Overview
Wilms' Tumour (Nephroblastoma)
1. Clinical Overview
Summary
Wilms' Tumour (Nephroblastoma) is the most common renal malignancy of childhood, typically presenting in children under 5 years of age. It originates from embryonic renal precursor cells (metanephric blastema). The classic presentation is a large, smooth, unilateral abdominal mass that does NOT cross the midline (distinguishing it from Neuroblastoma). It is associated with several congenital syndromes including WAGR Syndrome (Wilms, Aniridia, Genitourinary malformations, intellectual Retardation) and Beckwith-Wiedemann Syndrome. Treatment involves multimodal therapy (chemotherapy + surgery +/- radiotherapy) with excellent cure rates (>90% for localised disease). [1,2]
Clinical Pearls
Does NOT Cross the Midline: Wilms' tumour is intrarenal, typically remaining confined to one side. Neuroblastoma (adrenal origin) often crosses the midline.
"Cannonball" Lung Metastases: Wilms' tumour metastasises haematogenously, primarily to the Lungs. CXR shows characteristic large, round "cannonball" lesions.
DO NOT RUPTURE THE TUMOUR: Surgical handling must be meticulous. Tumour rupture upstages the disease and worsens prognosis. Many centres use pre-operative chemotherapy (SIOP protocol) to shrink the tumour before surgery.
Aniridia = Screen for Wilms': A child with congenital absence of the iris (Aniridia) should be screened for WAGR syndrome and has a high lifetime risk of Wilms' tumour (requires regular renal ultrasound surveillance).
2. Epidemiology
Demographics
- Incidence: ~1 in 10,000 children. 500-600 cases/year in UK.
- Peak Age: 2-5 years. Rare after age 10.
- Sex: Slightly more common in females.
- Bilateral: 5-10% of cases are bilateral (often associated with genetic syndromes).
Associated Syndromes
| Syndrome | Gene/Mutation | Features |
|---|---|---|
| WAGR Syndrome | WT1 deletion (11p13) | Wilms, Aniridia, Genitourinary malformations (hypospadias), intellectual Retardation. |
| Beckwith-Wiedemann Syndrome | Chromosome 11p15 (Imprinting) | Macroglossia, Macrosomia, Hemihypertrophy, Omphalocele, Ear pits/creases. 5-10% develop Wilms'. |
| Denys-Drash Syndrome | WT1 mutation | Male pseudohermaphroditism, Nephropathy, Wilms' tumour. |
| Perlman Syndrome | DIS3L2 mutation | Macrosomia, Renal abnormalities. High risk of Wilms'. |
3. Pathophysiology
Origin
- Embryonic Remnants: Wilms' tumour arises from Nephrogenic Rests – persistent embryonic metanephric blastema cells that failed to differentiate.
- WT1 and WT2 Genes: Tumour suppressor genes on Chromosome 11. Mutations or loss of function lead to uncontrolled proliferation.
- Triphasic Histology: Classic Wilms' tumour contains three cell types: Blastemal, Stromal, and Epithelial (trying to form primitive nephrons).
- Anaplasia: Unfavourable histology. Presence of anaplasia (large, hyperchromatic nuclei, atypical mitoses) indicates poorer prognosis and resistance to chemotherapy.
Spread
- Local: Directly into surrounding structures, renal vein (tumour thrombus extending into IVC).
- Haematogenous: Lungs (most common), Liver.
- Lymphatic: Regional lymph nodes.
4. Differential Diagnosis (Paediatric Abdominal Mass)
| Condition | Key Features |
|---|---|
| Wilms' Tumour | Smooth, unilateral flank mass. Does NOT cross midline. Child usually well. Age 2-5 years. |
| Neuroblastoma | Irregular mass. CROSSES midline. Ill child. Periorbital bruising ("Raccoon eyes"). Raised Catecholamines (urinary VMA/HVA). |
| Hydronephrosis | Ballotable flank mass. Ultrasound shows dilated collecting system. |
| Polycystic Kidney Disease | Bilateral enlarged kidneys. Family history. Multiple cysts on imaging. |
| Hepatoblastoma | Right upper quadrant mass. Raised AFP. Liver origin. |
| Multicystic Dysplastic Kidney | Unilateral. Non-functioning kidney replaced by cysts. Often detected antenatally. |
5. Clinical Presentation
History
Examination
Asymptomatic Abdominal Mass
Most common presentation (80%). Often noticed by parent during bathing or dressing.
Abdominal Pain/Distension
Due to large tumour size.
Haematuria
~20%. Microscopic or macroscopic.
Malaise, Fever, Weight Loss
Occasionally.
Hypertension
~25%. Due to renin secretion by tumour.
6. Investigations
Imaging
| Modality | Findings |
|---|---|
| Abdominal Ultrasound | First-line. Shows intrarenal solid mass. Assess IVC for tumour thrombus. |
| CT / MRI Abdomen | Staging. Defines tumour extent, lymph nodes, contralateral kidney a abnormalities, IVC involvement. |
| Chest X-ray | Screening for lung metastases ("Cannonball" lesions). |
| CT Chest | If CXR abnormal or for staging. |
Laboratory
| Test | Finding |
|---|---|
| FBC | May show anaemia (chronic disease or haemorrhage). |
| U&Es | Assess renal function (especially if bilateral or contralateral kidney abnormal). |
| Urinalysis | Haematuria. |
| LFTs | Baseline before chemotherapy, assess for liver mets. |
| Urinary Catecholamines (VMA/HVA) | Normal in Wilms' tumour. Elevated in Neuroblastoma. Important differentiator. |
No Biopsy (Usually)
- Avoid percutaneous biopsy: Risk of tumour rupture and spillage. Diagnosis made on imaging + surgery.
7. Management
Management Algorithm
SUSPECTED WILMS' TUMOUR
(Renal Mass in Child less than 5 yrs)
↓
USS + CT ABDOMEN/CHEST
Urinary Catecholamines (to exclude Neuroblastoma)
↓
MDT DISCUSSION
(Paediatric Oncology, Surgery, Radiology)
↓
┌───────────────────┴───────────────────┐
↓ ↓
SIOP PROTOCOL COG PROTOCOL
(Europe) (North America)
↓ ↓
PRE-OP CHEMOTHERAPY UPFRONT NEPHRECTOMY
(4-6 weeks to shrink tumour) (Histology first)
↓ ↓
└──────────────────┬──────────────────┘
↓
RADICAL NEPHRECTOMY
(Tumour + Kidney + Ureter)
- DO NOT RUPTURE TUMOUR
- Examine contralateral kidney
- Sample lymph nodes
↓
HISTOLOGY (STAGING)
- Favourable vs Unfavourable (Anaplasia)
↓
POST-OP CHEMOTHERAPY
(Actinomycin D, Vincristine +/- Doxorubicin)
↓
+/- RADIOTHERAPY
(If higher stage or anaplasia)
Treatment Protocols
| Protocol | Approach | Notes |
|---|---|---|
| SIOP (Europe/UK) | Pre-operative Chemotherapy → Surgery → Post-op Chemotherapy | Shrinks tumour, easier surgery, lower rupture rate. Histology may be altered. |
| COG (North America) | Upfront Surgery → Chemotherapy | Provides accurate histological staging. Larger surgery initially. |
Chemotherapy Agents
- Actinomycin D (Dactinomycin)
- Vincristine
- Doxorubicin (Adriamycin) - for higher stage/unfavourable histology.
Radiotherapy
- Indicated for:
- Stage III disease (local spread).
- Unfavourable histology (anaplasia).
- Tumour rupture.
- Lung metastases not cleared by chemotherapy.
8. Staging (SIOP / COG)
| Stage | Description |
|---|---|
| Stage I | Tumour confined to kidney, completely resected. Capsule intact. |
| Stage II | Tumour extends beyond kidney but completely resected. No residual disease. |
| Stage III | Residual non-haematogenous tumour (lymph node involvement, peritoneal contamination, tumour rupture, incomplete resection). |
| Stage IV | Haematogenous metastases (Lung, Liver, Bone, Brain). |
| Stage V | Bilateral Wilms' tumour at diagnosis. |
9. Complications
Of Disease
- Metastases: Lung (most common), Liver, rarely Bone/Brain.
- Tumour Rupture: Pre-operative or intra-operative. Upstages to Stage III. Increases recurrence risk.
- IVC Tumour Thrombus: Risk of pulmonary embolism. Requires cardiothoracic surgery for removal.
Of Treatment
- Chemotherapy: Myelosuppression, Infection, Nausea, Vincristine neuropathy, Doxorubicin cardiotoxicity.
- Radiotherapy: Growth abnormalities, Scoliosis, Secondary malignancy (long-term).
- Nephrectomy: Single kidney (need to protect remaining kidney lifelong).
10. Prognosis and Outcomes
| Stage / Histology | 5-Year Survival |
|---|---|
| Stage I / Favourable | >95% |
| Stage II / Favourable | ~90% |
| Stage III / Favourable | ~85% |
| Stage IV (Lung Mets Only) | ~75-80% |
| Unfavourable (Anaplastic) | ~40-70% (depends on stage) |
| Overall | >90% for localised disease |
- One of the most curable childhood cancers with multimodal therapy.
- Long-term follow-up essential for late effects (cardiac, renal, secondary malignancy).
11. Evidence and Guidelines
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Wilms Tumour Management | SIOP-RTSG | Pre-operative Chemotherapy protocol. Staging. Risk stratification. |
| Childhood Cancer Guidelines | NICE (UK) | Referral pathways, MDT management, long-term follow-up. |
| Children's Oncology Group | COG (USA) | Upfront surgery protocol. Risk stratification. |
Landmark Trials
- SIOP Trials (WT-2001, UMBRELLA 2016): Established the safety and efficacy of pre-operative chemotherapy.
- NWTS (National Wilms Tumor Study): Established staging and risk stratification (USA).
12. Patient and Layperson Explanation
What is Wilms' Tumour?
Wilms' tumour is a type of kidney cancer that affects young children, usually under 5 years old. It is one of the most treatable childhood cancers.
How is it treated?
Treatment usually involves:
- Chemotherapy: Medicine to shrink the tumour (may be given before or after surgery).
- Surgery: Removing the kidney containing the tumour.
- Radiotherapy: Sometimes needed for larger tumours or if it has spread.
What are the chances of cure?
Very good. With modern treatment, over 90% of children with Wilms' tumour that has not spread are cured.
Will my child be okay with one kidney?
Yes. People can live completely normal lives with one kidney. We will monitor the remaining kidney to make sure it stays healthy.
13. References
Primary Sources
- SIOP-RTSG. Wilms Tumour UMBRELLA Protocol. 2016.
- Dome JS, et al. Children's Oncology Group's 2013 Blueprint for Research: Renal Tumors. Pediatr Blood Cancer. 2013;60:994-1000. PMID: 23255213.
14. Examination Focus
Common Exam Questions
- Diagnosis: "3-year-old with smooth unilateral flank mass not crossing midline?"
- Answer: Wilms' Tumour (Nephroblastoma).
- Differentiation: "How to differentiate from Neuroblastoma?"
- Answer: Wilms' does NOT cross midline, child is well, Urinary Catecholamines are normal. Neuroblastoma crosses midline, child is often unwell, raised VMA/HVA.
- Association: "Child with Aniridia (no iris). What to screen for?"
- Answer: WAGR Syndrome. Screen for Wilms' Tumour with renal Ultrasound.
- Metastasis: "Where does Wilms' tumour metastasise?"
- Answer: Lungs ("Cannonball" metastases on CXR).
Viva Points
- Favourable vs Unfavourable Histology: Anaplasia = Unfavourable histology = worse prognosis, needs more intensive treatment.
- Tumour Rupture: Why is it bad? Upstages to Stage III, peritoneal seeding, needs radiotherapy.
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