Hodgkin Lymphoma

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Hodgkin lymphoma (HL)\: haematological malignancy from B lymphocytes in the lymphatic system. In the UK, 2,100
diagnoses annually, with peaks in young adults (20-34 years) and older adults (>70 years).
Prognosis\: 75% of HL patients survive ≥10 years. Five-year survival\: 95% (under 40) and \<50% (over 70).
Aetiology\: Mutation of B lymphocytes in lymphoid tissues, forming Reed-Sternberg cells (large, multi-nucleated) and
Hodgkin cells (large, mono-nucleated).
Classi
sclerosis (70%), Mixed cellularity (25%), Lymphocyte-rich (5%), and Lymphocyte-depleted (\<1%).
Risk factors\: EBV (40% of HL cases in the UK), HIV (11 times higher risk), immunosuppression, previous NHL, family history
(HL, NHL, CLL), cigarette smoking.
Symptoms\: Painless, rubbery, enlarged lymph node(s), B symptoms (fever >38°C, night sweats, weight loss >10%), chest
discomfort/cough/dyspnoea, abdominal pain, alcohol-induced nodal pain, pruritis, malaise, fatigue.
Examination
cerebellar degeneration, neuropathy, Guillain-Barré).
Di
toxoplasmosis.
Investigations\: FBC, U&Es, LFTs, LDH, ESR, Monospot® test, sputum culture, viral screen (HIV, HBV, HCV), chest X-ray,
contrast-enhanced CT, PET-CT (gold-standard for staging), lymph node excision biopsy (Reed-Sternberg cells),
immunocytochemistry (CD15, CD30).
Staging\: Ann Arbor system, stages I-IV based on lymph node involvement and extranodal sites, with modifying features (A\:
no symptoms; B\: fever, night sweats, weight loss).
Management\: Pre-treatment tests (cardiac, pulmonary, reproductive counselling, vaccinations). Early-stage\: combination
chemotherapy + radiotherapy. Advanced stage\: intensive chemotherapy. Relapsed disease\: high-dose chemotherapy +
autologous stem cell transplant. Irradiated blood products for transfusion lifelong.
Complications\: Disease-related\: immunosuppression, infection risk. Treatment-related\: neutropenia, secondary solid
tumours and leukaemias, subfertility, cardiovascular disease, lung
vomiting, hair loss.
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A comprehensive topic overview

Introduction

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
less than 50%.
1,2Aetiology
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
3
Figure 1. The lymphatic system.
6
Lymphatic
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
.
Classi
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 subclassi
Table 1. Classical Hodgkin lymphoma sub-classi
Type of cHL Epidemiology and clinical features
70% of cHL cases. Mediastinal mass is common.
Nodular sclerosis
Mixed cellularity
25% of cHL cases. Prevalent in patients with HIV and in
developing countries. Splenic in
of patients.
5% of cHL cases. Mediastinal mass is rare.
Lymphocyte-rich
Lymphocyte-
depleted
\<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

Risk factors

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.
3Human immunode
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)
Cigarette smoking

Clinical features

History
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 a
Chest discomfort +/- cough or dyspnoea\: a mediastinal mass is present in 80% of patients with HL and may cause these
symptoms
8
Abdominal discomfort or pain\: if abdominal lymphatic organs such as the liver or spleen have been a
Alcohol-induced pain at nodal sites\: this is a ‘classical’ textbook symptom of Hodgkin Lymphoma but not often seen
Pruritis
Malaise
Fatigue
Clinical examination
All patients with suspected Hodkin lymphoma require a through lymphoreticular system examination.
On examination, clinical
Lymphadenopathy
Hepatomegaly
Splenomegaly
Superior vena cava (SVC) syndrome\: a mediastinal mass may cause SVC obstruction
Paraneoplastic syndromes such as cerebellar degeneration, neuropathy or Guillain-Barré syndrome

Di

The clinical presentation of Hodgkin lymphoma is similar to several other conditions including\:
Infectious mononucleosis
Non-Hodgkin lymphoma
Acquired immunode
Tuberculosis
Sarcoidosis
Leukaemia
Myeloma
Toxoplasmosis

Investigations

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 prognosisLDH\: increased levels are associated with a poorer prognosis
ESR\: increased levels are associated with a poorer prognosis
Tests to exclude di
TB, viral screen including HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) tests
Imaging
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
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 classi
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.
Figure 2. A Reed-Sternberg cell.
9
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
Staging
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.
Stage
I Involvement of one lymph-node region or lymphoid structure (e.g. spleen or thymus).
II Two or more lymph node regions on the same side of the diaphragm.
III Lymph nodes on both sides of the diaphragm.
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

Management

Prior to treatment, patients usually undergo cardiac function testing, pulmonary function testing and reproductive
counselling due to the potential side e
Due to the increased risk of opportunistic infections following chemotherapy, patients are also usually vaccinated with the
following\:
8
Polyvalent pneumococcal vaccine
In
Meningococcal group C conjugate vaccine
H a e m o p h i l u s i n
Initial therapy8
radiotherapy.
Early-stage disease (stage IA, IB, IIA) is usually treated with one or more cycles of combination chemotherapy plus
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
BEACOPP\: Bleomycin, Etoposide, Doxorubicin (Adriamycin®), Cyclophosphamide, Vincristine (Oncovin®), Procarbazine,
Prednisolone
Relapsed disease10
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 o
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.

Complications

Disease-related complicationsHodgkin 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
Treatment-related complications may include\:
Neutropenia\: due to the e
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 tract
1
Secondary leukaemias\: especially acute myeloid leukaemia
Subfertility\: patients should be counselled prior to treatment
Cardiovascular disease\: secondary to adriamycin/doxorubicin
Lung
Endocrine dysfunction
Neuropathy
Nausea and vomiting
Hair loss

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References

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Journal of

Reviewer

Dr Alex Langridge
Speciality Haematology Trainee (ST7)
Founder of Buku Medicine, a free app answering the commonest questions put to haematology, renal and endocrine
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