Neuroblastoma (ORPHA:635)
Neuroblastoma is a malignant tumor of neural crest cells, the cells that give rise to the sympathetic nervous system, which is observed in children.
Epidemiology
It represents about 10% of solid tumors in infants and children under the age of 15, with an annual incidence of about 1/70,000 in children in this class of age.
Clinical description
In 90% of cases the neuroblastoma is diagnosed before the age of five. The clinical presentation of neuroblastoma is very variable and depends on the stage and location of the tumor, which can develop at any site in the sympathetic nervous system (around 80% of cases develop in the abdomen). Localized forms are discovered fortuitously or are revealed by the presence of an abdominal or thoracic mass that can be associated with pain. At the time of diagnosis, metastatic forms represent about 50% of cases. The most frequent metastatic sites are bone marrow, bone, liver and skin. Symptoms of metastasis including bone pain, limp, paralysis, hepatomegaly (Pepper's syndrome), and exophthalmia (Hutchinson's syndrome), indicate metastatic neuroblastoma. The disease can also be associated with arterial hypertension, fever, and an altered general state (weight loss, pain, irritability, and anemia).
Etiology
Neuroblastoma has been linked to numerous genetic anomalies which affect prognosis: amplification of the oncogene MYCN (2p24.3) is a factor for poor prognosis; triploidy, numerical anomalies of chromosomes are associated with a good prognosis, while di- or tetraploidy and segmental chromosomal anomalies (including loss from 1p, from 11q, or gains of 17q) are associated with poor prognosis. Recently, a mutation of the ALK gene has been described in about 12% of cases.
Diagnostic methods
Diagnosis is based on evidence of an elevated level of metabolites of urinary catecholamines (VMA, HVA, and dopamine) and on an image of the initial tumor by ultrasound and brain scan or by MRI. MIBG (iodine-131-meta-iodobenzylguanidine) scintigraphy and medullary analysis are useful for finding metastases. Tumor biopsy confirms the diagnosis, allows histological classification and helps find amplification of MYCN.
Differential diagnosis
Differential diagnoses include nephroblastoma, which makes it necessary to systematically check urinary catecholamines in case of an abdominal tumor. Bone pain and limp can be interpreted as synovitis of the hip. Possible bilateral peri-orbital hematomas, caused by orbital metastases, should not lead to a diagnosis of maltreatment.
Antenatal diagnosis
Neuroblastoma can be identified using antenatal ultrasound and therefore adequate management after the birth can be provided.
Management and treatment
Localized forms of neuroblastoma are treated by surgical resection, sometimes preceded by chemotherapy. Treatment of metastatic forms in children of more than one year and forms with amplification of MYCN is by: conventional chemotherapy, surgery of the initial tumor, high dose chemotherapy with hematopoietic stem cell transplantation, local radiotherapy and maintenance therapy with retinoic acid.
Prognosis
The majority of localized tumors have an excellent prognosis after surgery. Children under one year have a better prognosis than older children. Some tumors may even show spontaneous regression. In contrast, approximately 60% of children older than one year with neuroblastoma present metastatic disease at diagnosis with poor outcome, even with intensive treatment. In children older than one year, the five-year survival rate varies between 95% for some localized tumors to 30% in cases of metastatic neuroblastoma.

                            Last update: 
                            March 2009


                            - Expert reviewer(s): 
                            Dr Dominique VALTEAU-COUANET