Neuroblastoma is a malignant neuroendocrine tumor of the sympathetic nervous system that originates from neural crest cells. It is the most common extracranial solid malignancy in children and the most common malignancy found in infants. Given its origin, neuroblastoma can occur in any aggregation of sympathetic nervous tissue, including the adrenal glands, the sympathetic chain, and the paraganglia (e.g., the carotid body). The clinical presentation is mainly determined by the site of the primary tumor, if it secretes catecholamines, and whether it has metastasized. In most cases, neuroblastomas stem from the adrenal glands within the abdominal cavity and present as a palpable abdominal mass that can cross the midline. Urine tests for catecholamine metabolites homovanillic acid (HVA) and vanillylmandelic acid (VMA) play an important role in diagnosis. Treatment is determined mainly by patient age at the time of diagnosis, clinical stage, and possible amplification of the MYCN oncogene. The prognosis depends on disease progression and is very good in early stages. Spontaneous remission may occur even in cases of metastatic disease.
- Most common malignancy of the adrenal medulla in infants and third most common childhood cancer overall following leukemia and brain tumors
- Mean age at diagnosis: 1–2 years
- The majority of children have progressed to advanced-stage disease by the time of diagnosis.
Epidemiological data refers to the US, unless otherwise specified.
- Cause: unclear
- Genetic associations: chromosomal abnormalities, especially deletions (found in ∼ 50% of neuroblastomas)
- Risk factors
|Location of primary tumors||Associated signs and symptoms|
Abdomen (in > 60% of cases)
Chest (in ∼ 20% of cases): particularly paravertebral ganglia
|Location of metastases||Associated signs and symptoms|
- Chronic diarrhea → electrolyte imbalances
- Opsoclonus-myoclonus-ataxia; : a paraneoplastic syndrome of unclear etiology characterized by rapid and multi-directional eye movements, rhythmic jerks of the limbs, and ataxia (dancing eyes dancing feet syndrome)
- Possibly hypertension, tachycardia, palpitations, sweating, flushing; (hypertension is more commonly seen in pheochromocytoma)
|International Neuroblastoma Staging System (INSS) |
- Imaging: to identify the primary site
- Homer Wright rosettes: Halo-like clusters of neuroblast cells surrounding a central pale area containing neuropil (associated with tumors of neuronal origin such as neuroblastoma, medulloblastoma, primitive neuroectodermal tumors, and pineoblastoma)
- Small round blue cells with hyperchromatic nuclei
- Bombesin and NSE positive
Neuroblastoma patients are treated based on their risk category (low, intermediate, or high), which is based on the stage of their neuroblastoma (extent of disease), age at diagnosis, and the presence/absence of MYCN amplification.
- Low risk: generally children with early-stage disease (Stages 1–2) and no MYCN amplification
- Intermediate risk: generally children with intermediate and late-stage disease (Stages 3–4) and no MYCN amplification
- High risk: generally children with late-stage disease and/or MYCN amplification
Stage 4S (an exception): disseminated disease in infants (< 12 months)
- Better prognosis than other stage 4 neuroblastoma and spontaneous regression is very common
- Children with Stage 4S belong to the low-risk or intermediate-risk groups unless they have a MYCN amplification, in which case they are high-risk patients
|Treatment of neuroblastoma|
|Treatment||Low-risk neuroblastoma||Intermediate-risk neuroblastoma||High-risk neuroblastoma|
|Preoperative chemotherapy (e.g., doxorubicin, cyclophosphamide, etoposide, and a platinum drug)||X||X||X|
|GD2 antibody, dinutuximab, granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin 2 (IL-2), and cis-retinoic acid||X|
|Other postoperative therapies (e.g., )||X|