2. Hodgkin lymphomas are characterised by the presence of Hodgkin/Reed-
Sternberg cells.
Lymphoma is a haematological malignancy arising from lymphoid tissue.
They are commonly categorised as Hodgkin or Non-Hodgkin lymphoma:
• Hodgkin lymphoma (HL): Characterised by the presence of Hodgkin/Reed-
Sternberg cells. Further categorised as classical Hodgkin's lymphoma
(nodular sclerosis, mixed cellularity, lymphocyte-rich and lymphocyte-
depleted) and nodular lymphocyte-predominant Hodgkin's lymphoma.
Non-Hodgkin lymphoma (NHL): Reed-Sternberg cells are not seen in NHL.
There are more than 60 subtypes and they can be B-cell or NK/T-cell in
origin. B-cell lymphomas are more common accounting for around 80%,
though there is significant geographic variation. NHLs are more common
than Hodgkin lymphoma, accounting for around 80-85% of lymphomas.
3. EPIDEMIOLOGY
In the UK, there are approximately 2,100 cases of Hodgkin lymphoma
diagnosed each year.
It is more common in men (1,300 cases in 2017) than women (880
cases in 2017). In the past decade incidence has increased by almost
20%.
HL is far less common than NHL which has around 14,000 cases a
year. Approximately 330 people die from Hodgkin lymphoma each year.
4.
5. HRS CELLS
Multinucleated Reed-Sternberg cell seen in centre of image
A rare form of HL, nodular lymphocyte-predominant Hodgkin
lymphoma is characterised by the lymphohistiocytic Reed-
Sternberg variant.
6. TYPES
HL may be subdivided into classical and nodular lymphocyte-
predominant Hodgkin lymphoma.
7. Classical
The four ‘classical’ forms of HL (cHL) account for around 95% of cases of HL. There are four subtypes:
• Nodular sclerosis: Most common subtype, accounts for around 70% of cHL.
• Mixed cellularity: Accounts for around 20% of cHL.
• Lymphocyte-rich: Accounts for around 5% of cHL. Has the best prognosis.
• Lymphocyte-depleted: Rare, accounting for <1% of cHL. Has the the worst prognosis.
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL)
An exceedingly rare condition accounting for around 5% of HL. It is characterised by the
lymphohistiocytic Reed-Sternberg variant.
It shows a significant male preponderance and is more common in those of black ethnicity. It tends to
follow a different course and is managed uniquely. This is beyond the scope of this note which focuses
on cHL.
8. CLINICAL FEATURES
HL tends to present with gradual lymphadenopathy, malaise and fatigue.
•Lymphadenopathy: Typically painless, firm, enlarged lymph nodes, most commonly found in the
neck.
•‘B’ symptoms: ‘B’ symptoms refer to fever, night sweats and weight loss (unexplained, >10% in 6
months).
•Mediastinal mass: May be incidental finding on chest imaging or present with shortness of breath,
cough, pain or superior vena cava obstruction.
•Pruritis
•Hepatosplenomegaly
•Malaise
•Fatigue
9. DIAGNOSIS
Excision biopsy of affected lymph nodes is normally required in patients
with suspected cHL.
Excisional biopsy is preferred to fine needle aspiration or core
biopsy. cHL is diagnosed following biopsy and immunophenotyping of
HRS cells.
10. INVESTIGATIONS
PET/CT is the preferred imaging modality for staging disease.
Bloods
• FBC
• UE
• LFT
• Bone profile
• LDH
• Uric acid
• ESR
• HIV, Hep B and Hep C
• HTLV-1
Imaging
• Chest x-ray
• PET CT: Used in the staging of disease.
• CT neck, chest, abdomen and pelvis: May have been organised prior to diagnosis. Also used to characterise disease seen
on PET, particularly in the neck.
• MRI: MRI brain used If CNS involvement suspected, also useful to image the liver.
11. Additional
• Lumbar puncture and CSF analysis: In those with suspected CNS
disease.
• Echocardiogram: Assess cardiac function, particularly if
considering doxorubicin chemotherapy.
• Pulmonary function tests: Tests pulmonary function, particularly if
considering bleomycin chemotherapy.
• Bone marrow biopsy: Due to modern imaging techniques biopsy is
often not needed. May be considered if diagnosis uncertain or imaging
indeterminate.
14. MANAGEMENT
Chemotherapy and radiotherapy are the mainstay of management in patients with cHL.
The management of cHL is complex and depends on the Lugano staging and other
prognostic markers (age, ESR, number of regions involved and presence of bulky
mediastinal disease).
ABVD
ABVD is a commonly used regimen in the treatment of cHL, and the one you will be expected
to be aware of at an undergraduate level. It consists of four chemotherapy agents:
• Doxorubicin (A): An anthracycline that inhibits topoisomerase II leading to inhibition of DNA
and RNA synthesis. Side effects include cardiomyopathy, myelosuppresion and skin
reactions.
• Bleomycin (B): Inhibits DNA synthesis. Side effects include pulmonary fibrosis and severe
idiosyncratic reaction (characterised by hypotension, confusion, fever, wheeze)
• Vinblastine (V): Inhibits microtubule formation by binding to tubulin. Side effects include
peripheral neuropathy and bladder atony.
• Dacarbazine (D): Converted to MTIC an alkylating agent that acts on guanine and causes
methylation. Side effects include bone marrow suppression and hepatic necrosis.
15. Early stage
In patients with stage I/II disease ABVD chemotherapy is the mainstay of treatment.
Number of cycles vary case to case but 3 to four are common. This may be followed by
radiotherapy.
Advanced stage
Advanced stage refers to stage III/IV, sometimes stage II bulky disease will be included
here. A number of treatment regimens may be used:
• ABVD
• BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine,
procarbazine, and prednisolone)
• Stanford V (doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide,
and prednisolone)
Radiotherapy may be used as an adjunct to chemotherapy.
16. Relapse
Treatment of relapsed disease depends on many factors including
prognostic indicators, timing (following first treatment) and number of
relapses. Treatment options include salvage chemotherapy, radiotherapy
and autologous haematopoietic cell transplantation.
Blood transfusion
If a blood transfusion is required, patients with or treated for Hodgkin
lymphoma must received irradiated blood. This is to reduce the risk of
transfusion-associated graft-versus-host disease.
The advice is 'all adults and children with Hodgkin lymphoma at any stage
of the disease should have irradiated red cells and platelets for life'. There
are a number of other indications for irradiated blood products.
17. PROGNOSIS
Overall cHL has a reasonably good prognosis.
• Limited disease: Of those with stage I and II disease, 90% survive 5
years.
• Advanced disease: Of those with stage III and IV disease, 75-90%
survive 5 years.
Upwards of 75% of patients will be cured of the condition, though this is
dependent somewhat on the staging at diagnosis.
