Neuroblastoma

Epidemiology

Neuroblastoma affects children and is the third most common cancer afflicting this population, after leukemia and brain tumors. In infants less than 1 year of age, it is the most common cancer. More than 600 cases are diagnosed in the United States each year. The average age at diagnosis is 17 months old, and there is a higher predilection among Caucasian children than in those of African descent.

Established risk factors for the development of neuroblastoma include insufficient maternal consumption of folate and maternal use of opiates. There is also an association between neuroblastoma and Turner syndrome, Hirschsprung's disease, and neurofibromatosis type 1 (NF1). Although most cases are sporadic, in 1 to 2 percent of patients, there is a family history of autosomal dominant inheritance.

Clinical Presentation

Because neuroblastomas arise anywhere in the sympathetic nervous system, they have a variety of ways of presenting to clinical attention. The most common primary sites are the adrenal gland, abdomen, and thorax; these three sites account for 80 percent of tumor locations. Neuroblastomas can also metastasize to various locations in the body via the circulatory and lymphatic systems. As such, presenting symptoms reflect the location of the neuroblastoma. Tumors that arise in the abdomen typically cause sensations of pain or fullness, constipation, decreased bladder capacity, and even swelling of the legs due to obstructed venous or lymphatic drainage. Thoracic tumors can cause tracheal deviation with resultant breathing difficulties, and neuroblastomas that form along the spine can cause pain, neurologic deficits, and loss of bowel and/or bladder control.

Neuroblastomas are made up of neuroectodermal cells, which originate from the fetal neural crest and are targeted for the sympathetic nervous system (including the adrenal medulla). They develop from nodules of these residual neuroectodermal cells that are thought to incompletely respond to normal signals that stimulate morphologic differentiation.

As with most health problems, there is a genetic basis to the development of neuroblastoma. In half of cases, chromosomal deletions are present from chromosomes 1p, 11q, and/or 14q. There can also be gains of chromosomes, such as with 17q. Deletions of 1p are associated with an increased amplification and expression of the oncogene MYCN, which is a DNA-binding transcription factor that can cause malignant transformation.

Diagnosis

As with all medical disorders, a history, physical examination, and laboratory evaluation are helpful in the diagnosis of neuroblastoma. A definitive diagnosis, however, requires histology from either tumor primary tissue or bone marrow metastases.

Imaging studies can be useful in diagnosing neuroblastoma. Ultrasound is often the initial study used to evaluate an abdominal mass, and can also be used in the prenatal diagnosis of neuroblastoma. Computed tomography (CT) and magnetic resonance imaging (MRI) can give a clearer picture. Other imaging modalities include radionuclide bone scans to evaluate metastatic spread to bone, and scintigraphy which can detect specific chemicals (such as metaiodobenzylguanidine, or MIBG) that are concentrated in neuroblastoma and other nervous tissue.

Staging

Neuroblastomas are staged according to the International Neuroblastoma Staging System (INSS). According to this system, there are six different tumor stages: 1, 2A, 2B, 3, 4, and 4S. Stage 1 is localized tumor with complete gross excision. Stage 2A is localized tumor with incomplete gross excision. Stage 2B is localized tumor plus tumor present in ipsilateral nonadherent lymph nodes. Stage 3 is unresectable unilateral tumor. Stage 4 is tumor disseminated to lymph nodes, bone, bone marrow, and/or skin. Stage 4S is tumor dissemination in infants less than 1 year of age only to skin, liver, and/or bone marrow; a high rate of spontaneous regression is seen with tumors of this type.

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