Wilms' tumour: Assessing and managing nephroblastoma
Wilms' tumour (WT) accounts for 5.9 per cent of all childhood malignancies.1 In 5-10 per cent of patients, it may be bilateral, either synchronously or metachronously. Survival rates have improved to 80-90 per cent from approximately 30 per cent in the 1930s.2
WT arises from pluripotent embryonic renal precursors.3 The most common genetic abnormalities in WT are WT1 and WT2 gene deletions.1 A WT1 suppressor gene at chromosomal band 11p13 of WT1 was identified by studying children with WAGR syndrome (WT, aniridia, genitourinary anomalies, and mental retardation).
Characterisation of the WT1 gene has revealed that it is the target of mutations and deletions in those with sporadic nephroblastoma, as well as those with Denys-Drash syndrome (male pseudohermaphroditism and glomerulonephritis).
A further predisposing gene, WT2 at 11p15, has been identified. This predisposition was found because of a link between WT and Beckwith-Wiedemann syndrome (a congenital overgrowth syndrome). Other chromosomal abnormalities, such as loss of heterozygosity of 16q, 1p, and 7p, have been identified.1 Familial WT occurs in 1-2 per cent of all cases.4
Clinical features and diagnosis
WT is usually diagnosed between the ages of one and five years, with a generally asymptomatic palpable abdominal mass. The peak age is three years. Other features may include abdominal pain, haematuria (30 per cent) and hypertension (25 per cent), the latter due to compression of the juxtaglomerular apparatus.
Malaise, fever, weight loss, and a varicocele may be present. If the disease has metastasised to the lungs, respiratory symptoms may be present.4 WAGR and Beckwith-Wiedemann syndromes should be considered in a child with an asymptomatic palpable abdominal mass. WT may be associated with congenital anomalies, such as cryptorchidism, horseshoe kidney, and hypospadias.1
When the diagnosis is suspected, baseline blood tests and urinalysis should be performed. Hormones such as erythropoietin and adrenocorticotrophic hormone may be secreted in WT and there is often a reduction in von Willebrand factor.1
Imaging may include renal ultrasound and CT. Typically, there is calyceal distortion with renal displacement caused by the tumour. WT can arise within the renal medulla or cortex and can protrude into the calyces and ureter. In 6 per cent of patients, WT may extend into the renal vein or inferior vena cava.3 Imaging is used to determine the origin of the mass and whether there is bilateral kidney or liver involvement, as well as lymphovascular spread. Doppler ultrasonography may demonstrate vena cava invasion.1
If lung nodules are seen on CT scanning, they may be amenable to biopsy. In some patients, echocardiography may help to identify atrial tumour extension. The most common site of metastasis is the lung, followed by lymph nodes and liver.4
In classical WT, histology usually reveals epithelial, blastermal and stromal elements.1 Anaplastic WT, with multipolar mitotic figures and hyperchromasia with enlarged cells, has a poorer outcome. Anaplastic WT comprises 4-8 per cent of all cases.1 Nephrogenic rests and dysplastic lesions of metanephric origin are precursor lesions for WT. The diagnosis of WT may be confirmed by cytogenetic studies to look for genetic mutations or deletions.
Management and follow-up
Management involves a multidisciplinary team approach linking oncology and surgical specialties. Treatment is dependent on histology and staging. The European-based International Society of Paediatric Oncology (SIOP) advocates preoperative chemotherapy and staging after preoperative treatment and subsequent surgery. This is in contrast to the advice from the US-based National Wilms' Tumor Study Group (NWTSG), which prefers treating patients with surgery, then staging.5 A staging system is shown in Box 1.
For surgery, a transabdominal, transperitoneal incision is recommended. Risk factors for surgical complications include intravascular extension into the inferior vena cava and/or the atrium, a flank or paramedian surgical approach, and a tumour diameter >10cm.6
In the US, patients with suspected unilateral WT undergo nephrectomy, then the contralateral kidney is explored to assess spread. Lymph node biopsies are taken for staging.7 The SIOP approach is to reduce the risks of immediate nephrectomy by shrinking the tumour with chemotherapy, so reducing the risk of tumour rupture and intra-abdominal spread.4 The SIOP protocol downstages WT, so the overall burden of treatment is less. In the SIOP studies, if a tumour has the typical imaging and clinical features of WT, chemotherapy is commenced without histological diagnosis. This results in about 1 per cent of children with a non-malignant renal lesion receiving chemotherapy.4 Percutaneous needle biopsy is controversial because there has been concern about the risk of recurrence and the possibility of seeding in the needle tract. Survival rates are similar for both.2
Partial nephrectomy or nephron-sparing surgery should only be performed in selected patients, for example, those with bilateral tumours and tumours within a solitary kidney.3