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.[3] Abdominal ultrasound is the initial test of choice to establish the diagnosis, 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 should be documented.[3] Specific phenotypic anomalies that are associated with overgrowth or nonovergrowth syndromes should be excluded.[17] 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.[35] 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][2]​​

The tumor most commonly presents as a painless, unilateral upper abdominal/flank mass.[2] Bilateral tumors are uncommon and occur in around 10% of patients; they may present simultaneously in both kidneys (synchronous) or may involve one kidney followed by the other (metachronous).[3][5]​​ Other clinical features, such as pallor, abdominal pain, fever, hematuria (visible or nonvisible), poor appetite, and weight loss may be present.[2][3][17]​​​​​ Shortness of breath may be associated with anemia or lung metastasis.

Very rarely, Wilms tumor occurs in extrarenal locations.[6] The presentation (rapidly growing painless mass) is usually similar to the classic Wilms tumor, but signs and symptoms are unique to the location of the tumor.

Physical exam

The location and extent of the abdominal mass should be documented. The mass is usually retroperitoneal ("ballotable"), and does not move with respirations.[3] It is smooth, firm to touch, and nontender. The patient may have abdominal distention. Genitalia should be examined for any congenital urogenital anomalies (i.e., hypospadias, atypical genitalia, or cryptorchidism).[16][29] Presence of a varicocele in supine position may be associated with tumor extension into the inferior vena cava or the renal vein.[36] Hypertension is present in approximately 25% of patients, and is secondary to compression of renal vasculature, or due to renin hypersecretion.[4][37]​​

Hepatomegaly may indicate metastatic disease.[3] Intracardiac extension of Wilms tumor is rare.[10] Phenotypic abnormalities that may be characteristic of Wilms tumor-associated syndromes should be documented.[3]

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).[9]

Laboratory investigations

Renal and hepatic function, complete blood count, urinalysis, serum protein/albumin, and coagulation studies should be ordered, although they are not required for diagnosis.

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 and is usually adequate for this purpose.[3][38] Typical finding is 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 major pediatric cancer center where further imaging will be planned.

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, signs of possible rupture, infiltration into adjacent organs, presence and extent of tumor thrombus, and presence of metastatic disease to organs such as the liver.[38] The International Society of Paediatric Oncology (SIOP) protocol as well as the Children's Oncology Group (COG) protocol use chest CT for detection of lung lesions at diagnosis.[38] In resource-limited regions, chest x-ray can be used to identify lung metastasis; however, plain radiography may miss smaller pulmonary lesions (typically <1cm).[3]

The role of positron emission tomography scan in the staging and assessment of response is not established.[39][Figure caption and citation for the preceding image starts]: Wilms tumor: MRI findingsUHRAD.com; used with permission [Citation ends].com.bmj.content.model.Caption@7819cc28

Tumor histology

Definitive diagnosis is based on histology of tumor following surgical resection (nephrectomy) or biopsy (if tumor is unresectable).[3]

An open biopsy with a minimum of 10-12 cores is required in the COG protocol if a tumor is unresectable.[3][40]​ In the SIOP UMBRELLA protocol, pretreatment biopsy is not routinely recommended.[41] Percutaneous cutting needle biopsy (tru-cut biopsy) can 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 age groups.[41][42]

Genetic testing

Molecular genetic testing is a useful diagnostic tool for the identification of phenotypic syndromes that may be associated with Wilms tumor. Specifically, patients with isolated Wilms tumor, or those with Wilms tumor and associated anomalies, may be tested for deletions of WT1 and other contiguous genes such as PAX6 by fluorescent in situ hybridization (FISH). Patients with clinical features suggestive of Beckwith-Wiedemann syndrome may be tested for a duplication of 11p15.5 by high-resolution chromosomal analysis and FISH.[43]

Loss of heterozygosity (LOH) studies for 16q and 1p are performed on freshly frozen tumor tissue.[44]  

In every child with Wilms tumor, biobanking of tumor material (fresh frozen tumor tissue) and healthy kidney tissue should be done to perform research studies helping to define new risk factors and targets for better treatment options.

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