Wilms Tumor

Original Editors - Students from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - Rachel Flaherty and Allison Hafele 

Definition/Description

Wilms’ Tumor, also known as nephroblastoma, is a solid tumor of the kidney that develops from immature kidney cells. It is the most common cancer of the kidneys in children, and the fourth most common type of cancer in children. Wilms’ tumors are most often unilateral, affecting only one kidney. 5-10% of children with Wilms’ tumors have more than one tumor in the same kidney, and approximately 5% of children with the cancer have bilateral Wilms’ tumors, affecting both kidneys.

                                          

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Prevalence

Wilms’ tumor is most common in children ages 3 to 4 and becomes much less common after the age of 5. Wilms’ tumor affects boys are girls equally, and can also be found in adults, though it is very rare. On average, there are 460 new cases of Wilms’ tumor diagnosed in the United States every year. Approximately 1 in 8,000-10,000 children are affected. About 5% of all cancers in children are Wilms’ tumors.

Characteristics/Clinical Presentation

Wilms’ tumor is often hard to find early because the tumor can grow large without any signs or symptoms. These children may look and act normally. The most common first clinical sign is swelling or a hard mass in the abdomen. It is often firm and large enough to be palpated on both sides of the abdomen, and is usually not painful.

Some children may also experience:

• Fever
• Loss of appetite
• Shortness of breath
• Constipation
• Nausea
• Blood in the urine
• Abdominal pain

Wilms’ tumors may also cause high blood pressure. The blood pressure can get high enough to cause bleeding in the eye or a change in consciousness in rare cases.

Associated Co-morbidities

The types of secondary cancers include bone and soft tissue sarcomas, breast cancer, lymphoma, tumors of the digestive tract, melanoma and acute leukaemias. Certain birth defects and also correlated with Wilms tumor including Aniridia, hemihypertrophy, cryptorchidism, hypospadias. There are also several syndromes that are often associated with Wilms tumor including Sotos syndrome, Perlman syndrome, Simpson-Golabi-Behmel syndrome, Bloom syndrome, Frasier syndrome, Beckwith-Wiedemann Syndrome, Denys -Drash syndrome, and WAGR syndrome which are explained in further detail in etiology. Hypertension is also a common co-morbitity associated with Wilms' tumor. 

Medications

Medications: The most effective chemotherapeutics in treatment of nephroblastoma are: Actinomycin D (ACT), vincristine (VCR), doxorubicin (ADM), cyclophosphamide (ctx), ifosfamide (IFO), etoposide and carboplatin. NGWTS recommends polchemotherapy treatment (ACT, VCR, ADM) for a period of 15 weeks in stage III. Less aggressive treatment using two medications (VCR and ACT) can be used in cancer stages I and II.

Toxicity: It is important to note toxicity of such treatment is higher in adults than in children. Among vinicristine, dactinomycin and Adriamycin, the main acute toxicity was neuropathy due to vincristine. The type, timing, and dosage of chemotherapy have been major risk factors in combined therapy.

Side Effects: Late side effects include cardiotoxicity, reproductive problems, renal dysfunction and the development of benign and malignant second tumors. In some cases fertility may be impaired.  Other side effects of chemotherapy include: hair loss , mouth sores , loss of appetite , nausea and vomiting , diarrhea or constipation , increased chance of infections (from having too few white blood cells), Easy bruising or bleeding (from having too few blood platelets), Fatigue or extreme tiredness (from having too few red blood cells) 

Diagnostic Tests/Lab Tests/Lab Values

Physical Examination: Usually first symptoms in adults include pain and haematuria, while children experience palpation detectable, painless, rapidly increasing size, abdominal mass.  Blood and Urine Tests: A urinalysis may also be performed to look for blood and other substances like catecholamines to rule out adrenal issues. Wilms tumor can not be diagnosed by a blood or urine test, but it can provide an overall assessment of health.

Imaging Tests:

This may include ultrasound, Magentic resonance imaging (MRI), and Computerized tomogrpahy (CT) scan. Definite diagnosis can only be made by surgical resection or biopsy.

Abdominal Ultrasound: High frequency sound waves create an image of internal organs,blood vessels and tissues.  Ultrasonography is the first choice for diagnostic imaging because it creates a panoramic image of the abdomen.  Photo obtained from: 

Bone scan: detects decreased bone density

Chest X-ray: produces images of the heart, lungs, and bones  Photo obtained from: 

Biopsy: This helps confirm the diagnosis and aids in developing a treatment plan

Other Lab values: A small percentage of Wilms tumors are caused by changes in the WT1 and WT2 genes, which are tumor suppressor genes on chromosome 11. Pathological diagnosis of adult nephroblastoma is based on criteria including: the presence of primitive blastemic spindle or round cell component; abortive or embryonal tubules or glomerular structures. Cytokeratin, vimentin,desmin,actin, and WTI allows to distinguish between other rare cancer types. An elevated serum IL-6 level has already been demonstrated to correlate with poor survival and unfavorable clinical outcome in some solid tissue cancers. 

Etiology/Causes

Wilms’ tumor is typically seen in otherwise healthy children, and the exact cause in most children is unknown. However, approximately 10% of patients with the tumor have a congenital anomaly, including certain birth defect syndromes and genetic changes. Wilms’ tumor, whether hereditary or sporadic, shows evidence of changes in one or more of at least ten different genes.

Kidneys are developed early in fetal growth. Gene mutations in early kidney cells may lead to undeveloped mature kidney cells. These early kidney cells may remain after birth. If the cells do not mature, they may grow out of proportion, forming a Wilms’ tumor. Genes WT1 and WT2 on chromosome 11 are tumor suppressor genes, and mutations of these cause a small number of Wilms’ tumors.

Common syndromes that are associated with Wilms’ tumor include the following:
WAGR Syndrome: WAGR stands for Wilms tumor, Aniridia (lack of the iris of the eyes), Genitourinary tract abnormalities, and mental retardation. Children who have WAGR syndrome have approximately 30-50% chance of developing a Wilms’ tumor, and often have them bilaterally. In this syndrome, cells are missing part of chromosome 11, which involves the WT1 gene.
Beckwith-Wiedemann sydrome: These children are at a 5% risk of having a Wilms’ tumor. This syndrome is caused by a malformation of chromosome 11.
Denys-Drash Syndrome: This syndrome is also caused by mutations to the WT1 gene. The risk for Wilms’ tumor in these patients is greater than 90%. In this disease, the kidneys become diseased and no longer function at a very young age, leading to a Wilms’ tumor.

Less common syndromes linked to Wilms’ tumor:

• Perlman sydrome
• Sotos syndrome
• Simpson-Golabi-Behmel Syndrome
• Bloom syndrome
• Li-Fraumeni Syndrome
• Frasier Syndrome
• Trisomy 18
• Alagille syndrome

Systemic Involvement

Wilms’ tumors often grow to a large size before any symptom manifestation. However, most Wilms’ tumors do not metastasize, despite their large size. Hematuria occurs in approximately 30% of cases, and about 25% of children with the tumor will have hypertension.
As with all cancer treatment, there may be systemic side effects from chemotherapy and radiation. These may affect the heart, lungs, fertility, skin reactions, and may increase the risk for a second cancer.

                               

Medical Management (current best evidence)

Management of Wilms’ tumor involves surgery, chemotherapy, and radiation therapy. Most children will receive more than one type of treatment. Treatment is based on both the stage and histology of the Wilms’ tumor.

Surgery: The goal of surgery is to remove the tumor in one unit to prevent the spread of cancer cells into the abdomen. There are several types of nephrectomy that can be performed:

• Simple Nephrectomy: The entire kidney is removed, and the remaining kidney can increase its capacity and filter all of the blood.
• Partial Nephrectomy: This surgery includes resection of the tumor and a section of the kidney tissue surrounding it. Partial nephrectomy is common when the other kidney is damaged or removed.
• Radical Nephrectomy: The kidney and surrounding tissues of adrenal gland and ureter are removed.

Chemotherapy: Most children diagnosed with a Wilms’ tumor will receive chemotherapy as one of their treatments. Powerful anti-cancer drugs are typically injected via vein, and the blood carries the drug throughout the entire system.8 Chemotherapy is typically used after the tumor has been surgically removed.
Radiation Therapy: This treatment utilizes x-rays and other high-energy rays to destroy cancer cells and shrink the tumor size.

The type of treatment received is determined by the stage of the cancer, the type of cell, and the general health of the patient.

• Stage I or II: The cancer is limited to the kidney or surrounding structures. Typically the kidney will be removed, as well as tissues and lymph nodes surrounding it. This will be followed with chemotherapy, and some stage II may need radiation.
• Stage III or IV: The cancer has spread outside of the kidney and cannot be removed with surgery. Radiation, along with surgery and chemotherapy will most likely take place.
• Stage V: Wilms’ tumors in bilateral kidneys. Chemotherapy is typically given first to shrink the tumor initially, followed by surgery and radiation.

                    

Physical Therapy Management (current best evidence)

There are several long-term side effects of chemotherapy. Childhood cancers tend to respond better to chemotherapy than adult cancers. Children’s bodies also tend to tolerate it better than adults do.  Side effects of chemotherapy can include fatigue or extreme tiredness from having too few red blood cells.

Musculoskeletal complications that can occur due to radiation therapy include growth abnormalities and hypoplasia. Mild scoliosis and mild asymmetry of all musculoskeletal structures can occur due to reduced growth of bone and paravertebral muscles.These effects are more pronounced the younger the patient is at the time of radiation therapy. 

Physical therapy interventions may include strengthening postural muscles and also increasing endurance to promote a higher quality of life. Patients should avoid heavy lifting due to the decreased bone density and risk of osteoporosis.

Alternative/Holistic Management (current best evidence)

Complementary medicine is treatment used in combination with regular medical care. Alternative treatments are used instead of the traditional medical treatment.

Although there are not any alternative medicines to surgery, radiation or chemotherapy, there are complementary treatments including art therapy or play therapy to reduce stress, peppermint tea to relieve nausea, and acupuncture to help relieve pain. 

See Resources for a link to healthy living after treatment for childhood cancer

Differential Diagnosis

Differential diagnosis of Wilms tumor includes: 

- Clear cell sarcoma  

- Malignant rhaboid tumor  

- Autosomal recessive polycystic kidney disease (ARPKD)

- Autosomal dominant polycystic kidney disease (ADPKD)

- Hydronephrosis

- Renal carbuncles

- Hemorrhage

- Neuroblastoma, an embryonal malignancy of the adrenal gland, usually affect the same age group and commonly arise in the same general region of the abdomen 

Case Reports/ Case Studies

add links to case studies here (case studies should be added on new pages using the case study template)

WT1 mutation as a cause of 46 XY DSD and Wilm's tumour a case report and literature review

A Report of Three Cases Cured of Pumonary and Hepatic Metastases

Wilms' Tumor Metastatic to Bilateral Testes at Presentation Case and Review of the Literature

Extrarenal Wilms' Tumor of the Ovary- A Case Report and Short Review of the Literature

 Resources

American Cancer Society: Wilms Tumor

National Cancer Institute: General Information about Wilms' Tumor and Other Childhood Kidney Tumors

Wilms Tumor: Parent Resource

Educational Issues Following Treatment for Childhood Cancer