11/14/24, 10\:51 AM Paediatric Lymphoma

Paediatric Lymphoma

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Lymphoma\: malignancies within the lymphatic system (lymph nodes, spleen, thymus, bone marrow); third most common
childhood cancer, 10% of new cases.
Types\: Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL).
Aetiology\: genetic alterations trigger abnormal proliferation of lymphocytes; mature lymphocytes arise outside bone
marrow.
Hodgkin’s lymphoma\: characterised by Reed-Sternberg cells from B lymphocytes; types include classical HL (nodular
sclerosis, mixed cellularity, lymphocyte-rich, lymphocyte-depleted) and non-classical HL (nodular lymphocyte-
predominant HL).
Non-Hodgkin’s lymphoma\: more common in boys; often high-grade and of B-cell origin; a
head, neck, chest), can be extranodal.
Risk factors\: immunode
Symptoms\: painless progressive lymphadenopathy, B symptoms (fever, night sweats, weight loss), pruritus, dyspnoea,
cough, chest pain, symptoms of extranodal involvement (anaemia, infections, bleeding, abdominal pain, urinary retention,
skin lesions, CNS symptoms).
Examination
lymphadenopathy (NHL), mediastinal mass, hepatosplenomegaly, skin lesions, testicular mass, neurological signs.
Investigations\: bedside (observations, swabs, urine dip, ECG), laboratory (FBC, U&Es, LDH, urate, LFTs, monospot, ESR,
hepatitis/HIV tests, G6PD), imaging (chest X-ray, CT/MRI/PET, liver/spleen ultrasound), biopsies (lymph node, bone
marrow, lumbar puncture).
Staging\: Ann Arbor classi
involvement and extranodal sites.
Management\: chemotherapy is main treatment; HL may also use radiotherapy; NHL may use biologics (Rituximab), bone
marrow transplant, CNS treatments (intrathecal chemotherapy); supportive care includes hydration, allopurinol, rasburicase.
Complications\: short-term (SVC obstruction, bowel perforation, cytopenias, tumour lysis syndrome, neutropenic sepsis),
long-term (secondary cancers, cardiotoxicity, pulmonary toxicity, renal impairment, growth issues, infertility).
Prognosis\: approximately 90% remission in HL and >90% in NHL; long-term follow-up needed for recurrence and late side
e
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A comprehensive topic overview

Introduction

Lymphoma is a group of malignancies which arise within the lymphatic system, which includes lymph nodes, the spleen,
the thymus and the bone marrow.
1
The two main types of lymphoma are Hodgkin’s lymphoma and non-Hodgkin’s lymphoma.
Lymphoma is the third most common cancer in childhood and accounts for 10% of new cancer cases in children.
1,2
Lymphoma is more common in teenagers and young adults (15 - 24 years).
2,3
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Aetiology

Lymphoma results from genetic alterations which trigger the abnormal proliferation of lymphocytes.
Although the underlying cause of lymphoma is not known, chromosomal abnormalities have been identi
associated with subtypes of lymphoma and can indicate prognosis.
One of the key features which distinguish most lymphomas from leukaemia is that the malignant cells are mature
lymphocytes, and they arise within sites outside of the bone marrow (e.g. lymph nodes). In contrast, leukaemia develops
from immature blasts and arises within the bone marrow.
The exceptions to this general rule are the less common lymphoblastic lymphomas (B-cell lymphoblastic lymphoma, and
T-cell lymphoblastic lymphoma), which develop from immature precursor lymphoblasts similarly to leukaemia.
The way in which lymphoblastic lymphomas are distinguished from lymphoblastic leukaemia is the degree of bone
marrow in
treated the same as acute lymphoblastic leukaemia (ALL).
4

Classi

Hodgkin’s lymphoma (HL)
Each year, approximately 70 children aged 0 - 14, 120 teenagers aged 15 - 19, and 180 young adults aged 20 - 24 are
diagnosed with Hodgkin's lymphoma.
3
Hodgkin's lymphoma is characterised histologically by the presence of Reed-Sternberg cells (giant multinucleated cells),
with associated smaller mononuclear cells, which arise from B lymphocytes.
5-8
Table 1\: Types of Hodgkin’s lymphoma.
5-7
Classical HL (85% cases)
Non-classical HL
Type Features
Nodular sclerosis (70%)
Mixed cellularity (20-25%)
Lymphocyte-rich (5%)
Lymphocyte-depleted
(\<1%)
Nodular lymphocyte-
predominant HL (NLPHL)
Lymph nodes contain
scar tissue (sclerosis)
Good prognosis
Increased frequency in
HIV/immunocompromis
ed, EBV association
Good prognosis
Early presentation with
peripheral adenopathy
Aggressive
HIV/immunocompromis
ed, EBV association
Reed-Sternberg cells are
not present
Slow growing but has a
risk of transforming to
high-grade non-
Hodgkin’s lymphoma
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Figure 1. A comparison of a normal lymphocyte and a Reed-Sternberg cell.
Non-Hodgkin’s lymphoma (NHL)
Non-Hodgkin's lymphoma a
9
The majority of cases are high-grade lymphomas, often of B-cell origin.
10-11
B-cell NHL usually a
while T-cell NHL usually a
10,12
Extranodal NHL develops in sites outside of the lymph nodes.
Table 1. Types of non-Hodgkin’s lymphoma categorised by cell type and grade. Lymphomas seen more commonly in
paediatric patients are highlighted in bold (Burkitt’s, large B-cell, lymphoblastic, anaplastic), with their respective
frequency.
10,13
Mature cell\: High-grade
Mature cell\: Low-grade
Precursor
cell/lymphoblastic
B-cell T-cell
Burkitt’s lymphoma (50-
60%)
Large B-cell
lymphomas* (10-15%)
Primary CNS lymphomas
Follicular lymphoma
Marginal zone
lymphoma
Precursor B-
lymphoblastic
lymphoma (5%)
Anaplastic large-cell
lymphoma (10-12%)
Peripheral T-cell
lymphoma
Mycosis fungoides and
cutaneous T-cell
lymphomas (very rarely
seen)
Precursor T-
lymphoblastic
lymphoma (15%)
*Large B-cell lymphomas include di

Risk factors

Risk factors for lymphoma include\:
Immunode
Nijmegan-Breakage syndrome, HIV, and immunosuppressant drugs.
3,5,7,10,12,13
Epstein-Barr virus infection
3,5,6-8
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Clinical features

History

Patients commonly present with painless, progressive lymphadenopathy (develops over weeks-months).
2,3,5-9,12-14
Infection is the most common cause of lymphadenopathy in children, so make sure to take a careful history which includes
infective symptoms.
Other symptoms of lymphoma include\:
2,3,5-9,12-14
o
B symptoms\: fatigue, drenching night sweats, fever >38 C, weight loss (>10% in 6 months).
Pruritus
Mediastinal involvement (thymus or mediastinal lymph nodes)\: dyspnoea, cough, chest pain.
The following symptoms indicate extranodal involvement, which is more common in NHL\:
13
Bone marrow\: symptoms of anaemia, infections, easy bruising/bleeding.
Abdomen\: bloating, early satiety, pain, unable to pass stools and vomiting if obstructed.
Retroperitoneal lymphadenopathy\: urinary retention.
Skin\: new skin lesions (such as mycosis fungoides), or jaundice.
Testicular swelling
Central nervous system\: behavioural change, headache, confusion, nausea and vomiting, seizures, weakness, sensory
changes.

Clinical examination

Typical clinical
Non-tender,
Hodgkin’s\: often cervical, supraclavicular, axillary
Non-Hodgkin’s\: more rapidly growing bulky lymphadenopathy
Mediastinal mass\: may cause severe e
Abdomen\: splenomegaly, hepatomegaly, abdominal mass
Skin\: T cell lymphomas including mycosis fungoides, jaundice
Testicular mass
Neurological\: weakness, sensory abnormalities, features of raised intracranial pressure

Di

Table 2. Di
14
Infective (viral) Infective (bacterial) Other
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Common upper
respiratory tract
infections
Infectious
mononucleosis
Rubella, measles
Cytomegalovirus
HIV
HHV-6
Adenovirus
Tuberculosis
Typhoid
Syphilis
Lyme disease
Brucellosis
Malignant
Leukaemia
Neuroblastoma
Protozoal
Toxoplasmosis
Leishmaniasis
Trypanosomiasis
Autoimmune
Juvenile idiopathic
arthritis
Systemic lupus
erythematosus
Drug reactions
Infection is the most common cause of lymphadenopathy in children

Investigations

Bedside investigations

Relevant bedside investigations include\:
5,13
Observations\: fever can be caused by malignancy or infection, respiratory rate and SpO 2
are important to assess for
patients presenting with mediastinal disease.
Swabs\: identify any infective causes of lymphadenopathy
Urine dip\: exclude infection if febrile
Electrocardiogram (ECG)\: chest disease may cause e
useful to have prior to starting cardiotoxic chemotherapies.

Laboratory investigations

Relevant laboratory investigations include\:
5,13
Full blood count (FBC)\: may show pancytopenia or leukaemic presentation - leukaemia (important di
will cause anaemia, thrombocytopenia, and usually a raised WBC.
Urea and electrolytes (U&E)\: baseline kidney function is important prior to starting chemotherapy, and electrolytes can
show tumour lysis syndrome if rapid cell turnover occurs (but this is more common following chemotherapy).
Lactate dehydrogenase (LDH) and urate\: these indicate a high cell turnover when raised.
Liver function tests (LFT)\: baseline liver function is important prior to starting chemotherapy, while derangement may
indicate hepatic involvement. Low albumin is associated with a worse prognosis.
Monospot test\: exclude Epstein-Barr virus infection
Erythrocyte sedimentation rate (ESR)\: if raised this is associated with worse prognosis
Hepatitis B/HIV tests\: risk of hepatitis reactivation with rituximab treatment
Glucose-6-phosphate dehydrogenase (G6PD)\: G6PD de
it can cause a haemolytic crisis.

Imaging

Relevant imaging investigations include\:
5,13
Chest X-ray\: can show a mediastinal mass arising from the lymph nodes or thymus, intrathoracic lymph nodes, or
e
CT/MRI/PET scans\: for staging purposes
Ultrasound of the liver and spleen
Biopsies3,5-9,12-14
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Biopsy of the enlarged lymph node is used for diagnosis, usually under a general anaesthetic. Excision biopsy or a partial
biopsy are used, as
an alternative method of diagnosis for very unwell children, reducing the need for general anaesthetic and biopsy.
Bone marrow biopsy can be used for staging purposes to detect in
cerebrospinal

Staging

An overview of the staging system for lymphoma is shown (simpli
between Hodgkin’s and non-Hodgkin’s.
The Ann Arbor classi
more extranodal involvement.
3,5,7-10,12-13
Table 3. Simpli
Stage Features
I
II III
IV Hodgkin’s
IV Non-Hodgkin’s
1 group of lymph nodes is a
side of the diaphragm
≥2 groups of lymph nodes are a
on 1 side of the diaphragm
Lymphoma is present in nodes on both
sides of the diaphragm
Involvement of extranodal sites
beyond those designated by ‘E’ (below)
Disseminated/multifocal involvement
of ≥1 extralymphatic site OR isolated
extralymphatic organ involvement with
distant node involvement
Letters are used to denote other details in staging\:
A\: no systemic symptoms loss/fever/night sweats
B\: systemic symptoms present\: weight
E\: involvement of single, contiguous, or proximal extranodal site (Hodgkin’s)

Management

Hodgkin’s lymphoma3,5,7,8
Chemotherapy is the main treatment used for Hodgkin's lymphoma.
Other management options for Hodkin's lymphoma include\:
Radiotherapy is used in \<50% children. A PET scan is used to assess response after 2 cycles of chemotherapy, and
patients with ongoing PET avidity will receive adjuvant radiotherapy.
Lymphocyte-predominant HL has less intensive treatment (due to a slower growth rate); usually surgery or low-dose
chemotherapy is su
Non-Hodgkin’s lymphoma9-13
Chemotherapy is the main treatment used for non-Hodgkin's lymphoma.
The speci
intensive chemotherapy, while T-cell NHL will have less intensive chemotherapy that lasts 2-3 years. Intrathecal
chemotherapy is used as prophylaxis/treatment of CNS lymphoma.
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Other management options for non-Hodgkin's lymphoma include\:
Biologics\: Rituximab (anti CD20 antibody) is the standard of care in high-risk mature B-cell NHL.
Radiotherapy is used rarely in addition to chemotherapy.
Bone marrow transplant (BMT)\: high dose chemotherapy with BMT can be used for relapsed patients.
Lymphoblastic lymphoma is treated according to chemotherapy protocols for ALL.

Complications

Table 4. Long-term and short-term complications of lymphoma and treatments.
5,7,8,12-13
Short-term
Condition-related Treatment-related
Superior vena cava
obstruction
Bowel
obstruction/perforation
Cytopenias
Pericardial or pleural
e
Pain from tumour
invasion
Tumour lysis syndrome
Neutropenic sepsis
Mucositis, diarrhoea
Anorexia and weight loss
Alopecia
Nausea and vomiting
Fatigue
Tumour lysis syndrome
Long-term
Secondary cancers
Cardiotoxicity
Pulmonary toxicity
Renal impairment
Growth impairment
Infertility
Tumour lysis syndrome10,13
Tumour lysis syndrome is an oncological emergency caused by lysis of tumour cells, either due to chemotherapy
treatment or sometimes spontaneously in highly proliferative tumours.
It results in electrolyte imbalances including hyperphosphataemia, hyperkalaemia, hypocalcaemia,
hyperuricaemia.
Clinical manifestations include\:
Acute kidney injury
Cardiac arrhythmias
Nausea and vomiting
Seizures.
Prophylactic hydration and allopurinol are important prior to chemotherapy. Rasburicase may be used if white cell
count is >50, as this will actively break down the uric acid, while allopurinol prevents uric acid production.
Treatment involves aggressive hydration, rasburicase or allopurinol, and haemo
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G6PD de

Prognosis

Approximately 90% of patients with Hodgkin’s lymphoma and >90% of children with Non-Hodgkin’s lymphoma achieve
remission.
3,9
However, excellent survival rates mean that the long-term e
term follow-up, assessing for recurrence and the onset of any late side e

References

Children’s Cancer and Leukaemia Group. L y m p h o m a . Available from\: [LINK]
Lymphoma Action. L y m p h o m a i n C h i l d r e n . November 2018. Available from\: [LINK]
Children’s Cancer and Leukaemia Group. H o d g k i n L y m p h o m a . August 2016. Available from\: [LINK]
Dana-Farber Cancer Institute and Boston Children’s Hospital. L y m p h o b l a s t i c l y m p h o m a . Available from\: [LINK]
Patient UK. H o d g k i n’ s L y m p h o m a . May 2019. Available from\: [LINK]

Related notes

Wang e t a l . D i a g n o s i s o f H o d g k i n L y m p h o m a i n t h e M o d e r n E r a . January 2020. Available from\: [LINK]
Shanbhag and Ambinder. H o d g k i n L y m p h o m a \: a r e v i e w a n d u p d a t e o n r e c e n t p r o gr e s s . March 2018. Available from\: [LINK]
Acute Myeloid Leukaemia
Children with Cancer UK. H o d g k i n L y m p h o m a . Available from\: [LINK]
Anaemia Overview
Children’s Cancer and Leukaemia Group. N o n-H o d g k i n L y m p h o m a . December 2016. Available from\: [LINK]
Chronic Myeloid Leukaemia
Minard-Colin e t a l . N o n-H o d g k i n L y m p h o m a i n C h i l d r e n a n d A d o l e s c e n t s \: P r o gr e s s T h r o u g h E
C u r r e n t K n o w l e d g e , a n d C h a l l e n g e s Disseminated Intravascular Coagulation (DIC)
A h e a d . September 2015. Available from\: [LINK]
Sandlund and Haemolytic anaemia
Martin. N o n-H o d g k i n l y m p h o m a a c r o s s t h e p a e d i a t r i c a n d a d o l e s c e n t a n d y o u n g a d u l t a ge s p e c t r u m .
December 2016. Available from\: [LINK]
Children with Cancer UK. N o n-H o d g k i n L y m p h o m a . Available from\: [LINK]

Test yourself

Patient UK. N o n-H o d g k i n’ s L y m p h o m a . December 2015. Available from\: [LINK]
Patient UK. G e n e r a l i s e d L y m p h a d e n o p a t h y . March 2019. Available from\: [LINK]
Radiopaedia. M e d i a s t i n a l L y m p h o m a . Available from\: [LINK]

Contents

Science Direct. T u m o u r l y s i s s y n d r o m e . Available from\: [LINK]

Image references

Introduction
Figure 1. National Cancer Institute. R e e d-S t e r n b e r g C e l l . License\: [Public domain]. Available from\: [LINK]
Aetiology

Reviewer

Risk factors
Dr Simon Bomken
Clinical features
MRC Clinician Scientist and Honorary Consultant Paediatric Oncologist
Wolfson Childhood Cancer Research Centre
Di
Investigations
Management
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