WAGR syndrome

Definition

Wilms' tumor is a cancerous tumor of the kidney that usually occurs in young children.

Description

When an unborn baby is developing, the kidneys are formed from primitive cells. Over time, these cells become more specialized. The cells mature and organize into the normal kidney structure. Sometimes, clumps of these cells remain in their original, primitive form. If these cells begin to multiply after birth, they may ultimately form a large mass of abnormal cells. This is known as a Wilms' tumor.

Wilms' tumor is a type of malignant tumor. This means that it is made up of cells that are significantly immature and abnormal. These cells are also capable of invading nearby structures within the kidney and traveling out of the kidney into other structures. Malignant cells can even travel through the body to invade other organ systems, most commonly the lungs and brain. These features of Wilms' tumor make it a type of cancer that, without treatment, would eventually cause death. However, advances in medicine during the last 20 years have made Wilms' tumor a very treatable form of cancer.

Wilms' tumor occurs almost exclusively in young children. The average patient is about three years old. Females are only slightly more likely than males to develop Wilms' tumors. In the United States, Wilms' tumor occurs in 8.3 individuals per million in white children under the age of 15 years. The rate is higher among African-Americans and lower among Asian-Americans. Wilms' tumors are found more commonly in patients with other types of congenital conditions. These conditions include:

• absence of the colored part (the iris) of the eye (aniridia)

• enlargement of one arm, one leg, or half of the face (hemihypertrophy)

• certain birth defects of the urinary system or genitals

• certain genetic syndromes (WAGR syndrome, Denys-Drash syndrome, and Beckwith-Wiedemann syndrome)

Causes and symptoms

The cause of Wilms' tumor is not completely understood. Because 15% of all patients with this type of tumor have other heritable defects, it seems clear that at least some cases of Wilms' tumor may be due to an herited alteration. It appears that the tendency to develop a Wilms' tumor can run in families. In fact, about 1.5% of all children with a Wilms' tumor have family members who have also had a Wilms' tumor. The genetic mechanisms associated with the disease are unusually complex.

Some patients with Wilms' tumor experience abdominal pain, nausea and vomiting, high blood pressure, or blood in the urine. However, the parents of many children with this type of tumor are the first to notice a firm, rounded mass in their child's abdomen. This discovery is often made while bathing or dressing the child and frequently occurs before any other symptoms appear. Rarely, a Wilms' tumor is diagnosed after there has been bleeding into the tumor, resulting in sudden swelling of the abdomen and a low red blood cell count (anemia).

About 5% of Wilms' tumor cases involve both kidneys during the initial evaluation. The tumor appears on either side equally. When pathologists look at these tumor cells under the microscope, they see great diversity in the types of cells. Some types of cells are associated with a more favorable outcome in the patient than others. In about 15% of cases, physicians find some degree of cancer spread (metastasis). The most common sites in the body where metastasis occurs are the liver and lungs.

Researchers have found evidence that certain types of lesions occur before the development of the Wilms' tumor. These lesions usually appear in the form of stromal, tubule, or blastemal cells.

Diagnosis

Children with Wilms' tumor generally first present to physicians with a swollen abdomen or with an obvious abdominal mass. The physician may also find that the child has fever, bloody urine, or abdominal pain. The physician will order a variety of tests before imaging is performed. These tests mostly involve blood analysis in the form of a white blood cell count, complete blood count, platelet count, and serum calcium evaluation. Liver and kidney function testing will also be performed as well as a urinalysis.

Initial diagnosis of Wilms' tumor is made by looking at the tumor using various imaging techniques. Ultrasound and computed tomography scans (CT scans) are helpful in diagnosing Wilms' tumor. Intravenous pyelography, where a dye injected into a vein helps show the structures of the kidney, can also be used in diagnosing this type of tumor. Final diagnosis, however, depends on obtaining a tissue sample from the mass (biopsy), and examining it under a microscope in order to verify that it has the characteristics of a Wilms' tumor. This biopsy is usually done during surgery to remove or decrease the size of the tumor. Other studies (chest x rays, CT scan of the lungs, bone marrow biopsy) may also be done in order to see if the tumor has spread to other locations.

Treatment

Treatment for Wilms' tumor almost always begins with surgery to remove or decrease the size of the kidney tumor. Except in patients who have tumors in both kidneys, this surgery usually will require complete removal of the affected kidney. During surgery, the surrounding lymph nodes, the area around the kidneys, and the entire abdomen will also be examined. While the tumor can spread to these surrounding areas, it is less likely to do so compared to other types of cancer. In cases where the tumor affects both kidneys, surgeons will try to preserve the kidney with the smaller tumor by removing only a portion of the kidney, if possible. Additional biopsies of these areas may be done to see if the cancer has spread. The next treatment steps depend on whether/where the cancer has spread. Samples of the tumor are also examined under a microscope to determine particular characteristics of the cells making up the tumor.

Information about the tumor cell type and the spread of the tumor is used to decide the best kind of treatment for a particular patient. Treatment is usually a combination of surgery, medications used to kill cancer cells (chemotherapy), and x rays or other high-energy rays used to kill cancer cells (radiation therapy). These therapies are called adjuvant therapies, and this type of combination therapy has been shown to substantially improve outcome in patients with Wilms' tumor. It has long been known that Wilms' tumors respond to radiation therapy. Likewise, some types of chemotherapy have been found to be effective in treating Wilms' tumor. These effective drugs include dactinomycin, doxorubicin, vincristine, and cyclophosphamide. In rare cases, bone marrow transplantation may be used.

The National Wilms' Tumor Study Group has developed a staging system to describe Wilms' tumors. All of the stages assume that surgical removal of the tumor has occurred. Stage I involves "favorable" Wilms' tumor cells and is usually treated successfully with combination chemotherapy involving dactinomycin and vincristine and without abdominal radiation therapy. Stage II tumors involving a favorable histology (cell characteristics) are usually treated with the same therapy as Stage I. Stage III tumors with favorable histology are usually treated with a combination chemotherapy with doxorubicin, dactinomycin, and vincristine along with radiation therapy to the abdomen. Stage IV disease with a favorable histology is generally treated with combination chemotherapy with dactinomycin, doxorubicin, and vincristine. These patients usually receive abdominal radiation therapy and lung radiation therapy if the tumor has spread to the lungs.

In the case of Stage II through IV tumors with unfavorable, or anaplastic, cells, then the previously mentioned combination chemotherapy is used along with the drug cyclophosphamide. These patients also receive lung radiation therapy if the tumor has spread to the lungs. Another type of tumor cell can be present in Stages I through IV. This cell type is called clear cell sarcoma of the kidney. If this type of cell is present, then patients receive combination therapy with vincristine, doxorubicin, and dactinomycin. All of these patients receive abdominal radiation therapy and lung radiation therapy if the tumor has spread to the lungs.

Prognosis

The prognosis for patients with Wilms' tumor is quite good, compared to the prognosis for most types of cancer. The patients who have the best prognosis are usually those who have a small-sized tumor, a favorable cell type, are young (especially under two years old), and have an early stage of cancer that has not spread. Modern treatments have been especially effective in the treatment of this cancer. Patients with the favorable type of cell have a long-term survival rate of 93%, whereas those with anaplasia have a long-term survival rate of 43% and those with the sarcoma form have a survival rate of 36%.

Prevention

There are no known ways to prevent a Wilms' tumor, although it is important that children with congenital conditions associated with Wilms' tumor be carefully monitored.

KEY TERMS

Biopsy

A procedure in which a small sample of tissue is removed, prepared, and examined with a microscope to determine the characteristics of the tissue's cells.

Blastemal

An immature material from which cells and tissues develop.

Cancer

A process where abnormal cells within the body begin to grow out of control, acquire the ability to invade nearby structures, and travel through the bloodstream in order to invade distant structures.

Congenital

Present at birth.

Malignant

Refers to cancer or cancer cells.

Sarcoma

A type of cancer that originates from connective tissue such as bone or muscle.

Stromal

A type of tissue that is associated with the support of an organ.

Tubule

Tissues and cells associated with the structures that connect the renal pelvis to the glomeruli.