presentation on Neuroblastoma & Wilms tumor

1. Neuroblastoma & Wilms tumor
By
Dr Irfan Malik
PGR URO IKD

2. Learning objectives
• Background
• Incidence
• Embryology
• Genetics
• Pathophysiology
• Clinical presentation
• Diagnosis
• Management
• Prognosis
• Follow up

3. Neublastoma
• Background
• Neuroblastoma is the most common extracranial
solid tumor of childhood.
• Neuroblastoma is known to arise from cells of the
neural crest that form the adrenal medulla and
sympathetic ganglia.
• Tumors may occur anywhere along the sympathetic
chain within the neck, thorax, retroperitoneum, or
pelvis or in the adrenal gland.

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• These tumors can undergo spontaneous
regression , differentiate to benign neoplasms,
or exhibit extremely malignant behavior.
Unpredictable behaviour
Retroperitoneum 75%
Adrenal 50%
paravertebral ganglia 25%

5. Incidence
• 8% to 10% of all childhood cancers.
• Annual incidence is 10 cases per million in US.
• Most common tumor of infancy.
• Median age at diagnosis is 18 months which
reduces to 9 months in familial form.

6. Embryology
• Neuroblastoma is known to arise from cells of
the neural crest that form the adrenal medulla
and sympathetic ganglia.

7. Genetics
Neuroblastoma
Familial
Autosomal
dominant
Chromosomal
abnormality
Sporadic
20% have bilateral adrenal or multifocal
primary tumor.
Risk in sibling is <6%
Deletion
Translocation
Amplification
40% in advance disease
5 t0 6% in low stage disease
Adverse prognostic indicator
MYCN oncogene at 2p24
25 to 35% cases
Adverse prognosis
IT ARISES DUE TO SOMATIC
MUTATION IN THE BODY
CELLS

8. Prognostic Markers
• Intensity of chemotherapy is determined not
only by staging of tumor but also by its biologic
markers.
• Favourable markers unfavourable markers
• DNA Aneuploidy > >Amplification of the
MYCN oncogene at 2p24
> >Deletion of the short arm
of chromosome 1p,
> > 11q deletion ,
> > 17q gain

9. Pathophysiology
• Neuroblastoma Malignant
• Ganglioneuroblastoma Intermediate
• Ganglioneuroma Benign
• Unpredictable tumor
• Natural Course?

10. Shimada classification
• Stroma Rich Stroma Poor
Nodular
Intermixed Favourable Unfavourable
well differentiated
Based on the patient's age
at diagnosis, the degree of
histologic maturation, and
the mitotic rate.

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13. Clinical Presentation
• Local disease
abdominal pain or a palpable mass
• Metastatic
bone or joint pain, periorbital ecchymosis.
• Thoracic lesions may produce respiratory symptoms of
cough or dyspnea.
• Neurologic deficits as a result of cord compression.
• Extrinsic compression of the bowel and bladder can
produce symptoms of urinary retention and
constipation
• Metastases are present in 70% of patients with
neuroblastoma at diagnosis.

14. • Para neoplastic syndrome.
Catecholamine mimic pheochromocytoma
VIP severe watery diarrhea and
hypokalemia.
• Unusual presentation.
acute myoclonic encephalopathy, in which patients
develop myoclonus, rapid multidirectional eye
movements (opsoclonus), and ataxia.
• It is thought to result from an interaction of antibodies
produced against the neuroblastoma to normal neural
tissues.

15. Diagnosis
• Laboratory Evaluation
urinary metabolites of catecholamines,
vanillylmandelic acid (VMA) and homovanillic acid
(HVA), are found in 90% to 95% of patients.
Anemia. In children with widespread bone marrow
involvement.

16. • Imaging
• Plain radiographs. May demonstrate a calcified
abdominal or posterior mediastinal mass.
• CT. local extent of the primary tumors and vascular
involvement. Invasion of the renal parenchyma is not
common, but it can be detected radiographically by CT.
• The finding of intratumoral calcifications, vascular
encasement, or both on preoperative CT may help
distinguish neuroblastoma from Wilms tumor.

17. • Metaiodobenzylguanidine (MIBG) scan.
Use 123I-MIBG
determine the extent of disease and detect
tumor recurrence after completion of therapy.
• Positron emission tomography (PET) can be
used if MIBG can not be used or not available.

18. • MRI. local extent & vascular involvement.
• MRI has advantages over CT in
the evaluation of intraspinal tumor extension,
relationship between the major vessels and
the tumor.

19. Screening
• Started in Japan & has been there since 20 years.
• Patients diagnosed with screening have uniform
survival of >97%.
• Before screening, 20% diagnosis before age 1 which
increased to 55% after screening implementation.
• However, the number of children older than 1 year
of age diagnosed with advanced-stage disease has
not decreased.
• Biologic differences between tumors diagnosed by
screening and those detected clinically.

20. Staging

21. Treatment
• Surgery, chemotherapy, and radiation therapy.
• The role of each in individual patients varies
depending on tumor stage, age, and biologic
prognostic factors.

22. Low-Risk Disease (Stages I, II, and IV-
S).
• Children with stage I neuroblastoma have a
disease-free survival rate of greater than 90%
with surgical excision alone
• Chemotherapy is indicated only in the event
of recurrence unless the child has MYCN
amplification and unfavorable histology.
• Radiation therapy has no role in this subset of
patients.

23. Intermediate and High-Risk Disease
(Stages III and IV).
• Chemotherapy Surgery
• Usually the safest approach for advanced
tumors is to defer resection until after initial
chemotherapy.
• The tumors are smaller and firmer, with less
risk of rupture and hemorrhage after
chemotherapy, resulting in a decreased rate of
complications, particularly nephrectomy.

24. • Surgery usually is performed 13 to 18 weeks
after initiation of chemotherapy, allowing
three to four courses of treatment.
• Extensive surgical resection can result in
Diarrhoea & Chylus acities.

25. RADIOTHERAPY
• Radiotherapy has a role in neuroblastoma
because tumor is radiosensitive.it is most
useful in achieving local control and palliation
of disease uncontrollable by other modalities.
• DOSE= Ranged b/w 15 and 30 Gy

26. New Innovative Biologic Therapies
• Double autologous bone marrow
transplantation. Has allowed the use of
myeloablative therpies.
• Multiple monoclonal antibodies.

27. Wilms tumor
• Wilms tumor, or nephroblastoma, is the most
common primary malignant renal tumor of
childhood. It is an embryonal tumor that develops
from remnants of immature kidney.

28. Epidemiology
• Wilms tumor accounts for approximately 6% to 7% of
all childhood cancers.
• It is the most common renal tumor of childhood,
accounting for 95% of all kidney cancers in children
under the age of 15 in the United State.
• Incidence rate of Wilms tumor is 8.0 per million.
• More than 80% of cases are diagnosed before 5 years
of age, with a median age of 3.5 years.
• It is lower in bilateral cases & in children with
syndromic predisposition.
• Incidence in East Asian population is lower than black
population.

29. Genitics
Wilms tumor
Sporadic familial
Early age, B/L
WTI(11p13)10% WT2(11p15)4% LOH 16q (20%) WTX(30%)
Mutation. DDS LOS BWS risk of relpase same pathway as WTI
Deltion. WAGR LOH 1p (10%)
risk of relpase
combined loss will result in worse replase

30. Clinical presentation
• Most common presentation is abdominal mass.
• Haematuria 20%. Gross haematuria warrants
further workup.
• Anorexia, weight loss, malaise 10%
• Hypertension 20-25%
• Asymptomatic
• Atypical presentation. Persistent vericocele,
hepatomegaly, CCF.

31. Examination
• Head to toe examination is imp
• Exclude associated condition
• BP

32. Labs
• CBC, S/E, LFTS, RFTs, S.calcium
• Coagulation profile. As 8% of newly diagnosed
patients have acquired von Willebrand
disease.

33. Diagnosis
• Ultrasound
solid mass of the kidney
• Doppler ultrasound can determine vena caval
involvement.
• Give good idea of association with spleen,
liver & other solid organs.

34. • Triphasic CT
Should be chest,abdomen & pelvis
• Arterial, venous & excretory phase
• CT chest. Lung is the most common site for
distant metastasis
• MRI. Same as CT but require sedation or
anaesthesia in children

35. Staging
• The most important determinants of outcome
in children with Wilms tumor are the
histopathology and tumor stage.

36. Management
• Multidisciplinary team work
• Surgeon Radiologist pathologist
Oncologist Radiotherapist Geneticist

37. • Two management arms
• NWTGS/COG SIOP
• Surgery > pre op chemo
• Followed by chemo, > followed by surgery
XRT >further chemo or
• Pre op chemo only in radio if needed
selected cases.
• The overall survival in both groups is >90% in low
stage tumor & >80% in high stage tumor

38. Advantages & disadvantages
NWTGS/COG SIOP
Advantages disadvantages
Accurate histology Increased risk of
surgical
complications
Benign vs malignant Chances of tumor
spillage
Accurate stage Failure to sample
node leads to under
treatment
Advantages disadvantages
Fever surgical
complications
Modification of yumor
histology
Lower incidence of
tumor rupture
Loss of staging
information
Asses tumor response Chemotherapy in a
benign disease
Downstaging of
patient
Chemotherapy to a
different malignant
tumor
Possible role of renal
sparing surgery in the
affected kidney
International Version.
No biopsy
UK version. Pre chemo
biopsy

39. Neoadjuvant chemotherapy
• Local disease. 4 weeks, 2 drugs( actinomycin,
Vincristine)
• Metastatic disease. 6 weeks,3 drugs(Act,VCR, Dox)
• Special situations.
B/L tumor
tumor in solitory kidney
horse shoe kidney
• Where the oncologist can modify the chemo.

40. Surgery
• Role of the surgeon
Before surgery the surgeon must know.
????
• surgical approach
• Laparoscopic surgery. In selected cases.

41. Lymph nodes
• 7 locoregional lymph nodes shpuld be
sampled.
• Hilar & paraaortic lymph node should be
sampled even if not suspicious.
• Involved lymph node should be excised.
• Radical lymph node dissection is not
recommended.
• Post chemo necrotic lymph node should be
considered positive.

42. • Role of nephron sparing surgery.

43. After surgery
• Histolgy
Percentage of necrosis
100%
Complete
necrosis
66-99%
Regressive
type
<66%
Histological
subtypes
Balstemal
stromal epithelial Mixed
Diffuse
anaplasia

44. SIOP protocols
Intermed
iate risk

45. NWTSG protocols
• Favourable hostology Unfavurable Histology
Epithelial predominant Diffuse anaplasia
Stromal predominant Focal anaplasia
Blastemal predominant

46. COG protocols
Stage & histology Surgery Chemotherapy Radiation therapy
I or II favourable
histo without LOH at
1p & 16q
Nephrectomy Vancristine,
Actinmomycin-D
No
I or II favourable
histo withLOH at 1p
& 16q
Nephrectomy Vancristine,
Actinmomycin-D,
Doxurubicin
No
III & IV favourable
histo without LOH at
1p & 16q
Nephrectomy Vancristine,
Actinmomycin-D,
Doxurubicin
Yes
III & IV favourable
histo with LOH at 1p
& 16q
Nephrectomy Vancristine,
Actinmomycin-D,
Doxurubicin
Cyclophosphamide,
Etoposide
Yes

47. COG high risk group management
• Focal anaplastic stage I-III Wilms tumors and diffuse anaplastic
stage I Wilms tumors
Nephrectomy followed by vincristine, actinomycin-D, and
doxorubicin in addition to local radiotherapy.
• Focal anaplastic stage IV Wilms tumors and diffuse anaplastic
stage II-III tumors
Patients undergo the same treatment, with the addition of
cyclophosphamide, etoposide, and carboplatin.
• Stage IV diffuse anaplastic Wilms tumors
More aggressive treatment is delivered; nephrectomy is followed by
initial irinotecan and vincristine administration, which in turn is
followed by actinomycin-D, doxorubicin, cyclophosphamide,
carboplatin, etoposide, and radiotherapy.

48. B/L wilms tumor
• Synchronous bilateral Wilms tumors occur in
5% to 7% of children with Wilms tumor.
• Children with bilateral tumors should not
undergo initial radical nephrectomy.
• These children should receive preoperative
chemotherapy with the goal of tumor
shrinkage and renal-sparing surgery
• Pre chemo for 6 weeks. Responders can be
allowed for surgery.
• Non responder should B/L open renal biopsy.

49. • If nephron sparing surgery is not feasible then
additional chemo is given based on biopsy
report. 2 drugs initially, if poor response then
3 drugs.
• All patients are recommended to undergo
surgical resection within 12 weeks of therapy.
• Can undergo partial nephrectomies on both
sides or radical on one & partial on other side.
• Rarely b/l nephrectomies

50. Follow up
• General well being & growth of the child
• Ultrasound
• Chest x ray
• Yearly serum creatinine if renal function is
normal
• Three monthly creatinine & S/E if renal
dysfunction
• Yearly urine R/E for protienuria

51. •
Thank you