Wilms tumor

Wilms tumour, also known as nephroblastoma, is a malignant paediatric renal tumour.

Epidemiology

Wilms tumours are the most common paediatric renal mass, accounting for over 85% of cases ^1,8 and account for 7% of all childhood cancers ¹². They typically occur in early childhood (1-11 years) with peak incidence between 3 and 4 years of age. Approximately 80% of these tumours are found before the age of 5 years. When part of a syndrome (see below) they occur even earlier, typically between 2 and 24 months of age ¹.

There is no recognised gender predilection, however, presentation is a little later in females ². The vast majority are unilateral with <5% occurring bilaterally.

Risk factors

• nephroblastomatosis

Associations

Although most cases are sporadic and only 2% of cases are familial, a number of associations are recognised ^1,2:

• overgrowth syndromes (WT2 gene)

  • Beckwith-Wiedemann syndrome

  • Perlman syndrome

  • Simpson-Golabi-Behmel syndrome

  • Sotos syndrome

• non-overgrowth syndromes (WT1 gene)

  • WAGR syndrome

  • Denys-Drash syndrome

  • Frasier syndrome

  • Bloom syndrome ¹³

• isolated abnormalities:

  • cryptorchidism: 3%

  • hemihypertrophy: 3%

  • hypospadias: 2%

  • sporadic aniridia

  • renal fusion

Clinical presentation

Clinical presentation is typically with a painless upper quadrant abdominal mass. Haematuria is seen in ~20% of cases ² and pain is uncommon. On examination hypertension due to excessive renin production is found in up to 25% of patients ¹ and acquired von Willebrand disease is seen in 8% ². 

Pathology

The tumour typically arises from mesodermal precursors of the renal parenchyma (metanephros). Increasingly gene loci are being implicated on chromosome 11 (WT1: 11p13 and WT2: 11p15) as well as WTX on chromosome X, β-catenin on chromosome 3 or TP53 on chromosome 17 ¹.

On gross inspection, these tumours are usually well-circumscribed or macrolobulated. Haemorrhage and central necrosis are common findings ¹⁰. 

Radiographic features

Wilms tumours are usually large heterogeneous solid masses which displace adjacent structures. Occasionally they may be mostly cystic. 

Metastases are most commonly to lung (85%), liver and local lymph nodes ¹. Similar to renal cell carcinoma, tumour thrombus into the renal vein, IVC and right atrium is also characteristic of advanced disease. See also: Wilms tumour staging.

Plain radiograph

Abdominal x-ray typically reveals a large soft tissue opacity displacing bowel. This is only relevant if found incidentally since a radiograph should never be used for the assessment of an abdominal mass. The only exception would be a resource-poor setting where an abdominal radiograph is the only imaging modality available.

Ultrasound

Ultrasound is a very useful examination and in almost every situation will be the primary investigation of choice. It is helpful to localise the mass to the kidney and also distinguish from other causes of renal masses (e.g. hydronephrosis). Although many of the features seen on CT/MRI can also be identified on US, the former are required to adequately stage the disease and is established in protocols for Wilms tumour staging in North America and Europe ⁹.

Wilms tumour appears as solid mass on ultrasound that may have vascular invasion with smooth margins. Cystic or necrotic areas may be anechoic and hypoechoic respectively while haemorrhage/fat/calcification appear as hyperechoic ¹⁴.

Doppler examination can be performed to examine the renal vein and IVC to assess for the presence of tumour thrombus.

CT

There is no value of CT multiphase abdomen and pelvis in characterising renal tumours in children. CT scan done in portal venous phase is sufficient to characterise Wilms tumour ¹².

Wilms tumours are heterogeneous soft-tissue density masses with infrequent areas of calcification (~15%) ¹⁰ and fat-density regions. Enhancement is also patchy and allows for better delineation of the relationship between the mass and kidney. 10-20% of cases have lung metastases at the time of diagnosis ¹¹.

MRI

Where MRI is available it is the investigation of choice for staging since it does not involve ionising radiation. It is also the most accurate modality in assessing for IVC involvement ¹ where protocols have been optimised. These tumours appear heterogeneous on all sequences and frequently contain blood products. 

• T1: hypointense

• T1 C+ (Gd): heterogeneous enhancement

• T2: hyperintense

Nuclear medicine

Bone scans are not routine as the tumour metastasises to bones very late. F-18 FDG PET-CT is increasingly used as a problem-solving tool and to distinguish scar tissue from residual active tumour.

Treatment and prognosis

Unilateral Wilms tumours are usually treated by a combination of nephrectomy and chemotherapy. Occasionally chemotherapy can be administered prior to surgery to downstage the tumour ¹. This is especially useful when tumours are bilateral.

Radiotherapy has a limited role, but may be employed in cases of peritoneal spread or incomplete resection ¹.

Cure is now possible in ~90% of cases. Recurrence is seen both within the tumour bed, as well as distantly within the lungs or liver ^1,2.

History and etymology

This entity was popularised by Max Wilms in 1899, although prior descriptions had been published by Osler in 1880 and Birch-Hirschfeld in 1898 ^3-5.

• Max Wilms (1867-1918), surgeon; Heidelberg, Germany ³

• Felix Victor Birch-Hirschfeld (1842-1899), physician; Leipzig, Germany ⁶

• William Osler(1849-1919), physician; Montreal, Canada ⁷

Differential diagnosis

General imaging differential considerations include:

• neuroblastoma: see neuroblastoma vs Wilms tumour

• cystic partially differentiated nephroblastoma and paediatric cystic nephroma: appear identical to very cystic Wilms tumour ¹

• clear cell sarcoma: generally indistinguishable on the bases of imaging, but may show early skeletal metastasis, a site which is unusual for Wilms tumour ¹³.

• renal rhabdoid tumour: generally, it can not be distinguished from Wilms on imaging, but the former has an established association with brain tumours, especially in the posterior fossa

• renal abscess

• angiomyolipoma

• childhood renal cell cancer: extremely rare in the paediatric population (outnumbered by Wilms tumours 30:1 ⁸); it becomes more common in the second decade of life ¹⁰

See also

• WHO classification of tumours of the kidney