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 tumor, and computed tomography (CT) or magnetic resonance imaging (MRI) of abdomen and pelvis are used to stage the tumor and plan further therapy.

Definitive diagnosis of suspected Wilms tumor is based on histology of tumor following surgical resection (nephrectomy) or biopsy (if tumor 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 tumor 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, hyperinsulinemic hypoglycemia, 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 hypoglycemia should be noted.[45]

Epidemiologic features may help; Wilms tumor 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, hematuria (visible or nonvisible), poor appetite, and weight loss.​[4]​​​​​​​ Shortness of breath may be associated with anemia, lung metastasis, or abdominal compression on the diaphragm.[4]

Physical exam

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 nontender. 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 tumor 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 tumor is less common.[11] Phenotypic abnormalities that may be characteristic of Wilms tumor-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., generalized weakness, fatigue, ptosis, hypokinesis, dysarthria, urinary retention, facial diplegia, ophthalmoplegia, and autonomic dysfunction).[10]

Laboratory investigations

Complete 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 tumor.[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 tumor is suspected on ultrasound, the patient should be promptly referred to a pediatric cancer center for further evaluation and management.

Tumor 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 tumor thrombus, and presence of metastatic disease to organs such as the liver.[49][Figure caption and citation for the preceding image starts]: Wilms tumor: MRI findingsUHRAD.com; used with permission [Citation ends].com.bmj.content.model.Caption@575827f3

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 tumor: MRI findingsUHRAD.com; used with permission [Citation ends].com.bmj.content.model.Caption@74c14e2b

Tumor histology

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

If the tumor is unresectable, the COG protocol recommends an open biopsy or core needle biopsy with a minimum of 10-12 nonnecrotic 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 tumors are suspected not to be Wilms tumor, such as young children with stage IV disease and in children >10 years of age (as the frequency of non-Wilms renal tumors 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 tumor.

Genetic testing for changes in WT1 and other genes associated with Wilms tumor may be considered for all children with Wilms tumor. 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 (age <2 years), family history of Wilms tumor, 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 tumor 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]​​​[56]

Testing strategies may combine a Wilms tumor gene panel with testing for Beckwith-Wiedemann syndrome, or may be targeted for patients with clinical features suggestive of a specific syndrome.[56]

Tumor molecular markers

Evaluated to help guide risk assessment and treatment for favorable risk Wilms tumors.[48]

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

Tumor biobanking

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

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