Approach

The diagnostic approach includes obtaining a thorough history for key diagnostic symptoms such as a painless, unilateral upper abdominal/flank mass, congenital syndromes, and congenital urogenital anomalies.[4]

Abdominal ultrasound is the initial test of choice to establish the diagnosis of a renal tumour, and computed tomography (CT) or magnetic resonance imaging (MRI) of abdomen and pelvis are used to stage the tumour and plan further therapy.

Definitive diagnosis of suspected Wilms' tumour is based on histology of tumour following surgical resection (nephrectomy) or biopsy (if tumour is unresectable). Metastatic disease should be ruled out on CT chest (or chest x-ray in resource-limited areas) and abdominal/pelvis CT or MRI.

History

Family history of Wilms' tumour and presence of any congenital urogenital anomalies or a known predisposition syndrome should be documented.[4] Any specific phenotypic anomalies that are associated with overgrowth or other genetic predisposition syndromes should be identified. For example, hyperinsulinaemic hypoglycaemia, which may be transient or persistent, occurs in 50% of children with Beckwith-Wiedemann syndrome during the neonatal period and infancy; therefore, if this syndrome is suspected, birth history for hypoglycaemia should be noted.[45]

Epidemiological features may help; Wilms' tumour is more common in black and white children compared with Asian children, and most commonly occurs in the first 5 years of life.[1][16]​​​​​

Children usually present with a painless, unilateral upper abdominal/flank mass.[4] Additional clinical features may include pallor, abdominal pain, fever, haematuria (visible or non-visible), poor appetite, and weight loss.​[4]​​​​​​​ Shortness of breath may be associated with anaemia, lung metastasis, or abdominal compression on the diaphragm.[4]

Physical examination

The location and extent of the abdominal mass should be documented, if possible. The mass is usually retroperitoneal ('ballotable'), and does not move with respirations.[4] It is smooth, firm to touch, and non-tender. The child may have abdominal distention. Genitalia should be examined for any congenital urogenital anomalies (i.e., hypospadias, atypical genitalia, or cryptorchidism).[20][21]​ Presence of a varicocele in supine position may be associated with tumour extension into the inferior vena cava or the renal vein.[46] Hypertension is present in approximately 25% of patients, and is secondary to compression of renal vasculature, or due to renin hypersecretion.[5][47]​​​

Hepatomegaly may indicate metastatic disease.[4] Intracardiac extension of Wilms' tumour is less common.[11] Phenotypic abnormalities that may be characteristic of Wilms' tumour-predisposition syndromes should be documented.[4]

Very rarely, children may present with a paraneoplastic syndrome that affects the central and peripheral nervous system (e.g., generalised weakness, fatigue, ptosis, hypokinesis, dysarthria, urinary retention, facial diplegia, ophthalmoplegia, and autonomic dysfunction).[10]

Laboratory investigations

Full blood count, renal and hepatic function, urinalysis, and coagulation studies are typically ordered, although they are not required for diagnosis.​[48]

Imaging

Initial studies are aimed at establishing renal origin and extent of the mass. Abdominal ultrasonography is the recommended first-line test for establishing presumptive diagnosis of a renal tumour.[4][49]​ Relatively easy to perform without sedation in young children, abdominal ultrasound establishes the renal origin, and the number and location of renal masses.[49] Typical findings are a large echogenic, heterogenous, unilateral, mainly solid (although small areas of cystic changes may be seen) intrarenal mass.

If Wilms' tumour is suspected on ultrasound, the patient should be promptly referred to a paediatric cancer centre for further evaluation and management.

Tumour staging

Either CT or MRI of the abdomen and pelvis should be obtained for locoregional staging by evaluating the contralateral kidney for synchronous disease and determining the size and number of ipsilateral masses, presence of lymphadenopathy, presence and extent of tumour thrombus, and presence of metastatic disease to organs such as the liver.[49][Figure caption and citation for the preceding image starts]: Wilms' tumour: MRI findingsUHRAD.com; used with permission [Citation ends].com.bmj.content.model.Caption@3a78268e

Signs of possible rupture and infiltration into adjacent organs may be observed; however, imaging has a poor predictive value for preoperative rupture.[50]​ 

The International Society of Paediatric Oncology (SIOP) protocol, and the Children's Oncology Group (COG) protocol, advocate chest CT for detection of lung lesions at diagnosis.[49] In resource-limited regions, chest x-ray can be used to identify lung metastasis; however, plain radiography may miss smaller pulmonary lesions (typically <1 cm).[4]

Ultrasound to assess venous involvement and additional urogenital tract imaging to assess for ureteric involvement is controversial and not routinely needed. The role of positron emission tomography scan in the staging and assessment of response is not established.[51][Figure caption and citation for the preceding image starts]: Wilms' tumour: MRI findingsUHRAD.com; used with permission [Citation ends].com.bmj.content.model.Caption@2f258a5f

Tumour histology

Definitive diagnosis is based on histology of tumour following surgical resection (nephrectomy).[4][48]​​

If the tumour is unresectable, the COG protocol recommends an open biopsy or core needle biopsy with a minimum of 10-12 non-necrotic cores to ensure sufficient tissue for molecular testing.[4][52]​​ The SIOP protocol does not routinely recommend pretreatment biopsy.[53]

Percutaneous cutting needle biopsy (tru-cut biopsy) can potentially be considered in patients whose tumours are suspected not to be Wilms' tumour, such as young children with stage IV disease and in children >10 years of age (as the frequency of non-Wilms renal tumours is increased in these patient populations).[53][54]

Genetic and molecular biomarker testing

Molecular genetic testing is a useful diagnostic tool for the identification of phenotypic syndromes that may be associated with Wilms' tumour.

Genetic testing for changes in WT1 and other genes associated with Wilms' tumour may be considered for all children with Wilms' tumour. In particular, genetic testing is recommended for patients at high risk for an underlying​predisposition syndrome. Features suggestive of a predisposition syndrome include bilateral or multifocal disease, early onset (aged <2 years), family history of Wilms' tumour, multiple nephrogenic rests, unexplained proteinuria or renal failure, or urogenital or other phenotypic anomalies associated with predisposing syndromes.[48][55]​​​ 

Gene panels are available for Wilms' tumour predisposition that include WT1, REST, TRIM28, and other relevant genes.[38][48][56][57]​​​​​

Patients with clinical features suggestive of Beckwith-Wiedemann syndrome may be tested for genetic and/or epigenetic changes at the 11p15.5 imprinted region, which may also be mosaic.[37][38]​​[57]

Testing strategies may combine a Wilms' tumour gene panel with testing for Beckwith-Wiedemann syndrome, or may be targeted for patients with clinical features suggestive of a specific syndrome.[57]

Tumour molecular markers

Evaluated to help guide risk assessment and treatment for favourable risk Wilms' tumours.[48]

Assays for biomarkers associated with unfavourable outcomes, such as loss of heterozygosity (LOH) in 16q, 11p, and 1p, and gain of chromosome 1q, are performed on tumour tissue.[33][48][58]​​[59]

Tumour biobanking

In every child with Wilms' tumour, biobanking of tumour material (fresh frozen tumour tissue) and healthy kidney tissue should be offered to facilitate research studies to define new risk factors and treatment targets.

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