NEUROBLASTOMA
DR. SALHA
Objectives
• Describe Neuroblastoma
• Describe epidemiology of Neuroblastoma
• Explain aetiology/risk factors of Neuroblastoma
• Identify clinical features and Complications of Neuroblastoma
• Establish provisional diagnosis and differential diagnoses of
Neuroblastoma
• Request appropriate investigations
• Refer as appropriate
Introduction
• Neuroblastoma (NB) is an embryonal cancer of the peripheral
sympathetic nervous system; arising from neural crest that
form adrenal medulla and sympathetic ganglia
• Most common solid tumor of childhood
• Has variable range of outcome, some types have spontaneous
regression and some are very aggressive tumors
• Age and stage are important prognostic factors
Definition
• Neuroblastoma is a type of cancer that most commonly
affects young children, typically under the age of 5.
• It develops from immature nerve cells (called neuroblasts)
found in several areas of the body, but most often starts in the
adrenal glands, which sit above the kidneys and produce
hormones.
• Arises from the sympathetic nervous system, especially in the
adrenal glands, neck, chest, abdomen, or spine.
Neural crest cells
• Are multi-potent crest cells in embryos.
• They play a wide role in development of various cells types
including sensory, autonomic neurons, bones, cartilage,
melanocytes, chromaffin cells (produce adrenaline) and other
connective tissues
• Their function is to differentiate into specialized cells.
Epidemiology
• 8-10% of all childhood cancers and it is the commonest
malignant tumor of infancy
• Neuroblastoma occur more in white than in black children,
though this does count in the outcome of disease
• Incidence in males is slightly higher to females (1.2:1)
• 40% of patients are younger than 1 year, and at 2 years, a total
of 75% of cases have been diagnosed. 90% of cases are
diagnosed by 5 yr of age the disease become rare after 10 years
of age
Etiology
• Cause is unknown
• Even the risks appear to be inconclusive, and are still under
study
• However, age and heredity are strong risks
• Those under study include
• exposure to chemicals in some industries such electrical
• smoking
• alcohol consumption
• use of medicinal drugs during pregnancy
Clinical features
• Since NB can arise from multiple sites; specific signs and
symptoms reflect the tumor site and extent of disease
• Abdomen tumor (commonest)
• palpable firm, nodular mass in the flank or midline causing
abdominal discomfort, swollen abdomen and changes in
bowel habits, such as diarrhea or constipation
• Tumor in the chest
• may cause breathing difficulties such as wheezing; chest
pain
• Tumor in the spine
• symptoms of spinal cord and nerve root compression,
weakness with inability to use he limbs (difficult walking or
standing); back pain
• Metastatic disease present with many different signs and
symptoms. Commonest sites are long bones and skull, bone
marrow, liver, lymph nodes, and skin
• Bone lesions
• long bones and bone marrow; pain & limping, anemia
• Orbits; orbital proptosis (as drooping eyelids and unequal
pupil size), periorbital ecchymoses as bruises around the
eyes (raccoon eyes); may present with Horner’s syndrome
• Some tumors produce excess catecholamines; (plays role in
stress and physiological process)
• causing increased sweating and hypertension
• Also; production of vasoactive intestinal peptide
(neuropeptide hormone regulating gastro-intestinal function)
• causing a secretory diarrhea
• Other non-specific symptoms include
• fever; irritability
• loss of appetite
• unexplained weight loss
• failure to thrive
• bluish subcutaneous nodules (lumps of tissue under the
skin)
• malaise, joint pains
• High blood pressure or rapid heart rate (if adrenal glands
involved)
• In advanced cases: symptoms from metastasis (e.g., bone
pain, bruising, etc.)
Staging
International Neuroblastoma Staging System
• Stage 1:
• Localized tumor with complete gross excision, with or
without microscopic residual disease; representative
ipsilateral lymph nodes negative for tumor microscopically
(nodes attached to and removed with the primary tumor may
be positive)
• Stage 2A:
• Localized tumor with incomplete gross excision;
representative ipsilateral nonadherent lymph nodes negative
for tumor microscopically
• Stage 2B:
• Localized tumor with or without complete gross excision,
with ipsilateral nonadherent lymph nodes positive for tumor.
Enlarged contralateral lymph nodes must be negative
microscopically
• Stage 3:
• Unresectable unilateral tumor infiltrating across the midline,
with or without regional lymph node involvement; or
localized unilateral tumor with contralateral regional lymph
node involvement; or midline tumor with bilateral extension
by infiltration (resectable) or by lymph node involvement
• Stage 4:
• Any primary tumor with dissemination to distant lymph
nodes; bone, bone marrow, liver, skin, and other organs
(except as defined for stage 4S)
• Stage 4S:
• Localized primary tumor (as defined for stage 1, 2A, or 2B),
with dissemination limited to skin, liver, and bone marrow [‡]
(limited to infants <1 yr of age)
Diagnosis
• NB usually diagnosed as a mass or multiple masses on plain
radiographs, CT, or MRI
• Tumor markers, including homovanillic acid (HVA) and
vanillylmandelic acid (VMA) in urine, are elevated in 95% of
cases and help to confirm the diagnosis
• A pathologic diagnosis is made from tissue biopsy.
• Also, it can be diagnosed in a typical presentation without a
primary tumor biopsy if neuroblasts can be observed in bone
marrow (after bone marrow aspirate) and elevated VMA or
HVA in the urine
Differential diagnosis
• These include;
• Pediatric rhabdomyosarcoma
• Ewing sarcoma
• Wilm’s tumor
Investigations
• Diagnostic investigations include
i. Plain radiography or CT of the mass; often contains
calcification and hemorrhage.
ii. Elevated tumor markers, the homovanillic acid (HVA)
and vanillylmandelic acid (VMA) in urine
iii. Tissue biopsy.
iv. Bone marrow aspirate (alongside elevated VMA or HVA
in the urine)
v. Routine investigations
vi. Full blood picture
vii. Serum creatinine
• Liver function tests
• Alanine aminotransferase (ALT) & Aspartate
aminotransferase (AST)
• Total bilirubin; Alkaline phosphatase
• Albumin and total protein
• Prothrombin time (PT)/activated prothrombin time (aPTT)
• Serum electrolytes
• Uric acid; Serum lactate dehydrogenase (LDH); Ferritin
• Thyroid-stimulating hormone (TSH), T4 are all important in
monitoring the patient
• Immunoglobulin (Ig)G levels
Treatment
• Pre-referral treatment for a patient suspected to have the
disease is mainly symptomatic aimed at alleviating the
condition. However, this should not delay referral
• Counselling to parents/and or care-takers is equally important,
on the outcomes of treatment with early attendances to
treatment centres
Various treatment modalities
exist
• Observation /palliative care
• Surgery
• Chemotherapy
• Radiation therapy
• High dose chemotherapy/radiation therapy and stem cell
transplant (involves harvesting the patient's own stem cells,
administering high-dose chemotherapy to eliminate cancer
cells, and then reinfusing the stem cells to restore bone
marrow function.)
• Retinoid therapy (retinoid- vitamin A Derivatives after
chemotherapy to encourage cell differentiation and reduce risk
of relapse)
• Immunotherapy (patient's T-cells are genetically modified to
better recognize and attack cancer cells )
• The most important clinical and biologic prognostic factors
currently used to determine treatment are the age of the patient
at diagnosis, stage of disease, MYCN status, and Shimada
histology
• The usual treatment for low-risk NB is surgery for stages 1 and
2 and observation for stage 4S.
• Overall cure rate are high
Chemotherapy agents
• Vincristine, cyclophosphamide, and doxorubicin
• Carboplatin and etoposide
• Cisplatin and etoposide
• Ifosfamide and etoposide
• Cyclophosphamide and topotecan
Follow up
The intensity and duration of follow-up depend on:
• Risk group (low, intermediate, high)
• Initial stage and treatment
• Time since treatment completion
Prevention
• ????
