Wilms tumor is among the most common abdominal malignancies of childhood and constitutes nearly 90% of all pediatric renal tumors.^1,2 Its peak incidence is at 3 to 4 years of age, and 80% of patients present before 5 years of age.^{1, 2, 3 and 4} The majority of children present with a palpable mass, abdominal distension, or pain. Wilms tumors arise from nephrogenic rests, which are foci of embryonic precursor kidney cells that persist postnatally (see next section “Nephroblastomatosis”). Postmortem studies have found nephrogenic rests in 1% of infants who died of other causes and in 30% to 40% of infants with Wilms tumors.^5,6 The vast majority of Wilms tumors arise from a single kidney; bilateral tumors are present in 4% to 13% of children.^2,3 Bilateral disease occurs almost exclusively in cases of nephroblastomatosis.

Wilms tumor has been linked to two loci on chromosome 11. WT1 gene (11p13) mutations are associated with WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) and Denys-Drash syndrome. WT2 gene (11p15) mutations are responsible for Beckwith-Wiedemann syndrome and hemihypertrophy.^1,2,5,7,8 Familial cases account for less than 5% of children with Wilms tumor. They have an earlier age of onset and increased frequency of bilateral lesions.^7,8

On US, Wilms tumors exhibit heterogeneous echogenicity and variable perfusion on color Doppler imaging (Fig. 23.1). They have a propensity for venous invasion, so evaluation for tumor thrombus within the renal vein and IVC is warranted (Fig. 23.2). Within the tumor, there may be anechoic or hypoechoic cystic necrosis, or hemorrhage. On contrastenhanced CT, Wilms tumor is typically a spherical hypodense mass that distorts the surrounding renal parenchyma and collecting system (Figs. 23.1, 23.2 and 23.3). Fat, hemorrhage, necrosis, and calcification may be identified. Wilms tumor often grows like a solid sphere or ball, displacing adjacent structures such as vessels and bowel. This propensity to displace rather than encase vessels is an important distinguishing feature of Wilms tumor, in contradistinction to neuroblastoma (refer to “Neuroblastoma” section). Dystrophic calcification is seen in about 10% of lesions—far less frequent than in neuroblastoma. The “claw sign”
with Wilms tumor refers to strips of parenchyma that extend around the mass, confirming its renal origin (Fig. 23.1B). On MR, Wilms tumors are generally T1W iso- to hypointense, T2W hyperintense, and enhance less than the adjacent renal parenchyma. Treated tumors may show hypointense T2W signal. The masses are often well defined with a pseudocapsule, but have the potential to transgress the renal capsule and directly invade the mesentery or seed the peritoneal cavity. The lungs are the most common site of metastatic disease. Ten to twenty percent of children have lung metastases at time of presentation. Additional
metastatic locations include the liver and regional lymph nodes. Skeletal metastases are atypical for Wilms tumors, and bone scans are not generally performed. The vast majority of lesions are FDG avid on PET-CT.^{1, 2 and 3,7,9, 10 and 11}

In the United States, staging for Wilms tumor is determined surgically (Table 23.1). In stage 1 disease, the tumor is limited to the kidney and has been completely resected. In stage 2, the tumor extends beyond the renal capsule but is completely resected. In stage 3 disease, there is residual tumor after surgery that is confined to the abdomen. Stage 4 disease involves either hematogenous metastases or lymph nodal metastases outside of the abdomen or pelvis. Stage 5 is bilateral Wilms tumors (Fig. 23.3).^12,13

The standard treatment for unilateral Wilms tumor is radical nephrectomy. En bloc resection of the tumor is highly desirable, as tumor spillage results in a sixfold increase in local abdominal recurrence.⁷ Preoperative chemotherapy is used for unresectable bulky masses, for bilateral Wilms tumors, and when tumor thrombus extends into the right atrium from the IVC.¹⁰ The prognosis for Wilms tumor is generally favorable. Long-term survival exceeds 90% for children with localized disease and is greater than 70% for patients with metastases.¹

The kidneys begin developing by 5 weeks of fetal life and are fully developed by the 36th week of gestation. Nephrogenic rests are foci of embryonic renal parenchyma (metanephric blastema) that persist beyond 36 weeks gestational age. Multiple or diffuse rests are referred to as nephroblastomatosis.^2,3,5 Nephrogenic rests are found in 1% of healthy neonates and are usually absent by 4 months of age. They are asymptomatic and are discovered either incidentally when imaging the abdomen for another purpose or in conjunction with a Wilms tumor.³ The potential for
these renal precursor cells to undergo malignant degeneration in Wilms tumor is why they garner attention from oncologists and radiologists. Nephrogenic rests may be categorized by their location within the kidney as either perilobar or intralobar. While perilobar rests are much more common, intralobar rests are more likely to degenerate into Wilms tumor.¹ Nearly all cases of bilateral Wilms tumors arise from preexisting nephroblastomatosis.

On ultrasound, nephrogenic rests may be either hypoechoic or isoechoic to the surrounding normal parenchyma (Figs. 23.4 and 23.5). In the perilobar form, multiple peripheral, hypoechoic masses may be seen. Contrast-enhanced CT is more sensitive and specific for this condition. Diffuse perilobar nephroblastomatosis manifests as confluent hypodense masses along the periphery of the kidney (Figs. 23.4 and 23.5). The rests are distinguished from the more avidly enhancing surrounding parenchyma, and the affected kidney is often enlarged and distorted. On MR, compared to normal renal parenchyma, nephrogenic rests are T1Wisointense, T2W slightly hyperintense and show less enhancement. On all modalities, concern for Wilms tumor transformation should be raised when one or more of these masses enlarges rapidly or becomes more heterogeneous in appearance.^{1, 2 and 3,10,14}

Most cases of nephroblastomatosis spontaneously regress. Currently, there is no consensus guideline regarding imaging surveillance of nephroblastomatosis. It is common practice to perform a CT at time of diagnosis, usually when the child is less than 1 year old, and renal US every 3 months until 8 years of age. If there is suspicion for malignant degeneration on ultrasound, then contrast-enhanced CT or MR is performed.^1,7,10,15

Clear cell sarcomas constitute 5% of pediatric renal tumors. It used to be considered a subtype of Wilms tumor, but was subsequently reclassified as a distinct lesion because of its unique histologic and biologic features. Clear cell sarcomas present as palpable abdominal masses in children aged 1 to 4 years, and there is a 2:1 male predilection. Virtually all cases are unilateral. On imaging, clear cell sarcomas appear as heterogeneous solid renal masses that are very similar to Wilms tumors (Fig. 23.6). In contrast to Wilms, clear cell tumors have a tendency to metastasize to the skeletal system. Therefore, bone scintigraphy or radiographic skeletal surveys are warranted. Treatment consists of radical nephrectomy and chemotherapy. Clear cell sarcoma is more aggressive than Wilms tumor and carries increased rates of recurrence and mortality. Long-term survival rates are 60% to 70%.^{1,2,7,16, 17 and 18}

These lesions include multilocular cystic nephroma, a benign lesion containing mature fibrous septa and tubules, and cystic partially differentiated nephroblastoma, which contains foci of renal blastema cells within the septa. Multilocular cystic tumors are distinguished from cystic Wilms tumors pathologically by the lack of solid nephroblastomatous tissue. They have an unusual bimodal demographic presentation—young boys aged 3 months to 4 years, and middle-aged women. Multilocular cystic renal tumors are nonfamilial, are not associated with cystic disease in
other organs, and are only sporadically linked with other congenital anomalies. They present as a palpable abdominal mass in a male infant or toddler.^1,2,10,19

On all imaging modalities, multilocular cystic renal tumors appear as well-defined masses containing cysts of variable size (Fig. 23.7). The cysts are typically anechoic on US, fluid density on CT, and T2W-hyperintense on MR. When the cysts are small and numerous, the lesion may take on a solid appearance on US because of the acoustic interfaces, similar to autosomal recessive polycystic kidney disease. Hemorrhage and calcification may be seen with these tumors. Septations are also of variable thickness. Postcontrast imaging generally shows only peripheral and septal enhancement (Fig. 23.7B). Large masses will show the “claw sign,” confirming renal origin and may herniate into the renal pelvis.1,2,7,10,19-21

While multilocular cystic renal tumors are benign, differentiating these histopathologies from more aggressive ones such as cystic Wilms tumor is not possible by imaging. Therefore, these patients undergo complete or partial nephrectomy. Surgery is typically curative, and the prognosis is very favorable.^{19, 20 and 21}