Pediatric Wilms tumor
Introduction
Introduction to Pediatric Nephroblastoma Wilms tumor is not like hematuria in adult kidney embryonal tumors. The first thing that attracts attention is that there is a lump in the abdomen. Renal embryonal tumors can occur anywhere in the kidney, and the renal pelvis is often deformed by compression. The clinical manifestations of nephroblastoma are not complicated, but rather fairly consistent. Generally unilateral, bilateral tumors are rare. The surface of the tumor is smooth, moderately stiff, and has no tenderness. In the ribs of the upper abdomen, the abdominal viscera can be pushed to one side beyond the midline. In a few cases, there may be anemia and abnormal urination. Occasionally, people with hematuria often have high blood pressure. basic knowledge The proportion of illness: 0.001% Susceptible people: children Mode of infection: non-infectious Complications: anemia, hematuria, hypertension
Cause
Pediatric nephroblastoma etiology
(1) Causes of the disease
Wilms tumor may be due to abnormal proliferation of the posterior kidney germ that has not formed into tubules and globules. The nephroblastomatosis complex may also be a pre-neoplastic lesion of Wilms. In recent years, it has been confirmed that the deletion of the tumor suppressor genes WT1 and WT2 is associated with the occurrence of partial nephroblastoma.
The cause of nephroblastoma is still unclear, and there is a certain familial tendency, the incidence rate is 1% to 2%. Some people think that there is hereditaryness. A few children can grow the tumor successively; Schweisguth reported that among the 600 cases, 5 pairs are brothers and sisters. Xinhua Hospital also encountered two pairs of brothers who had grown this tumor and met a young father who had undergone unilateral nephroblastoma surgery when he was young. He also had a nephroblastoma at the age of 3 years. It has also been reported that 3 pairs of twin brothers are ill. Brown et al. encountered a very rare three-generation case of continuous disease.
(two) pathogenesis
Wilms tumor originates from the embryo and develops in the kidney parenchyma. During the process of growth, it is distorted and invades the surrounding kidney tissue. Kidney tumors in children are almost all of this category. From the original mesenchymal leaves, a variety of undifferentiated tissues can be seen in the pathological sections. Sometimes the tumor breaks through the membrane, invades the diaphragm, the adrenal gland, and the colon. Tumor tissue is found in the renal vein in 10% to 45% of surgical specimens.
Pathological change
Renal cell carcinoma originates from renal tubular epithelial cells. It was found that 88.5% of clear cell carcinomas express proximal convoluted tubule antigen, while 87.5% of granulosa cell carcinomas express distal convoluted tubule antigen, so it is speculated that clear cell carcinoma may originate from proximal convoluted tubules. Granulosa cell carcinoma may be derived from distal convoluted tubules. Tumors of different pathological types have different appearances. In general, clear cell carcinoma is yellow, clear boundaries with normal tissues, seemingly enveloped, slow growth, and good prognosis. Granulosa cell carcinoma, cancer cells are cuboidal or polygonal, the cytoplasm of cancer cells is rich in organelles, especially mitochondria, so the cytoplasm is red-granular, the glandular structure is clear, and the interstitial is composed of capillaries. The clear cell type of the clear cell is significantly different, the cell arrangement is chaotic, the malignancy is high, and the prognosis is poor. Undifferentiated cancer cells are fusiform or irregular, resembling sarcomas.
The pathological grading of tumors is a reliable factor in assessing prognosis and is also an important basis for developing treatment options. Fuhrman Nuclear Grading Standard (1992):
Level 1: Cancer cells have a small, round, deep-stained nucleus with a chromatin that is ambiguous and has no nucleoli.
Level 2: The cancer cells are slightly larger, and the chromatin is clearer. The nucleolus is visible in some cells under high magnification, but it is not significant.
Level 3: Cancer cells are larger and are characterized by nucleoli.
Level 4: Similar to level 3, but the nucleus is pleomorphic, multi-lobed and huge nucleoli.
2. Staging
Kidney cancer can occur in any part of the renal parenchyma. The incidence of left and right kidney cancer is equal, and the vast majority are unilateral single lesions, and bilateral lesions only account for 1% to 2%.
Giant examination: The appearance of the tumor is an irregular circular or elliptical mass with a pseudo-fibrous capsule formed by the compressed renal parenchyma and fibrous tissue.
It is densely grayish white with no obvious capsule and poor prognosis. The dark red and red parts are usually bleeding areas, sometimes accompanied by cystic changes, necrosis and irregular calcification.
Microscopic examination: Undifferentiated cancer cells are fusiform, with large or different nuclei, more mitotic figures, and a higher degree of malignancy.
Staging of renal embryonal tumors:
Stage I: limited to the kidney.
Stage II: limited to the periphery of the kidney.
Stage III: limited to adjacent organs in the abdominal cavity.
Stage IV: There is a distant transfer.
V period: bilateral.
3. Diffusion transfer
In the early stage of nephroblastoma, there is a complete envelope, which can cause rupture when the tumor is enlarged, causing the tumor cells to directly invade the peri-renal fat layer or adjacent tissues, such as the adrenal gland, the mesenteric membrane, and the part of the liver that is in contact with it. Lymph node metastasis of nephroblastoma is rare, and most of it is limited to local lymph nodes, but blood-borne spread is very common, first through the renal vein, which often has tumor emboli, can spread to the inferior vena cava, even to the right Atrial, hematogenous spread 80% to the lungs, sometimes to the liver, and occasionally to the bones.
4. Microscopy
The main pathological types of renal cell carcinoma include: clear cell carcinoma, granulosa cell carcinoma, and undifferentiated cell carcinoma. Clear cell carcinoma is the most common. The transparent cells are large in volume, clear in edge, polygonal in shape, uniform in the nucleus and deep in staining, and the cell mass is mostly transparent. The cells are often arranged in a sheet, papillary and tubular shape. The granulosa cells are round, polygonal or irregular in shape, dark in color, and the cytoplasm is frosted glass. The cytoplasm is filled with fine particles, the cell mass is small, and the nucleus is slightly stained. Two types of cancer cells may exist alone or in a single tumor. If the tumor is mostly transparent cells, it is called renal clear cell carcinoma, and vice versa is renal granulosa cell carcinoma. 60% to 70% of this tumor is a mixed type of kidney cancer composed of two types of cancer cells. Undifferentiated cancer cells are fusiform, with large or different nuclei, more mitotic figures, and a higher degree of malignancy.
The experience of the International Society for Pediatric Oncology (SIOP) and the American Wilms Cancer Research Organization (NWTS) has demonstrated that cell histology types play an important role in estimating prognosis. This tumor is divided into 2 types:
(1) Favorable histology (FH): polycystic, fibroid-like.
(2) Unfavorable histology (UH): interstitial, clear cell sarcoma, rod cell sarcoma. Currently, both SIOP and NWTS develop treatment options based on the above-mentioned histological types combined with staging.
There are also some variant nephroblastomas in histology, such as fetal rhabdomyomatous nephroblastoma, osteocartilagino-us nephroblastoma, and lipomatous nephroblastoma (lipomatous). Nephroblastoma) and so on.
Prevention
Pediatric nephroblastoma prevention
The occurrence of this disease has a certain hereditary. Refer to the general tumor prevention methods, understand the risk factors of tumors, and develop appropriate prevention strategies to reduce the risk of cancer. There are two basic clues to prevent tumors. Even if tumors have begun to form in the body, they can help the body to increase resistance. These strategies are as follows:
1. Avoid harmful substances (promoting factors) that can help us avoid or minimize exposure to harmful substances.
Some related factors of tumorigenesis are prevented before onset. Many cancers are preventable before they are formed. A US report in 1988 compared the international malignant tumors in detail, suggesting that many of the known malignancies are preventable in principle, that is, about 80% of malignant tumors can be changed through simple lifestyles. prevention. Continuing with the retrospective, a study by Dr. Higginson in 1969 concluded that 90% of malignant tumors are caused by environmental factors. Environmental factors and lifestyle refer to the air we breathe, the water we drink, the food we choose to make, the habits of activities, and social relationships.
2. Improve the body's immunity against tumors can help improve and strengthen the body's immune system and cancer. The focus of our current cancer prevention efforts should first focus on and improve those factors that are closely related to our lives, such as smoking cessation, proper diet, regular exercise, and weight loss. Anyone who follows these simple and reasonable lifestyles can reduce their chances of developing cancer.
The most important thing to improve the function of the immune system is: diet, exercise and control troubles, healthy lifestyle choices can help us stay away from cancer. Maintaining a good emotional state and proper physical exercise can keep your body's immune system at its best, and it is also good for preventing tumors and preventing other diseases. In addition, studies have shown that appropriate activities not only enhance the body's immune system, but also reduce the incidence of colon cancer by increasing the peristalsis of the human intestinal system. Here we mainly understand some of the problems of diet in preventing tumorigenesis.
Human epidemiology and animal studies have shown that vitamin A plays an important role in reducing the risk of cancer. Vitamin A supports normal mucosa and vision, and it directly or indirectly participates in most of the body's tissue functions. Vitamin A is found in animal tissues such as liver, whole egg and whole milk. Plants are in the form of beta-carotene and carotenoids, which can be converted into vitamin A in the human body. Excessive intake of vitamin A can cause adverse reactions in the body, while -carotene and carotenoids do not. The low vitamin A content in the blood increases the risk of malignant tumors. Studies have shown that those with low levels of vitamin A in the blood People who enter are more likely to develop lung cancer, and those who have low levels of vitamin A in their bloodstream may have an increased risk of lung cancer. Vitamin A and its mixture can help remove free radicals in the body (free radicals can cause damage to genetic material), and secondly stimulate the immune system and help differentiate cells in the body to develop into ordered tissues (and tumors are characterized by disorder) . Some theories suggest that vitamin A can help cells that have been previously mutated by carcinogens to reverse and become normal growing cells.
In addition, some studies suggest that supplementation with -carotene alone does not reduce the risk of cancer, but rather increases the incidence of lung cancer. However, when beta-carotene binds to vitamins C, E and other anti-toxins, its protective effect is revealed. The reason is that when it consumes itself, it can also increase free radicals in the body. In addition, there are interactions between different vitamins. Both human and mouse studies have shown that the use of -carotene can reduce 40% of vitamin E levels in the body, which is safer. The strategy is to eat different foods to maintain the balance of vitamins to fight cancer, because some protective factors have not been discovered so far.
Vitamins C and E are another anti-tumor substance that can prevent the harm of carcinogens such as nitrosamines in food. Vitamin C protects sperm from genetic damage and reduces the risk of leukemia, kidney cancer and brain tumors in their offspring. . Vitamin E can reduce the risk of skin cancer. Vitamin E has the same anti-tumor effect as vitamin C. It is an anti-toxin and a scavenger that scavenges free radicals. The combination of vitamins A, C, and E produces a protective effect against the toxin that is better than a single application.
At present, research on phytochemistry has attracted widespread attention. Phytochemistry is a chemical found in plants, including vitamins and other substances found in plants. The chemical constituents of thousands of plants have been found, many of which have anticancer effects. The protective mechanism of these chemicals not only reduces the activity of carcinogens but also enhances the body's immunity against carcinogens. Most plants provide antioxidant activity that exceeds the protective effects of vitamins A, C, and E. For example, a cup of cabbage contains only 50 mg of vitamin C and 13 U of vitamin E, but its antioxidant activity is equivalent to 800 mg of vitamin C and The antioxidant activity of 1100 U of vitamin E can be inferred that the antioxidant effects in fruits and vegetables are far more effective than the vitamins we know. Undoubtedly natural plant products will help future cancer prevention work.
Complication
Pediatric nephroblastoma complications Complications, anemia, hematuria, hypertension
This disease can have symptoms of acute abdomen, anemia, hematuria, and high blood pressure. 12% to 15% of nephroblastoma may be associated with other congenital malformations, including half-body hypertrophy, hypospadias, testicular undescending, bilateral ureter, bisexual kidney, horseshoe kidney, and anuridia. Consideration should be given to the possibility of the disease. Common people are:
1. Absence of iris: This tumor is associated with non-familial bilateral iris dysplasia or complete absence is not uncommon, about 1 in about 70 cases. Sometimes there are congenital cataracts, but also central nervous system abnormalities, such as microcephaly, head abnormalities, auricular abnormalities, urinary system malformations and mental retardation. In recent years, cytogenetics of children with iris deficiency and nephroblastoma Studies have shown that it has a phenomenon of short arm displacement or partial absence of chromosome 11.
2. Partial hypertrophy: generally the left or right side of the body is hypertrophy, or only the lower extremity is hypertrophy. Infancy was mostly undetected and was noticed even when the tumor was diagnosed. The incidence of partial hypertrophy was 1:14300 in the population, and 1 in 32 children with nephroblastoma, mostly in girls.
3. Genitourinary malformations: The incidence rate is 4.5%, such as renal duplication, horseshoe kidney, polycystic kidney, ectopic kidney and so on. It is also not uncommon for patients with hypospadias and cryptorchidism. In addition, in recent years, children with hermablastoma and hermaphroditism, which are difficult to distinguish between male and female genitalia, have been found. RaIFer reported 10 cases, including 7 cases of unilateral nephroblastoma and 3 cases of bilateral nephroblastoma.
4. Beckwith-Wiedemann syndrome: The syndrome mainly includes visceral hypertrophy (kidney, pancreas, adrenal gland, gonad, liver, etc.), umbilical bulge, giant tongue and large development or partial hypertrophy. The kidney, adrenal cortex and liver of patients with this syndrome are prone to malignant tumors. Reddy et al reported 34 cases of Beckwith-Wiedemann syndrome, 3 cases of growth nephroblastoma, 3 cases of adrenocortical carcinoma, hepatoblastoma. And 1 case of gonadal tumor.
Symptom
Pediatric nephroblastoma symptoms Common symptoms High heat appetite decreased abdominal mass hemoptysis hypertension pale pale anemia acute abdomen severe pain nausea
Wilms tumor is not like hematuria in adult kidney embryonal tumors. The first thing that attracts attention is that there is a lump in the abdomen. Renal embryonal tumors can occur anywhere in the kidney, and the renal pelvis is often deformed by compression. The clinical manifestations of nephroblastoma are not complicated, but rather fairly consistent. Generally unilateral, bilateral tumors are rare. The surface of the tumor is smooth, moderately stiff, and has no tenderness. In the ribs of the upper abdomen, the abdominal viscera can be pushed to one side beyond the midline. In a few cases, there may be anemia and abnormal urination. Occasionally, people with hematuria often have high blood pressure.
1. Abdominal mass: 80% to 90% of cases are treated with abdominal masses, mostly unintentionally found, can be asymptomatic, usually when the mother is taking a bath or dressing for the child, or the medical staff finds the abdomen for other reasons. There are chunks. The lumps are located on the side of the abdomen and have an elliptical shape. The surface is smooth and flat, the texture is firm, no tenderness, the inner and lower margins of the margin are clear, and the upper boundary is covered by the costal margin. The palpation of the hands can be felt at the waist. Filled in. The tumor is relatively fixed and cannot be moved. The size of the mass varies, and the larger one can account for 1/3 to 1/2 of the total abdomen. In the later cases, the mass often exceeds the midline of the abdomen, pushing the abdominal viscera to the opposite side. It should be pointed out that repeated percussive compression of the tumor can cause the tumor cells to enter the bloodstream and undergo distant metastasis, so special attention should be paid.
2. Pain and digestive symptoms: It has been reported that the first symptom of 25% of nephroblastoma is low back pain. In fact, most of the pain is not serious, and the children are not well-narred, so most are not aware. Children with acute abdomen symptoms when they fall, fall or abdominal trauma. Occasionally, children may have sudden onset pain, which is caused by sudden bleeding in the tumor, excessive expansion of the renal capsule or temporary blockage of the ureter. Children often have ambiguous gastrointestinal symptoms such as nausea, vomiting and loss of appetite.
3. Hematuria: Hematuria occurs in 20% of cases, and about 10% of cases have hematuria as the first symptom to be noticed to make a tumor diagnosis. Generally it is painless and intermittent whole blood urine, the amount is not much, sometimes accompanied by blood clots. When the pediatrician sees this symptom, even if the abdomen does not touch the mass, B-ultrasound, intravenous pyelography or CT examination should be performed, and a small tumor in the central part of the kidney may be found. However, in most cases, hematuria is a more advanced symptom, the tumor is quite large, infiltrating the renal pelvis, and entering the renal pelvis. Urine microscopy, about 1/3 of cases contain multiple red blood cells.
4. Fever: Children with nephroblastoma may have different degrees of fever, mostly intermittent, and high fever (39 °C) is rare. It has been noted that children with vomiting often have increased body temperature due to dehydration and metastasis or necrosis in the tumor.
5. Hypertension: There may be a large number of children with mild or severe hypertension, but often because of neglect to measure the blood pressure of infants and young children, there are not many reporters. However, there are also many cases of severe hypertension in the literature. When the tumor is resected, the blood pressure drops. This phenomenon suggests two possibilities, either because the tumor compresses the renal artery and causes an increase in blood pressure, or because the tumor itself is produced. Some kind of boosting substance. When the local or metastatic lesions recur, the blood pressure rises again. After radiotherapy and chemotherapy, the lesions disappear and the blood pressure also drops. This further indicates that the tumor may secrete a certain boosting substance. The plasma renin or hypertensive proteinase content of children with nephroblastoma is higher than that of normal children, and the tumor returns to normal after resection. In recent years, there have been people who have done a quantitative analysis of renin from the leukemic of nephroblastoma, which is much higher than the normal renal cortex.
6. General condition: Generally affected by certain effects, loss of appetite, mild weight loss, lack of spirits, not as lively and fun as before, pale and uncomfortable. When the lungs have metastasis, the general condition is more fading, but there are few symptoms such as cough and hemoptysis.
7. Tumor rupture and metastasis Symptoms: Occasionally, the tumor ruptures spontaneously or after injury. Generally, there is severe pain first. The child has acute anemia, and the diagnosis is liver or spleen rupture. The tumor may rupture in the abdominal cavity, or in the lumbar fossa of the retroperitoneal space. There are also tumors with only a crack and a hematoma under the capsule. Tumors are mainly metastasized by blood flow, so metastasis to the lungs is the most common. After the transfer, there are few symptoms such as cough and hemoptysis. Therefore, X-ray lung examination is very important. Liver metastases are less common.
Examine
Examination of pediatric nephroblastoma
1. Blood examination: blood routine examination can be normal, generally mild anemia, but there are also a small number of red blood cells, which may be related to increased erythropoietin. It can be used as an indicator to track the presence or absence of bone marrow hematopoietic inhibition during treatment.
2. Blood test: normal renal function. The erythrocyte sedimentation rate generally increased rapidly, 15 ~ 90mm / h, and the extra-large tumor settlement rate increased more significantly, which is considered to be an indicator of poor prognosis. Blood urea nitrogen, creatinine and other tests reflect kidney damage. When the kidneys are severely damaged, erythropoietin is reduced. Liver function tests can be used to observe the toxic effects of treatment.
3. Urine examination: There are many hematuria and proteinuria in urinary microscopy, but many cancer cells cannot be found in the urine. Urine tests and culture can detect hematuria and urinary tract infections.
4. Bone marrow examination: This disease is very rare to metastasize to the bone marrow, and neuroblastoma often has bone marrow metastasis, so bone marrow examination is helpful for the differential diagnosis of the two diseases.
5. Puncture biopsy: In recent years, it has been reported that the rapid needle aspiration cytology diagnosis method can be diagnosed by fine needle. The method is simple and the correct rate is 90%. Puncture biopsy has a certain significance for large tumors and is estimated to be unresectable, because the histological type can be determined before surgery, and the prognosis of the child is estimated to facilitate the development of preoperative and postoperative chemotherapy and radiotherapy.
However, there have been reports of tumor implantation in puncture path.
6. X-ray inspection:
(1) Abdominal plain film: It can show the location and extent of the tumor, and the common intestinal tube is pushed to the opposite side. In most cases, the affected side of the flank is inflated, and the inflated intestine is shadowed around the soft tissue density of the tumor and is pushed by the mass to the middle of the abdomen. Calcified spots are extremely rare, and if they are, most appear to be curved at the edges. The lateral radiograph shows the soft tissue block shadow in front of the spine, pushing the inflated gastrointestinal tract forward.
(2) Chest radiograph: The posterior, lateral and oblique images of the posterior thoracic cavity were performed to find metastatic lesions in the lungs. Lung metastasis accounts for about 10%.
7. Intravenous pyelography:
It is the main diagnostic method, and all cases should be examined for the diagnosis of nephroblastoma. About 2/3 of the children showed renal pelvis, renal pelvis deformation, displacement or defect. When the tumor squeezed the renal pelvis, it was significantly elongated or accumulated. All the above forms should be carefully photographed in the right and lateral positions. Observed. The suprarenal tumor may rarely alter the shape of the renal pelvis, or only transposition and decline; the subrenal tumor often moves the ureter to the midline, forming a concave outward curve. One third of the affected children's kidneys are not developed on the conventional tablets because they are mostly oppressed. At this time, they should be delayed to 6h or even 24h. Generally, there are different degrees of contrast agent excretion. If the kidneys are still not developed, it will prompt. The kidneys have been severely damaged, with 36% of domestic reports and only about 10% of foreign countries. It is important to pay attention to the normal shape and function of the contralateral kidney. The author has encountered cases of contralateral kidney malformations (such as repeated kidneys).
Retrograde pyelography is generally not indicated. Inferior vena cava angiography through the femoral vein can be used to see if the tumor has grown into the inferior vena cava. Selective renal angiography is an injury test that is only applied to bilateral nephroblastoma. The extent of surgical resection is determined to understand the distribution of blood vessels, but it is generally unnecessary to diagnose this tumor. Occasionally used to understand the metastasis of the liver and other organs in the abdomen. Both CT and MRI are valuable for diagnosis.
8.B type ultrasonic inspection:
The distinguishable mass is parenchymal or cystic. The echocardiogram of the nephroblastoma shows a mixed image of a small fluid level (necrotic hemorrhage, hydronephrosis) in the front of the lumbar wall. Since this method is non-invasive and painless, it should be listed as the first inspection method.
Ultrasound examination is very helpful for the differential diagnosis of this disease. It is found that cystic signs should pay attention to the possibility of hydronephrosis, polycystic kidney disease or common bile duct dilatation. Ultrasound sees that the tumor has a high-intensity irregular echo that is shown as a malignant tumor.
9. Angiography:
Retrograde abdominal aortic angiography and inferior vena cava angiography can be performed. The blood flow in the distribution area of the affected renal artery is abundant, and abnormal blood vessel formation can be seen in the whole tumor range. It can be seen that the tumor blood vessels increase with the increase of the tumor, and the disorder of the blood vessels is often very obvious. Angiography can help detect smaller tumors. Inferior vena cava angiography can detect the invasive pressure of the tumor on the inferior vena cava.
10. CT, magnetic resonance imaging (MRI) and radionuclide scanning:
CT, MRI, and radionuclide scans have the value of imaging diagnosis for tumors and metastases, so as to understand the location and extent of the tumor, the destruction of its surrounding tissues, and whether there is obvious metastasis.
Diagnosis
Diagnosis and diagnosis of pediatric nephroblastoma
diagnosis
Most of the nephroblastomas are diagnosed due to abdominal masses. X-rays and other special tests help to fully diagnose and understand the spread. For the diagnosis of tumor metastasis and spread, firstly, all patients should be photographed with positive and lateral radiographs of the lungs. The small early metastatic lesions must be carefully viewed repeatedly before they can be found. According to foreign statistics, about 10% of children have lung metastases at the time of diagnosis. The diagnosis of liver metastases is difficult, and radionuclide scanning can only be shown when the liver mass is quite large. Skeletal metastasis has clinical manifestations such as local pain, swelling and tenderness, and only when the symptoms are present, the bone radiographs are taken.
Differential diagnosis
Wilms tumor should first be differentiated from neuroblastoma and differentiated from hematuria caused by acute nephritis and renal tuberculosis. Wilms tumor is differentiated from neuroblastoma, which can be directly extended into the kidney. The tumor usually has nodules on the surface, which is closer to the midline of the abdomen. The determination of catecholamine metabolites (VMA and HVA) can confirm the diagnosis. Renal multi-atrial cyst may be the most difficult disease to distinguish from nephroblastoma. This cyst can be quickly enlarged and has a solid texture. There may be a renal pelvis similar to nephroma on the intravenous urography. And the renal pelvis deformed, the ultrasound checkpoint is also the same, is also a small interval of images, but the incidence of renal multi-atrial cyst is only 1 / 100 of the nephroblastoma, its treatment is very simple, do nephrectomy Surgery, open the tumor, see the size of the cellular sac. Renal cell carcinoma is occasionally seen in children's age, and it is difficult to distinguish it from nephroblastoma before surgery. The diagnosis depends on pathological examination. Hydronephrosis and choledochal cysts are cystic, and ultrasound can be used to identify nephroblastoma.
