NEUROBLASTOMA

INTRODUCTION
• 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.
• Most common extracranial solid tumor of childhood.

• Most common malignant tumor of infancy.

• 8 - 10% of all childhood cancers.

• Accounts for >15% of the mortality from cancer in children.

• The median age of children at diagnosis of neuroblastoma is

22 mo, and 90% of cases are diagnosed by 5 yr of age.
CLINICAL MANIFESTATIONS
• 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.
The most common sites of metastasis are

• regional or distant lymph nodes

• long bones and skull
• bone marrow
• Liver
• 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
Cytopenia
Bluish subcutaneous nodules
Orbital proptosis
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
• 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.

• Paraspinal neuroblastoma tumors can invade the neural

foramina, causing spinal cord and nerve root compression.
• 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, with
• limited bone marrow disease
• small primary tumor
• massive liver involvement
• widespread subcutaneous tumor nodules
• no bone involvement or other metastases.
DIAGNOSIS
Laboratory Evaluation
• Increased levels of urinary metabolites of
Catecholamines,
Vanillylmandelic acid (VMA) Homovanillic acid (HVA)
(found in 90% to 95% of patients)

• Anemia
(widespread bone marrow involvement.)
IMAGING
• Plain radiographs
(calcified abdominal or posterior mediastinal mass.)
• USG Abdomen

• CT/ MRI should be performed in cases with suspected or

potential spinal cord compression, but imaging of the brain
with either CT or MRI is not routinely performed unless
dictated by the clinical presentation.

• Both a radionuclide bone scan and

meta-iodobenzylguanidine (MIBG) scans for staging, and to
define the extent of disease.
• Bone marrow aspiration and biopsy:

(Neuroblastoma often spreads to the bone marrow

If blood or urine levels of catecholamines are increased,
then finding cancer cells in a bone marrow sample is enough
to diagnose neuroblastoma (without getting a biopsy of the
main tumor).
INTERNATIONAL
NEUROBLASTOMA STAGING
SYSTEM (INSS)
• The International Neuroblastoma Staging System (INSS) is
based on
-clinical
-radiographic
-surgical evaluation of children
with neuroblastoma
TREATMENT
The treatment modalities-
• Surgery
• Chemotherapy
• Radiation therapy
• High-dose chemotherapy/radiation therapy and stem cell
transplant
• Retinoid therapy
• Immunotherapy
surgery
• The goals of surgery are to establish the diagnosis, stage
the tumor, excise the tumor (if localized), and provide
tissue for biologic studies.

• Resectability of the primary tumor should take into

consideration tumor location, mobility, relationship to
major vessels, and overall prognosis of the patient.

• Neoadjuvant chemotherapy, is very successful in

reducing the size of primary tumors.
chemotherapy
• Usually includes a combination of drugs
• Cyclophosphamide or ifosfamide
• Cisplatin or carboplatin
• Vincristine
• Doxorubicin (Adriamycin)
• Etoposide
• Topotecan
• Busulfan and melphalan

The most common combination of drugs include

carboplatin (or cisplatin), cyclophosphamide,
doxorubicin, and etoposide
Radiation therapy
• Used for local control in neuroblastoma

• Doses of external beam irradiation used, have ranged

between 15 and 30 Gy.
(depending on the patient’s age, location,
and extent of residual disease)

• Intraoperative radiation therapy

- patients with unresectable disease.
Immunotherapy
• A monoclonal antibody called ch14.18 attaches to GD2, a
substance found on the surface of many neuroblastoma
cells.

• This antibody can be given together with cytokines

(immune system hormones) such as GM-CSF and
interleukin-2 (IL-2) to help the child’s immune system
recognize and destroy neuroblastoma cells.
THANK YOU