Nb is the most common childhood tumor

1. BY: Fayera A.(R3)
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2. Differential diagnosis- Abdominal
mass
Based on
 Age
 Anatomic location
 Organ of origin
 Consistency( solid or cystic)
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3. Neuroblastoma
This is a neoplasm of neural crest origin,
arising in the adrenal medulla and along
the sympathetic ganglion chain from the
neck to the pelvis
 Arise during fetal or early postnatal
life
 Is the most common extra cranial
solid tumors in children
 10% of all childhood cancer and 15%
of all cancer deaths
 Incidence 1 in 7500 – 10,000 children
 40% in children younger than 1yr, 75% at age
7 and 98% at age 10
 More than 50% occur in children under 2yrs of
age
 Boys : Girls = 1.2:1
 Majority occur sporadically but familial NB
occur in 2% of cases
 Primary Sites of tumor:
 Abdominal cavity 75%
Adrenal medulla 50%
Para spinal ganglia 25%
 Posterior mediastinal 20%
 Pelvic 4%
 Cervical 1%
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4. Gross Appearance
 NB : Grossly, neuroblastoma usually appears as a highly vascular
purple-gray mass that is often solid, with friable pseudocapsule.
 Wilm’s Tumor - cut section - soft, homogeneous, tan to gray,
with occasional foci of hemorrhage, cyst & necrosis
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5. Clinical Presentation
 Related to the
 site of the primary tumor,
 presence of metastases,
 production of certain metabolic tumor byproducts
 In 50% to 75% present with an abdominal mass
 Generalized symptoms
 Horner syndrome (Ipsilateral ptosis, miosis, anhidrosis)
 associated with a paraneoplastic syndrome of
autoimmune origin, termed opsoclonus-myoclonus–ataxia
syndrome(OMS), in which patients experience rapid,
uncontrollable jerking eye and body movements,poor
coordination, and cognitive dysfunction.
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6. Clinical Presentation
 Symptoms due to metastatic
diseases
 70% of patients have metastatic disease
at diagnosis mainly to bone marrow,
lymph nodes, liver and bone
 Bone pain and limping
 Anemia/pancytopenia  weakness,
infection, and abnormal bleeding or
bruising
○ “Blueberry muffin” nodules
 Symptoms related to excessive
catecholamine or VIP secretion
  flushing, diarrhea, weight loss,
hypertension(25%), headache
 Dumb-bell(Hour-glass) Tumor
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7. Diagnostic Imaging
 Radiographs
 Fine calcification and as
mediastinal and mediastinal
mass
 CT scan
 Calcification in ~ 85% of tumors,
and intraspinal extension of the
tumor on contrast-enhanced CT
 Overall, contrast-enhanced CT
has 82% accuracy in defining
neuroblastoma extent, with the
accuracy increasing to nearly
97% when performed with a
bone scan
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►Imaging findings
 Stippled calcification or
LN with calcification
 Displace the kidney
inferiorly
 Crossing the midline
 Encasing/displace vessels
 Paravertebral mass—
spinal extension

8. Diagnostic Imaging
 MRI
 More accurate than CT for detection
of stage 4 disease
○ The sensitivity of MRI is 83%(CT-
43%) and the specificity of MRI is
97%(CT-88%)
○ Metastases to the bone and bone
marrow and intraspinal tumor
extension are better detected by
MRI
 MIBG bone scintigraphy
 82% sensitivity and 91% specificity
for detection of metastases to the
bone and bone marrow
 Required imaging studies
○ CT and/or MRI to address IDRFs is
mandatory for imaging the primary
tumor and metastatic sites
○ MIBG scintigraphy is mandatory
to define metastatic disease.
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9.  BM EXAM:
 Bilateral bone marrow biopsy is a
routine method for detecting bone
marrow involvement
 At least two aspirates and two
biopsies from bilateral sites
 Tissue biopsy— requires 1cm³ of
tissue
 Including immunohistochemistry and
genetic analysis whenever possible
 LAB IX
 LDH >1500 IU/L
 Ferritin >150 ng/ml
 Neuron-Specific Enolase (NSE >100
ng/mL)
 Catecholamine Metabolites  VMA &
HVA
 Elevated in 90–95 % of
neuroblastomas
 DIAGNOSIS OF NB
 The minimum international
diagnostic criteria of
neuroblastoma –Needs one of
the following:
1. A tissue biopsy with
histologic confirmation or
2. The presence of
unequivocal tumor cells
within a bone marrow
biopsy/aspirate and
increased levels of
urinary/serum
catecholamine metabolites
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10. Staging And Risk
Classification of
Neuroblastoma
 Shimada histopathologic system: classifies
tumors into favorable or unfavorable categories
based on Stromal pattern, Age, degree of
neuroblastic Differentiation, Mitosis karyorrhexis
index (MKI relating to fragmentation of the
nucleus), and Nodularity (mnemonic: SADMaN).
 Favorable Shimada: young age, low MKI, mature
neuroblast differentiation, rich stroma with non-
nodular pattern.
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11. ►The International Neuroblastoma Staging System (INSS)
is a surgicopathologic staging system that depends on:
 The completeness of resection of the primary tumor
 Highly subjective
 Assessment of ipsilateral and contralateral lymph
nodes, and
 The relation of the primary tumor to the midline
 4S Disease<12 months
Staging And Risk
Classification…
INSS Stage Description
1 Localized tumor, grossly resected, no lymph node involvement
2A
Unilateral tumor, incomplete gross excision, negative lymph
nodes
2B Unilateral tumor with positive ipsilateral lymph nodes
3
Tumor infiltrating across midline or unilateral tumor with
contralateral lymph nodes or midline tumor with bilateral
lymph nodes
4 Distant metastatic disease
4S
Localized primary tumor as defined by stage 1 or 2 in patient
under 12 months with dissemination limited to the liver, skin,
and/or bone marrow (<10% involvement)
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12. Management
 Treatment is determined by risk stratification into low, intermediate, and high
risk.
 Factors incorporated into the most recent COG risk grouping include: Stage,
Age, N-myc, DNA ploidy, and Shimada histology (mnemonic “SANDS,”)
 Low-Risk Disease
 surgical resection alone
 Infants with stage 4S disease who are not experiencing substantial symptoms may
undergo an initial biopsy and observation only
 Intermediate-Risk Disease
 Chemotherapy + surgical resection
 Radiation therapy (if does not respond to initial chemotherapy)
 Biopsy+ Chemotherapy,then Delayed surgery
 High-Risk Disease
 intensive induction chemotherapy
 myeloablative consolidation therapy with BMT &13-cis-retinoic acid
 radiation therapy is administered to the region of the primary tumor site, including involved
adjacent LNDs
 delayed surgical resection
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13. Surgical Principles In
Neuroblastoma
 Approach depends on
 Exact tumor location of the tumor
 Tumor size
 The extent of vascular encasement
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►Operative principles
1. Approach the operation as a vascular-
type operation
 Identification and skeletonization of the
major vessels
 Dissecting in a subadventitial plane
2. The tumor should be removed
piecemeal
3. Dissection starts distal to the lower edge
of the tumor, along the common or
external iliac artery, and proceeds
proximally

14. Operative Complication
 Bleeding
 80% of patients will that
requires transfusion
 Injury to a major
vascular structure—
10%
 Injury to other viscera
(stomach, bowel, liver,
spleen, or kidney)—5%
 Necessitates removal of
the injured organ—
most commonly –the
kidney
 Wound complications ,
bowel obstruction1–
5%
 Others
 Hypertension, chyle leak,
pleural effusion, infection
and sepsis, diarrhea .
 Depending on site:
 Horner syndrome,
paralysis, foot drop,
nephrectomy
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15. WILMS’ TUMOR
 It is the second most common malignant abdominal tumor in
childhood after neuroblastoma
 6-7% of all pediatric malignancies and by far the most
common of Renal tumors (91%)
 The mean age at diagnosis is 36 months, with most children
presenting between the ages of 12 and 48 months.
 Tumors tend to occur about 6 months later in girls than in
boys.
 WT is rare at greater than 10 years and at less than 6
months of age.
 >80% of cases are diagnosed before 5 years of age
 Tumors can be unilateral or bilateral
 Bilateral Wilms’ tumors (BWT) occur in 4% - 13% of patients
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16. Associated Congenital anomalies
syndrome description genetics incidence
WAGR Wilm’s ,aniridia
GU malform. &
MR
Constitutional
deletion at
11P 13
30-50%
Dennys-Drash
Syndrome
(DDS)
Pseudohermaphro
ditism ,NS &
Wilm’s
WT1 mutation >30%
Beckwith-
Wiedemann
Syndrome(BW
S)
Mocroglosia,organ
omegaly,
hemihyperthrophy
Wilm’s
11P15 , loss of
mathernal
allele/imprinting
<5%
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17. The classic WT is triphasic
○ Blastemal – undifferentiated cells
○ Stromal – immature spindle cells
& hetrologus skeletal muscle,
cartilage, osteoid or fat
○ Epithelial – glomerular & tubules
 Histologic classification
○ Favorable histology – 90%
○ Unfavorable histology –10%
 Focal anaplasia
 Diffuse anaplasia
Pathology
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18. Clinical Presentation
Typical pt – Healthy preschool child
- with Asymptomatic abdominal mass
Most children present with only an abdominal mass - 90%
 Abdominal pain (30-40%)
 Hematuria (18%)
 fever (10%)
 Hypertension (25%)- Renin
 Extension into the renal vein(10%),
IVC(4-8%) & Atrium(1-2%)
 varicocele
 hepatomegaly, ascites
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19. Diagnostic imaging
objective – to establish
1. Size & extent of abdominal mass
2. organ of origin
3. presence of functioning contralateral kidney
4. bilateral disease
5. patency of IVC & renal vein
6. distant metastasis
Abdominal Ultrasound
 Site & origion of the mass
 Vascular extension
 Ureteral extension
 R/O – hydronephrosis & multicystic kidney
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20.  Contrast enhanced CT
 Confirm renal origin
 Further evaluate nature & extent
 Detect small tumors or NRs in the
opposite kidney
 MRI – not superior to CT
 CXR – pulmonary metastasis
 CYSTOSCOPY – hematuria (ureteral
extension)
 IVP – distortion of collecting system
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21. Laboratory tests
• CBC - Anemia
 RFT & Urine analysis
○ Creatinine – reduction in GFR prior to surgery
○ Protienurea & hematuria
 LFT – liver metastasis
 Coagulation studies
○ Acquired Von Willebrand’s disease in WT – 10%
○ Prolonged PT, aPTT
○ Should be determined prior to surgery
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22. Staging
Stage I – limited to kidney
- completely resectable
- intact capsule
- no rupture before & after
removal
- no residual tumor beyond
resection margin
Stage II – extends beyond kidney
- completely excised
- regional extension beyond
capsule
- BV may be infiltrated
- local spillage confined to
ipsilateral flank
- no residual tu beyond margins of
resection
Stage III – non hematogenous tu
within the abdomen
- regional LN metastasis
- diffuse peritoneal implants
- gross or microscopic tumor
post Op
- incomplete resection
Stage IV – hematogenous metastasis
( lung , liver , bone , brain etc.)
- LN metastasis outside
abdomen & pelvis
Stage V – bilateral disease at Dx
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24. Management of WT
 The management is guided by the NWTS protocol in the United States and the
SIOP protocol in Europe according to the stage of the tumor
 Options of RX – Surgery, Chemotherapy & Radiotherapy
 Prognostic factors
 Histology
 Stage
 Response to Rx
 LOH at 1p & 16q
 The principles of surgery are as follows:
 Palpation of liver, abdomen, and para-aortic region for regional spread of disease
 Removal of intact specimen in total
 Avoidance of local “spillage”
 Nodal sampling
 Palpation of the renal vein and IVC before ligation to rule out thrombus
 Proper identification and avoidance of injury to contralateral renal vessels, aorta,
and iliac and superior mesenteric arteries
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Unresectable Tumors
 Extension of tumor thrombus above the level of the hepatic Veins
 Bilateral tumors
 Tumor in a solitary kidney
 Pulmonary compromise resulting from extensive pulmonary
Metastases
When actual invasion is identified and radical en bloc resection (spleen, pancreas, and
colon ) is required to remove tumour

25. Chemotherapy
 Dactinomycin is the backbone in the chemoRx against
WT
○ vincristine, doxorubicin, cyclophosphamide &
etoposide.
Vincristine & actinomycin D
Stage I & II favorable
Stage I unfavorable
Doxorubicine added
Stage III & IV favorable
Stage I – IV clear cell sarcoma
Cyclophosphamide added
Stage II – IV unfavorable
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26. Radiotherapy
 In the COG protocols, it is recommended that abdominal irradiation be
delivered as soon as practical after nephrectomy and not later than 14 days
after surgery.
 Flank Irradiation
 -- Stage III favorable histology and Recurrent Wilms’ tumor
 Whole Abdominal Irradiation
 --Preoperative tumor rupture
 -- Peritoneal metastases are found at initial surgery
 -- A large intraoperative tumor spill affecting areas outside the tumor bed
as
 determined by the surgeon/
 --Diffuse unresectable peritoneal implants
 Liver Irradiation
 -- Patients with residual tumor will receive supplemental irradiation
 Whole lung radiation
 it is a major cause of long-term morbidity
○ CHF, Pulmonary fibrosis & second malignancy.
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27. Comparison of NB & WT
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28. THANK YOU!!
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