Author: Dr Selene Ting, Medical Registrar, Whangarei Hospital, New Zealand. DermNet Editor in Chief: Adjunct A/Prof Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. December 2017. Copy edited by Maria McGivern/Gus Mitchell.
Lymphomas are cancers that develop in the lymphatic system of the body. These cancers form when there is abnormal and excessive growth of B lymphocytes and T lymphocytes in the lymph nodes and other parts of the body. There are many different subtypes of lymphoma, categorised into Hodgkin lymphoma and non-Hodgkin lymphoma (NHL).
What is Hodgkin lymphoma?
Hodgkin lymphoma is a B-cell lymphoma characterised by a tumour cell called the Reed-Sternberg cell [1]. These are large abnormal lymphocytes with multiple nuclei that are found on the histology of affected lymph nodes.
Reed-Sternberg cell
Hodgkin lymphoma typically presents with painless swelling of superficial lymph nodes or with an asymptomatic mass on a chest X-ray. Patients with Hodgkin lymphoma occasionally present with severe generalisedpruritus or with skin lesions.
How is Hodgkin lymphoma classified?
There are two distinct types of Hodgkin lymphoma according to the World Health Organization (WHO) Classification of Tumours of Haematopoietic and Lymphoid Tissues [2]; these being:
Classical Hodgkin lymphoma (95% of cases)
Nodularlymphocyte-predominant Hodgkin lymphoma (5% of cases).
Classical Hodgkin lymphoma is further histologically classified into:
Nodular sclerosis classical Hodgkin lymphoma
Lymphocyte-rich classical Hodgkin lymphoma
Mixed cellularity classical Hodgkin lymphoma
Lymphocyte-depleted classical Hodgkin lymphoma.
Who gets Hodgkin lymphoma?
Hodgkin lymphoma is a relatively rare disease, accounting for approximately 0.6% of all cancers diagnosed in the developed world annually.
Around 66,000 new cases of Hodgkin lymphoma were diagnosed worldwide in 2012.
Around 75 New Zealanders are diagnosed with this disease each year [1].
The incidence rates of Hodgkin lymphoma are highest in Northern America and lowest in Eastern Asia [3]. This variation between countries may be due to different prevalence of risk factors, use of screening, and/or diagnostic methods.
Hodgkin lymphoma develops in two main age groups.
Hodgkin lymphoma is mostly diagnosed in young adults aged 15–35 years but can also develop in people over 55 years of age.
The younger age group tends to be more commonly affected by the nodular sclerosis subtype [4].
Hodgkin lymphoma is generally more common in males, although the nodular sclerosis subtype is seen more frequently in females.
What causes Hodgkin lymphoma?
Hodgkin lymphoma is caused by a change in the DNA of a B-cell lymphocyte. This mutation causes a large number of abnormal and oversized B cells to accumulate in the lymphatic system, and, over time, spread to other organs. It is not clear what causes DNA mutation.
A family history of a specific subtype of Hodgkin lymphoma is most strongly associated with the risk for that subtype, supporting the likelihood of a geneticpredisposition [5,6].
The risk of lymphoma increases slightly in patients with chronicinfections or autoimmune diseases.
What are the clinical features of Hodgkin lymphoma?
Hodgkin lymphoma usually starts within a single lymph node and then progresses to nearby lymph nodes via the lymphatic channels before spreading to distant sites and organs [8,9]. It typically presents with painless swelling of superficial lymph nodes (in the neck, axilla, or groin) or as an asymptomatic mass seen on a chest X-ray.
Some patients present to their doctors with non-specific, or 'B', symptoms. They can have one or more of the following symptoms:
Fevers
Drenching night sweats
Unintentional weight loss
Lethargy.
Occasionally, patients can present with symptoms and signs that reflect the involvement of organs in the disease such as:
Jaundice and itching due to liver involvement
Tetany (muscular spasms) due to high levels of calcium
Tiredness due to anaemia
Oedema due to kidney involvement.
Cutaneous manifestations of Hodgkin lymphoma
Direct cutaneous infiltration
Cutaneous Hodgkin lymphoma is very rare.
The chest is the most common site.
It usually presents as dermalpapules and plaques.
There may be a single nodule or a cluster of subcutaneousnodules.
They may be solitary, grouped, or (rarely) generalised [10–12].
Cutaneous lesions in Hodgkin lymphoma
Infected eczema
Infected eczema
Excoriations
How is Hodgkin lymphoma diagnosed?
A thorough history and physical examination is the initial step in the diagnosis of Hodgkin lymphoma, which is confirmed by the presence of Reed-Sternberg cells on the pathological examination of a lymph node biopsy [8].
A full blood count and inflammatory markers are used to check for signs of anaemia and inflammation.
The lymph node evaluation can be an excisional biopsy (where an entire lymph node is removed), an incisional biopsy, ie where part of a lymph node is removed), or a core biopsy (where part of a lymph node is removed using a wide needle).
A skin biopsy of an infiltrated nodule may be diagnostic of Hodgkin disease in patients with direct cutaneous infiltration with Hodgkin lymphoma. Typically, histology reveals Reed-Sternberg cells within an infiltration of small lymphocytes, histiocytes, eosinophils, and plasma cells.
What is the differential diagnosis for Hodgkin lymphoma?
Any disease presenting with enlarged lymph nodes with constitutional symptoms, such as fevers and weight loss, should be considered in the differential diagnosis of Hodgkin lymphoma [12].
Non-Hodgkin lymphoma
NHL is difficult to clinically differentiate from Hodgkin lymphoma, and the diagnosis requires pathological confirmation.
Hodgkin lymphoma tends to spread from one lymph node chain to another, whereas extra-nodal sites are usually involved in NHL.
Patients with Hodgkin lymphoma tend to be younger than patients with NHL.
Other malignancies
Many malignancies may present with enlarged lymph nodes due to metastasis.
Head and neck cancers can often spread to the cervical lymph nodes.
Breast cancer commonly spreads to the axillary lymph nodes.
The best way to differentiate Hodgkin lymphoma from other malignancies is to do a lymph node biopsy.
Infectious mononucleosis
The enlarged lymph nodes in infectious mononucleosis are usually tender.
Patients with infectious mononucleosis typically present with a sore throat.
The infection is diagnosed by blood count findings and positive serology for EBV.
Reactive lymph nodes
Lymph nodes can also become enlarged from any infectious or inflammatory causes.
These enlarged lymph nodes typically return to normal within a few weeks.
When enlarged lymph nodes or symptoms persist, a lymph node biopsy can be considered to rule out Hodgkin lymphoma.
What is the treatment for Hodgkin lymphoma?
The treatment for Hodgkin lymphoma may include [12]:
Chemotherapy involves either taking oral tablets or the drug is injected into a vein or muscle, depending on the type and stage of the cancer being treated.
Radiation therapy can be used to treat solitary or localised specific skin lesions. For a pregnant woman with Hodgkin lymphoma, radiation therapy should be postponed until after delivery, if possible, to avoid any risk to the fetus.
Other treatment options, especially for pregnant patients, include watchful waiting (monitoring) and systemic steroids.
Treatments for Hodgkin lymphoma currently being evaluated include radiation therapy with stem cell transplant and monoclonalantibody therapy.
Non-specific cutaneous symptoms may be treated with:
Hodgkin lymphoma can usually be cured if found and treated early. The prognosis of Hodgkin lymphoma has improved in recent decades, with a current 5-year survival rate of over 80%.
The prognosis depends largely on the following:
The patient’s signs and symptoms
Their age, sex, and general health.
The type of Hodgkin lymphoma
The stage of cancer.
Cutaneous Hodgkin lymphoma usually represents advanced disease and carries a poor prognosis despite aggressive treatment [1].
References
Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. European Journal of Cancer (2013) 49, 1374-1403. PubMed
Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375-90.What is Hodgkin Lymphoma? | Leukaemia & Blood Cancer NZ (LBC) [Internet]. Leukaemia & Blood Cancer NZ. 2017. Available from: https://www.leukaemia.org.nz/information/about-blood-cancers/lymphoma/hodgkin-lymphoma/. Cited 29 July 2017.