Wilms' Tumor

What Is A Wilms' Tumor? What Causes A Wilms' Tumor?

Wilms' tumor, also known as Wilms tumor or nephroblastoma is a kidney cancer that generally affects children, and very rarely adults. The tumor was named after Dr. Max Williams (1867-1918), a German surgeon who first described it.

Wilms' tumors are rare, even though they are the most common malignant tumors of the kidneys in children, especially around the ages of 3 to 4 years - humans very rarely develop Wilms' tumors after the age of 6. About 500 cases are reported in the USA each year. Over three-quarters of cases occur in otherwise healthy children, while one quarter are linked to other developmental abnormalities. Treatment generally has a high success rate, with over 90% of patient surviving at least five years - in other words, outlook is good.

Usually just one kidney is affected; however, sometimes both may be. The tumor is thought to have developed from immature kidney cells.

Experts say that a Wilms' tumor is caused by the loss or inactivation of a tumor suppressor gene called QT1 on chromosome 11. Tumor suppressor genes generally hold back tumor growth and control cell growth.
According to Medilexicon's medical dictionary:

Wilms tumor is "a malignant renal tumor of young children, composed of small spindle cells and various other types of tissue, including tubules and, in some cases, structures resembling fetal glomeruli and striated muscle and cartilage; often inherited as an autosomal dominant trait [MIM*194070, *194080, *194090]."

What are the signs and symptoms of Wilms' tumor?

A symptom is something the patient senses and describes, while a sign is something other people, such as the doctor notice. For example, drowsiness may be a symptom while dilated pupils may be a sign.

During the early stages there may be no signs and symptoms at all. Even a fairly large tumor may be painless. However, in the majority of cases the tumors are found before they have started to metastasize (spread to other parts of the body), even the larger ones. The following signs and symptoms are possible:

• A swelling in the abdomen
• A non-tender abdominal mass may be felt
• Elevated body temperature (fever)
• Hematuria - bloody urine
• Abnormal urine color
• Lack of appetite (reduced appetite)
• Hypertension - high blood pressure
• Pains in the abdomen - caused by pressure on other organs near the tumor
• Nausea
• Constipation
• Large and distended veins that appear across the abdomen
• Malaise
• Vomiting
• Hemihypertrophy - enlargement of one side of the body

What are the causes of Wilms' tumor?

Experts do not know what the exact cause of Wilms' tumor is. Most agree that the cancer probably started when the baby was still in the womb, when some supposed kidney cells did not develop properly. The abnormal cells multiply in their primitive state and become a tumor, which is usually detectable at the age of 3 to 4 years.
Genes that control growth mutate (become altered), allowing cell multiplication (reproduction) to get out of control, which in this case could be Wilms' tumor cells.

Family history - some cases of Wilms' tumor may be caused by a genetic defect the child inherits from a parent. There are two genes which have been found to have defects - WT1 (Wilms' tumor 1) or WT2. Experts say that there may also be mutations in other chromosomes. Less than 2% of cases will have an affected close relative.

Sometimes something may go wrong in the child's early development, resulting in an altered gene which leads to cancer.

The majority of Wilms' tumor cases occur by chance, they are sporadic - the result of genetic mutations that affect cell growth in the kidney. In most cases, these alterations (mutations) start after birth.

In a small number of cases patients with Wilms' tumor may also have one of these genetic syndromes:

• WAGR syndrome - WAGR stands for four diseases/conditions:
  
  
  • Wilms' tumor
  • Aniridia - the baby is born with no iris (colored part of the eye)
  • Genitourinary malformations
  • Mental retardation
  WAGR is caused by the inactivation or loss of WT1 on chromosome#11 - WT1 is a tumor suppressor gene; it holds back (suppresses) the growth of tumors and controls cell growth.
• Denys-Drash syndrome (DDS) - this is a very rare disorder that causes kidney failure before the age of 3 years. There is abnormal development of the sexual organs. Children with this syndrome are at high risk of developing some other types of cancer, apart from Wilms' syndrome. Also caused by inactive or lost WT1.
• Beckwith-Wiedemann syndrome - the baby is born with a significantly higher-than-normal birth weight, a large tongue, enlarged organs (especially the liver), overgrowth of one side of the body, low blood sugar in the newborn period, ear creases and ear pits. The body grows asymmetrically. Experts say it is caused by an overactive oncogene copy on chromosome#11 (IGF2). Oncogenes regulate cell growth - if there is something wrong with them cell growth may get out of control.
  
  Patients with Beckwith-Wiedemann syndrome have an increased risk of developing hepatoblastoma, neuroblastoma, adrenocortical cancer, and rhabdomyosarcoma, as well as Wilms' tumor.

Gender - females have a slightly higher risk of developing Wilms' tumor than males.

Ethnic origin - people of black African ancestry have a slightly higher probability of developing Wilms' tumors compared to those of other ancestries. In the USA Asian-Americans have the lowest risk.

Cryptorchidism - if one or both testicles fail to descend into the scrotum. Babies with cryptorchidism have a higher risk of developing Wilms' tumor.

Hypospadias - male babies born with the urethra not located where it should be at the tip of the penis have a higher risk of developing Wilms' tumor.

Diagnosing Wilms' tumor

The doctor will ask about the signs and symptoms, check the child's medical history as well as details on the mother's pregnancy, and carry out a physical examination. The following diagnostic tests may be ordered:

Blood test - although Wilms' tumor cannot be diagnosed from a blood test, it can help provide the doctor with information regarding the child's general state of health.

Urine test - the aim here is to exclude other possible types of cancer. Also evaluates kidney function.

Abdominal ultrasound scan - this device uses ultrasound waves which bounce off tissues; the echoes are converted into a sonogram (an image) which the doctor can see on a monitor. The doctor can get an inside view of soft tissues and body cavities. The doctor will be able to see an outline of the kidneys, the tumor, and determine whether there is anything wrong in the renal or other veins in the abdomen. The doctor will also check the other kidney.

Abdominal CT (computed tomography) scan - the CT scanner uses digital geometry processing to generate a 3-dimensional (3-D) image of the inside of an object. The 3-D image is made after many 2-dimensional (2-D) X-ray images are taken around a single axis of rotation - in other words, many pictures of the same area are taken from many angles and then placed together to produce a 3-D image. It is a painless procedure.

MRI (magnetic resonance imaging) scan - uses a magnetic field and radio waves to create detailed images of the body. Most MRI machines look like a long tube, with a large magnet present in the circular area. When beginning the process of taking an MRI, the patient is laid down on a table. Then depending on where the MRI needs to be taken, the technician slides a coil to the specific area being imaged. The coil is the part of the machine that receives the MR signal.

Chest X-ray - used to determine whether the cancer has spread (metastasized) into the lungs.

Biopsy - a small piece of the tumor is taken out and examined under a microscope.

Staging - staging is used to assess the extent (stage) of the cancer; how advanced it is:

• Stage 1 - the cancer can usually be completely surgically removed. It is limited to the kidney.
• Stage 2 - the cancer has reached tissues and structures close to the kidney, such as blood vessels and fat. However, it can still be completely surgically removed.
• Stage 3 - the cancer has spread further and reached nearby lymph nodes or other parts of the abdomen. Removing it surgically (completely) may not be possible.
• Stage 4 - the cancer has spread further still to other parts of the body, including perhaps the brain, liver or lungs.
• Stage 5 - both kidneys have cancer cells.

What are the treatment options for Wilms' tumor?

Treatment for Wilms' tumor depends on several factors, including the child's age, overall health, medical history, the extent of the disease, tolerance to certain medications and/or procedures, and the parents' preferences.

Standard treatment usually involves surgery, chemotherapy, and sometimes radiotherapy (radiation therapy).

Histology (study of the form of structures seen under the microscope) - the doctor may tell the parent/guardian that the tumor appears favorable or anaplastic (unfavorable). A favorable histology means the outlook looks good for the child; survival rate is good. Even though an anaplastic histology is not such good news, many such patients also have good outcomes.

As Wilms' tumor is rare, the doctor may advise that treatment be done at a pediatric cancer center.

Nephrectomy - surgical removal of kidney tissue:

• Simple nephrectomy - the whole kidney is surgically removed. The other kidney is enough to maintain the patient in good health.
• Partial nephrectomy - the tumor and part of the kidney tissue that surrounds it is surgically removed. This type of surgery is done if the other kidney is not 100% healthy, or has already been surgically removed.
• Radical nephrectomy - the whole kidney, nearby adrenal gland and lymph nodes, as well as other surrounding tissue are surgically removed.

During the surgical procedure the surgeon may check both kidneys, as well as the abdominal cavity, and samples may be taken for testing.

Kidney transplant - if both kidneys need to be taken out, the patient will require dialysis until he/she are ready for a transplant.

Chemotherapy - the tumor cells are examined to determine whether they are aggressive or susceptible to chemotherapy. Chemotherapy is the use of chemicals (medication) to treat disease - more specifically, it usually refers to the destruction of cancer cells. Cytotoxic medication prevents cancer cells from dividing and growing. When health care professionals talk about chemotherapy today, they generally tend to refer more to cytotoxic medication than others.

Chemotherapy targets rapidly multiplying cells, such as cancer cells - however, hair follicles, cells in the GI tract (gut) and bone marrow, and some other cells are also affected. Therefore, the patient receiving chemotherapy may experience undesirable side effects, including:

• Hair loss
• Loss of appetite
• Low white blood cell count
• Nausea
• Vomiting

Soon after a course of chemotherapy is stopped side effects usually go away

If the patient needs high-dose chemotherapy, the marrow cells may be removed beforehand and frozen, and then returned through an intravenous line afterwards. High-dose chemotherapy can destroy bone marrow cells.

Radiotherapy (radiation therapy) - involves the use of beams of high-energy X-rays or particles (radiation) to destroy cancer cells. Radiotherapy works by damaging the DNA inside the tumor cells, destroying their ability to reproduce.

Radiotherapy usually begins a few days after surgery. Very young patients may be given a sedative so that they are still during a radiotherapy session. The doctor marks the targeted area with a dye, while shielding non-targeted areas of the body. Radiation therapy may result in the following side effects:

• Diarrhea (if the abdomen is targeted) - patients commonly report symptoms within a few days of the commencement of treatment. As the radiotherapy course progresses symptoms may get worse. The patient will usually get better a few weeks after treatment is completed.
• Fatigue - the most common symptom.
• Nausea - this may occur at any time during the course of treatment, or a short time afterwards. It is important to tell the doctor because it is easily treatable with medication.
• Skin irritation - areas that were hit by the radiation beam may become reddened and sore. Patients should protect that area of skin from sunlight and cold winds, as well as from perfumed soaps. Scratching and rubbing will irritate the skin more.

Treatments according to the stage of the cancer:

• Stages 1 or 2 - if the cancer cell type is not aggressive, the kidney, surrounding tissues and some nearby lymph nodes will be surgically removed. This will be followed by chemotherapy. In some cases, Stage 2 patients may also receive radiation therapy.
• Stages 3 or 4 - if the cancer cannot be completely removed because it has spread into the abdomen and removing it would damage major blood vessels or other key structures, combination therapy will be used, consisting of surgery, radiation and chemotherapy. Chemotherapy may occur before surgery to shrink the tumor.
• Stage 5 - if both kidneys have tumor cells, part of the cancer from each kidney will be surgically removed, while nearby lymph nodes will be examined to determine whether they contain cancer cells. Afterwards, the patient will receive chemotherapy to shrink the remaining tumor. Later, more of the tumor is surgically removed. The surgeon will try to spare as much good kidney tissue as possible. This may be followed by more radiation therapy and chemotherapy.

The child's outlook (prognosis) depends on several factors, including:

• The stage of the cancer
• What cell type the cancer is
• The age and general health of the patient at diagnosis
• How big the primary tumor is/was
• How the patient responded to therapy
• How well the child tolerated specific medications, procedures or therapies

For the best outcome the child should receive prompt and aggressive therapy. He/she should receive continued follow-up care.

According to the NIH (National Institutes of Health), USA, children whose tumor has not spread have a 90% cure rate with appropriate treatment.