This document discusses neuroblastoma, a common childhood cancer. Some key points: - Neuroblastoma arises from neural crest cells and can occur in adrenal glands or sympathetic nervous system. Half of children present with metastatic disease. - It is the most common cancer in infancy and accounts for 8-10% of childhood cancers. The median age of diagnosis is 19 months. - Familial cases have an autosomal dominant pattern of inheritance and a younger median age of diagnosis. Amplification of the N-MYC oncogene and deletion of chromosome 1p are common genetic factors. - Treatment involves surgery to remove the tumor if possible, chemotherapy, and sometimes radiation therapy to control local

1. Dr Ranjeet Patil(MS)
Paediatric Urology

2. • Most common extracranial solid tumor of
childhood
• Over half of the children present with metastatic
disease
• Arise from cells of the neural crest that form the
adrenal medulla and sympathetic ganglia

3. • Adrenal gland
• Sympathetic chain
• Neck
• Thorax
• Retroperitoneum
• Pelvis

4. • 8% to 10% of all childhood cancers
• 10 cases per 1 million live births
• Most common malignant tumor of infancy
• Median age at diagnosis of 19 months
• *(Brodeur and Maris, 2006)
• There are no geographic or racial variations

5. • Autosomal dominant pattern of inheritance
• *(Knudson and Strong, 1972a; Robertson et al, 1991)
• In familial cases median age decreses to 9 months
• Hereditary neuroblastoma predisposition gene
chromosome 16p12-13
• * (Maris et al, 2002)
• Amplification of the N-MYC oncogene seen in roughly
20%
• *(Look et al, 1991; Muraji et al, 1993)
• Deletion of the short arm of chromosome 1
• *(Brodeur et al, 1992; Caron et al, 1996)

6. • Homer-Wright
pseudorosettes- consist of
eosinophilic neutrophils
surrounded by neuroblasts
• Schwann cell-Other type

7. Histopathologic Features and
Ages
Shimada Favourable Shimada Unfavourable Joshi
Stroma rich, all ages, no
nodular pattern
Stroma poor, age <1.5 yr, MKI
>200
Grade 1-low mitotic rate and
calcification present
Stroma rich, all ages, nodular
pattern
Stroma poor, age >5 yr Grade 2-either low mitotic
rate or calcification present
Stroma poor, age 1.5-5 yr,
differentiated,
MKI <100
Stroma poor, age 1.5-5 yr,
undifferentiated
Grade 3-neither low mitotic
rate nor calcification present
Stroma poor, age <1.5 yr, MKI
<200
Stroma poor, age 1.5-5 yr,
differentiated,
MKI >100
(MKI-mitosis-karyorrhexis
index)

8. • Abdominal pain
• Palpable mass
• fixed, hard abdominal mass
• Bone or joint pain
• Periorbital ecchymosis
• Cough
• Dyspnea
• Neurologic deficits
• Urinary retention
• Constipation
• Paraneoplastic syndromes
• Paroxysmal hypertension
• Palpitations
• Flushing
• Headache
• Severe watery diarrhea
• Hypokalemia
• Acute myoclonic
encephalopathy

9. • Laboratory Evaluation
• Routine Investigations
• Haemoglobin-Anemia in bone mets
• Vanillylmandelic acid (VMA)-24 hour Urinary and Serum
• Homovanillic acid (HVA)
• Two bone marrow aspirates and two biopsies

10. • Imaging
• Ultrasound-First line, Detects incidentaloma
• Plain radiographs-calcified abdominal or posterior
mediastinal mass
• Computed Tomography-local extent of the primary
tumors, Invasion of the renal parenchyma
• Magnetic resonance imaging-evaluation of intraspinal
tumor extension, demonstrating the relationship
between the major vessels and the tumor
• Radionuclide bone scan
• Meta-iodobenzylguanidine scan

15. Evans et al Pediatric Oncology Group International Neuroblastoma Staging System
Stage I—tumor confined to
organ or structure of origin
Stage II—tumor extending in
continuity beyond organ or
structure of origin, but not
crossing midline. Regional lymph
nodes on ipsilateral side may be
involved.
Stage III—tumor extending in
continuity beyond midline.
Regional lymph nodes may be
involved bilaterally
Stage IV—remote disease
involving skeleton, bone
marrow, soft tissue, and Distant
lymph node groups
Stage IVS—patients who would
otherwise be stage I or II, but
who have remote disease
confined to liver, skin, or bone
marrow
Stage A—complete gross resection
of primary tumor, with or without
microscopic residual. Intracavitary
lymph nodes not adhered to and
removed with primary tumor,
histologically free of tumor. If
primary tumor in abdomen or
pelvis, liver histologically free of
tumor
Stage B—grossly unresected
primary tumor.
Nodes and liver same as stage A
Stage C—complete or incomplete
resectionof primary tumor.
Intracavitary nodes not
adhered to primary tumor
histologicallypositive for tumor.
Liver as in stage A
Stage D—any dissemination of
disease beyond intracavitary notes
(i.e., extracavitary nodes, liver, skin,
bone marrow, bone)
Stage DS—infants <1 yr with stage
IVSdisease
Stage I—localized tumor with complete gross excision
without microscopic residual disease; representative
ipsilateral lymph nodes negative for tumor microscopically
Stage IIA—localized tumor with incomplete gross excision;
representative ipsilateral nonadherent lymph nodes
negative for tumor microscopically
Stage IIB—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 III—unresectable unilateral tumor infiltrating across
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 (unresectable)
or by lymph node Involvement
Stage IV—any primary tumor with dissemination
to distant lymph nodes, bone, bone marrow, liver, skin, or
other organs
Stage IVS—localized primary tumor as defined for stage I,
2IIA, or IIB with dissemination limited to skin, liver, or
bone marrow

17. • Surgery
• Chemotherapy
• Radiation therapy

18. • Goals
• Establish the diagnosis
• Stage the tumor
• Excise the tumor (if localized)
• Provide tissue for biologic studies

19. • Surgical excision
• Children with stage I neuroblastoma have a disease-free
survival rate of greater than 90% after exicision
• Low-Risk Disease (Stages I, II, and IV-S)
• Complete excision should be undertaken only when
there is not a concern for undue morbidity to vital
organs or the patient
• Sacrifice of major organs such as the kidney or
spleen should be avoided, especially in children less
than one year of age.

20. • Abdominal tumors-generous transverse incision
• Ligation of feeding vessels, Tumor excised
• Lymph node sampling
• noncontiguous nodes above and below the tumor
• Liver biopsy indicated if Stage 4S
• Patients with incomplete resection initially-delayed
attempt at resection of residual tumor is
undertaken at the end of induction chemotherapy
• Surgery is not indicated for those patients who
have progressive disease at this time

21. • Thoracic tumors-posterior-lateral thoracotomy
• Dumbbell-shaped tumors that enter the neural
foramina are generally treated initially with
chemotherapy

22. • Atelectasis
• Infection
• Ileus
• Haemorrhage

23. • Local control
• stage IV or bulky stage III tumors*
• *(Matthay et al, 1989; Castleberry 1991; Evans et al,
1996)
• Dose-15 and 30 Gy
• Intraoperative radiation therapy-unresectable
disease

24. • Chemotherapy
• Reserve laminectomy for children with progressive
neurologic deterioration (Katzenstein et al, 2001).
• Radiotherapy-avoided, because of its adverse effect
on growth of the spine.

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