Wilms' Tumour

Wilms' tumour, also known as nephroblastoma, is a rare kidney cancer primarily affecting children, typically presenting between the ages of 3 and 4. Named after Max Wilms, the German surgeon who first described it, this malignancy is highly responsive to treatment, with approximately 90% of children being cured.

Signs and Symptoms

Typical signs and symptoms include a painless, palpable abdominal mass, loss of appetite, abdominal pain, fever, nausea, vomiting, and hematuria (present in about 20% of cases). Hypertension may occur, especially if both kidneys are involved. Rarely, varicocele can be a symptom.

Pathogenesis

Wilms' tumour can be syndromic or non-syndromic. Syndromic cases arise from genetic mutations such as those in the Wilms Tumour 1 (WT1) or Wilms Tumour 2 (WT2) genes and present with various other symptoms. Non-syndromic cases occur without additional symptoms. Often, the tumour originates from nephrogenic rests—abnormal tissues in or around the kidney that become cancerous postnatally.

Pathologically, a triphasic nephroblastoma consists of blastema, mesenchyme (stroma), and epithelium. The tumour includes metanephric blastema and its derivatives—abortive tubules and glomeruli surrounded by a spindled cell stroma, which may contain various tissues like muscle, cartilage, and bone. Tumours are classified into favourable and anaplastic groups based on their cell development.

Molecular Biology and Related Conditions

Mutations in the WT1 gene (chromosome 11p13) are found in about 20% of Wilms' tumours, often inherited from the germline. Additionally, mutations in CTNNB1, the gene for beta-catenin (chromosome 3p22.1), are frequently observed.

Several genetic syndromes are associated with increased Wilms' tumour risk:

• WAGR syndrome (Wilms tumour, aniridia, genital anomalies, retardation): 45-60% risk.
• Denys-Drash syndrome: 74% risk.
• Beckwith-Wiedemann Syndrome: 7% risk.

Diagnosis

Diagnosis typically starts with identifying an asymptomatic abdominal mass. For children with predisposing syndromes, routine screening may reveal renal tumours. Initial diagnostic steps include medical history, physical exam, and tests like blood and urine analysis, followed by imaging tests like ultrasound, CT, or MRI. A definitive diagnosis is made via pathological examination of the nephrectomy specimen.

Staging

Staging helps determine the extent of the tumour spread and guides treatment:

• Stage I: Tumour confined to the kidney, completely excised.
• Stage II: Tumour extends beyond the kidney but is completely excised.
• Stage III: Residual tumour present post-surgery, lymph node metastasis, or tumour spillage.
• Stage IV: Haematogenous metastases (lung, liver, bone, brain) or lymph node metastases outside the abdominopelvic region.
• Stage V: Bilateral kidney involvement.

Treatment and Prognosis

Treatment often involves nephrectomy, sometimes preceded by chemotherapy (especially in Europe). Radiotherapy may follow. The overall 5-year survival rate is around 90%, though it varies based on stage and specific tumour characteristics. Tumour-specific loss-of-heterozygosity (LOH) for chromosomes 1p and 16q can indicate a higher relapse risk.

Epidemiology

Wilms' tumour is the most common malignant renal tumour in children, affecting about one in 10,000 before age 15. It is slightly more prevalent in individuals of African descent and peaks between ages 3 and 4. Genetic predispositions, such as deletions on chromosome 11p13, are well-documented.

History

Significant advancements in Wilms' tumour treatment began in the 1950s with Sidney Farber's use of actinomycin D alongside surgery and radiotherapy, increasing cure rates significantly. The introduction of CT scans in the 1970s further revolutionised diagnosis and treatment.

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Self-assessment MCQs (single best answer)

What is another name for Wilms' tumour?

At what age does Wilms' tumour most commonly present in children?

Which of the following is NOT a common symptom of Wilms' tumour?

What genetic mutation is found in approximately 20% of Wilms' tumours?

Which syndrome is associated with the highest risk of developing Wilms' tumour?

What is the typical initial diagnostic step for Wilms' tumour?

What characterises a triphasic nephroblastoma?

Which stage of Wilms' tumour involves haematogenous metastases?

What is the overall 5-year survival rate for children with Wilms' tumour?

What is an indicator of higher relapse risk in Wilms' tumour based on tumour-specific genetic features?