Neuroblastoma

Dr Amir Rezaee and Dr Elhamy Bekhit et al.

Neuroblastomas are tumours of neuroblastic origin corresponding to the most common extracranial
solid childhood malignancies, and the third commonest childhood tumours after leukaemia and brain
malignancies. It accounts for ~15% of childhood cancer deaths 2.

Epidemiology
The tumours typically occur in infants and very young children (mean age of presentation being 22 months)
with 95% of cases diagnosed before the age of 10 years. Occasionally, they may be identified antenatally or
immediately at birth (see congenital neuroblastoma) 2.

Clinical presentation
Typically with pain or a palpable mass and abdominal distension, although numerous other presentations may
be encountered due to local mass effect.
Other accompanying syndromes include:

Hutchinson syndrome: bony metastases may present with skeletal pain or a palpable lump or limping
and irritability due to skeletal metastases

Pepper syndrome: hepatomegaly due to extensive liver metastasis

blueberry muffin syndrome: multiple cutaneous lesions

opsomyoclonus 5: rapid, involuntary conjugate fast eye movements

Pathology
The tumours arise from the primitive neuroectodermal cells or neural crest cells (adrenal medulla precursor).
The histology is similar to small round blue cell tumours 3. The majority of them demonstrate chromosome 1p
deletion and N-myc amplification.
Macroscopically, they tend to be large grey tan colour, soft lesions with or without fibrous pseudocapsule hence
some are well defined and some are infiltrative. Areas of necrosis, haemorrhage, and particularly calcification
are very common.
Microscopically, they form Homer Wright rosettes 3. Most of them secrete catecholamines: vanillylmandelic acid
(VMA) and homovanillic acid (HVA) 2.

Location
Neuroblastomas arise from the sympathetic nervous system 2-3:

Intra-abdominal disease (two-thirds of cases) is more prevalent than the intrathoracic disease. Specific sites
include:

adrenal glands: most common site of origin, 35%

retroperitoneum: 30-35%
o

organ of Zuckerkandl

coeliac axis

paravertebral sympathetic chain

posterior mediastinum: 20%

neck: 1-5%

pelvis: 2-3%

Associations
The vast majority of neuroblastomas are sporadic, however in rare instances they may be associated with

Beckwith-Wiedemann syndrome

central failure of ventilation

DiGeorge syndrome

Hirschsprung disease

neurofibromatosis type 1

1-4

Radiographic features
Radiograph
Appearances are non-specific, typically demonstrating an intrathoracic or intraabdominal soft-tissue mass.
Pressure on adjacent bones may cause remodelling of ribs, vertebral bodies or pedicle thinning. Up to 30%
may have evidence of calcification on the plain film.
Skeletal metastases are usually ill-defined and lucent, with periosteal reaction or metaphyseal lucency.
Sclerotic metastases are uncommon 2.

Ultrasound
Neuroblastoma on ultrasound demonstrates a heterogeneous mass with internal vascularity. Often there are
areas of necrosis that appear as regions of low echogenicity. Calcification may or may not be evident on
ultrasound 2.

CT

On CT, the tumour typically is heterogeneous with calcifications seen in 80-90% of cases 2. Areas of necrosis
are of low attenuation.
The tumour morphology is often helpful, with the mass seen insinuating itself beneath the aorta and lifting it off
the vertebral column. It tends to encase vessels and may lead to compression. Adjacent organs are usually
displaced, although in more aggressive tumours direct invasion of the psoas muscle or kidney can be seen. In
the latter it can make distinguishing neuroblastoma from Wilms tumour difficult (see neuroblastoma vs. Wilms
tumour).
Lymph node enlargement is often present.

MRI
MRI is superior to all other modalities in assessing the organ of origin, intracranial or intraspinal disease and
bone marrow disease 2.

T1: heterogeneous and iso to hypointense

T2
o

heterogeneous and hyperintense

cystic/necrotic areas very high intensity

signal voids may be evident

C+ (Gd): variable and heterogeneous enhancement

Nuclear medicine
A number of compounds are used for diagnosis and staging:

pentetreotide labeled to Indium-In111 (somatostatin analog)

o

not specific for neuroblastic tissue

MIBG (metaiodobenzylguanidine labeled to Iodine-123)

95% of neuroblastomas secrete catecholamines, however, 10-30% of neuroblastomas are

negative on MIBG

sensitivity: 88%

specificity: 99% (for sympathetic tissue) 2

does not distinguish between

neuroblastoma, glanglioneuroblastoma, ganglioneuroma, carcinoid, andpheochromocytoma

FDG PET/CT

Surveillance for metastatic recurrence

Tc-99m MDP
o

36% of primary tumours negative

mainly to evaluate skeletal metastases

also able to detect some lung and liver metastases

Staging and metastatic disease

For staging refer to: neuroblastoma staging
Metastatic disease is common and has a variety of patterns:

bone
most common

liver
o

diffuse infiltration (more common in stage 4S)

focal hypo-enhancing masses

lung and pleura

o

discrete nodules

diffuse consolidation

pleural disease is uncommon

brain and meninges

o

dural metastases can be diffuse of nodular

brain metastases are uncommon but variable in appearance

Treatment and prognosis

Treatment depends on the patients stage. Localised tumours considered to be 'low-risk' are surgically excised
and patients tend to do very well (see below). In 'high-risk' tumours, a combination or surgery, chemotherapy
+/- bone marrow transplantation is employed, unfortunately with poor overall results. In some cases, where
tumours are very large, pre-surgical chemotherapy to attempt to down-stage the tumour may be administered 2.
Patients with stage 1, 2 or 4S have a better prognosis. Unfortunately 40-60% of patients present with stage
3 or 4 disease 4. For advanced disease, the age of the child is most important 3.

stage 1, 2 or 4S: 75-90% 3 year survival

stage 3
o

<1 year of age: 80-90% 1 year event free survival

>1 year of age: 50% 3 year survival

stage 4
o

<1 year of age: 60-75% 1 year event free survival

>1 year of age: 15% 3 year survival

Poor prognostic factors

later age of onset: >18 months

higher stage: particularly in presence of metastasis

N-Myc mutation

chromosome 1p deletion

unfavourable Shimada histology index

Better prognostic factors

TRK-A expression

Differential diagnosis
For an intra-thoracic neuroblastoma consider:

intrathoracic lymphoma

extra lobar pulmonary sequestration

round pneumonia

ganglioneuroma

ganglioneuroblastoma

For an intra-abdominal neuroblastoma consider:

ganglioneuroma

ganglioneuroblastoma

rhabdomyosarcoma

Wilms tumour

References
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Article Information:

Cases and Figures

Case 2: retroperitoneal mass


Case 3

Case 4

Case 5

Case 6


Case 7

Case 9

Case 10: thoracic

Case 11


Case 12: metastases

Imaging Differential Diagnosis

Wilms tumour