Wilms' Tumor

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•Background
•Pathophysiology
•Frequency
•Mortality/Morbidity
•Clinical Examinination
•Differential Diagnoses
•Treatment Modalities
•Prognosis
•Jordanian Perspective

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  • Max Wilms, MDInitially, German surgeon Max Wilms, born in Hünshoven, Germany, studied law as did his father and his oldest brother. After only one semester, however, he decided to switch to medicine. This fateful choice led him to discoveries to which he dedicated the rest of his years.At the start of his medical career, Wilms examined children’s kidney tumors, added seven cases to a thorough review of the literature, and produced what was the definitive work on the subject in 1899. Throughout his life he studied ulcers, burns, tuberculosis, and the uses of radiation, and co-edited a book on surgery. He may be best remembered for his thorough work with childhood cancer.Max Wilms would probably be surprised to learn that his name is now linked with this childhood disease. But Dr. Wilms would be even more surprised and delighted, no doubt to learn how many children can now be cured of Wilms tumor.In light of recent events it is important to note that Dr. Wilms died saving the life of an enemy prisoner of war. In May 1918, during World War I, Wilms died of diphtheria. He was infected by one of his patients, a French officer, on whom he had operated. This utterly dedicated physician never lived to know that his last patient would fully recover.
  • BackgroundWilms tumor, or nephroblastoma, is the most common childhood abdominal malignancy. Over the past 4 decades, the multidisciplinary approach to this tumor has become an example for successful cancer treatment. At present, survival rates of children with this neoplasm are approximately 85-90%. This is in contrast to the rate 50 years ago, when only 10% of children survived. The addition of radiation therapy to surgery alone improved survival rates to approximately 40%. Since the use of chemotherapy began, survival rates of 80-90% have been observed.The National Wilms Tumor Study Group (NWTSG) and the International Society of Pediatric Oncology (SIOP) have identified several chemotherapeutic agents through their clinical trials.  When used together, these agents lead to a cure in most children with this renal tumor. In addition, the guidelines for surgical treatment and the role of radiation therapy are better defined now than ever before.With overall survival rates approaching 90%, therapeutic trials have focused on limiting treatment-related toxicity.1Understanding of the molecular mechanisms that contribute to the development of Wilms tumor has also greatly increased, making Wilmstumorigenesis a model for the understanding of the development of other tumors.
  • FrequencyUnited StatesWilms tumor affects approximately 10 children and adolescents per 1 million before the age of 15 years. Therefore, it accounts for 6-7% of all childhood cancers in North America. As a result, about 450-500 new cases are diagnosed each year on this continent. In 5-10% of patients, both kidneys are affected at the same time (synchronous bilateral Wilms tumor) or one after the other (metachronous bilateral Wilms tumor).InternationalWilms tumor appears to be most common among blacks and least common in the East Asian population.6 The incidence in Europe is similar to that reported in North America.
  • Mortality/MorbidityBefore the multimodality approach was available, the survival rate of patients was less than 50%. With the current NWTSG and SIOP strategies, survival rates are approaching 90%. Most survivors of Wilms tumor have good functional outcomes and quality of life. See also Prognosis.RaceWilms tumor is relatively more common in blacks than in whites and is rare in East Asians. Estimates suggest 6-9 cases per million person years in whites, 3-4 cases per million person years in East Asians and more than 10 cases per million person years among black populations.6SexAmong patients with unilateral Wilms tumor enrolled in all NWTSG protocols, the male-to-female ratio was 0.92:1. For patients with bilateral disease, the male-to-female ratio was 0.60:1.AgeThe median age at diagnosis is approximately 3.5 years. The median age is highest for patients with unilateral unicentric disease (36.1 mo) and lowest for those with synchronous bilateral Wilms tumors (25.5 mo).6
  • Mortality/MorbidityBefore the multimodality approach was available, the survival rate of patients was less than 50%. With the current NWTSG and SIOP strategies, survival rates are approaching 90%. Most survivors of Wilms tumor have good functional outcomes and quality of life. See also Prognosis.RaceWilms tumor is relatively more common in blacks than in whites and is rare in East Asians. Estimates suggest 6-9 cases per million person years in whites, 3-4 cases per million person years in East Asians and more than 10 cases per million person years among black populations.6SexAmong patients with unilateral Wilms tumor enrolled in all NWTSG protocols, the male-to-female ratio was 0.92:1. For patients with bilateral disease, the male-to-female ratio was 0.60:1.AgeThe median age at diagnosis is approximately 3.5 years. The median age is highest for patients with unilateral unicentric disease (36.1 mo) and lowest for those with synchronous bilateral Wilms tumors (25.5 mo).6
  • Mortality/MorbidityBefore the multimodality approach was available, the survival rate of patients was less than 50%. With the current NWTSG and SIOP strategies, survival rates are approaching 90%. Most survivors of Wilms tumor have good functional outcomes and quality of life. See also Prognosis.RaceWilms tumor is relatively more common in blacks than in whites and is rare in East Asians. Estimates suggest 6-9 cases per million person years in whites, 3-4 cases per million person years in East Asians and more than 10 cases per million person years among black populations.6SexAmong patients with unilateral Wilms tumor enrolled in all NWTSG protocols, the male-to-female ratio was 0.92:1. For patients with bilateral disease, the male-to-female ratio was 0.60:1.AgeThe median age at diagnosis is approximately 3.5 years. The median age is highest for patients with unilateral unicentric disease (36.1 mo) and lowest for those with synchronous bilateral Wilms tumors (25.5 mo).6
  • Saudi Journal of Kidney Disease and Transplantation2000IsamHaddadin, Pediatric OncologistIssaHazza, Pediatric Nephrologist
  • Saudi Journal of Kidney Disease and Transplantation2000IsamHaddadin, Pediatric OncologistIssaHazza, Pediatric Nephrologist
  • OVERGROWTH ABNORMALITIESThese in turn can be subdivided into hemihypertrophy and the Beckwith-Wiedemann Syndrome(BWS). Hemihypertrophy means that one side of the body—in whole or in part—is larger than the other side. Thus, one whole leg or arm may be longer and bigger around than the other, but even smaller parts like one side of the face may be asymmetrical. The BWS is more complex. It is characterized by a large tongue that may protrude from the mouth, a hernial sac in the belly button (called an omphalocele), and low blood sugar levels. Children with the BWS may exhibit enlargement of other organs such as the liver and pancreas. Hemihypertrophy may also be seen. They can develop cancers other than Wilms tumor (for example malignant growths in the liver and the gland above the kidney which therefore is called the suprarenal gland).
  • THE WAGR SYNDROMEThe W stands for Wilms tumor, the A for Aniridia, the G for abnormalities of the Genito-urinary organs, and the R for Retardation. Aniridia is the absence of the iris of the eye present at birth. The genito-urinary malformations include major anatomic mal developments. These include mixed development of the sexual organs making identification of sex uncertain, undescendedtesticle, or severe hypospadius. In this latter condition the urinary stream issues not at the tip of the urethra but from an abnormal orificealong the shaft of the penis or even higher than that; for instance, in the perineum. The R in mental Retardation completes the acronym.
  • ClinicalHistoryThe most common manifestation of Wilms tumor is an asymptomatic abdominal mass; an abdominal mass occurs in 80% of children at presentation. Abdominal pain or hematuria occurs in 25%. Urinary tract infection andvaricocele are less common findings than these. Hypertension, gross hematuria, and fever are observed in 5-30% of patients. A few patients with hemorrhage into their tumor may present with hypotension, anemia, and fever. Rare patients with advanced disease may present with respiratory symptoms related to lung metastases.PhysicalExamination often reveals a palpable abdominal mass. Pay special attention to features of those syndromes (WAGR syndrome and Beckwith-Wiedemann syndrome [BWS]) associated with Wilms tumor (ie, aniridia, genitourinary malformations, and signs of overgrowth).The abdominal mass should be carefully examined. Palpating a mass too vigorously could lead to the rupture of a large tumor into the peritoneal cavity.CausesWilms tumor is thought to be caused by alterations of genes responsible for normal genitourinary development. Examples of common congenital anomalies associated with Wilms tumor are cryptorchidism, a double collecting system, horseshoe kidney, and hypospadias. Environmental exposures, although considered, seem relatively unlikely to play a role. See Pathophysiology.
  • Laboratory StudiesThe following studies are indicated in patients with Wilms tumor:CBC countChemistry profile, including kidney function tests and routine measurements of electrolytes and calciumUrinalysisCoagulation studiesCytogeneticsstudiesResults may reveal an 11p13 deletion as in WAGR syndrome.Studies may show a duplication of the paternal allele 11p15, as in Beckwith-Wiedemann syndrome (BWS).Mutational analysis of the WT1 gene may be indicated when Denys-Drash syndrome (intersexual disorders, nephropathy, Wilms tumor) is suspected.
  • Imaging StudiesRenal ultrasonography Often, the initial study as ultrasonography does not expose children to the detrimental effects of radiation.CT scanning[8]Abdominal CT scanning helps in determining the origin of the tumor, involvement of the lymph nodes, bilateral kidney involvement, invasion into major vessels (eg, inferior vena cava), and liver metastases.CT scan in a patient with a right-sided Wilms tumor with favorable histology.CT scan of child with a stage IV Wilms tumor with favorable histology. Note the bilateral pulmonary metastases.If chest CT findings are positive and chest radiographic findings are negative, diagnostic biopsy of the lesions noted on the chest CT scan is recommended.MRI scanning Abdominal MRI scanning has been reported to be the most sensitive imaging modality for determination of caval patency and may be important in determining whether the inferior vena cava is directly invaded by tumor.Wilms tumor demonstrates low signal intensity on T1-weighted images and high signal intensity on T2-weighted images.Four-field chest radiography Images may depict lung metastases.Patients with lung lesions on chest radiography have traditionally been given whole-lung radiation therapy.Histopathologic confirmation of Wilms tumor is essential.In North America, patients with suspected Wilms tumor undergo nephrectomy immediately. During this procedure, the contralateral kidney is explored to ensure that the disease is indeed unilateral, and lymph node biopsy samples are obtained for staging purposes. Lymph node dissection is not indicated.In contrast to immediate surgery, most European centers make a presumptive diagnosis of Wilms tumor based on imaging findings alone. Clinicians in Europe prefer to administer chemotherapy before nephrectomy without survival compromise.[9, 10]In North America, immediate nephrectomy is not performed in patients with bilateral disease at presentation when sparing of the renal tissue becomes important.Transcutaneous biopsy is not usually recommended and may in fact complicate treatment by causing preoperative tumor spill, requiring whole abdominal radiotherapy.Patients with negative findings on chest radiography and positive findings on CT of the lungs require tissue diagnosis of the lung nodules because several conditions (eg, histoplasmosis, atelectasis, pseudotumor, intrapulmonary lymph node, pneumonia) can mimic pulmonary metastases. Studies from the NWTS have not shown any survival benefit by treating nodules that have negative chest radiograph findings but positive CT scan findings with whole lung radiotherapy. In one study, patients treated with whole lung radiotherapy had fewer lung relapse but had higher treatment-related deaths.[11]Histologic FindingsThe classic histologic pattern is triphasic and composed of epithelial, blastemal, and stromalelements.Approximately 90% of all renal tumors have favorable histology.About 3-7% of Wilms tumors are characterized by anaplastic changes. If these changes are present diffusely throughout the tumor, they are predictive of a poor outcome. Wilms tumors with anaplastic changes have unfavorable histology.Two tumor types previously included in the category with unfavorable histology are, in fact, clearly separate malignant entities. These types are clear cell sarcoma of the kidney (CCSK) and rhabdoid tumor of the kidney (RTK).The improved histopathologic classification of childhood renal tumors has not only helped to define appropriate treatment strategies for these patients but has also contributed to the understanding of the molecular genetic events underlying the Wilmstumor.For instance, nephrogenic rests, dysplastic lesions of metanephric origin, are now believed to represent precursor lesions. These lesions are observed in approximately one third of kidneys affected by Wilms tumors.The relationship between the pathology of the nephrogenic rests, the tumor, and the congenital disorders is of particular interest. These associations have been helpful in evaluating a potential correlation between a Wilms tumor phenotype in one regard and molecular genetic events leading to the development of that same tumor in another.Children younger than 12 months diagnosed with perilobarnephrogenic rests have a markedly increased risk of developing a contralateralWilms tumor.[12]StagingThe current Children's Oncology Group (COG) staging for Wilms tumor is as follows:Stage I: Tumor is limited to kidney and is completely resected. The renal capsule is intact. The tumor was not ruptured or biopsied prior to removal. The vessels of the renal sinus are not involved. No evidence of tumor is present at or beyond margins of resection.Stage II: The tumor is completely resected, and no evidence of tumor at or beyond the margins of resection is noted. The tumor extends beyond the kidney (penetration of renal capsule, involvement of renal sinus).Stage III: A residual nonhematogenous tumor is present following surgery and is confined to the abdomen. Positive lymph nodes in abdomen or pelvis are noted. Penetration through peritoneal surface is observed. Peritoneal implants are present. Gross or microscopic tumor remains postoperatively, including positive margins of resection. Tumor spillage is noted. The tumor is treated with preoperative chemotherapy. The rumor is removed in more than one piece.Stage IV: Hematogenous metastases (eg, lung, liver, bone, brain) or lymph node metastases beyond abdomen or pelvis is noted.Stage V: Bilateral renal involvement by tumor is present at diagnosis.
  • Histologic FindingsThe classic histologic pattern is triphasic and composed of epithelial, blastemal, and stromalelements.Approximately 90% of all renal tumors have favorable histology.About 3-7% of Wilms tumors are characterized by anaplastic changes. If these changes are present diffusely throughout the tumor, they are predictive of a poor outcome. Wilms tumors with anaplastic changes have unfavorable histology.Two tumor types previously included in the category with unfavorable histology are, in fact, clearly separate malignant entities. These types are clear cell sarcoma of the kidney (CCSK) and rhabdoid tumor of the kidney (RTK).The improved histopathologic classification of childhood renal tumors has not only helped to define appropriate treatment strategies for these patients but has also contributed to the understanding of the molecular genetic events underlying the Wilmstumor.For instance, nephrogenic rests, dysplastic lesions of metanephric origin, are now believed to represent precursor lesions. These lesions are observed in approximately one third of kidneys affected by Wilms tumors.The relationship between the pathology of the nephrogenic rests, the tumor, and the congenital disorders is of particular interest. These associations have been helpful in evaluating a potential correlation between a Wilms tumor phenotype in one regard and molecular genetic events leading to the development of that same tumor in another.Children younger than 12 months diagnosed with perilobarnephrogenic rests have a markedly increased risk of developing a contralateralWilms tumor.[12]
  • Stage I.The tumor is limited to the kidney, isencapsulated, and can be completelyremoved surgically.Stage II.The tumor extends beyond thekidney but is completely removed.Stage III.The tumor is not completely removedsurgically, but disease is still limitedto the abdomen.Stage IV.The disease has spread to the lung,liver, bone, brain, or to lymph nodesoutside the pelvic region.Stage V.Both kidneys contain tumor atdiagnosis.
  • oss of heterozygosity (LOH)Dome JS, Cotton CA, Perlman EJ, et al. Treatment of anaplastic histology Wilms' tumor: results from the fifth National Wilms' Tumor Study. J ClinOncol. May 20 2006;24(15):2352-8.
  • Wilms' Tumor

    1. 1. Wilms’ Tumor<br />Nephroblastoma<br />AbdulQadir J. Nashwan<br />
    2. 2. Road Map<br />
    3. 3. Max Wilms, MD<br />To know more about Max Wilms<br />
    4. 4. Background<br />Wilms’ tumor, or nephroblastoma, is the most common childhood abdominal malignancy<br />(Coppes & Pritchard-Jones, 2000)<br />
    5. 5. Frequency<br /><ul><li>Wilms’ tumor affects approximately 10 children and adolescents per 1 million before the age of 15 years.
    6. 6. Accounts for 6-7% of all childhood cancers in North America.
    7. 7. About 450-500 new cases are diagnosed each year</li></ul>(ACS, 2010) <br />
    8. 8. Facts<br /><ul><li>In 7% of children with Wilms’ tumor, both kidneys are involved at diagnosis.
    9. 9. In only 1% of the children who have a kidney removed due to Wilms’tumor, does the cancer re-appear later in the other kidney.
    10. 10. Possible causable factors in the environment of parents or their child that might lead to Wilms’tumor have not been determined.
    11. 11. There is a family history of the disease in only 1% of cases.</li></ul>(NWTSG) <br />
    12. 12. Race<br />6-9 cases <br />per million <br />3-4 cases <br />per million <br />10 cases <br />per million <br />(Breslow, Olshan, Beckwith & Green, 1993)<br />
    13. 13. Gender<br />:<br />1<br />0.6<br />(Breslow, Olshan, Beckwith & Green, 1993)<br />
    14. 14. Age<br />The median age at diagnosis is approximately 3.5 years<br />(Breslow, Olshan, Beckwith & Green, 1993)<br />
    15. 15. Wilms’ Tumor Experience at King Hussein Medical Center<br />Saudi Journal of Kidney Disease and Transplantation<br />2000<br />IsamHaddadin, Pediatric Oncologist<br />IssaHazza, Pediatric Nephrologist<br />
    16. 16.
    17. 17. Associated Signs & Syndromes<br />Omphalocele<br />
    18. 18.
    19. 19. Wilms’ Tumor<br />
    20. 20. Clinical Features<br />
    21. 21. Diagnoses<br />
    22. 22. Diagnoses<br />
    23. 23. Diagnoses<br />
    24. 24. Diagnoses<br />Nephrogenic rests (NRs) <br />believed to represent precursor lesions. <br />
    25. 25. Staging<br />Stage I.<br /><ul><li>The tumor is limited to the kidney, is encapsulated, and can be completely removed surgically.</li></ul>Stage II.<br /><ul><li>The tumor extends beyond the kidney but is completely removed.</li></ul>Stage III.<br /><ul><li>The tumor is not completely removed surgically, but disease is still limited to the abdomen.</li></ul>Stage IV.<br /><ul><li>The disease has spread to the lung, liver, bone, brain, or to lymph nodes outside the pelvic region.</li></ul>Stage V.<br /><ul><li>Both kidneys contain tumor at diagnosis.</li></ul>(NWTSG) <br />
    26. 26. Treatment & Medication<br />Table 1. Current Approach to Favorable Histology WilmsTumo by Stage<br />
    27. 27. References<br />Coppes MJ, Pritchard-Jones K. Principles of Wilms' tumor biology. UrolClin North Am. Aug 2000;27(3):423-33, viii.<br />Breslow N, Olshan A, Beckwith JB, Green DM. Epidemiology of Wilms tumor. Med PediatrOncol. 1993;21(3):172-81<br />Dome JS, Cotton CA, Perlman EJ, et al. Treatment of anaplastic histology Wilms' tumor: results from the fifth National Wilms' Tumor Study. J ClinOncol. May 20 2006;24(15):2352-8.<br />Coppes MJ, Arnold M, Beckwith JB, et al. Factors affecting the risk of contralateralWilms tumor development: a report from the National Wilms Tumor Study Group. Cancer. Apr 1 1999;85(7):1616-25.<br />

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