Wilms Tumor: Symptoms, Types, Causes and Treatment

Wilms tumor—also known as nephroblastoma—is the most common kidney cancer in children, primarily affecting those between 2 and 5 years old. Despite its rarity in adults, Wilms tumor is a critical pediatric health concern due to its potential for rapid progression. Thanks to remarkable advances in diagnosis and therapy, most children diagnosed today experience excellent outcomes. But recognizing symptoms early, understanding the different types, knowing what causes Wilms tumor, and being aware of current treatment approaches are all essential for patients, families, and healthcare providers. This article offers a comprehensive exploration of Wilms tumor, following the latest research and clinical consensus.

Symptoms of Wilms Tumor

Early detection of Wilms tumor can dramatically improve outcomes. However, the disease often presents with subtle signs that may be mistaken for more common childhood illnesses.

Symptom	Description	Frequency/Significance	Source(s)
Abdominal Mass	Swelling or palpable lump in abdomen	Most common presentation	1 2 3 4
Abdominal Pain	Discomfort or pain in belly	Often present	1 4
Hematuria	Blood in urine	Occasional, notable sign	1 2 4
Hypertension	High blood pressure	Not uncommon	1 2
Anemia	Low red blood cells	May cause pallor/fatigue	1 4
Fever	Elevated body temperature	Sometimes present	1 4
Weight Loss	Unintentional loss of weight	Less common, late symptom	1 4
Nausea/Vomiting	Stomach upset/vomiting	Possible, non-specific	1 4
Lethargy	Unusual tiredness	May occur	1 4
Poor Appetite	Reduced interest in eating	May accompany other signs	2 4
Dyspnea	Breathing difficulty (rare)	In cases with metastasis	2

Table 1: Key Symptoms

The Classic Presentation

The hallmark symptom of Wilms tumor is a painless swelling or mass in the abdomen, often discovered accidentally by a parent during bathing or dressing. Unlike many childhood illnesses, this mass is usually not tender and can grow quite large before causing discomfort.

Other Common and Rare Symptoms

• Abdominal pain is reported in a significant number of cases, sometimes with fever.
• Hematuria, or blood in the urine, is a red flag but not always present.
• Hypertension can develop due to hormone production by the tumor or kidney compression.
• Non-specific symptoms such as loss of appetite, weight loss, nausea, vomiting, and lethargy may occur, especially as the disease advances.
• In rare cases, Wilms tumor can present with unusual symptoms like dyspnea (shortness of breath), especially if it has metastasized to the lungs or, as reported in rare cases, causes secondary effects like dilated cardiomyopathy 2.

How Symptoms Guide Diagnosis

A combination of these symptoms—particularly a palpable abdominal mass with or without hematuria and hypertension—should prompt urgent evaluation for Wilms tumor. However, these signs are not exclusive, and misdiagnosis can occur, especially as some other pediatric cancers may present similarly 3. Diagnostic imaging (such as ultrasound or CT scan) and laboratory tests help confirm the diagnosis and assess the extent of disease.

Types of Wilms Tumor

Wilms tumor is not a singular disease; it shows considerable variation in its biological and clinical features. Understanding the types helps determine prognosis and guide treatment decisions.

Type	Characteristics	Clinical Importance	Source(s)
Unilateral	Affects one kidney	Most common (~95%)	9 12
Bilateral	Involves both kidneys	~5% of cases; more in syndromic	5 9 12
Favorable Histology	Typical cell appearance	Best prognosis	15 16 18
Unfavorable Histology (Anaplastic)	Abnormal cells	Poorer prognosis	15 16 18
Syndromic	Occurs with genetic syndromes	Higher risk of bilateral/multiple tumors	5 9
Extra-renal	Occurs outside the kidney	Very rare	7 8

Table 2: Wilms Tumor Types

Unilateral vs. Bilateral Wilms Tumor

• Unilateral tumors (one kidney) account for the vast majority of cases.
• Bilateral tumors (both kidneys) are rare, seen in about 5% of cases, and are more likely in children with certain genetic syndromes. Bilateral cases are often diagnosed at a younger age and require specialized treatment to preserve as much kidney function as possible 5 9 12.

Histological Subtypes

Wilms tumor is classified based on its microscopic appearance:

• Favorable histology: The majority of Wilms tumors fall into this category, characterized by the absence of anaplasia (abnormal cell changes). These tumors respond well to standard therapy and have excellent survival rates 15 16 18.
• Unfavorable histology (anaplastic Wilms tumor): Displays marked cellular atypia and resistance to therapy. This subtype is associated with a poorer prognosis and often requires more aggressive treatment 15 18.

Syndromic and Extra-Renal Variants

• Syndromic Wilms tumor: Occurs in association with inherited syndromes such as WAGR, Beckwith-Wiedemann, or Denys-Drash, often due to underlying genetic mutations. These cases are more likely to be bilateral or multifocal and require lifelong surveillance 5 9.
• Extra-renal Wilms tumor: Exceptionally rare, these tumors arise outside the kidneys, including the ovaries, retroperitoneum, or even spinal cord. Diagnosis is challenging, and optimal treatment protocols are not yet standardized 7 8.

Causes of Wilms Tumor

The causes of Wilms tumor are complex, involving genetic, developmental, and sometimes environmental factors. While most cases are sporadic, a significant subset is associated with identifiable genetic changes or inherited syndromes.

Cause Type	Key Features	Proportion/Impact	Source(s)
Genetic Mutations	WT1, WT2, CTNNB1, others	Major role in syndromic and some sporadic cases	6 11 12 13
Syndromic	WAGR, Denys-Drash, BWS, others	9-17% of cases	5 9 12
Embryonal Clones	Abnormal kidney cell precursors	Observed in many cases	10
Familial Patterns	Autosomal dominant inheritance (rare)	<1% of cases	12
Somatic Mutations	Acquired in kidney cells	Most sporadic cases	11 13

Table 3: Causes and Risk Factors

Genetic and Molecular Factors

• WT1 and WT2 genes: Mutations or deletions in these genes on chromosome 11 are central to Wilms tumor development. WT1 mutations disrupt kidney cell differentiation, leading to tumor formation 6 11 12 13.
• Other genes: CTNNB1, TP53, and genes involved in microRNA processing (e.g., DROSHA, DGCR8) are also implicated, though less commonly 13.
• Loss of heterozygosity at specific chromosomal regions (1p, 11p, 16q) is associated with higher risk and poorer outcomes 13.

Syndromic Associations

Children with certain syndromes are at much higher risk:

• WAGR syndrome (Wilms tumor, Aniridia, Genitourinary anomalies, mental Retardation)
• Denys-Drash syndrome
• Beckwith-Wiedemann syndrome These children are prone to early, bilateral, or multifocal tumors and may also be at risk for other malignancies 5 9 12.

Embryonal Origins

Recent research shows that Wilms tumor can originate from clonal expansions of mutant cells in the developing kidney—essentially, a "pre-cancerous" field forms in utero, from which the tumor eventually arises 10. This model helps explain why most Wilms tumors occur in young children and why some cases are bilateral.

Familial and Sporadic Cases

• Familial Wilms tumor is rare (<1%) and follows an autosomal dominant inheritance with variable penetrance. These families have a higher risk of bilateral disease and earlier onset 12.
• Sporadic Wilms tumor comprises the majority of cases and is thought to result from new (de novo) somatic mutations during kidney development 11 12.

Treatment of Wilms Tumor

Treatment for Wilms tumor is considered a major success in pediatric oncology, with survival rates now exceeding 90% for most children. Success relies on a multimodal approach, tailored to the tumor's type, stage, and biology.

Treatment	Main Components	Indications/Goals	Source(s)
Surgery	Nephrectomy (removal of tumor/kidney)	First-line for most cases	15 16 17 18
Chemotherapy	Vincristine, actinomycin D, adriamycin	All but very low-risk cases	15 16 18 19
Radiotherapy	Targeted radiation	High-risk, advanced, or residual disease	15 16 17 18
Nephron-sparing	Partial kidney removal	Bilateral/syndromic cases	5 18
Surveillance	Regular imaging	High-risk syndromic cases	5
Precision Medicine	Targeted therapies (in trials)	Relapsed/refractory disease	11 18

Table 4: Wilms Tumor Treatment Approaches

Surgery

• Nephrectomy (removal of the affected kidney and tumor) is the cornerstone of Wilms tumor treatment.
• In bilateral or syndromic cases, nephron-sparing surgery is preferred to preserve kidney function, especially in children at risk for subsequent tumors or chronic kidney disease 5 18.
• Surgical expertise is vital, particularly when the tumor is fragile or at risk of rupture, which can lead to tumor spread within the abdomen 9.

Chemotherapy

• Chemotherapy is used in nearly all cases, either before surgery (neoadjuvant) to shrink the tumor or after surgery (adjuvant) to eliminate microscopic disease.
• Standard drugs include vincristine, actinomycin D, and adriamycin (doxorubicin), sometimes with cyclophosphamide for high-risk cases 15 16 18 19.
• The intensity and duration of chemotherapy are tailored according to tumor stage, histology, and genetic risk markers 18 19.

Radiotherapy

• Radiation therapy is reserved for children with advanced-stage, unfavorable histology, or residual tumor after surgery.
• Modern protocols have reduced radiation doses to minimize long-term side effects, especially in young children 15 16 18.

Risk-Adapted and Precision Approaches

• International protocols (such as those by the Children’s Oncology Group and SIOP) now use risk stratification based on stage, histology, and molecular features (e.g., loss of heterozygosity at specific chromosomes) to individualize therapy and reduce toxicity 18 19.
• Precision medicine approaches, including targeted therapies, are under active investigation for relapsed or refractory Wilms tumor 11.

Surveillance and Special Considerations

• Children with syndromic predispositions require regular ultrasound screening to detect new tumors early 5.
• For rare extra-renal Wilms tumors, treatment is extrapolated from standard protocols, but optimal management is still evolving 8.

Outcomes and Future Directions

• Overall survival now exceeds 90% for most children with Wilms tumor 15 18.
• Challenges remain for children with bilateral disease, unfavorable histology, or relapse—groups where new treatments and international collaboration are most urgently needed 18 19.

Conclusion

Wilms tumor is a highly treatable childhood cancer, but early recognition and specialized care are essential. Here’s what we’ve covered:

• Symptoms: Painless abdominal mass is most common, but other signs include hematuria, hypertension, and systemic symptoms. Early detection is crucial 1 2 4.
• Types: Most are unilateral with favorable histology, but bilateral, syndromic, and extra-renal types require specialized management 5 9 12.
• Causes: Primarily genetic, involving WT1/WT2 and other genes, with both sporadic and familial cases. Syndromic associations increase risk and complexity 5 11 12 13.
• Treatment: Multimodal, risk-adapted therapy including surgery, chemotherapy, and sometimes radiotherapy. Outcomes are excellent for most, but challenges remain for high-risk groups 15 16 18 19.

Key takeaways:

• Early detection and multidisciplinary management are vital.
• Genetic insights continue to improve diagnosis and therapy.
• International collaboration is driving ongoing improvements in survival and quality of life for affected children.

If you suspect Wilms tumor or need guidance, consult a pediatric oncology specialist promptly. Advances in research and treatment are offering hope for every child facing this diagnosis.