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).
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 associated with an increased likelihood of developing HL include:
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.
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.
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.
Relevant laboratory investigations include:
Relevant imaging investigations include:
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.
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.
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).
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. 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 may include:
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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