This document discusses Wilms' tumor, a type of childhood kidney cancer. It accounts for about 6% of pediatric cancers and develops from immature kidney tissue. Survival rates have improved from 30% in the 1930s to over 85% currently. Treatment typically involves surgery to remove the kidney along with chemotherapy and sometimes radiation therapy. Prognosis depends on factors like tumor stage, histology, and presence of anaplasia. Coordinated treatment protocols through organizations like the National Wilms Tumor Study Group have helped increase survival rates by standardizing treatment.

1. CHILDHOOD SOLIDCHILDHOOD SOLID
TUMORSTUMORS

3. WILMS’ TUMORWILMS’ TUMOR
Osler in 1879, Wilms in 1899Osler in 1879, Wilms in 1899
Wilms’ tumor, or nephroblastoma, accounts forWilms’ tumor, or nephroblastoma, accounts for
about 6% of all pediatric malignant disease.about 6% of all pediatric malignant disease.
This embryonal tumor develops from remnantsThis embryonal tumor develops from remnants
of immature kidney.of immature kidney.
Survival has improved from 30% in 1930s toSurvival has improved from 30% in 1930s to
over 85% currentlyover 85% currently

4. Median age of 3.5 years.Median age of 3.5 years.
More than 80% of patients identified before 5More than 80% of patients identified before 5
years of age.years of age.
Male-to-female ratio 0.92 : 1Male-to-female ratio 0.92 : 1
Relatively more common in blacks than inRelatively more common in blacks than in
whites and is less common in East Asians.whites and is less common in East Asians.
Bilateral disease occurs in 5-7% of patientsBilateral disease occurs in 5-7% of patients
with WT.with WT.

5. Associated disordersAssociated disorders
 Children with various congenital abnormalities have anChildren with various congenital abnormalities have an
increased predisposition to wilms tumorincreased predisposition to wilms tumor
Sporadic aniridiaSporadic aniridia
WAGR syndrome ( wilms, aniridia, genitourinaryWAGR syndrome ( wilms, aniridia, genitourinary
malformations, mental retardation)malformations, mental retardation)
Denys - Drash syndrome ( wilms, intersex, nephropathy)Denys - Drash syndrome ( wilms, intersex, nephropathy)
Perlman syndrome (overgrowth syndrome with mentalPerlman syndrome (overgrowth syndrome with mental
retardationretardation))

6. Beckwith-Wiedemann syndromeBeckwith-Wiedemann syndrome --
exomphalosexomphalos
visceromegalyvisceromegaly
macroglossiamacroglossia
umbilical defectsumbilical defects
hemihypertrophyhemihypertrophy
hypoglycemiahypoglycemia
increased susceptibility to a number ofincreased susceptibility to a number of
pediatric cancers including wilms,pediatric cancers including wilms,
adrenocortical carcinomaadrenocortical carcinoma
& hepatoblastoma& hepatoblastoma
Exom
phalo
Hem
hype
Macro-
glossia
Hypogly-
cemia

7. Molecular biologyMolecular biology
WT1 gene - deletion at 11p13 – tumorWT1 gene - deletion at 11p13 – tumor
suppressor gene seen in WAGR & Denys-suppressor gene seen in WAGR & Denys-
DrashDrash
WT2 gene - 11p15 locus. OverWT2 gene - 11p15 locus. Over
expression of this gene results inexpression of this gene results in
overgrowth seen in BWS.overgrowth seen in BWS.

8. PathologyPathology
Classic wilms tumor has three components seenClassic wilms tumor has three components seen
in normal kidney differentiation: Blastema, tubulesin normal kidney differentiation: Blastema, tubules
& stroma.& stroma.
When all three components are seen it is calledWhen all three components are seen it is called
triphasic. Tumor can be mono or diphasic.triphasic. Tumor can be mono or diphasic.
Tumor may exhibit aberrant differentiation –Tumor may exhibit aberrant differentiation –
adipose, skeletal muscle, cartilage & boneadipose, skeletal muscle, cartilage & bone
Tendency to grow into veins – tumor thrombusTendency to grow into veins – tumor thrombus

9. Tumor with differentiated components have bestTumor with differentiated components have best
prognosis and the histology is termed favorable.prognosis and the histology is termed favorable.
Anaplastic tumors are characterized by cells withAnaplastic tumors are characterized by cells with
nuclear enlargement from two –three times thenuclear enlargement from two –three times the
diameter of adjacent cells, hyperchromatic nuclei &diameter of adjacent cells, hyperchromatic nuclei &
abnormal mitotic figures.abnormal mitotic figures.
Overall incidence of anaplasia varies from 3 – 7%Overall incidence of anaplasia varies from 3 – 7%
The single most important indicator of poorThe single most important indicator of poor
prognosis is presence of anaplasia – calledprognosis is presence of anaplasia – called
unfavorable histology.unfavorable histology.

10. Nephrogenic restsNephrogenic rests
These are potentially premalignant lesionsThese are potentially premalignant lesions
found within the kidneys of 30 – 40% offound within the kidneys of 30 – 40% of
patients with wilms tumor.patients with wilms tumor.
These are small foci of persistent primitiveThese are small foci of persistent primitive
blastemic cells that are normally found inblastemic cells that are normally found in
neonatal kidney.neonatal kidney.

11. Clinical FeaturesClinical Features
Usually presents as asymptomatic abdominal massUsually presents as asymptomatic abdominal mass
Urinary disturbances, microscopic haematuria,Urinary disturbances, microscopic haematuria,
malaise, weight loss, anemia, left sided varicocoelemalaise, weight loss, anemia, left sided varicocoele
Thrombus in IVC can present with venous edema ofThrombus in IVC can present with venous edema of
lower limb. Thrombus can extend into the heart &lower limb. Thrombus can extend into the heart &
produce cardiac malfunction.produce cardiac malfunction.
Urologic anomalies such as cryptorchidism,Urologic anomalies such as cryptorchidism,
Hypospadias may be seen.Hypospadias may be seen.
Occasionally hypertension due to renal veinOccasionally hypertension due to renal vein
occlusion by tumor thrombusocclusion by tumor thrombus

12. InvestigationsInvestigations
IVP: Spider leg appearanceIVP: Spider leg appearance
USG – Organ of origin, consistency, Tumor thrombusUSG – Organ of origin, consistency, Tumor thrombus
in renal vein/IVC/atrium, anomalies of kidney.in renal vein/IVC/atrium, anomalies of kidney.
CT – Assess operability, Structure & function ofCT – Assess operability, Structure & function of
opposite kidney, Liver/node involvementopposite kidney, Liver/node involvement
MRIMRI
Xray Chest/CT.Xray Chest/CT.

14. NWTS – National Wilms TumorNWTS – National Wilms Tumor
Study groupStudy group ..
As there were only an estimated 450 – 500As there were only an estimated 450 – 500
cases of wilms tumor occurring annually incases of wilms tumor occurring annually in
the united states it was realized thatthe united states it was realized that
collaboration was mandatory in order tocollaboration was mandatory in order to
obtain statistically significant numbers ofobtain statistically significant numbers of
patients, hence NWTS was born in 1969 topatients, hence NWTS was born in 1969 to
set up treatment protocols trials & giveset up treatment protocols trials & give
guidelines.guidelines.
Currently NWTS – 5 is in progress.Currently NWTS – 5 is in progress.

15. StagingStaging
II –– Tumor limited to kidney & completely resectedTumor limited to kidney & completely resected
with intact renal capsulewith intact renal capsule
IIII - Tumor extended beyond kidney & completely- Tumor extended beyond kidney & completely
resected.resected. There may be penetration of the capsule,There may be penetration of the capsule,
tumor violated by previous biopsy, spillage confinedtumor violated by previous biopsy, spillage confined
to the flankto the flank
IIIIII – Residual non-hematogenous tumor– Residual non-hematogenous tumor like renallike renal
hIlar nodes, tumor implants on peritoneal surface,hIlar nodes, tumor implants on peritoneal surface,
local infiltration into vital structures, gross tumorlocal infiltration into vital structures, gross tumor
spillage not confined to the flank.spillage not confined to the flank.
IVIV – Hematogenous metastatic disease– Hematogenous metastatic disease to theto the
lungs, liver, bone & brainlungs, liver, bone & brain
VV – Bilateral renal involvement at diagnosis– Bilateral renal involvement at diagnosis

17. SurgerySurgery
According to the NWTSG protocol, the first step inAccording to the NWTSG protocol, the first step in
the treatment of WT is surgical staging followed bythe treatment of WT is surgical staging followed by
radical nephrectomy, if possible.radical nephrectomy, if possible.
Thorough exploration of the abdominal cavityThorough exploration of the abdominal cavity
through a transverse abdominal incision .through a transverse abdominal incision .
Formal exploration of the contralateral kidneyFormal exploration of the contralateral kidney
should be performed before nephrectomyshould be performed before nephrectomy
If bilateral disease is diagnosed, nephrectomy isIf bilateral disease is diagnosed, nephrectomy is
not performed but biopsy specimens are obtained.not performed but biopsy specimens are obtained.

18. If the disease is unilateral, radical nephrectomyIf the disease is unilateral, radical nephrectomy
and regional lymph node dissection or samplingand regional lymph node dissection or sampling
are performedare performed
The renal vein and IVC are palpated to excludeThe renal vein and IVC are palpated to exclude
intravascular tumor extension before vesselintravascular tumor extension before vessel
ligation.ligation.
If the tumor is unresectable, biopsies areIf the tumor is unresectable, biopsies are
performed and the nephrectomy is deferredperformed and the nephrectomy is deferred
until after chemotherapy.until after chemotherapy.

19. TreatmentTreatment
 FH:FH:
Stages I & II: Surgery + chemo ( Actinomycin + Vincristine)Stages I & II: Surgery + chemo ( Actinomycin + Vincristine)
Stage III: Surgery + Radiotherapy + chemo ( Actinomycin +Stage III: Surgery + Radiotherapy + chemo ( Actinomycin +
Vincristine + Doxorubicin)Vincristine + Doxorubicin)
Stage IV: Surgery + Radiotherapy + chemo ( Actinomycin +Stage IV: Surgery + Radiotherapy + chemo ( Actinomycin +
Vincristine +Doxorubicin)Vincristine +Doxorubicin)
Local Excision of secondariesLocal Excision of secondaries
 Anaplastic:Anaplastic:
Stage I: Surgery + ChemotherapyStage I: Surgery + Chemotherapy
Stages II – IV: Surgery + Radiotherapy + chemoStages II – IV: Surgery + Radiotherapy + chemo
( Actinomycin + Vincristine + Doxorubicin +/-( Actinomycin + Vincristine + Doxorubicin +/-
Cyclophosphamide)Cyclophosphamide)

20. Stage V (FH/Ana):Stage V (FH/Ana):
Obtain biopsiesObtain biopsies
Each side staged individually.Each side staged individually.
Chemo/radio as per higher stageChemo/radio as per higher stage
Repeat CT. Once tumor reduces in size renalRepeat CT. Once tumor reduces in size renal
preserving surgery on both sides & closepreserving surgery on both sides & close
follow up for recurrencefollow up for recurrence
In case of thrombus in the IVC/Atrium giveIn case of thrombus in the IVC/Atrium give
chemotherapy at least 3 courses & repeatchemotherapy at least 3 courses & repeat
imaging. Then Surgery.imaging. Then Surgery.

21. PrognosisPrognosis
Approximately 80-90% of diagnosedApproximately 80-90% of diagnosed
children survive with current multimodalitychildren survive with current multimodality
therapy.therapy.
Patients with FH tumors have at least anPatients with FH tumors have at least an
80% overall survival rate at 4 years after80% overall survival rate at 4 years after
initial diagnosis, even in patients with stageinitial diagnosis, even in patients with stage
IV disease.IV disease.
Synchronous bilateral cases have a 70-80%Synchronous bilateral cases have a 70-80%
survival ratesurvival rate

22. NeuroblastomaNeuroblastoma
Tumor of neural crest originTumor of neural crest origin
May arise in the adrenal medulla orMay arise in the adrenal medulla or
sympathetic ganglia from neck to pelvissympathetic ganglia from neck to pelvis
Spontaneous tumor regression & tumorSpontaneous tumor regression & tumor
maturation from malignant to benignmaturation from malignant to benign
histologic form have been noted rarely,histologic form have been noted rarely,
especially under 3 months of age.especially under 3 months of age.
Incidence 1 in 8000 – 10000Incidence 1 in 8000 – 10000

23. 90% occur in first 8 yrs of life90% occur in first 8 yrs of life
> 50% are under the age of 2yrs at the time of> 50% are under the age of 2yrs at the time of
diagnosisdiagnosis
M:F IS 1.2:1M:F IS 1.2:1
Most common intraabdominal malignancy ofMost common intraabdominal malignancy of
newbornnewborn
Associations: BWS, Hirschsprung’s disease,Associations: BWS, Hirschsprung’s disease,
fetal alcohol syndrome, fetal hydantoinfetal alcohol syndrome, fetal hydantoin
syndromesyndrome

24. Neuroblast is derived from primordial neuralNeuroblast is derived from primordial neural
crest cells that migrate from the mantlecrest cells that migrate from the mantle
layer of developing spinal cordlayer of developing spinal cord
Locations:Locations:
75% in retroperitoneum – adrenal75% in retroperitoneum – adrenal
medulla(50%), paraspinal ganglia(25%)medulla(50%), paraspinal ganglia(25%)
20% in posterior mediastinum20% in posterior mediastinum
5% in neck / pelvis5% in neck / pelvis

25. PathologyPathology
Gross examination: Highly vascular purple-greyGross examination: Highly vascular purple-grey
solid mass with necrotic and hemorrhaghic areas.solid mass with necrotic and hemorrhaghic areas.
Microscopy: Appears like small round cell tumor. InMicroscopy: Appears like small round cell tumor. In
undifferentiated form there are closely packedundifferentiated form there are closely packed
small spheroidal cells with hyper chromatic nuclei.small spheroidal cells with hyper chromatic nuclei.
Rosette formation is a classical finding inRosette formation is a classical finding in
neuroblastoma. The center is formed by a tangle ofneuroblastoma. The center is formed by a tangle of
fine nerve fibres surrounded by a palisade offine nerve fibres surrounded by a palisade of
neuroblasts/ganglion cells – calledneuroblasts/ganglion cells – called Homer - WrightHomer - Wright
pseudo rosettes.pseudo rosettes.
Stroma rich tumors carry better prognosis.Stroma rich tumors carry better prognosis.

27. Clinical presentationClinical presentation
Related to site of tumor, presence ofRelated to site of tumor, presence of
metastases & production of certain metabolicmetastases & production of certain metabolic
byproductsbyproducts
Nodular, painful abdominal mass, weightNodular, painful abdominal mass, weight
loss, failure to thrive, distension, fever,loss, failure to thrive, distension, fever,
anemiaanemia
25% have hypertension due to production of25% have hypertension due to production of
catecholamines. Flushing, sweating &catecholamines. Flushing, sweating &
irritability may be seenirritability may be seen
Respiratory distress / Dysphagia due toRespiratory distress / Dysphagia due to
compression in the mediastinumcompression in the mediastinum

28. Neoplasms in neck/mediastinum may present withNeoplasms in neck/mediastinum may present with
Horner’s syndromeHorner’s syndrome – ptosis, miosis, enophthalmos,– ptosis, miosis, enophthalmos,
heterochromia of iris & anhydria on affected side.heterochromia of iris & anhydria on affected side.
Tumor extension through intervertebral foramina mayTumor extension through intervertebral foramina may
produce paraplegiaproduce paraplegia
Acute cerebellar ataxia – opsomyoclonus with nystagmusAcute cerebellar ataxia – opsomyoclonus with nystagmus
–– Dancing eye syndromeDancing eye syndrome – occasionally seen in mediatinal– occasionally seen in mediatinal
tumors, represents antigen-antibody reactiontumors, represents antigen-antibody reaction

29. WDHA syndrome due to VIP productionWDHA syndrome due to VIP production
Spontaneous rupture – hemoperitoneumSpontaneous rupture – hemoperitoneum
Metasases to liver, bone marrow, bone cortex &Metasases to liver, bone marrow, bone cortex &
nodesnodes
Metasasis to orbit produces proptosis or b/l orbitalMetasasis to orbit produces proptosis or b/l orbital
ecchymosis –ecchymosis – Panda eye signPanda eye sign

30. Diagnosis:Diagnosis:
Plain X ray – Stippled tumor calcificationPlain X ray – Stippled tumor calcification
USGUSG
CT – adrenal massCT – adrenal mass
MRI for spinal extensionMRI for spinal extension
Isotopic bone scintigraphy using technitium99Isotopic bone scintigraphy using technitium99
Meta iodo benzyl guanidine scanMeta iodo benzyl guanidine scan
Bone marrow aspirationBone marrow aspiration
Tumor markers (APUD):Tumor markers (APUD):
24 hr urine HVA & VMA24 hr urine HVA & VMA
Serum adrenaline, nor adrenaline, dopamineSerum adrenaline, nor adrenaline, dopamine
Serum LDH, Ferritin, NSESerum LDH, Ferritin, NSE

32. EVANS STAGING SYSTEMEVANS STAGING SYSTEM
II: confined to organ of origin: confined to organ of origin
IIII: beyond organ of origin, not crossing: beyond organ of origin, not crossing
midline, ipsilateral nodes may be involvedmidline, ipsilateral nodes may be involved
IIIIII: Extends beyond midline, b/l nodes: Extends beyond midline, b/l nodes
involvementinvolvement
 IVIV: Distant metastasis: Distant metastasis
 IV-SIV-S: Infants younger than 1yr,stg I or II,: Infants younger than 1yr,stg I or II,
remote disease confined to liver,remote disease confined to liver,
subcutaneous tissue & bone marrow.subcutaneous tissue & bone marrow.

33. Factor Good Prognosis Poor Prognosis
Age < 1yr > 1yr
Stage I.II,IV-S III, IV
Pathology Stroma rich Stroma poor
Site Mediastinum,
Pelvis, Neck
Adrenal, Coeliac
axis
> 10 copies of N-myc gene No Yes
Elevated Serum Ferritin No Yes
NSE No Yes
LDH No Yes
Diarrhea Yes No
Dancing eye Yes No
High HVA/VMA No Yes
Prognostic indicators

34. TreatmentTreatment
 Stage I: Complete surgical excisionStage I: Complete surgical excision
 Stage II: Complete surgical excisionStage II: Complete surgical excision
+/- Radiotherapy+/- Radiotherapy
Poor prognostic indicators – Surgery + ChemoPoor prognostic indicators – Surgery + Chemo
(Cisplatin, Doxorubicin, Cyclophosphamide,(Cisplatin, Doxorubicin, Cyclophosphamide,
Etoposide)Etoposide)
 Stages III & IV: Chemotherapy is mainstay followedStages III & IV: Chemotherapy is mainstay followed
by excision if mass responds to chemo & becomesby excision if mass responds to chemo & becomes
operableoperable

35. Aggressive management includes nearAggressive management includes near
fatal chemo (myeloablative) withfatal chemo (myeloablative) with
irradiation with BMTirradiation with BMT
New modalities include use of biologicalNew modalities include use of biological
response modifiers like 13-cis retinoicresponse modifiers like 13-cis retinoic
acid that causes tumor differentiation, Iacid that causes tumor differentiation, I131131
labeled antiGD2 antibody therapy.labeled antiGD2 antibody therapy.
(monoclonal antibodies).(monoclonal antibodies).