History and exam
Key diagnostic factors
common
presence of risk factors
Patients may have a family history of neuroblastic tumours or neurocristopathies.
age <4 years
The majority of neuroblastoma cases occur in children ≤4 years of age (34% in children <1 year; 49.9% in those aged 1-4 years).[12]
Median age at diagnosis is 17 months.[12]
Infants typically present with an asymptomatic adrenal mass detected on routine prenatal ultrasound. Patients with localised disease may also be asymptomatic.
abdominal distention
abdominal mass
May be felt on palpation if the primary site is the abdomen.
In the UK, the National Institute for Health and Care Excellence (NICE) recommend very urgent referral (an appointment within 48 hours) for specialist assessment for neuroblastoma in children with a palpable abdominal mass or an unexplained enlarged abdominal organ.[31]
pain
Abdominal pain is common if the primary site is the abdomen.
Bone pain is common in patients with metastatic disease. Back pain may indicate spinal disease. The presence of neurological signs and symptoms may indicate spinal cord compression.
decreased appetite
Patients commonly present with general systemic symptoms which may indicate metastatic spread.
weight loss
Patients commonly present with general systemic symptoms which may indicate metastatic spread.
fussiness (infants)
Patients commonly present with general systemic symptoms which may indicate metastatic spread.
fatigue
Patients commonly present with general systemic symptoms which may indicate metastatic spread.
periorbital ecchymosis (panda eyes)
Common in patients with orbital metastases.
uncommon
family history of neuroblastic tumours
Approximately 1% to 2% of patients have a family history of neuroblastoma.[13]
Most hereditary neuroblastomas are caused by alterations in the ALK (anaplastic lymphoma kinase) gene.[14] Germline PHOX2B (paired-like homeobox 2b) mutations are a relatively rare cause of hereditary neuroblastoma.[15][16]
signs of spinal cord compression
If the tumour extends into the spinal canal, patients may initially present with signs of spinal cord compression including loss of bowel and bladder function, lower-extremity weakness, and back pain.
signs of Horner's syndrome
signs of superior vena cava syndrome
If the primary lesion is in the upper portion of the thoracic outlet or cervical sympathetic chain, patients will often present with superior vena cava syndrome (characterised by dyspnoea, facial swelling, cough, distended neck/chest veins, oedema of the upper extremities) due to mass effect on the vascular system.[1]
intractable secretory diarrhoea
May occur in patients with tumour secretion of vasoactive intestinal protein (VIP), a paraneoplastic syndrome associated with neuroblastoma.[9]
opsoclonus-myoclonus ataxia (OMA)
Paraneoplastic syndrome is sometimes associated with neuroblastoma. OMA (also known as opsoclonus-myoclonus syndrome) occurs in <3% of patients with neuroblastoma.[33]
In patients with OMA, nearly one half will be diagnosed with neuroblastoma; therefore, all children with OMA should be evaluated for neuroblastoma.[34] Rapid, dancing eye movements, rhythmic jerking of limbs/trunk, and ataxia are pathognomonic for OMA.[8]
Other diagnostic factors
common
constipation
Common presenting symptom. Usually secondary to mass effect of abdominal tumour.
uncommon
pallor
May indicate metastatic spread to bone marrow.
bleeding
May indicate metastatic spread to bone marrow.
infections
May indicate metastatic spread to bone marrow.
hypertension
Caused by mass effect of abdominal tumour, which may compromise renal vasculature resulting in alterations of the renin-activating system pathway, or may be a result of tumour-associated catecholamine secretion.[1]
Risk factors
weak
neurocristopathies or other syndromes
A few medical conditions, some of which are related to aberrant neural crest development, have been shown to predispose a patient to developing neuroblastoma, including Turner syndrome, Hirschsprung's disease, congenital central hypoventilation syndrome, and neurofibromatosis type 1.[17][18] Given that neuroblastoma arises from the sympathetic nervous system, the rationale that it may be associated with other disorders of the neural crest is biologically sound.
family history of neuroblastic tumours or genetic predisposition
Approximately 1% to 2% of patients have a family history of neuroblastoma.[13]
Most hereditary neuroblastomas are caused by alterations in the ALK (anaplastic lymphoma kinase) gene.[14] Germline PHOX2B (paired-like homeobox 2b) mutations are a relatively rare cause of hereditary neuroblastoma.[15][16]
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