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KEY POINTS
■ The most common primary site for neuroblastomas are the adrenal glands, but they can also occur in the mediastinum, neck, and lower extremities. The adrenal medulla and the extra-adrenal paraspinal ganglia account for two-thirds of retroperitoneal lesions, with the other third coming from the paravertebral sympathetic chain or presacral area. Occasionally, a tumor will arise in the celiac axis or the organ of Zuckerkandl.
■ The most prudent initial imaging modality for diagnosing disease in the abdomen is ultrasonography (US), and it can be particularly helpful when examining the bladder, kidneys, or liver for metastasis. However, neuroblastoma staging requires the more advanced CT or MRI, and metaiodobenzylguanidine (MIBG) scintigraphy to determine primary tumor size; regional extent; and metastatic spread to sites in the neck, thorax, abdomen, or pelvis.
■ Tumor stage, as defined by the International Neuroblastoma Staging System, is determined by where the tumor originated, whether it can be excised, and if there are other tumors elsewhere in the body. In addition to tumor stage and age at presentation, prognosis also depends on histopathology, DNA index, and amplification of the MYCN gene. Stage and age at diagnosis are the most important prognostic factors.
Neuroblastoma is the second most common extracranial solid tumor in children, accounting for 8% to 10% of childhood cancers and 15% of all childhood cancer deaths.
1 It is the most common malignancy diagnosed in infancy, and its progression is largely based on patient age and stage at the time of diagnosis. The median patient age at presentation is 23 months with peak incidence from birth to 4 years.
1 In addition, 40% of patients first present clinically at younger than 1 year, and only 5% of patients older than 10 years present with symptoms.
1
Neuroblastomas can arise from any site along the sympathetic nervous system chain because they originate from primordial neural crest cells.2 The most common primary sites for neuroblastomas are the adrenal glands, but they can also occur in the mediastinum, neck, and lower extremities.3 The adrenal medulla and the extra-adrenal paraspinal ganglia account for two-thirds of the retroperitoneal lesions, with the other third coming from the paravertebral sympathetic chain or presacral area. Occasionally, a tumor will arise in the celiac axis or the organ of Zuckerkandl, a chromaffin body derived from neural crest cells at the bifurcation of the aorta or at the origin of the inferior mesenteric artery.2,3
PRESENTATION
Neuroblastomas typically manifest within the first 4 years of life. A neuroblastoma is discovered incidentally as a palpable mass in an otherwise healthy child or is found in a child who is clearly ailing, which can be a sign of disseminated disease.2 A wide spectrum of symptoms and paraneoplastic syndromes are associated with neuroblastoma, which may indicate the presence of metastatic disease. As most tumors (65%) occur in the abdomen, pain and abdominal distention are common symptoms.1 Larger abdominal neoplasms can put pressure on the kidneys, which causes renin-associated hypertension. In addition, 7% to 15% of patients have paraspinal tumor extensions through the vertebral foramina that compress the nerve roots or sometimes the spinal cord itself.2,4 These patients can present with paralysis, problems associated with the urinary tract and/or bowel, weakness, paresthesias, and gait abnormalities.4 Patients with cervical or thoracic masses may present with Horner syndrome, a constellation of symptoms that includes unilateral ptosis, myosis, and anhidrosis—all of which remain permanent, even after tumor resection.1,5 In rare cases (2%), the patient presents with opsoclonus-myoclonus-ataxia syndrome, which is a disease involving myoclonic jerking and rapid eye movement either with or without cerebellar ataxia.
Neuroblastoma dissemination usually occurs through lymphatic and hematogenous routes, with the bone, bone marrow, and liver as the most common sites of metastasis. Metastatic disease that involves the liver can cause Pepper syndrome, which includes respiratory compromise due to increased intra-abdominal pressure from massive hepatic tumors.1 Subcutaneous dark nodules may give a "blueberry muffin" appearance to the skin.2 Periorbital swelling and ecchymoses ("raccoon eyes") is the result of metastasis to the periorbital bones and soft tissues of the skull and is thought to be common because cranial bones constitute a large proportion of the skeleton in infants.2,5
IMAGING STUDIES
The initial imaging modality for diagnosing disease in the abdomen is ultrasonography (US), and it can be particularly helpful when examining the bladder, kidneys, or liver for metastasis.2,6 However, neuroblastoma staging requires the more advanced CT or MRI, and metaiodobenzylguanidine (MIBG) scintigraphy to determine primary tumor size, regional extent, and metastatic spread to sites in the neck, thorax, abdomen, or pelvis1 (Figure 1). Most neuroblastomas appear to be irregularly shaped, unencapsulated, and lobulated on CT or MRI.3 CT shows calcification in approximately 85% of cases.3 Both CT and MRI are helpful in identifying morphologic features and determining presence of disease in the retroperitoneal lymph nodes, liver, and central vessels; however, MRI is better for verifying marrow infiltration and vertebral canal tumor extension.2,3
The radiopharmaceutical metaiodobenzylguanidine is an analog of norepinephrine and a derivative of the ganglionic blocking drug guanethidine. It concentrates in adrenergic tissue when administered intravenously.7,8 MIBG scintigraphy is an imaging modality that uses metaiodobenzylguanidine to confirm the presence of neuroblastoma in neural crest tissues. The modality is a single best imaging study for neuroblastoma because of its usefulness for initial disease staging, evaluating response to treatment, and for follow-up imaging.8 MIBG scintigraphy has the advantage of scanning the whole skeleton, and it is highly sensitive (90%) with nearly 100% specificity for detecting neuroblastoma.9 The study is as sensitive as MRI for detecting bone marrow involvement during initial diagnosis but is more specific than MRI for evaluating response to treatment. Therefore, MIBG scintigraphy should be used throughout treatment as well as for disease staging.2,7