one lymph-node region or lymphoid structure (e.g. spleen or thymus).
  • Stage II: Two or more lymph node regions on the same side of the diaphragm.
  • Stage III: Lymph nodes on both sides of the diaphragm.
  • Stage IV: Involvement of extranodal site(s) beyond that designated E (see below).

Modifying features:

  • A: No symptoms
  • B: 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 usually vaccinated with polyvalent pneumococcal vaccine, influenza vaccine, meningococcal group C conjugate vaccine, and Haemophilus influenzae type b vaccine.

Initial Therapy

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, Bleomycin, Vinblastine, and Dacarbazine) and BEACOPP (Bleomycin, Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Procarbazine, and Prednisolone).

Relapsed Disease

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.

Blood Transfusion

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.


Disease-related complications

Hodgkin lymphoma causes immunosuppression. Clonal expansion of B lymphocytes is abnormal and does not function properly. Patients have a heightened risk of infection if there is bone marrow involvement.

Treatment-related complications

Treatment-related complications may include:

  • Neutropenia due to the effect of chemotherapy on the bone marrow. Antibiotics are needed urgently if patients are suspected to have neutropenia and symptoms of infection or pyrexia. Patients may also be given granulocyte colony-stimulating factor (G-CSF) to stimulate neutrophil production, which can reduce the duration of chemotherapy-induced neutropenia and reduce the risk of associated sepsis.
  • Secondary solid tumours, particularly in the lung, skin, breast, and gastrointestinal tract1
  • Secondary leukaemias, most notably acute myeloid leukaemia
  • Subfertility, for which patients should be counselled prior to treatment
  • Cardiovascular disease due to adriamycin/doxorubicin
  • Lung fibrosis due to bleomycin, which presents months to years after treatment
  • Endocrine dysfunction
  • Neuropathy
  • Nausea and vomiting
  • Hair loss

Key points

  • Hodgkin lymphoma (HL) is a haematological malignancy that arises from B lymphocytes in the lymphatic system.
  • Hodgkin lymphoma is characterised by Reed-Sternberg cells, which are derived from germinal centre B lymphocytes.
  • The main risk factor for Hodgkin lymphoma is previous EBV infection.
  • Hodgkin lymphoma usually presents with a painless, rubbery, enlarged lymph node and/or 'B symptoms'.
  • The diagnosis is confirmed by lymph node biopsy. PET-CT is used to stage cHL.
  • Treatment for Hodgkin lymphoma is usually combination chemotherapy (ABVD or BEACOPP) plus radiotherapy for early-stage disease, or a longer and more intensive course of chemotherapy for advanced-stage disease. High dose chemotherapy and autologous stem cell transplantation may be utilized in relapsed disease.
  • Complications include immunosuppression, low blood cell counts, secondary cancers, lung fibrosis, cardiovascular disease, and subfertility.
  • Prognosis is generally good, with a 75% ten-year survival rate.


  1. World Health Organisation. Hodgkin Lymphoma (Adult). Published in 2014. Available from: LINK
  2. Cancer Research UK.

Hodgkin Lymphoma Incidence Statistics

Cancer Research UK. About Hodgkin lymphoma. Published in 2020. Available from: LINK.

Patient UK. Hodgkin’s Lymphoma. Published in 2019. Available from: LINK.

Küppers R et al. Identification of Hodgkin and Reed-Sternberg cell-specific genes by gene expression profiling. Journal of Clinical Investigation. Published in 2003. Available from: LINK.

Cancer Research UK. Diagram of the Lymphatic System. License: Public Domain. Available from: LINK.

Townsend W et al. Hodgkin’s Lymphoma in Adults. The Lancet. Published in 2012. Available from: LINK.

Follows G et al. Guidelines for the first-line management of classical Hodgkin lymphoma. British Journal of Haematology. Published in 2014. Available from: LINK.

National Cancer Institute. Image of Reed-Sternberg Cell. License: Public Domain. Available from: LINK.

Ansell SM et al. Hodgkin lymphoma: 2012 update on diagnosis, risk-stratification, and management. American Journal of Hematology. Published in 2012. Available from: LINK.

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