Wilms tumor usually presents as an asymptomatic abdominal mass in the majority of children. The mother may have discovered the mass during bathing the infant. Other features include:

• Abdominal pain
• Gross hematuria
• Urinary tract infections
• Varicocele
• Hypertension or hypotension (Up to 1/3 of Wilms patients will demonstrate hypertension which normalizes after nephrectomy)
• Fever
• Anemia
• If the patient has lung metastases, dyspnea or tachypnea may occur.

Abdominal pain is the most common initial presenting symptom (30% to 40%) followed by hypertension (25%), and hematuria (12% to 25%).

The usual labs are not specific for Wilms tumor but need to be ordered to look for other pathologies. Routine blood work includes:[6][7][8][9]

• Complete blood count to look for anemia
• Chemistry profile
• Renal function
• Urinalysis
• Coagulation studies
• Cytogenetics studies to look for 1p and 16q deletion.

Imaging studies utilized include the following:

• Renal ultrasonography (often the initial study) but is operator dependent
• Chest x-ray to look for lung metastases
• Abdominal and chest CT with sedation
• Abdominal MRI is an optional study.

Imaging is particularly important in surgical planning. Surgical risk factors include larger tumor size, contralateral tumor extension and displacement of the great vessels which typically result in longer surgical times, increased blood loss and higher complications rates. 

The most common site of metastases are the lungs, so chest imaging is recommended. Abdominal CT and MRI appear to be about equal in diagnosing Wilms so either can be used. Metastases to bones are uncommon but ominous and typically develop later as a relapse or recurrence. 

Recently, MRI diffusion studies have possibly made it easier to differentiate Wilms tumor from neuroblastoma, the other common abdominal malignancy in children. It was found that the apparent diffusion coefficient (ADC) was substantially higher for Wilms. This differentiation is critical as the treatments for these two tumors are different. It was suggested that a cutoff ADC value of greater than or equal to 0.645 × 10 - 3 mm2 per second be used with higher values suggesting Wilms and lower values indicating neuroblastoma. While useful, this will need to be confirmed with additional studies before it can be considered a reliable indicator.

Treatment of Wilms tumor is usually nephrectomy followed by systemic chemotherapy, but some protocols initiate chemotherapy first and do the nephrectomy later. The opposite kidney may be explored to ensure that cancer has not spread although this is not necessary for low stage tumors with favorable histology if imaging is negative. Lymph nodes around the aorta are sampled for staging and to improve survival.[10][11][12][13]

There is no apparent significant difference in short term morbidity, mortality out to three years, hospital readmission rate or surgical margin status between traditional open surgery or minimally invasive techniques.  Open surgery, however, typically provides more lymph nodes in the surgical specimen.

Routine biopsies are not recommended except in unusual circumstances as a biopsy automatically increases tumor staging to Stage III.  This stage requires radiation and chemotherapy.

Postoperative radiation may or may not be administered depending on tumor histology and extent of spread. For patients without metastases who will be receiving radiation, initiation of therapy within 14 days of surgery appears to improve overall survival.  

Combination chemotherapy is usually administered for more aggressive disease. Initial chemotherapy most typically includes vincristine and dactinomycin. Doxorubicin, cyclophosphamide, etoposide, and carboplatin are also used.[14]

In children with bilateral disease, immediate nephrectomy is not performed. Some experts attempt high-dose chemotherapy to kill the tumor cells and hopefully salvage the kidney. Bilateral nephrectomy immediately mandates dialysis, and so all efforts are made to salvage the kidneys. Repeat biopsies are required to determine if the tumor is responding to therapy.  Nephron sparing surgery can be performed in select cases.bilatera[15]

Patients who relapse after initial combined therapy tend to have a worse prognosis than newly discovered Wilms patients. 

Hepatic veno-occlusive disease can occur in patients receiving therapy for Wilms.  It is characterized by right upper quadrant pain associated with jaundice, ascites, weight gain and/or hepatomegaly. Treatment for hepatic veno-occlusive disease is mainly supportive.[16]

Differential diagnosis of Wilms tumor can be tricky. While Wilms is the most common childhood renal tumor, the second most common is clear cell renal sarcoma. The prognosis is not as good as Wilms as it has higher mortality and relapse rates. It often metastasizes to bone. Histological appearance can sometimes be similar to Wilms which can lead to a misdiagnosis.[17]

Rhabdoid renal tumors are highly malignant and are most often seen before age two and almost never in children older than five years. It is often widely metastatic at the time of initial presentation and has a very poor prognosis with an 80% mortality rate within one year of diagnosis.

Congenital mesoblastic nephroma is typically found in the first year of life, most often by ultrasound. Hypertension and elevated renin levels usually accompany it.

Renal cell carcinoma is rare in the pediatric age group. However, when present, it is often at a more advanced stage than in adults. Neuroblastoma patients who are post-radiation and post-chemotherapy are at increased risk.

Renal medullary carcinoma is a very aggressive and dangerous cancer that is found almost exclusively in individuals with sickle cell disease, usually trait. It tends to be highly locally-invasive and metastasizes early.

Stage I indicates the tumor was completely contained within the kidney without any breaks or spillage outside the renal capsule and no vascular invasion.  This stage accounts for 40% to 45% of all Wilms tumors.

Stage II would be a tumor that has grown outside the kidney to some degree, such as into surrounding fatty tissue.  Usually, the tumor would be completely removable by surgery, and regional lymph nodes are negative. About 20% of all Wilms tumors are at this stage.

Stage III comprises about 20% to 25% of all Wilms tumors and indicates a tumor which could not be completely removed surgically such as the following:

• Cancer has spread to the regional lymph nodes but not to more distant nodes, such as in the chest
• Cancer has grown into nearby vital structures so it could not be surgically removed completely
• Deposits of the tumor (tumor implants) are found in the peritoneum, or there are positive surgical margins
• Cancer cells were accidentally “spilled” into the abdominal cavity during surgery
• The tumor was removed in separate pieces surgically; such as one piece from the kidney and another from the adrenal gland
• A renal biopsy of the tumor was done before it was surgically removed

Stage IV tumors are those that have spread through the vascular system to distant organs such as the lungs, liver, brain, or bones, or to distant lymph nodes.  These account for about 10% of all Wilms tumors.

Stage V are those cases where both kidneys are involved with tumor at the time of initial diagnosis.  About 5% of all Wilms tumors are at this stage.  Individual staging of each renal unit is needed as well. 

The prognosis varies by tumor stage and histology. Favorable histology has survival rates of 99% to 86% while unfavorable histology survival ranges from 84% to 38% depending on the stage.[18][19][20][21]

End-stage renal failure occurs in about 1% of patients; usually due to metachronous bilateral tumors.

A poorer prognosis is associated with the following characteristics:

• Anaplastic histology in stage II to IV tumors
• Diffuse anaplasia is worse than focal
• Loss of heterozygosity at chromosomes 1p, 1q, 11p15 and 16q or presence of TP53 
• Higher stage (most epithelial predominant tumors are stage I; most blastema predominant tumors are stage III and IV)
• Age older than two years
• Higher positive lymph node density
• Large tumor size
• Even small tumor foci can be associated with a poorer prognosis due to resistance to chemotherapy

Radiation and chemotherapy are effective in improving survival in higher stage Wilms tumor patients, but they may also be responsible for an increased risk of secondary malignancies years later. [22]

It is well established that radiation therapy will increase the risk for bone, breast, colon and thyroid cancers later on in life.  It will also increase the risk of osteoporosis.

Chemotherapy with dactinomycin, doxorubicin and vincristine contributes to a higher risk of secondary malignancies as well as specific toxicities such as hearing (carboplatin), cardiac function (adriamycin) and peripheral neuropathy (vincristine). [14]

About 5% to 10% of Wilms patients will present with Von Willebrand's disease which can complicate treatment.  Initial therapy for this should be DDAVP. If not successful, cryoprecipitate (concentrated Von Willebrand Factor) can be used. [23]

Follow-up visits for Wilms tumor are usually scheduled:[24]

• every 3 months for 2 years after diagnosis
• then every 6 months for another 2 years
• then once every 2 years

 Follow-up visits for Wilms tumor may include:

• feeling the abdomen for signs of any local recurrence or a liver tumor
• listening to the lungs for any signs of metastasis
• feeling the thyroid for any growths (if the child had radiation therapy to the chest)
• breast examination in female patients who received radiation therapy to the chest
• check for peripheral neuropathy (a complication of Vincristine therapy)
• check for liver/veno-occlusive disease in patients with right-sided tumors who received radiation therapy

 Tests are part of follow-up care. These will include:

• Abdominal ultrasound (yearly is recommended)
• CT scan
• MRI
• Chest x-ray
• Liver function testing
• Renal function blood tests
• Early screening for infertility
• Hearing tests for patients who received carboplatin
• Cardiac function tests, such as an echocardiogram or electrocardiogram at least every 3 years for patients who received doxorubicin (Adriamycin)
• Early screening for colon cancer in patients who received abdominal radiation (should start 10 years after radiotherapy treatment or by age 35, whichever is later)

After lung or chest radiation, the following is added:

• Thyroid-stimulating hormone (TSH) and free thyroxine (T4), to monitor thyroid function
• Thyroid US is recommended every 3 years to screen for thyroid nodules and masses
• Bone density testing should be started 10 years before it would normally be done due to early osteoporosis
• Early screening for breast cancer in women 

Present-day survival of patients after undergoing treatment is about 80% to 90%. The addition of radiation has made a significant difference in survival compared to the use of surgery alone. The primary research issue today in Wilms is to develop ways to prevent the drug toxicity associated with combination chemotherapy. Most children can live a normal life with one kidney.

Of note, recent studies indicate that in females who survive there is an increased risk of developing invasive breast cancer at an early age (younger than 40). This risk was highest in females who had been previously treated with chest radiation.

Patients with anaplastic histology face a recurrent risk of about 50%. Even patients with low-risk histological features can expect a 15% recurrence rate. There is some controversy about the potential for a renal biopsy to spread the disease or increase the risk of local recurrence, but this has not yet been conclusively determined. When a recurrence is found, it most often affects the lungs and is usually early; most often within two years of the initial tumor discovery.

There is also a risk of delayed development of Wilms in the contralateral kidney which is found in about 1% of patients, usually within two years of the initial discovery of the Wilms tumor in the original kidney. This is thought to be due to persistent focal nephrogenic rests in the contralateral kidney.

About 15% of patients with Wilms are at risk for a recurrence.  The majority of these will be found within the first 2 years after surgery.  

Circulating tumor DNA may prove to be a useful diagnostic tool in diagnosing pediatric tumors like Wilms but is still investigational. 

New chemotherapy drugs appear promising such as topotecan and irinotecan while stem cell transplants and targeted therapies represent promising new approaches to Wilms tumor treatment.

Wilms tumors are still relatively rare, but survival for most patients is quite good, especially for those with "favorable" histology who are diagnosed early and receive proper treated. The majority of patients first present to the pediatrician, nurse practitioner or the primary care provider. These clinicians need to be vigilant about infants with abdominal pain as the cause may be Wilms tumor. The key to improved survival is a prompt referral to the oncologist. Because the diagnosis is often devastating to the families, a mental health nurse should provide counseling in concert with the clinician. The pharmacist should educate the family about the chemotherapeutic medications and their adverse effects. The oncology nurse should educate the family on the surgery, the post-operative care and follow up as well as assist the clinician in monitoring the patient and provide regular follow-up. 

Social workers should be involved early in the care so that the patient has adequate support and does not miss out on treatment.

An interprofessional team approach is necessary for patients deemed candidates for surgery, as the recovery is prolonged and can be associated with complications. The message to the family should be consistent and realistic. Only through such an approach can client-patient relationships can be improved and hopefully translate into positive outcomes.

New approaches are being developed for those who do not initially respond well to treatment. Bilateral Wilms tumor can be particularly challenging and require close coordination between oncologists, pediatricians, nurse practitioners, primary care providers, radiologists and surgeons in the timing and implementation of neoadjuvant chemotherapy with bilateral nephron-sparing surgery or nephrectomies.[25]