Neuroblastic tumors: ~15% of neoplasms
in children <4 years, and > 90% cases diagnosed > 5 years, most
common solid neoplasm outside the central nervous system in
of the sympathetic
nervous system that originate from neural crest sympathogonia,
Neuroblastic tumors are
ganglioneuromas, ganglioneuroblastomas and neuroblastomas.
These tumors can grow wherever sympathetic nervous tissue is
found, but they most frequently occur in the abdomen. Common
locations include the adrenal gland, paraspinal retroperitoneum
(sympathetic ganglia), posterior mediastinum, head, and neck.
Locations such as the urinary bladder, bowel wall, abdominal
wall, and gallbladder are considered unusual.
neuroblastic tumors have been described. These tumors may have
malignant nerve-sheath or pheochromocytoma tumors growing within
them. In rare cases, von Recklinghausen disease, Beckwith-Wiedemann
syndrome, Hirschsprung disease, central failure of ventilation,
and DiGeorge syndrome are associated with ganglioneuroma and
The primary histologic features of these
tumors are neuroblasts (immature, undifferentiated sympathetic
cells), ganglion cells (mature cells), Schwann cells, and stroma
(tissue surrounding the ganglion cells). Secondary histologic
features include necrosis, mitosis, hemorrhage, fibrosis,
calcification, lymphocytic infiltrate, and karyorrhexis
(fragmentation of cellular nuclei that usually symbolizes cell
Neuroblastomas consist predominantly of neuroblasts, where
ganglioneuromas are composed entirely of well-differentiated
cells. Ganglioneuroblastomas contain about 50% or more mature
cells. Malignant potential is proportional to the percentage of
immature cells in the tumor with neuroblastomas being the most
malignant of the three and ganglioneuromas being benign.
Ganglioneuromas are mature tumors and do not
have immature elements, and they have a mixture of
ganglion cells and Schwann cells. The presence of neuroblasts automatically makes the tumor a ganglioneuroblastoma or
of adolescents and young adults (40-60%), mean age 7 years.
grow almost anywhere along the paravertebral sympathetic ganglia
and in the adrenal medulla.
Rare, benign, fully
mature Schwann cells, ganglion cells, fibrous tissue, and nerve
fibers. These tumors have no immature elements (such as neuroblasts), atypia, mitotic figures, intermediate cells, or
necrosis. In fact, the presence of any these tissue characteristics
excludes the diagnosis of ganglioneurom.
These tumors can arise de novo and result from the maturation of
a ganglioneuroblastoma or neuroblastoma into a ganglioneuroma. They
may also develop within a neuroblastoma treated with chemotherapy.
Metastases in these tumors are exceedingly rare. Metastasis is
thought to be the end result of matured ganglioneuroblastoma or
neuroblastoma metastases rather than true ganglioneuroma metastases.
is the most common site of metastasis. Up to 60% of patients
have a bone metastasis at the time of presentation.
Bone metastasis accompanied by limping and
irritability is called Hutchinson syndrome. Pepper syndrome is
the presence of large liver metastases in infants. In children younger than 1 year, skin metastases are common.
These metastases occur as darkly pigmented masses resembling
blueberries (blueberry muffin syndrome). The lung, dura, and brain are considered unusual locations for
asymptomatic regardless of their size.
These tumors may be hormonally active, and
hypertension, diarrhea, flushing, and virilization may occur as a result the secretion of catecholamine,
vasoactive intestinal polypeptide, or androgenic hormone.
As many as 37% of ganglioneuromas secrete catecholamines.
Overall, patients with ganglioneuroma have a favorable prognosis.
Ganglioneuroblastomas most commonly occur
in infants and young children and almost never occur after age
10 years. Ganglioneuroblastoma and neuroblastoma tend to occur in
young children with the median age of 2 years.
Ganglioneuroblastomas are a mix of malignant neuroblastoma and
benign ganglioneuroma, and they are sometimes called transitional
tumors. These lesions also originate from sympathetic cells.
Histologically, they are considered malignant because they contain
primitive neuroblasts along with mature ganglion cells.
Ganglioneuroblastomas have a propensity for secreting
catecholamines, and approximately 90-95% actively secrete
vanillylmandelic acid (VMA) and homovanillic acid (HVA). HVA tends to
be secreted by more mature and differentiated tumors, and VMA is
usually a product of less differentiated tumors. In fact, the ratio
of VMA to HVA can be used to assess tumor maturity, thereby being a
prognostic factor. In addition, more mature tumors may contain
vasoactive intestinal peptide (VIP) producing ganglion cells.
Despite these possible comorbidities, the prognosis for patients
with a ganglioneuroblastoma is still relatively good. These tumors
can spontaneously regress or mature. In fact,
all ganglioneuromas are thought to have once been
ganglioneuroblastomas/neuroblastomas at an earlier stage of their
development. Regression has an unknown cause and
occurs in 1-2% of tumors.
ganglioneuroblastomas often present with pain caused by either the
primary tumor or metastatic disease and abdominal distention.
Patients may also complain of irritability, weight loss, malaise,
shortness of breath, peripheral neurologic symptoms (nerve or nerve
root compression), and Horner syndrome (ptosis, myosis, and