Risk Factors
One risk factor for Wilms’ tumor is having a family member with a Wilms’ tumor. Certain birth defects also increase the risk of a Wilms’ tumor. These include WAGR, a syndrome that includes Wilms’ tumor; aniridia—a completely or partially missing iris (colored part) of the eyes; genitourinary abnormalities, such as defects of the kidneys, urinary tract, penis, scrotum, testicles, clitoris, or ovaries; and mental retardation.
Additional risk factors include having Beckwith-Wiedemann syndrome, in which patients have a larger than normal tongue, larger than normal internal organs, and one arm or leg that may be larger than the other; having Denys-Drash syndrome, which is the absence of the penis, scrotum, and testicles; and hemihypertrophy, in which one side of the body is larger than the other. Other genetic defects, including defects on chromosome 11, also increase risk. Patients with these abnormalities should be regularly screened for Wilms’ tumor during childhood.
Etiology and Genetics
The great majority of cases of Wilms’ tumor are sporadic (nonfamilial), and they are believed to arise as the result of genetic mutations in the kidney tissue either before or shortly after birth. Only about 5 percent of all cases are inherited, and even among these it appears that mutations in any of several different genes may be responsible. About one-third of patients with familial Wilms’ tumor have mutations in the WT1 gene, located on the short arm of chromosome 11 at position 11p13. The protein encoded by this gene is a regulatory molecule that acts to turn other genes on at appropriate times during the development of kidney and reproductive tissue. Failure to do so as a result of mutations in the WT1 gene may result in the uncontrolled growth of kidney tumors characteristic of the disease.
Other genes reported to be associated with genetic predisposition to Wilms’ tumor include WT2 (at position 11p15.5), WT3 (at position 16q), WT4 (at position 17q12-q21), WT5 (at position 7p14-p13), WTX (at position Xq11.1), GPC3 (at position Xq26), and BRCA2 (at position 13q12.3). A small percentage of patients with Wilms’ tumor have identifiable genetic syndromes in which this malignancy is one manifestation of a larger panoply of clinical presentations. These include Denys-Drash syndrome, Beckwith-Wiedemann syndrome, and WAGR syndrome.
The inheritance of familial Wilms’ tumor follows a classic autosomal dominant pattern, meaning that a single copy of the mutation is sufficient to cause full expression of the disease. An affected individual has a 50 percent chance of transmitting the mutation to each of his or her children. In some cases, however, the disease results from a spontaneous new mutation, so in these instances affected individuals will have unaffected parents. Curiously, it has been shown that at the molecular level within cells, both copies of the WT1 gene must be mutated in order to initiate the formation of kidney tumors. One of these mutations is the inherited one that is present in all cells, while the second occurs randomly during normal cell growth in kidney tissue. It is this acquired second mutation that triggers tumor formation in the affected tissue.
Symptoms
The first noticeable symptom is usually a large lump or hard mass in the abdomen. Other symptoms may include stomach pain; fever; blood in the urine; high blood pressure; and loss of appetite, nausea, vomiting, and constipation. Erythrocytosis (a condition where there are too many red cells in the blood) may also be a presenting sign that the doctor finds when taking a blood test. This is because Wilms’ tumor makes a protein that causes increased production of red cells. Wilms’ tumors may grow larger without causing any pain or other symptoms.
Screening and Diagnosis
The doctor will ask about a child’s symptoms and medical history and will perform a physical exam. Blood and urine tests may be done. The child will need one or more tests in order to look for tumors. These tests provide pictures of the kidney, surrounding blood vessels, and other organs to which the cancer may have spread.
These tests include ultrasound, a test that uses sound waves to examine the kidneys. A computed tomography (CT) scan, a type of x-ray that uses a computer to make pictures of the inside of the body, may also be done. In some CT scans, a dye is first injected into a vein. This dye makes structures in the body more visible on an x-ray. Additional tests include a magnetic resonance imaging (MRI) scan, a test that uses magnetic waves to make pictures of the inside of the body; a chest x-ray, a test that uses radiation to look for the spread of cancer to the lungs; a bone scan, in which a small amount of a radioactive material is injected into a vein to highlight any cancer that may have spread to the bones; and a biopsy, the removal of a sample of tissue to test for cancer cells. In Wilms’ tumor, the biopsy may actually be a major surgical procedure to remove the kidney.
Except for removal of the kidney, these tests are not invasive but require the child to remain still. Sedation may be needed.
Children who have risk factors for Wilms’ tumor should have a physical exam with a specialist and an ultrasound every three months until age six or seven. This screening should be done even if they do not have symptoms. It can help find tumors while they are small and have not yet spread to other parts of the body.
Treatment and Therapy
Wilms’ tumor can be cured in most children. The specific treatment depends on if the cancer has spread beyond the kidney to other parts of the body and, if so, how far. The process for determining this, called staging, uses the results of the diagnostic tests. Tumor size, cell type, whether the tumor is favorable or unfavorable, and the child’s age and health are also considered in choosing treatment. In general, tumors with a favorable histology are treated only with combinations of chemotherapy, and those with unfavorable patterns or that are recurrent often require the addition of radiation therapy.
Treatment may include surgery. The main treatment for Wilms’ tumor is a type of surgery called nephrectomy. This is the removal of the kidney with the tumor. The tissue around the kidney may also be removed, as well as some nearby lymph nodes. The remaining kidney will take care of all of the needed functions for the body.
Chemotherapy is the use of drugs to kill cancer cells. Chemotherapy can be given in many forms, including pill, injection, and via a catheter placed in a blood vessel. The drugs enter the bloodstream and travel through the body killing mostly cancer cells, but also some healthy cells.
Radiation therapy is the use of radiation to kill cancer cells and shrink tumors. Radiation may be external radiation therapy, in which radiation is directed at the tumor from a source outside the body.
Prevention and Outcomes
As of 2014 there is no known way to prevent Wilms’ tumor.
Bibliography
Dome, Jeffrey S., and Vicki Huff. "Wilms
Tumor
Overview." GeneReviews. Ed. Roberta A. Pagon et al. Seattle: U of
Washington, Seattle, 1993–2014. NCBI Bookshelf. Natl. Center for
Biotechnology Information, 19 Sept. 2013. Web. 29 Aug. 2014.
Driskoll, K. M.
Isakoff, and F. Ferrer. “Update on Pediatric Genitourinary Oncology.”
Current Opinion in Urology 17, no. 4 (July, 2007):
281-286.
EBSCO Publishing.
Health Library: Wilms’ Tumor. Ipswich, Mass.: Author,
2009. Available through http://www.ebscohost.com.
Kalapurakol, John A.,
and Patrick R. M. Thomas. “Wilms’ Tumor.” In Perez and Brady’s
Principles and Practice of Radiation Oncology, edited by Edward
C. Halperin, Carlos A. Perez, and Luther W. Brady. Philadelphia: Wolters
Kluwer Health/Lippincott Williams & Wilkins, 2008.
Mayo Clinic Staff. “Wilms’ Tumor.”
Mayo Clinic. Mayo Foundation for Medical Educ. and
Research, 2 Sept. 2011. Web. 29 Aug. 2014.
"Wilms Tumor and Other Childhood Kidney
Tumors Treatment (PDQ®)". National Cancer Institute. Natl.
Cancer Inst., 22 May 2014. Web. 29 Aug. 2014.
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