History and exam

Key diagnostic factors

common

age <4 years

The majority of neuroblastoma cases occur in children ≤4 years of age (34% in children <1 year; 49.9% in those ages 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 localized disease may also be asymptomatic.

abdominal distension

Most common symptom, caused by the presence of a large abdominal mass.[29][30]

abdominal mass

May be felt on palpation if the primary site is the abdomen.

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 neurologic 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 (raccoon eyes)

Common in patients with orbital metastases.

subcutaneous skin nodules

Palpable, nontender, nonerythematous skin nodules are common in infants, and are associated with metastatic spread.[34][35]​​​

uncommon

family history of neuroblastic tumors

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 tumor 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 syndrome

If the primary lesion is in the upper portion of the thoracic outlet or cervical sympathetic chain, patients will often present with Horner syndrome (characterized by ptosis, miosis, anhidrosis) due to sympathetic nerve compression.[1][5][6]

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 (characterized by dyspnea, facial swelling, cough, distended neck/chest veins, edema of the upper extremities) due to mass effect on the vascular system.[1]​ 

intractable secretory diarrhea

May occur in patients with tumor 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.[32] 

In patients with OMA, nearly one half will be diagnosed with neuroblastoma; therefore, all children with OMA should be evaluated for neuroblastoma.[33] 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 tumor.

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 tumor, which may compromise renal vasculature resulting in alterations of the renin-activating system pathway, or may be a result of tumor-associated catecholamine secretion.[1]​​

hepatomegaly

May indicate metastatic spread to the liver.

Severe hepatomegaly secondary to liver metastases may be present in patients <18 months with stage MS disease (International Neuroblastoma Risk Group Staging System).[2][31]

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 disease, congenital central hypoventilation syndrome, and neurofibromatosis type 1.[17][18]

family history of neuroblastic tumors 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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