Self-assessment

SELF-ASSESSMENT

PAE

Self-assessment

Questions

Question 1

(h) Serum HSV IgM and IgG antibodies

(i) Serum VZV IgM and IgG antibodies

A 9-year-old girl presents with a 3-month history of inter-

mittent frontal headaches. These are worse in the morning

and for the last 2 weeks have been associated with vomit-

ing. Her parents recall that she fell over in the playground

prior to the onset of headaches and that for the past month

she has also become clumsy. There are no other related

symptoms and, apart from having chickenpox four years

ago, she has no other past medical history of note. She is on

paracetamol and ibuprofen which provide partial relief

from the headaches, but no other regular medication.

Immunizations are up-to-date. Her parents report that she

has missed a significant amount of school in the mornings

as a result of her symptoms, but that she sometimes feels

well enough by lunchtime to be able to attend in the

afternoons.

On examination, her temperature is 37.3 �C, blood

pressure 102/55 mmHg and pulse 98 beats/min. Ataxia and

past-pointing are present. No abnormalities are detected on

fundoscopy.

(A) What is the most likely cause for this presentation?

(Choose ONE ONLY)

(a) Benign (idiopathic) intracranial hypertension

(b) Complex partial seizures

(c) Migraine with Todd’s paresis

(d) Posterior fossa tumour

(e) Varicella zoster virus (VZV) associated acute cere-

bellar ataxia syndrome

(f) School refusal

(g) Subdural haemorrhage

(h) Tuberculous meningitis

(i) Herpes simplex virus (HSV) encephalitis

(B) Which of the following single management steps would

be most appropriate at this stage? (Choose ONE ONLY)

(a) Chest X-ray

(b) Computed tomography (CT) head scan

(c) Electroencephalogram (EEG)

(d) Graded school re-introduction

(e) Lumbar puncture for cytology

(f) Mantoux test

(g) Therapeutic trial of a 5HT agonist, e.g. sumatriptan

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 20:6 304

Question 2

A 15-month-old boy presents to the rapid-referral clinic

with a 3-week history of fever, loss of appetite and general

lethargy. Over the last 5 days his parents have noticed

that a skin lesion has appeared on his back. He has

previously been fit and well with no past medical history

of note. On examination he is very pale, miserable and

cachectic with a temperature of 38.8 �C. Other positive

findings include significant abdominal distension with a 2

cm liver edge and gross splenomegaly extending to the

right iliac fossa. Dermatological examination reveals fine

petechiae and a 1.5 � 1.0 cm isolated ulcerated skin lesion

on his back.

Full blood count reveals: Hb 4.5 g/dl, WCC 1.8 �109/litre, neutrophils 0.2 � 109/litre, platelets 36 � 109/litre

(A) What is the most important feature to elicit from the

history now? (Choose ONE ONLY)

(a) Drug history including allergies

(b) Family history of eczema and atopy

(c) Family history of malignancy, particularly skin

malignancy

(d) Immunization record including BCG

(e) Recent foreign travel

(f) Recent infections

(B) Select the most likely diagnosis from the following list

(Choose ONE ONLY)

(a) Acute lymphoblastic leukaemia (ALL)

(b) Aplastic anaemia

(c) Idiopathic thrombocytopaenic purpura (ITP)

(d) Leishmaniasis

(e) Malaria

(f) Schistosomiasis

(g) Tuberculosis

(h) WiskotteAldrich syndrome

(C) What single test is most likely to establish the diagnosis?

(Choose ONE ONLY)

(a) Biopsy of skin lesion

(b) Blood film, including thick and thin film

(c) Bone marrow aspirate

(d) Chest X-ray

(e) Mantoux test

(f) Serum vitamin B12, ferritin and folate estimation

(g) Stool examination for eggs of Schistosoma species

(h) WiskotteAldrich syndrome protein (WASP) gene

mutation analysis

(D) What would be the most appropriate management for

this condition? (Choose ONE ONLY)

(a) Anti-tuberculous therapy for six months

(b) Bone marrow transplant

� 2010 Elsevier Ltd. All rights reserved.

liver

SELF-ASSESSMENT

(c) Chemotherapy

(d) Oral anti-histamines and topical emollients

(e) Oral prednisolone 2 mg/kg/day initially, gradually

tapered based on full blood counts

(f) Intravenous liposomal amphotericin B (AmBisome)

(g) Intravenous broad spectrum cephalosporin-based

antibiotics

(h) Intravenous immunoglobulin

(i) Splenectomy and lifelong penicillin prophylaxis

kidneymass

Figure 2 Axial CT scan revealing a large right-sided abdominal mass.

Question 3

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 3-year-old boy presents with increasing abdominal

distension, which his mother first noticed 2 weeks ago

whilst bathing him. Past medical history is unremarkable.

On palpation, a large right-sided abdominal mass is

palpated. Chest X-ray reveals multiple small round opacities

bilaterally (see Figure 1). CT scan confirms the abdominal

mass (Figure 2) and pulmonary findings (Figure 3).

(2) A 15-year-old post-pubertal boy presents to his

general practitioner with a 6-month history of a painless,

swollen left testicle. He is otherwise well with no fever and

no significant past medical history. Examination reveals an

enlarged, non-tender left hemiscrotum. Left testis length is

5.5 cm, right testis 3 cm. The scrotum does not trans-

illuminate. The rest of the examination is unremarkable.

pulmonaryopacities

pulmonaryopacities

Figure 1 PA chest X-ray demonstrating multiple, small round opacities

projected over the lung fields bilaterally.

PAEDIATRICS AND CHILD HEALTH 20:6 305

Answers

Question 1

A (d) Posterior fossa tumour

B (b) CT head scan

A

The history of headaches (particularly those worse in the

morning) and associated vomiting are the classical symp-

toms of raised intracranial pressure (RICP). Such symptoms

should not be confused with conditions such as school

refusal e the pattern of symptoms described is sinister and

should warrant further immediate investigation. Impor-

tantly, the absence of frank papilloedema, as occurs in this

case, does not rule out the possibility of RICP. RICP is often

associated with cerebellar symptoms such as nystagmus,

ataxia, past-pointing, as the most likely diagnosis in this

scenario is a posterior fossa tumour (medulloblastoma, low-

grade astrocytoma or occasionally ependymoma). A longer

history (months rather than weeks) is more suggestive of an

astrocytoma (benign) rather than a medulloblastoma

(malignant). However, an astrocytoma may have been

present asymptomatically for some time before presenting

pulmonarylesions

pulmonarylesions

heart

right hemi-diaphragm

Figure 3 Axial CT scan confirming chest X-ray findings seen in Figure 1.


SELF-ASSESSMENT

acutely with RICP when the tumour enlarges to a critical

size. Thus a short history per se cannot reliably distinguish

between the two. Subdural haemorrhages may also present

with RICP but are exceedingly rare in children of this age

and would not occur after such a simple, inconsequential

fall as described in this case. Nevertheless, parents will

often report such falls or events as a potential explanation

for their child’s headaches/symptoms.

With varicella zoster virus (VZV) associated cerebellar

ataxia, the symptoms present acutely with the primary

infection, and headaches are not a prominent feature. The

incidence is approximately one in 4000 cases. Benign

(idiopathic) intracranial hypertension presents with head-

ache and RICP, but very rarely cerebellar symptoms. The

nature of the headaches seen in this case (daily, worse in

mornings, often improved within a few hours and after

vomiting) is not typical of migraine, nor do they fit with

a seizure disorder.

B

An urgent CT head scan with contrast should be

arranged, which will identify the tumour and the presence

of any hydrocephalus, dictating the urgency of referral to

a neurosurgical centre. An MRI head scan will more clearly

delineate the tumour compared to a CT scan, and therefore

can be arranged in preference to a CT if it is readily avail-

able and will not result in diagnostic delay. If an MRI is

arranged, the spine should also be imaged as part of tumour

staging, to look for evidence of spinal metastases.

Lumbar puncture (LP) is contraindicated in the presence

of RICP. However, once RICP has been appropriately

controlled (see below), and at least 10e14 days after any

neurosurgical intervention [to allow traumatic cellular

debris within the cerebrospinal fluid (CSF) to settle], LP

should be performed for staging purposes, to look for

evidence of microscopic tumour cells within the CSF.

Microscopic disease (not visible on whole neuro-axis

imaging) is associated with a poorer prognosis and it is

therefore essential to establish its presence or absence. All

other management steps suggested are also inappropriate

given this history.

Initial management in such cases is directed at control-

ling RICP and providing adequate pain relief. RICP usually

occurs secondary to obstruction of CSF flow by the tumour.

Steroids such as oral or intravenous dexamethasone are

used to reduce oedema surrounding the tumour and may

well provide symptomatic improvement (given with an

agent such as ranitidine for protection of the gastric

mucosa). Urgent neurosurgery may be required for a CSF

diversion procedure, e.g. an extra-ventricular drain (EVD)

or third ventriculostomy, if RICP persists despite adminis-

tration of steroids. Occasionally a tumour biopsy is also

taken at the time of this procedure, but this is of secondary

importance to control of RICP.

Subsequent management is directed at establishing

a tissue diagnosis and completing staging investigations in


order to guide further management. In the majority of cases

attempt at complete excision is appropriate and associated

with better outcome. Neurosurgery is usually planned semi-

electively to allow for appropriate investigation and pre-

operative stabilization.

Question 2

A (e) Recent foreign travel

B (d) Leishmaniasis

C (c) Bone marrow aspirate

D (f) Intravenous liposomal amphotericin B (AmBisome)

A

Although all the questions listed should be asked as part of

a full history, including drug history, family history and

immunization record, enquiring about recent foreign travel

is vital in a case of an unexplained fever of such lengthy

duration, particularly when associated with atypical

features such as gross splenomegaly and skin lesions.

B

Leishmaniasis is the most likely diagnosis, caused by the

protozoan parasite (genus Leishmania) and transmitted by

the bite of the phlebotomine sandfly. In the UK, it is

presumed that all cases of leishmaniasis are acquired

abroad, and indeed a history of recent foreign travel to

endemic areas including tropical or Mediterranean coun-

tries occurs in the majority of cases. However, leishmani-

asis may rarely occur by vertical transmission from the

mother, and, furthermore, we are aware of a small number

of cases without the expected history of foreign travel or

evidence of vertical transmission.

The parasite exists in two forms, the smaller, round,

non-motile amastigote and the larger, spindle-shaped,

motile promastigote. It is the latter form in which the

sandfly introduces the parasite into the host, where it

invades macrophages and transforms back into the smaller

amastigote. After replication, the parasites lyse the host cell,

and the progeny migrate through the bloodstream to infect

new macrophage hosts. There are several different forms of

leishmaniasis, the most common being cutaneous (pre-

senting with skin lesions, which heal spontaneously to

leave scars) and the most severe called visceral (VL). VL,

also known as kala-azar, is caused by Leishmania donovani

and Leishmania infantum (Europe, Asia, Africa) or Leish-

mania chagasi (South America). In VL, the parasite

migrates to internal organs such as the spleen, liver and

bone marrow. Consequently, patients present with high

fever, malaise, significant weight loss, hepatosplenomegaly

and cytopaenias (such as anaemia) resulting from direct

bone marrow suppression. After malaria, VL is the second-

largest parasitic killer worldwide, responsible for an esti-

mated half a million deaths per year, and is invariably fatal

if untreated.

The symptoms of VL may be mistaken for other diag-

noses. Malaria may present with a very similar clinical


SELF-ASSESSMENT

picture, although skin lesions are uncommon. If patients do

not respond to anti-malarials then a low threshold for

investigation for VL should be maintained. ALL and aplastic

anaemia may present with a similar full blood count, but

skin lesions and gross splenomegaly as described in this

case would be unusual. The history and severe anaemia,

leucopaenia and neutropaenia also do not fit with ITP.

Tuberculosis rarely causes such severe splenomegaly.

WiskotteAldrich syndrome is an X-linked recessive

disorder characterized by eczema, immune deficiency and

thrombocytopaenia, due to mutations of the Wiskotte

Aldrich syndrome protein (WASP) gene, analysis of which is

used to confirm the diagnosis. The nature of the skin lesion

and generalized cytopaenia makes this diagnosis unlikely.

Schistosomiasis (also called bilharzia) is an often chronic

parasitic disease caused by the fluke of the genus Schisto-

soma species, including Schistosoma mansoni, Schistosoma

haematobium and Schistosoma japonicum, which is carried

by freshwater snails. It rarely causes such an acute

presentation as the one described. Finally, it is often diffi-

cult to distinguish the diagnosis of VL from the rare hae-

mophagocytic lymphohistiocytosis (HLH), which typically

presents with unrelenting fever, splenomegaly and cyto-

paenia. In HLH there is a deregulated inflammatory

response with hypercytokinaemias; histiocytes and

lymphocytes accumulate in organs including the skin,

spleen, and liver, and destroy erythrocytes. HLH may be

primary or secondary to infection or auto-immune disease.

Diagnosis may require multiple bone marrow aspirates to

demonstrate the classical morphological finding of haemo-

phagocytosis (engulfment of erythrocytes by histiocytes/

macrophages), in combination with other abnormalities

such as hyperferritinaemia. Untreated, the condition often

progresses rapidly to multiple organ failure and death, and

thus chemotherapy and/or bone marrow transplant is

required to achieve cure.

C

Diagnosis of leishmaniasis is by direct visualization of

the smaller, 2e6 mm diameter, amastigotes (also called

LeishmaneDonovan bodies) within macrophages/mono-

cytes. This may be diagnosed from peripheral blood, bone

marrow or splenic aspirates and lymph node or skin lesion

biopsy. A thin smear is spread on a slide and stained with

Leishman’s or Giemsa’s stain. The gold standard for diag-

nosis historically was visualization of a splenic aspirate, but

bone marrow aspirate has been shown to be equally effec-

tive, with a sensitivity of greater than 95%. Due to the risks

associated with splenic aspirates, bone marrow aspirate is

suggested as the diagnostic test of choice. Diagnosis from

the other listed sites, such as blood and skin lesions is less

effective.

D

In the west, the treatment of choice for VL is a course of

antifungal therapy with intravenous amphotericin B for


a number of weeks, in the liposomal form (AmBisome) if

available. Precise length of treatment should be dictated by

clinical response and advice from the infectious disease and

microbiology teams. The traditional treatment in endemic

areas is still with pentavalent antimonials such as sodium

stibogluconate and meglumine antimoniate. The other

treatment options listed are not appropriate for treatment

of VL.

Question 3

1 (D) Nephroblastoma (Wilms’ tumour)

2 (B) Germ cell tumour

(1) The imaging reveals a large right-sided abdominal mass

(Figure 2) with multiple, small round opacities in the lung

fields bilaterally (Figures 1 and 3), consistent with pulmo-

nary metastases. Nephroblastoma (Wilms’ tumour) is the

most likely diagnosis given the history of prominent

abdominal distension and these pulmonary findings. The

primary tumours are painless in many cases and the child

usually appears otherwise well. Haematuria and hyperten-

sion are present in about 30%, and about 75% of these

embryonal tumours occur in children less than 4 years of

age. Other potential differential diagnoses would include

neuroblastoma (but often unwell, lethargic and in pain at

presentation, with pulmonary metastases rarely seen) and

rhabdomyosarcoma (usually localized, often causing

discomfort). Information on these and other tumours can be

found via the Children’s Cancer and Leukaemia Group

(CCLG) website.

(2) The most likely diagnosis is a testicular germ cell

tumour (GCT), which present as a painless scrotal

swelling. Any mass where a GCT is considered as

a potential diagnosis should have serum tumour markers

(alpha-fetoprotein, AFP, and human choriogonadotropin,

HCG) performed. GCTs have a bimodal incidence in chil-

dren and teenagers, with a peak in those less than 5 years

and more than 12 years. There are a number of different

histological subtypes. In adolescence, testicular tumours

are often either seminomas or a mixed malignant subtype,

whereas in younger children benign teratomas and

malignant yolk sac tumours are most common. Presumed

testicular tumours must be excised via an inguinal

approach, as a scrotal approach risks local tumour seeding

which may require hemi-scrotectomy to achieve local

disease control. Subsequent treatment depends on stage

and histology. For stage 1 disease, there is the option of an

expectant ‘watch & wait’ (rather than a chemotherapy)

policy as in most patients, disease will not recur. This

entails regular clinical examination, imaging and tumour

marker estimation to ensure no abnormal elevation

persists post-operatively.

Occasionally an enlarged testis may be due to infiltration

by ALL (other signs and symptoms are usually, but not

universally, present) or to a rhabdomyosarcoma. Testicular

torsion, or infection e.g. due to epididymo-orchitis would

present acutely with significant pain.


SELF-ASSESSMENT

FURTHER READING

Beri S, Gosalakkal JA, Hussain N, Balky AP, Parepalli S. Idiopathic

intracranial hypertension without papilledema. Pediatr Neurol

2010; 42: 56e58.

Children’s Cancer and Leukaemia Group (CCLG) website: http://

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

da Silva MR, Stewart JM, Costa CH. Sensitivity of bone marrow

aspirates in the diagnosis of visceral leishmaniasis. Am J Trop

Med Hyg 2005; 72: 811e814.


Guess HA, Broughton DD, Melton LJ 3rd, Kurland LT. Population-based

studies of varicella complications. Pediatrics 1986; 78: 723e727.

Lewis DW. Pediatric migraine. Neurol Clin 2009; 27: 481e501.

National Travel Health Network and Centre (NATHNAC; funded by

the Health Protection Agency). Leishmaniasis information,

November 2007. http://www.nathnac.org/pro/factsheets/documents/

Leishmaniasisrevised1.pdf.

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

3rd Edn. Hodder Arnold 2004. ISBN: 034080775X.


http://www.cclg.org.uk/families/booklet.php%3Fbid%3D1%263id%3D4%262id%3D9





http://www.nathnac.org/pro/factsheets/documents/Leishmaniasisrevised1.pdf

http://www.nathnac.org/pro/factsheets/documents/Leishmaniasisrevised1.pdf

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Self-assessment