Wilms' Tumour

Synonym: Nephroblastoma

This is the commonest intra-abdominal tumour of childhood (20% of all childhood malignancies). It is an undifferentiated mesodermal tumour of the intermediate cell mass (primitive renal tubules and mesenchymal cells). It may be sporadic, or familial.

Wilms' tumor usually develops in otherwise healthy children, but approximately 10% occur in children with recognised malformations; either:

• 'Overgrowth syndromes' (excessive prenatal and postnatal somatic growth resulting in macroglossia, nephromegaly, and hemihypertrophy) - most commonly Beckwith-Wiedemann syndrome or isolated hemihypertrophy. Others include Perlman syndrome, Sotos syndrome, and Simpson-Golabi-Behemel syndrome.
• No 'overgrowth' - associated with with trisomy 18, Bloom syndrome, Denys-Drash syndrome; or Wilms' with Aniridia, Gonadoblastoma (GU malformations), and Retardation ('WAGR'*).

Hereditary Wilms' tumour (either bilateral tumours or a family history of the neoplasm) is uncommon. Several different families with Wilms' tumours have been identified. All are transmitted in an autosomal dominant manner, caused by mutations in one of at least 3 genes:

• One related to the WT1 gene on chromosome 11 (11p13) - (includes those patients with WAGR) encodes a protein which is a transcriptional repressor downregulating IGF-II, an insulin-like growth factor.³
• Other families (including those with Beckwith-Wiedemann syndrome) have a different mutation - of the WT2 gene on chromosome 11 (11p15.5)
• Other gene mutations, thought to be on chromosome 16 (WT3 - 16q) and/or chromosome 1p can also cause the tumour.⁴

The median age is 3 years.⁵ 95% are unilateral. Only 1-2% have a positive family history.⁶

Clinical features⁷

Fever, flank pain, abdominal mass. Haematuria is not common.

• Useful laboratory tests include full blood count, urea and electrolytes and urinalysis.
• Genetic studies may reveal the chromosome abnormalities consistent with the condition.
• Ultrasound and/or IVP may show renal pelvis distortion; hydronephrosis. Dynamic imaging of the renal vein and inferior vena cava may be contributory.
• Renal angiography may help to show a more detailed view of the blood vessels.
• Abdominal scanning may help to determine the nature of the tumour and may also reveal the degree of involvement of the lymph nodes, whether the other kidney is involved, and invasion into blood vessels or the liver.

• Renal biopsy should be avoided as this seems to make the condition worse.⁷
• For most patients, nephrectomy followed by chemotherapy with vincristine and doxorubicin can be curative. Radiotherapy to the flank is beneficial in patients with a stage 3 tumour.
• Patients with massive, nonresectable unilateral tumors, bilateral tumors, or venacaval tumor thrombus above the hepatic veins should be considered for preoperative chemotherapy because of the risk of initial surgical resection.

With current treatment 80-90% of patients are still alive 4 years after diagnosis. The prime factor governing prognosis is favourable histology. The prognosis after recurrence is poor, only 30-40% surviving after retrieval therapy.

Children with a predisposition to develop Wilms' tumor (e.g., Beckwith-Wiedemann, hemihypertrophy) should be screened with ultrasound. The exact frequency of screening, the age at which screening should cease and the cost-effectiveness of this approach requires further study.⁹

* The WAGR syndrome is one of the best-studied 'contiguous gene syndromes' - children with WAGR invariably have a constitutional chromosomal deletion at 11p13, the location of the WT1 gene. Those with Denys-Drash syndrome (DDS) usually have a germline point mutation, which is predicted to result in an amino acid substitution (i.e., missense mutation), in the eighth or ninth exon of the Wilms tumor gene.²