3. INTRODUCTION
It is the most common extra cranial solid tumor
of childhood.
It is an embryonal malignancy which arises from
cells of the neural crest that form the adrenal
medulla and sympathetic ganglia
Over half of the children present with metastatic
disease
4. EPIDEMIOLOGY
• 8% to 10% of all childhood cancers
• 9.5 cases per 1 million live births
• Median age at diagnosis of is 18 months
• More in white children
• M:F is 1.2:1
5. EPIDEMIOLOGY
• Over half of the children present with metastatic
disease.
• >50% present below 2 years of age.
• >90% present below 6 years of age.
• Association with Neurofibromatosis,
Hirschsprung disease and Fetal alcohol syndrome
.
6. ANATOMY AND PHYSIOLOGY
• In the 1st week of development, neural crest cells start
migrating along the spine.
• As they migrate, they differentiate into neurons of the
sympathetic chain on either side of the entire spinal cord.
• In the lumbar region they differentiate into the cells of the
Adrenal medulla.
• Sympathetic chain and adrenal medulla forms the
sympathetic nervous system.
7.
8. Physiology
• When stimulated, the sympathetic nervous
system releases epinephrine and nor
epinephrine .
• Which are eventually enzymatically converted
into the two metabolites Homovanillic acid
(HVA) and Vanillymandelic acid(VMA)
9.
10. PATHOPHYSIOLOGY
• In Neuroblastoma, some neural crest cells in
sympathetic chain or adrenal medulla don’t
differentiate properly and ultimately forms a
tumor.
• Grossly, it is a vascular tumour with areas of
necrosis, haemorrhage and often
calcifications.
11. PATHOLOGY
• Histologically : It contains uniform small
round blue cells with hyperchromatic speckled
nucleus, Homer-Wright rosettes and a central
fibrillar core.
• PAS stain is negative and NSE stain is positive.
• Often histochemistry is needed to
differentiate from other tumours.
17. ETIOLOGY
• The etiology is unknown.
• It has been linked to have an autosomal
dominant pattern of inheritance
• Hereditary neuroblastoma predisposition
gene chromosome 16p12-13
• Amplification of the N-MYC oncogene seen in
roughly 20%.
• Deletion of the short arm of chromosome 1.
18. Some risk factors for Neuroblastoma includes;
• Exposure to chemicals during pregnancy
• Smoking
• Alcohol
• use of hormones and fertility.
19. TYPES
1. Pepper type is right side adrenal
neuroblastoma with liver secondaries.
Common in infants.
2. Hutchinson’s type is left side adrenal
neuroblastoma with secondaries in orbit and
skull. Common in late childhood.
20. CLINICAL FEATURES
• Fatigue, loss of appetite, fever, and joint pain
are common.
• In the abdomen, a tumor may cause
abdominal pain, constipation and a fixed hard
palpable abdominal mass.
• A tumor in the chest may cause cough,
dyspnea .
21.
22. CLINICAL FEATURES
• A tumor pressing on the spinal cord may cause
neurologic deficits, including motor ,sensory
deficits, bladder and bowel dysfunction.
• A tumor around the eyes and orbits would
present as periorbital oedema.
• Bone lesions in the legs and hips results in
difficulty ambulating.
23.
24. CLINICAL FEATURES
• Symptoms of bone marrow failure may be present if there is
extensive involvement of bone.
• Secretory diarrhea and hypokalaemia may be the manifestation of
tumour secretion of vasoactive intestinal peptide (VIP).
• Skin involvement especially in infants with stage 4S, is characterised
by variable number of non-tender bluish subcutaneous nodules.
Blueberry muffin baby is the term sometimes to describe extensive
involvement of skin
25.
26. CLINICAL FEATURES
• Horner’s syndrome (Oculosympathetic
paresis);This results from interruption of
sympathetic nerve supply to the eye, and is
characterized by classic triad of symptoms
i.e miosis, partial ptosis and hemifacial
anhydrosis.
27. CLINICAL FEATURES
• Antineural antibodies against the tumour may
cross react with neurons in cerebellum and
cause opsomyoclonus.
• Also known as Opsoclonus Myoclonus
Syndrome(OMS) OR Opsoclonus-Myoclonus-
Ataxia(OMA).
28.
29. INVESTIGATION
• Routine Investigations
• 24 hour Urinary and Serum
Vanillylmandelicacid (VMA) and
Homovanillicacid (HVA) assay.
• Two bone marrow aspirates and two biopsies
30. Imaging
• Ultrasound, Detects incidentaloma
• Plain radiographs; calcified abdominal or
posterior mediastinal mass.
• Computed Tomography; local extent of the
primary tumors, Invasion of the renal
parenchyma
31. • Magnetic resonance imaging; Evaluation of
intra spinal tumor extension, demonstrating
the relationship between the major vessels
and the tumor
• Radionuclide bone scan
• Meta-iodobenzylguanidine Scan
32.
33. GRADING
Patients are classified into low, intermediate and
high risk groups based on
• Patient’s age
• International neuroblastoma Pathology
classification
• N-MYC oncogene amplification status
• Tumor stage (INSS)
• DNA ploidy
34. Low risk groups
• Stage I disease; Stage II disease with single
N myc value.
• Stage II with favourable Shimada histology.
35. • Intermediate risk groups;
Stage III without N myc amplification;
Stage III with favourable Shimada’s histology.
• High-risk groups;
All patients with N myc amplification;
Stage IV neuroblastoma
36. INTERNATIONAL NEUROBLASTOMA
STAGING SYSTEM
Stage I
• Localized tumor with complete gross excision
without microscopic residual disease;
representative.
• Ipsilateral lymphnodes negative for tumor
microscopically
37. STAGE II
Stage IIA:
• Localized tumor with in complete gross
excision; representative ipsilateral
nonadherentlymph nodes negative for
tumor microscopically
38. 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
39. 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
nodeInvolvement
40. 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
42. SURGERY
• Establish the diagnosis
• Stage the tumor
• Excise the tumor(if localized)
• Provide tissue for biologic studies
43. SURGICAL EXCISION
• Children with stage I neuroblastoma have a
disease-free survival rate of greater than 90%
after excision.
• Low-Risk Disease (Stages I, II, and IV-S).
.
44. Abdominal tumors
• Generous transverse incision
• Ligation of feeding vessels
• Tumor excised
• Lymph node sampling of noncontiguous
nodes above and below the tumor
• Liver biopsy indicated if Stage 4S
45. • 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
46. • Thoracic tumors; posterior-lateral
thoracotomy
• Dumbbell-shaped tumors that enter the
neural foramina are generally treated initially
with chemotherapy
49. RADIOTHERAPY
• Local control
• stage IV or bulky stage III tumors
• Dose-15 and 30 Gy
• Intraoperative radiation therapy unresectable
disease
50. SPINAL CORD COMPRESSION
• Chemotherapy
• Reserve laminectomy for children with
progressive neurologic deterioration
• Radiotherapy-avoided, because of its adverse
effect on growth of the spine.
52. Prognostic factors
• Age: Infants have better prognosis than older
children.
• Early stage of disease (I and II) is better
• Tumour site: Cervical neuroblastomas have
better prognosis, may be due to their early
detection.
• Pelvic and thoracic tumours carry a better
prognosis than abdominal tumours
53. • Cortical bone involvement is associated with
poor prognosis.
• Tumour pathology: Favorable or unfavorable
54. CONCLUSION
• Neuroblastoma is a malignant childhood
tumour with no specific aetiology.
• Prognosis is largely dependent on the stage of
the disease thus early detection is the key
reduction of morbidity and mortality.
• Hence high index of suspicion with
appropriate investigations would go a long
way to saving the lives of affected children
55. REERENCES
• Sriram Bhat M. 2013. SRB's Manual of Surgery.
Fourth Edition. Jaypee Brothers Medical
Publishers (P) Ltd.
• Emmanuel A. Ameh, et al. 2011. Paediatric
Surgery: A Comprehensive Text for Africa. Volume
II. Global HELP Organization.
• Richard E, et al. 2003. Nelson Textbook of
Pediatrics 17th edition .W B Saunders
• Norman S., et al. 2008. Bailey & Love’s Short
Practice Of Surgery. Edward Arnold (Publishers)
Ltd
