46  Nephroblastoma (Wilms’ Tumour)

46.1 Introduction

Nephroblastoma, commonly known as Wilms’ tumour, is the most common malignant renal tumour in childhood. It arises from embryonic renal tissue and typically presents between ages 2 and 5 years. The tumour has contributed greatly to the success story of paediatric oncology, with survival rates improving significantly due to advances in surgery, chemotherapy, and radiotherapy.
Although relatively rare compared to infections or malnutrition, nephroblastoma remains an important cause of morbidity and mortality in paediatrics, particularly in low- and middle-income countries where late presentation is common.

46.2 Incidence and Prevalence

Wilms’ tumour accounts for about 6–8% of all childhood cancers.
- The annual incidence is approximately 8 cases per million children under 15 years.
- Peak age of presentation: 3–4 years.
- Slight female predominance.
- Bilateral disease occurs in about 5–7% of cases.

In sub-Saharan Africa, including Ghana, the incidence is comparable to global figures, but outcomes are poorer due to late presentation, limited access to multimodal therapy, and higher rates of advanced disease at diagnosis.

46.3 Aetiology

Most cases are sporadic, but both genetic and environmental factors play roles.

• Genetic factors:
  • Mutations in WT1 (chromosome 11p13) and WT2 (11p15) are implicated.
  • Other genes: WTX (X chromosome), CTNNB1 (beta-catenin pathway).
• Syndromic associations:
  • WAGR syndrome (Wilms tumour, Aniridia, Genitourinary anomalies, mental Retardation).
  • Denys–Drash syndrome (gonadal dysgenesis, nephropathy, Wilms tumour).
  • Beckwith–Wiedemann syndrome (organomegaly, hemihypertrophy, increased tumour risk).
• Familial predisposition: Rare but recognised, with siblings sometimes affected.
• Environmental factors: No strong evidence, though intrauterine exposures have been explored.

46.4 Pathophysiology

Wilms’ tumour develops from persistent metanephric blastema, the embryonic renal precursor tissue that fails to differentiate normally.
- The tumour is typically a triphasic neoplasm, consisting of:
- Blastemal cells (small round blue cells).
- Stromal elements (spindle cells, connective tissue).
- Epithelial components (tubules, glomeruloid structures).
- Some tumours may be monophasic, dominated by one component.
- Tumour growth can distort the kidney, invade renal vessels, extend into the inferior vena cava, and metastasize, commonly to lungs, liver, and lymph nodes.

A subset of tumours shows anaplasia, which carries a poorer prognosis and resistance to therapy.

46.5 Clinical Features

Presentation depends on tumour size, stage, and presence of metastases.

• Most common feature:
  • Painless abdominal mass, often noticed by parents during bathing or dressing.
• Other features:
  • Abdominal pain or discomfort.
  • Hematuria (gross or microscopic).
  • Hypertension (due to increased renin secretion).
  • Anemia (from haemorrhage or bone marrow suppression).
  • Weight loss, anorexia, malaise (less common).
    
• Advanced disease:
  • Cough, dyspnea (lung metastases).
  • Hepatomegaly (liver metastases).

Unlike neuroblastoma, Wilms’ tumour rarely crosses the midline in the abdomen.

46.6 Differential Diagnosis

Important conditions to consider when a child presents with an abdominal mass:
- Neuroblastoma (usually crosses midline, calcification common).
- Multicystic dysplastic kidney.
- Hydronephrosis.
- Mesoblastic nephroma (in neonates).
- Renal cell carcinoma (rare in children).
- Hepatoblastoma or hepatomegaly from other causes.

46.7 Investigations

Workup aims at confirming diagnosis, assessing extent, and staging.

• Laboratory tests:
  • CBC (anemia, baseline counts).
  • Renal function tests (creatinine, electrolytes).
  • Liver function tests.
  • Urinalysis (hematuria).
    
• Imaging:
  • Abdominal ultrasound: First-line; identifies renal origin of mass.
  • CT or MRI of abdomen: Defines tumour extent, contralateral kidney involvement, vascular invasion.
  • Chest X-ray/CT: Evaluate for lung metastases.
• Histology: Usually obtained after nephrectomy or biopsy in bilateral/advanced disease.

46.8 Staging

The National Wilms’ Tumor Study (NWTS) staging system is widely used:
- Stage I: Limited to kidney, completely resected.
- Stage II: Extends beyond kidney but completely resected.
- Stage III: Residual tumour confined to abdomen (lymph nodes, peritoneal spillage).
- Stage IV: Hematogenous metastases (lung, liver, bone, brain).
- Stage V: Bilateral renal involvement.

46.9 Treatment

Successful management requires a multimodal approach: surgery, chemotherapy, and sometimes radiotherapy.

46.9.1 Emergency Management

• Stabilise child if anaemic, hypertensive, or in respiratory distress.
• Treat severe hypertension with antihypertensives.
• Blood transfusion for anaemia.
• Manage tumour rupture (can present with acute abdomen).

46.9.2 Definitive and Ongoing Treatment

• Surgery: Radical nephrectomy is standard for unilateral disease.
• Chemotherapy: Regimens typically include vincristine, actinomycin D, and doxorubicin (depending on stage and histology).
• Radiotherapy: Reserved for higher-stage disease or anaplastic histology.
• Bilateral disease (Stage V): Initial chemotherapy to shrink tumour, followed by nephron-sparing surgery.

46.9.3 Preparation for Discharge

• Educate caregivers on:
  • Medication adherence.
  • Infection prevention during chemotherapy.
  • Monitoring for hypertension and renal function.
  • Nutrition and follow-up visits.

46.9.4 Long-Term Management

• Regular follow-up for recurrence surveillance.
• Monitor growth and development.
• Monitor renal function (risk of chronic kidney disease, especially in bilateral disease).
• Monitor for late effects of chemotherapy/radiotherapy (cardiotoxicity, infertility, secondary malignancies).

46.10 Complications

• Tumour rupture leading to haemorrhage and peritonitis.
• Hypertension due to renin production.
• Metastasis (lungs, liver).
• Chemotherapy-related: myelosuppression, mucositis, cardiotoxicity.
• Chronic renal impairment in bilateral disease.
• Psychological and social impact on family.

46.11 Prognosis

Wilms’ tumour is one of the paediatric oncology success stories:
- Overall survival exceeds 85% in high-income countries.
- Prognosis depends on:
- Stage at diagnosis.
- Histology (anaplastic variants worse).
- Age of child.
- In sub-Saharan Africa, survival is significantly lower (20–50%) due to late presentation, limited resources, and treatment abandonment.

46.12 Prevention

There are no established preventive measures for sporadic cases. However:
- Genetic counselling for families with syndromic or familial cases.
- Surveillance imaging (ultrasound every 3 months until age 7) for high-risk children (e.g., WAGR, Denys–Drash, Beckwith–Wiedemann, bilateral disease).
- Early detection and treatment significantly improve outcomes.

46.13 Conclusion

Nephroblastoma is the most common childhood renal malignancy and a leading cause of paediatric abdominal masses. It exemplifies how combined surgery, chemotherapy, and radiotherapy can yield excellent outcomes when implemented effectively. For Ghana and similar settings, the major challenge remains late presentation and limited access to oncology services. Strengthening health systems, raising community awareness, and improving access to multimodal therapy are essential to bridge the survival gap.