SELF-ASSESSMENT

PAE

Self-assessment

Questions

Question 1

(i) Ultrasound abdomen

(j) Urea and electrolytes

(k) Urinary catecholamines (VMA and HVA)

A 6-year-old boy presents with a 2-week history of a rapidly

enlarging painless lump on the left side of his neck, despite

a course of oral amoxicillin. His parents also report that

some smaller lumps have appeared on the right side of his

neck over the last 3 or 4 days, and that he also had an

episode of tonsillitis 4 weeks ago, treated with oral peni-

cillin. He has been more pale and tired than usual with loss

of appetite. Apart from insertion of bilateral grommets aged

4 years for bilateral glue ear and associated conductive

hearing loss, there is no past medical history of note. On

examination, he appears flushed and unwell with

a temperature of 38.3 �C. A firm, rubbery, non-tender mass

measuring 5 cm by 4 cm in the left cervical anterior triangle

is present with two 3 cm by 2 cm masses in a similar

position on the right side. Left-sided supraclavicular

lymphadenopathy is also present. There are no colour or

temperature changes of the overlying skin. On general

examination there are no other positive findings.

Full blood count reveals: Hb 10.1 g/dl; WCC 6.3 � 109/

litre; neutrophils 3.7 � 109/litre; lymphocytes 2.4 � 109/

litre; platelets 164 � 109/litre.

(A) What is the most likely diagnosis? (Choose ONE only)

(a) Acute lymphoblastic leukaemia (ALL)

(b) Cat scratch disease

(c) Hodgkin’s lymphoma

(d) Infectious mononucleosis

(e) Kawasaki’s disease

(f) Neuroblastoma

(g) Non-Hodgkin’s lymphoma (NHL)

(h) Reactive lymphadenopathy secondary to tonsillitis

(B) What are the two next most urgent investigations to

arrange? (Choose TWO ONLY)

(a) Bartonella henselae indirect fluorescent antibody

(IFA) test

(b) Blood film

(c) Bone marrow aspirate

(d) Cervical lymph node biopsy

(e) Chest X-ray

(f) CT chest scan

(g) Echocardiogram

(h) Monospot test

Matthew Murray MB BChir MA MRCPCH DCH is a Paediatric Oncologist at the

Department of Paediatric Haematology and Oncology, Addenbrooke’s

Hospital, Cambridge, UK.

James Nicholson MB BChir MA MRCP MRCPCH DM is a Paediatric Oncologist

at the Department of Paediatric Haematology and Oncology,

Addenbrooke’s Hospital, Cambridge, UK.

DIATRICS AND CHILD HEALTH 20:7 347

Question 2

SELECT ONE ANSWER ONLY FOR EACH QUESTION

Note: Each answer may be used more than once

(A) Acute lymphoblastic leukaemia

(B) Germ cell tumour

(C) Hodgkin’s lymphoma

(D) Nephroblastoma (Wilms’ tumour)

(E) Neuroblastoma

(F) Non-Hodgkin’s lymphoma

(G) Osteosarcoma

(H) Reactive lymphadenopathy

(I) Rhabdomyosarcoma

(J) Ewing’s sarcoma

(1) A 12-year-old girl presents with an 8-month history

of bilateral neck swelling. For the last month she reports

being tired all the time, losing weight and having night

sweats. On examination there are multiple, bilateral ante-

rior and posterior cervical lymph nodes present, most of

which are 2e3 cm in diameter.

(2) A 4-year-old boy presents with a 4-month history of

lower abdominal discomfort. He has been treated with lactu-

lose for a presumed diagnosis of constipation with little

benefit. His parents have noticed lower abdominal swelling in

the last 2weeks,withpainnot responding to simpleanalgesics.

On examination, a mass is palpable arising from the pelvis

towards the umbilicus, confirmed by MRI scan (see Figure 1).

(3) A 12-year-old girl has a 4-month history of pain in

her left leg, which often wakes her at night. Over the last

6 weeks she has noticed a swelling over her left thigh. She is

Figure 1 Sagittal MRI pelvis demonstrating a large pelvic mass with

concomitant displacement of the bladder superiorly.

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SELF-ASSESSMENT

athletic and her parents initially attributed her symptoms to

growing pains. On examination, she appears well. There is

a tender, smooth 12 cm by 7 cm swelling over the anterior

aspect of the lower third of the left femur, with abnormal-

ities visible on plain X-ray (see Figure 2). The rest of the

examination is unremarkable. Bone scan confirms

abnormal uptake in this region (see Figure 3).

Answers

Figure 3 Bone scan showing abnormal uptake in the region of the left

distal femur.

Question 1

A (g) Non-Hodgkin’s lymphoma (NHL)

B (e) Chest X-ray

(j) Urea and electrolytes

A

Cervical lymphadenopathy is very common in children and

in most cases is reactive to a simple upper respiratory tract

infection, with malignancy only accounting for a small

percentage of cases (cancer occurs in approximately 1 in

600 children by the age of 15 years, corresponding to a total

of w1700 new cases per year in the UK). Nevertheless,

delay in diagnosis may have serious adverse consequences,

such as more advanced tumour stage/disease extent, length

and intensity of treatment required and overall prognosis. It

is important to investigate cases thoroughly and in a timely

fashion if there are features suggestive of malignancy.

In this case, suspicious features are the absence of signs

or symptoms of infection that would account for the severity

of lymphadenopathy; the presence of systemic or constitu-

tional symptoms such as weight loss and the size and

characteristics of the affected lymph nodes. When consid-

ering nodes, size, texture and mobility should all be

described. Nodes greater than 2 cm in diameter warrant

consideration for biopsy. In this case, the nodes are signif-

icantly larger than this and, in addition, are rapidly pro-

gressing. Furthermore, the nodes are described as firm,

non-tender and rubbery in texture, terms particularly

associated with malignancy. Fixed nodes that are tethered

to underlying structures such as muscle are also features

consistent with a diagnosis of malignancy.

Figure 2 Plain X-ray demonstrating abnormalities of the distal third of

the left femur.

PAEDIATRICS AND CHILD HEALTH 20:7 348

The child’s age is helpful in deciding which cancer type

is most likely. Non-Hodgkin’s lymphoma (NHL) and acute

lymphoblastic leukaemia (ALL) are more likely to be seen

in younger children, whereas Hodgkin’s lymphoma is more

common in older children (>8 years). Disseminated

neuroblastoma is unusual in children >5 years of age, but

may rarely present with cervical lymphadenopathy due to

malignant enlargement of the cervical sympathetic chain. In

addition, systemic and constitutional symptoms may help

identify the cause. Weight loss is a common finding in

children presenting with cancer and, when combined with

fever and night sweats, is particularly associated with

Hodgkin’s disease, when they are collectively referred to as

‘B symptoms’. Rate of progression is also useful, with

a timescale of days to weeks more suggestive of NHL or

ALL. Hodgkin’s disease tends to progress more slowly and

the history of lymphadenopathy may be many months and

in some cases 1 year or more. Systemic examination should

be thorough and may reveal evidence of a primary tumour

or of pallor, bruising and/or petechiae, suggestive of

pancytopenia, the most common cause of which would be

ALL in childhood. A child with advanced disease may look

pale and non-specifically unwell. The presence or absence

of other palpable nodes at all other lymph node stations and

of hepatosplenomegaly must be documented. Supra-

clavicular (as in this case) or axillary lymphadenopathy is

more likely to reflect an underlying malignant process.

In addition to the other differential diagnoses listed

above, distant spread from other solid malignancies should

� 2010 Elsevier Ltd. All rights reserved.

Classical electrolyte disturbance seen in cases oftumour lysis syndrome

Hyperkalaemia

Hyperuricaemia

Hyperphosphataemia

Hypocalcaemia

Metabolic acidosis, if severe

Table 1

SELF-ASSESSMENT

be considered, with rhabdomyosarcoma and nasopharyn-

geal carcinoma recognized causes in childhood. Other

possibilities to consider include bacterial and viral infection

including infectious mononucleosis (glandular fever), cat

scratch disease, toxoplasmosis and rarely connective tissue

disorders or Kawasaki disease. Infectious mononucleosis is

more common in older children, leucocytosis is common

(not present in this case) and the presentation would likely

be more temporally associated with the previous episode of

tonsillitis. The presence of other features of Kawasaki disease

(such as rash, conjunctivitis, cracked lips, red ‘strawberry’

tongue) are not reported, making this unlikely. Cat scratch

disease usually results in enlargement of a single group of

draining nodes, most commonly in the axilla, which are

likely to be tender and associated with warmth and colour

change of the skin overlying the nodes. Atypical mycobac-

teria may produce large nodes in an otherwise well child that

may be difficult to differentiate and will need complete

excision, both to treat effectively and to exclude malignancy.

In summary, NHL is the most likely cause in this case,

given the age of the patient, the node size and characteristics,

rapid progression of symptoms and the associated systemic

disturbance (anaemia, loss of appetite, tiredness). Informa-

tion on these and other tumours can be found via the

Children’s Cancer and Leukaemia Group (CCLG) website.

B

Although it is essential to establish the tissue diagnosis

and stage the patient as quickly as possible in such cases, the

safety of the patient must not be compromised in doing this.

Therefore, although blood film, lymph node biopsy, CT

chest scan and ultrasound abdomen will all be arranged, the

next two most important steps are to perform a standard PA

chest X-ray and check serum urea and electrolytes (U&Es).

The former is to look for mediastinal disease, which is quite

possible given the extensive cervical and supraclavicular

lymphadenopathy. In cases of NHL or certain types of ALL

(e.g. T-cell) this may progress to critical airway compression

and death. Such life-threatening airway compression may be

precipitated by asking patients to lie flat, or sedating or

anaesthetizing them, in order to perform a CT scan. Thus

a chest X-ray should always be performed first, in order to

plan for a CT scan and lymph node biopsy safely. Similarly,

patients with such extensive and rapidly growing disease are

also at risk of spontaneous tumour lysis syndrome (TLS),

where insoluble breakdown products of excessive tumour

cell death result in renal impairment. This produces a char-

acteristic picture of electrolyte disturbance (see Table 1),

which may result in some cases in total renal failure and

need for renal support. Performing U&Es will identify any

such derangement and allow appropriate management to be

instigated, including hyperhydration with strict fluid

balance. In addition, drugs are utilized to assist the break-

down of cellular products to more soluble forms that may be

excreted by the kidneys. For very bulky and rapidly

progressive disease, such as with very high count leukaemia

PAEDIATRICS AND CHILD HEALTH 20:7 349

or bulky NHL, where patients are at high risk of TLS,

recombinant urate oxidase enzyme (e.g. Rasburicase) is

utilized for TLS prevention. Otherwise, for standard TLS

prevention, the xanthine oxidase inhibitor allopurinol is

used. Other non-haematological malignant tumours very

rarely cause TLS and this management is not therefore

required. Chest X-ray and U&Es should therefore be

arranged as an absolute priority, before the other listed

investigations. This still means that lymph node biopsy

should be arranged as soon as is safely possible, to allow

definitive treatment to be commenced.

Question 2

1 (C) Hodgkin’s lymphoma

2 (I) Rhabdomyosarcoma

3 (G) Osteosarcoma

(1) See also answer to Question 1 above. The significant

cervical lymphadenopathy of many months duration,

association with B symptoms and older age of this child

makes Hodgkin’s disease the most likely diagnosis from

those listed.

(2) The MRI scan (Figure 1) demonstrates a large pelvic

mass. The most likely diagnosis is a rhabdomyosarcoma,

which is the most common soft tissue sarcoma in childhood

and usually occurs in children <10 years of age. They arise

from muscle and occur mainly in the nasopharynx, bladder,

pelvis, parameningeal regions, limbs and paratesticular

region. Most are sporadic, but some are associated with the

inherited cancer predisposition syndrome, Li Fraumeni

syndrome. Although it may present with abdominal disease,

B cell NHL is less likely as the presentation history is usually

much shorter. It should be noted that abdominal NHL may

present with intussusception and should be borne in mind

when this occurs outside the typical age range (i.e. a child

older than 2e3 years of age). Other diagnostic possibilities for

this presentation include a Ewing’s sarcoma and, in females,

an (ovarian) germ cell tumour, but these tend to occur in

older children (>8e10 years of age). A nephroblastoma

would not cause a mass arising from the pelvis and a neuro-

blastoma would also be very unlikely to present in this way.

(3) In the distal third of the left femur, the plain X-ray

(Figure 2) reveals an ill-defined permeative bone texture

with a wide zone of transition between normal and

abnormal bone. Furthermore, there is evidence of cortical

destruction and a spiculated periosteal reaction. Both these

� 2010 Elsevier Ltd. All rights reserved.

SELF-ASSESSMENT

PAE

features are associated with an aggressive pathological

process. Benign lesions such as bone cysts have a far more

clearly demarcated transition between normal and

abnormal bone. The ‘classical’ appearances of osteosar-

coma on plain X-ray include the cortical destruction shown

here, as well as chaotic new bone formation, and marked

cortical elevation and are known as ‘Codman’s triad’. The

plain X-ray in Figure 2 does not demonstrate the latter two

findings. These appearances are in contrast to the typical

findings in Ewing’s sarcoma, where bone destruction gives

rise to a more ‘‘moth-eaten’’ appearance and where cortical

thickening is often present. Furthermore, new bone

formation is rare and a soft tissue component of Ewing’s

tumours may also be visualized on plain X-ray. Osteosar-

comas and Ewing’s sarcoma account for over 90% of bone

tumours in childhood. Both have a peak incidence between

12 and 14 years of age, classically presenting with pain and

swelling over the affected area. Greater than 90% of oste-

osarcomas are located in the metaphysis (growth plate) of

bone with 80% occurring in the distal femur, proximal tibia

or fibula. In contrast, most Ewing’s sarcomas occur in the

diaphysis (mid-shaft) of the bone and only about 30% occur

in the leg. Ewing’s are more often associated with fever, soft

tissue masses and nerve root pain. Ewing’s (25%) have

metastases more commonly at presentation than in osteo-

sarcoma (10%), most commonly to the lungs in both

tumour types. In some cases it may be difficult to distin-

guish Ewing’s from chronic osteomyelitis.

In this case, the location of the lesion (distal femur), the

bone appearances on X-ray and the lack of associated soft

tissue swelling make osteosarcoma the most likely diag-

nosis, rather than Ewing’s sarcoma.

Often such symptoms are attributed to ‘growing pains’

and this may result in significant diagnostic patient delay.

Unilateral pain resulting in night waking is not consistent

with this label. Furthermore a history of minor trauma is

DIATRICS AND CHILD HEALTH 20:7 350

often reported e patients and families are frequently able to

recall such episodes in an attempt to explain symptoms that

turn out to be presentations of malignancies. The symptoms

may also sometimes be mistaken for the benign condition

OsgoodeSchlatter’s syndrome (apophysitis of the tibial

tuberosity). This occurs in children aged around 10e14

years and is nearly always bilateral. Pain and tenderness are

felt over the prominent tibial tuberosity and are

worse with strenuous exercise. Plain X-rays should be

performed to exclude other pathology; these demonstrate

benign prominence of the tibial tuberosity only. The

condition is self-limiting and responds to rest and simple

analgesics.

Once the likely diagnosis is established, the child should

be referred urgently to a specialist centre for further

investigation and staging, as further delay in diagnostic

work-up may ultimately affect prognosis. This work-up will

include MRI of the primary lesion to allow accurate

planning for biopsy, chest X-ray and CT scan, bone scan

and also bone marrow aspirates and trephines in presumed

Ewing’s cases. The bone scan (Figure 3) is performed to

look for evidence of metastases and in this case

confirms localized disease, with abnormal uptake at the site

of the left distal femur only. If other sites appear positive on

bone scan, then they should be imaged with MRI.

FURTHER READINGChildren’s Cancer and Leukaemia Group (CCLG), website: http://www.

cclg.org.uk/families/booklet.php?bid¼1&3id¼4&2id¼9.

Kim MS, Lee SY, Cho WH, et al. Prognostic effects of doctor-

associated diagnostic delays in osteosarcoma. Arch Orthop

Trauma Surg 2009; 129: 1421e25.

Pinkerton CR, Plowman PN, Pieters R, eds. Paediatric oncology. 3rd

Edn. Hodder Arnold 2004. ISBN: 034080775X.

� 2010 Elsevier Ltd. All rights reserved.