Hodgkin Lymphoma

Question 1

Hodgkin lymphomas are characterised by the presence of Hodgkin/… cells

Answer 1

Hodgkin lymphomas are characterised by the presence of Hodgkin/Reed-Sternberg cells.

Question 2

Lymphoma is a haematological malignancy arising from lymphoid tissue. They are commonly categorised as Hodgkin or Non-Hodgkin lymphoma:

Answer 2

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.

Question 3

Epidemiology

Hodgkin lymphoma

Answer 3

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.

Question 4

HRS cells

Answer 4

HL is characterised by the presence of Hodgkin/Reed-Sternberg cells (HRS cells)
Reed-Sternberg cells are large, multinucleated malignant cells - they are often described as having an owl like appearance. Hodgkin cells refer to the mononuclear variant of Reed-Sternberg cells.

Question 5

HL may be subdivided into classical and nodular lymphocyte-predominant Hodgkin lymphoma.

Answer 5

HL may be subdivided into classical and nodular lymphocyte-predominant Hodgkin lymphoma.

Question 6

Classical

The four ‘classical’ forms of HL (cHL) account for around 95% of cases of HL. There are four subtypes:

Answer 6

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.

Question 7

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL)

Answer 7

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.

Question 8

HL tends to present with gradual … (3)

Answer 8

HL tends to present with gradual lymphadenopathy, malaise and fatigue.

Question 9

Clinical features
HL

Answer 9

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

Question 10

Diagnosis of HL

Answer 10

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.

Question 11

Investigations in HL

Answer 11

PET/CT is the preferred imaging modality for staging disease.

Question 12

Bloods in HL

Answer 12

FBC
UE
LFT
Bone profile
LDH
Uric acid
ESR
HIV, Hep B and Hep C
HTLV-1

Question 13

Imaging - HL

Answer 13

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.

Question 14

HL additional tests

Answer 14

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.

Question 15

The … staging system is used to classify HL.

Answer 15

The Lugano staging system is used to classify HL.

Question 16

‘B’ symptoms: ‘B’ symptoms refer to fever, night sweats and weight loss (unexplained, >10% in 6 months). ’B’ denotes presence and ‘A’ denotes absence.
Extranodal involvement: In limited stage disease ‘E’ is used to denote extranodal tissue involvement.
Bulky disease: Definition of bulky is nuanced but typically refers to disease > 10cm.

Answer 16

‘B’ symptoms: ‘B’ symptoms refer to fever, night sweats and weight loss (unexplained, >10% in 6 months). ’B’ denotes presence and ‘A’ denotes absence.
Extranodal involvement: In limited stage disease ‘E’ is used to denote extranodal tissue involvement.
Bulky disease: Definition of bulky is nuanced but typically refers to disease > 10cm.

Question 17

Management of HL

Answer 17

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).

Question 18

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:

Answer 18

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.

Question 19

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.

Answer 19

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.

Question 20

Prognosis of HL

Answer 20

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.

Question 21

HL - patients cured?

Answer 21

Upwards of 75% of patients will be cured of the condition, though this is dependent somewhat on the staging at diagnosis.

Question 22

Two main types of HL -

Answer 22

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).

Question 23

Classical Hodgkin lymphoma (cHL) is further subclassified into four types.

Answer 23

Type of cHL

Nodular sclerosis
= 70% of cHL cases. Mediastinal mass is common.

Mixed cellularity
= 25% of cHL cases. Prevalent in patients with HIV and in developing countries. Splenic infiltration is seen in 30% of patients.

Lymphocyte-rich
= 5% of cHL cases. Mediastinal mass is rare.

Lymphocyte-depleted
=<1% of cHL cases. Prevalent in patients with HIV and in developing countries.

Question 24

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 …

Answer 24

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

Question 25

The following risk factors are associated with an increased likelihood of developing HL:

Answer 25

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.3
Human immunodeficiency virus (HIV): it is estimated that the risk of developing Hodgkin lymphoma is 11 times higher 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

Question 26

The most common symptom of Hodgkin lymphoma (HL) is a…

Answer 26

The most common symptom of Hodgkin lymphoma (HL) is a painless, rubbery, enlarged lymph node/nodes, typically in the cervical or supraclavicular region.7

Question 27

Define B symptoms

Answer 27

B symptoms: fever >38°C, drenching night sweats and unintentional weight loss of >10% within the last 6 months. These symptoms affect 25% of patient with HL.

Question 28

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:

Answer 28

B symptoms: fever >38°C, drenching night sweats and unintentional weight loss of >10% within the last 6 months. These symptoms affect 25% of patient with HL.

Question 29

On examination, clinical findings in HL may include:

Answer 29

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

Question 30

Differential diagnoses

The clinical presentation of Hodgkin lymphoma is similar to several other conditions including:

Answer 30

Infectious mononucleosis
Non-Hodgkin lymphoma
Acquired immunodeficiency syndrome (AIDS)
Tuberculosis
Sarcoidosis
Leukaemia
Myeloma
Toxoplasmosis