Neuroblastoma

• Neuroblastomas are embryonal cancers of the peripheral sympathetic

nervous system with heterogeneous clinical presentation and course,
ranging from tumors that undergo spontaneous regression to very
aggressive tumors unresponsive to very intensive multimodal therapy.
• Neuroblastoma is the most common extracranial solid tumor in
children and the most commonly diagnosed malignancy in infants.
Abdomen is the most frequent primary site (in 65% of cases)
• Th median age of children at diagnosis of neuroblastoma is 22 mo, and
90% of cases are diagnosed by 5 yr of age incidence is slightly higher in
boys and in whites
 pathology
• Neuroblastoma tumors, which are derived from primordial neural crest
cells, form a spectrum with variable degrees of neural diffrentiation,
ranging from tumors with primarily undiffrentiated small round cells
(neuroblastoma) to tumors consisting of mature and maturing Schwannian
stroma with ganglion cells (ganglioneuroblastoma or ganglioneuroma).
• Th tumors may resemble other small round blue cell tumors, such as
rhabdomyosarcoma, Ewing sarcoma, and nonHodgkin lymphoma.
• prognostic factors include the presence and amount of Schwannian stroma,
the degree of tumor cell diffrentiation, and the mitosis-karyorrhexis index
• Familial neuroblastoma accounts for 1-2% of all cases, is associated
with a
younger age at diagnosis, and is linked to mutations in the PHOX2B
and ALK genes
• Neuroblastoma is associated with other neural crest disorders,
including Hirschsprung disease, central hypoventilation syndrome, and
neurofiromatosis type I, and potentially congenital cardiovascular
malformations
• Children with Beckwith-Wiedemann syndrome and hemihypertrophy
also have a higher incidence of neuroblastoma.
• Increased incidence of neuroblastoma is associated with some
maternal and paternal occupational chemical exposures, farming,
and work related to electronics, although no single environmental
exposure has been shown to directly cause neuroblastoma.
• Genetic characteristics of neuroblastoma tumors that are of
prognostic importance include amplifiation of the MYCN (N-myc)
protooncogene and tumor cell DNA content, or ploidy
• Amplifiation of MYCN is strongly associated with advanced tumor
stage and poor outcomes
• Neuroblastoma may develop at any site of sympathetic nervous
system tissue. Approximately half of neuroblastoma tumors arise in
the adrenal glands, and most of the remainder originate in the
paraspinal sympathetic ganglia.
• Metastatic spread, which is more common in children older than 1
yr of age at diagnosis, occurs via local invasion or distant
hematogenous or lymphatic routes.
• Th most common sites of metastasis are the regional or distant
lymph nodes, long bones and skull, bone marrow, liver, and skin.
Lung and brain metastases are rare, occurring in >3% of cases.
• Metastatic disease can cause a variety of signs and symptoms, including
fever, irritability, failure to thrive, bone pain, cytopenias, bluish
subcutaneous nodules, orbital proptosis, and periorbital ecchymoses
• Localized disease can manifest as an asymptomatic mass or can cause
symptoms because of the mass itself, including spinal cord compression,
bowel obstruction, and superior vena cava syndrome.
• Children with neuroblastoma can also present with neurologic signs and
symptoms.
• Neuroblastoma originating in the superior cervical ganglion can result
in Horner syndrome.
• Neuroblastoma can also be associated with a paraneoplastic syndrome of
autoimmune origin, termed opsoclonus– myoclonus–ataxia syndrome, in which
patients experience rapid, uncontrollable jerking eye and body movements,
poor coordination and cognitive dysfunction.
• Some tumors produce catecholamines that can cause increased sweating and
hypertension, and some release vasoactive intestinal peptide, causing a
profound secretory diarrhea.
• Children with extensive tumors can also experience tumor lysis syndrome and
disseminated intravascular coagulation.
• Infants younger than 1 yr of age also can present in unique fashion, termed
stage 4S,
 DIAGNOSIS
• Neuroblastoma is usually discovered as a mass or multiple masses on plain radiography,
CT, or MRI
• Th mass oftn contains calcifiation and hemorrhage that can be appreciated on plain x-
ray , CT.
• Prenatal diagnosis of neuroblastoma on maternal ultrasound scans is sometimes possible.
• Tumor markers, including catecholamine metabolites homovanillic acid and
vanillylmandelic acid, are elevated in the urine of approximately 95% of cases and help to
confim the diagnosis.
• A pathologic diagnosis is established from tumor tissue obtained by biopsy.
Neuroblastoma can be diagnosed without a primary tumor biopsy if small round blue
tumor cells are observed in bone marrow samples and the levels of vanillylmandelic acid
or homovanillic acid are elevated in the urine
• Th usual treatment for children with low-risk neuroblastoma is
surgery for stages 1 and 2 and observation for stage 4S with cure
rates generally >90%
without further therapy.
• Treatment with chemotherapy or radiation for the rare child with
local recurrence can still be curative.
• Children with spinal cord compression at diagnosis also may
require urgent treatment with chemotherapy, surgery, or radiation
to avoid neurologic damage.
• Stage 4S neuroblastomas have a very favorable prognosis, and many
regress spontaneously without therapy.
• Chemotherapy or resection of the primary tumor does not improve
survival rates, but for infants with massive liver involvement and
respiratory compromise,
small doses of cyclophosphamide or low-dose hepatic irradiation may
alleviate symptoms.
• For children with stage 4S neuroblastoma who require treatment for
symptoms, the survival rate is 81%
• Th chemotherapy usually includes moderate doses of cisplatin or
carboplatin, cyclophosphamide, etoposide, and doxorubicin given
for several months.
• Radiation therapy is used for tumors with incomplete response to
chemotherapy.
• Children with intermediate-risk neuroblastoma, including children
with stage 3 disease and infants with stage 4 disease and favorable
characteristics, have an excellent prognosis and >90% survival
with this moderate treatment