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Epidemiology, pathogenesis, and pathology of neuroblastoma

Jason M Shohet, MD, PhD
Jed G Nuchtern, MD, FACS, FAAP
Section Editor
Julie R Park, MD
Deputy Editor
Sadhna R Vora, MD


The term neuroblastoma is commonly used to refer to a spectrum of neuroblastic tumors (including neuroblastomas, ganglioneuroblastomas, and ganglioneuromas) that arise from primitive sympathetic ganglion cells. The neuroectodermal cells that comprise neuroblastic tumors originate from the neural crest during fetal development, and are destined for the adrenal medulla and sympathetic nervous system. By contrast, pheochromocytomas and paragangliomas arise from a different type of cell, the chromaffin cell, that also migrates from the neural crest to the adrenal gland (figure 1). Together, both types of cells make up the adrenal medulla, a component of the sympathetic nervous system. (See "Pheochromocytoma and paraganglioma in children" and "Paragangliomas: Epidemiology, clinical presentation, diagnosis, and histology".)

Neuroblastomas, which account for 97 percent of all neuroblastic tumors, are heterogeneous, varying in terms of location, histopathologic appearance, and biologic characteristics [1]. They are most remarkable for their broad spectrum of clinical behavior, which can range from spontaneous regression, to maturation to a benign ganglioneuroma, or aggressive disease with metastatic dissemination leading to death [2]. Clinical diversity correlates closely with numerous clinical and biological factors (including patient age, tumor stage and histology, and genetic and chromosomal abnormalities), although its molecular basis remains largely unknown. For example, most infants with disseminated disease have a favorable outcome following treatment with chemotherapy and surgery, while the majority of children over the age of one with advanced-stage disease die from progressive disease despite intensive multimodality therapy.

The epidemiology, embryogenesis, molecular pathogenesis, and pathology of neuroblastoma will be presented here. The clinical presentation, diagnosis, evaluation, treatment, and prognosis of neuroblastoma are presented separately (see "Clinical presentation, diagnosis, and staging evaluation of neuroblastoma" and "Treatment and prognosis of neuroblastoma"). Neuroblastomas arising in the olfactory epithelium, which have a different cell of origin, presentation, and treatment than neuroblastoma, also are discussed separately. (See "Olfactory neuroblastoma (esthesioneuroblastoma)".)


Neuroblastoma is almost exclusively a disease of children. It is the third most common childhood cancer, after leukemia and brain tumors, and is the most common solid extracranial tumor in children. More than 600 cases are diagnosed in the United States each year [1], and neuroblastoma accounts for approximately 15 percent of all pediatric cancer fatalities.

Incidence rates are age-dependent (figure 2). The median age at diagnosis is 17.3 months, and 40 percent of patients are diagnosed before one year of age [1,2]. Neuroblastomas are the most common extracranial solid malignant tumor diagnosed during the first two years of life, and the most common cancer among infants younger than 12 months, in whom the incidence rate is almost twice that of leukemia (58 versus 37 per one million infants) [3]. The incidence of neuroblastoma is greater among white than black infants (ratio of 1.7 and 1.9 to 1 for males and females, respectively), but little if any racial difference is apparent among older children [1]. Neuroblastoma is slightly more common among boys compared with girls [1].

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Literature review current through: Nov 2017. | This topic last updated: Aug 19, 2016.
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