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Dr Ranjeet Patil(MS)
Paediatric Urology
• 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
• Adrenal gland
• Sympathetic chain
• Neck
• Thorax
• Retroperitoneum
• Pelvis
• 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
• 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)
• Homer-Wright
pseudorosettes- consist of
eosinophilic neutrophils
surrounded by neuroblasts
• Schwann cell-Other type
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)
• 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
• 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
• 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
Neuroblastoma
Neuroblastoma
Neuroblastoma
Neuroblastoma
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
Neuroblastoma
• Surgery
• Chemotherapy
• Radiation therapy
• Goals
• Establish the diagnosis
• Stage the tumor
• Excise the tumor (if localized)
• Provide tissue for biologic studies
• 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.
• 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
• Thoracic tumors-posterior-lateral thoracotomy
• Dumbbell-shaped tumors that enter the neural
foramina are generally treated initially with
chemotherapy
• Atelectasis
• Infection
• Ileus
• Haemorrhage
• 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
• 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.
THANK
YOU

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Neuroblastoma

  • 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.