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.
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.
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 2
- Pepper syndrome: hepatomegaly due to extensive liver metastasis
- blueberry muffin syndrome: multiple cutaneous lesions
- opsomyoclonus 5: rapid, involuntary conjugate fast eye movements
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.
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%
- organ of Zuckerkandl
- coeliac axis
- paravertebral sympathetic chain
- posterior mediastinum: 20%
- neck: 1-5%
- pelvis: 2-3%
The vast majority of neuroblastomas are sporadic, however, in rare instances, they may be associated with 1-4:
- Beckwith-Wiedemann syndrome
- central failure of ventilation
- DiGeorge syndrome
- Hirschsprung disease
- neurofibromatosis type 1
Appearances are non-specific, typically demonstrating an intrathoracic or intra-abdominal 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.
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.
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 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
- heterogeneous and hyperintense
- cystic/necrotic areas very high intensity
- signal voids may be evident
- C+ (Gd): variable and heterogeneous enhancement
Some compounds are used for diagnosis and staging:
- pentetreotide labelled to Indium-In111 ( a somatostatin analog)
- not specific for neuroblastic tissue
- MIBG (metaiodobenzylguanidine labelled to Iodine-123)
- FDG PET/CT
Surveillance for metastatic recurrence:
- Tc-99m MDP
- 36% of primary tumours negative
- mainly to evaluate skeletal metastases
- also able to detect some lung and liver metastases 2
Staging and metastatic disease
For staging refer to neuroblastoma staging.
Metastatic disease is common and has a variety of patterns:
- most common
- diffuse infiltration (more common in stage 4S)
- focal hypo-enhancing masses
- lung and pleura
- discrete nodules
- diffuse consolidation
- pleural disease is uncommon
- brain and meninges
- dural metastases can be diffuse of nodular
- brain metastases are uncommon but variable in appearance
Treatment and prognosis
Treatment depends on the patient's 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 downstage the tumour may be administered 2.
- stage 1, 2 or 4S: 75-90% 3 year survival
- <1 year of age: 80-90% 1-year event free survival
- >1 year of age: 50% 3-year survival
- <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 the presence of metastasis
- N-Myc mutation
- chromosome 1p deletion
- unfavourable Shimada histology index
Better prognostic factors
- TRK-A expression
For an intra-thoracic neuroblastoma consider:
- intrathoracic lymphoma
- extralobar pulmonary sequestration
- round pneumonia
For an intra-abdominal neuroblastoma consider:
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