Wilms' Tumor: Epidemiology, Pathogenesis, Histopathology, Symptoms, Diagnosis, Staging, Treatment and Prognosis

Wilms’ Tumor (Nephroblastoma)

~Introduction

Wilms’ tumor, also known as nephroblastoma, is the most common malignant renal tumor in children. It primarily affects infants and young children, with the majority of cases diagnosed before the age of five. Despite being a rare cancer overall, Wilms’ tumor represents a significant portion of pediatric oncology cases and has become a major success story in cancer treatment due to advances in multimodal therapy.

The tumor arises from primitive renal tissue and reflects abnormal embryologic development of the kidney. Over the past several decades, survival rates have improved dramatically, exceeding 90% in many developed healthcare systems. This article explores Wilms’ tumor in detail, covering its epidemiology, pathogenesis, clinical presentation, diagnostic evaluation, staging, treatment approaches, prognosis, and long-term outcomes.

~Epidemiology

Wilms’ tumor accounts for approximately 5–7% of all childhood cancers and nearly 90% of pediatric kidney tumors. The global incidence is about 1 case per 10,000 children, with slight variations across regions.

Age Distribution

• Peak incidence: 2–4 years

• Rare after age 10

• Congenital cases are uncommon but documented

Sex and Ethnicity

• Slight female predominance

• Higher incidence reported among children of African descent

• Lower incidence in East Asian populations

~Embryology and Pathogenesis

Wilms’ tumor originates from nephrogenic rests, which are remnants of embryonic kidney tissue that fail to differentiate normally. These rests can persist after birth and later transform into malignant tissue.

Genetic Basis

Wilms’ tumor is closely linked to genetic abnormalities, particularly involving tumor suppressor genes.

Key Genetic Alterations

• WT1 gene (chromosome 11p13)
  Essential for normal kidney and gonadal development

• WT2 locus (11p15)
  Involved in growth regulation and imprinting

• Loss of heterozygosity (LOH) at chromosomes 1p and 16q (associated with worse prognosis)

• β-catenin (CTNNB1) mutations

• TP53 mutations (linked to anaplastic histology)

Syndromic Associations

Wilms’ tumor may occur sporadically or as part of congenital syndromes:

Syndrome	Key Features
WAGR syndrome	Wilms’ tumor, Aniridia, Genitourinary anomalies, intellectual disability
Beckwith-Wiedemann syndrome	Macroglossia, hemihypertrophy, organomegaly
Denys-Drash syndrome	Nephropathy, pseudohermaphroditism
Perlman syndrome	Fetal overgrowth, high neonatal mortality

Children with these syndromes require regular surveillance due to increased tumor risk.

~Histopathology

Wilms’ tumor is classically triphasic, consisting of:

1. Blastemal component – primitive undifferentiated cells

2. Epithelial component – tubules and glomeruloid structures

3. Stromal component – fibrous, myxoid, or muscle tissue

Histologic Classification

• Favorable histology (FH) – ~90% of cases

• Unfavorable histology (UH) – characterized by anaplasia, associated with poorer outcomes

Anaplasia is defined by:

• Enlarged hyperchromatic nuclei

• Abnormal mitotic figures

• Resistance to chemotherapy

~Clinical Presentation

Wilms’ tumor often presents as a painless abdominal mass, typically discovered incidentally by parents or caregivers.

Common Symptoms

• Abdominal distension or mass

• Abdominal pain

• Hematuria

• Fever

• Hypertension (due to renin secretion)

• Anemia

Less Common Features

• Weight loss

• Vomiting

• Constipation

• Respiratory symptoms (due to lung metastases)

Importantly, abdominal palpation should be performed gently, as rough handling may risk tumor rupture.

~Diagnostic Evaluation

Imaging Studies

Ultrasound

• First-line diagnostic tool

• Differentiates solid from cystic masses

• Assesses contralateral kidney

Computed Tomography (CT) Scan

• Gold standard for evaluation

• Determines tumor size, extension, and vascular involvement

• Detects metastases

Magnetic Resonance Imaging (MRI)

• Useful for assessing inferior vena cava involvement

• Preferred in cases requiring reduced radiation exposure

Laboratory Tests

• Complete blood count (CBC)

• Renal function tests

• Urinalysis

• Liver function tests (if metastasis suspected)

Biopsy

• Generally avoided prior to surgery in North American protocols

• More commonly used in European protocols when preoperative chemotherapy is planned

~Staging

Wilms’ tumor is staged surgically according to the National Wilms Tumor Study Group (NWTSG) system:

Stage	Description
Stage I	Tumor limited to kidney, completely resected
Stage II	Extension beyond kidney, completely resected
Stage III	Residual tumor confined to abdomen
Stage IV	Distant metastases (lungs, liver, bone, brain)
Stage V	Bilateral renal involvement

Accurate staging is critical in determining therapy intensity.

~Treatment Approaches

Management of Wilms’ tumor involves a multidisciplinary approach, combining surgery, chemotherapy, and sometimes radiotherapy.

Surgical Treatment

• Radical nephrectomy with lymph node sampling is standard for unilateral tumors

• Nephron-sparing surgery considered in bilateral disease or solitary kidney

• Complete resection is the goal whenever feasible

Chemotherapy

Chemotherapy regimens depend on stage and histology.

Common Agents

• Vincristine

• Dactinomycin (Actinomycin D)

• Doxorubicin

• Cyclophosphamide

• Etoposide

Treatment duration ranges from 18 weeks to over 6 months, depending on risk stratification.

Radiotherapy

Indications include:

• Stage III disease

• Unfavorable histology

• Metastatic disease

Radiation doses are carefully calibrated to minimize long-term toxicity.

~Treatment Protocols: International Differences

COG (Children’s Oncology Group – North America)

• Primary surgery followed by adjuvant therapy

• Avoids preoperative chemotherapy

SIOP (International Society of Paediatric Oncology – Europe)

• Preoperative chemotherapy

• Reduces tumor size and rupture risk

Both strategies achieve comparable survival outcomes.

~Prognosis

Wilms’ tumor is among the most curable childhood cancers.

Survival Rates

• Overall 5-year survival: >90%

• Stage I–II (favorable histology): 95–98%

• Stage III–IV: 80–90%

• Anaplastic tumors: significantly lower survival

Prognostic Factors

• Tumor stage

• Histology

• Genetic markers (LOH at 1p/16q)

• Response to chemotherapy

• Age at diagnosis

~Complications and Long-Term Effects

With improved survival, long-term follow-up has become increasingly important.

Potential Late Effects

• Chronic kidney disease

• Hypertension

• Cardiotoxicity (from doxorubicin)

• Secondary malignancies

• Growth and developmental issues

• Fertility concerns

Survivorship programs play a crucial role in monitoring and managing these effects.

~Follow-Up and Surveillance

Post-treatment monitoring includes:

• Regular imaging (ultrasound or CT)

• Blood pressure monitoring

• Renal function assessment

• Screening for late complications

Follow-up is typically continued for at least 5–10 years after treatment completion.

~Current Research and Future Directions

Ongoing research aims to:

• Reduce treatment toxicity

• Improve outcomes in high-risk and relapsed cases

• Identify molecular targets for personalized therapy

• Enhance early detection in high-risk populations

Advances in genomics and precision medicine hold promise for further improving survival while minimizing long-term harm.

~Conclusion

Wilms’ tumor represents a remarkable success in pediatric oncology, transforming from a once-fatal disease into one with excellent survival outcomes. Early diagnosis, accurate staging, and risk-adapted therapy are key to successful treatment. Continued research and long-term follow-up are essential to ensure not only survival but also a high quality of life for survivors.

As medical science advances, the goal remains clear: to cure every child with Wilms’ tumor while minimizing the physical and emotional burden of treatment.