Clear Cell Sarcoma of the Kidney Article Last Updated: May 19, 2006 AUTHOR AND EDITOR INFORMATION Section 1 of 11
Authors and Editors Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Multimedia References
Author: Nita Seibel, MD, Professor of Pediatrics, Fellowship Training Program Director, Department of Hematology/Oncology, George Washington University School of Medicine, Children's National Medical Center of Washington, DC Nita Seibel is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society of Clinical Oncology, American Society of Hematology, and American Society of Pediatric Hematology/Oncology Editors: Kathleen Sakamoto, MD, Professor, Department of Pediatrics, Mattel Children's Hospital, David Geffen School of Medicine, Division of Hematology-Oncology and Pathology and Laboratory Medicine, University of California at Los Angeles; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Timothy P Cripe, MD, PhD, Associate Professor of Pediatric Hematology/Oncology, University of Cincinnati; Director, Translational Research Trials Office, Department of Pediatrics, Cincinnati Children's Hospital Medical Center; Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida, Clinical Professor, Department of Pediatrics, UNC, Adjunct Professor, Department of Pediatrics, Duke University; Max J Coppes, MD, PhD, MBA, Executive Director, Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, DC; Professor of Medicine, Oncology, and Pediatrics, Georgetown University Author and Editor Disclosure Synonyms and related keywords: clear cell sarcoma of the kidney, CCSK, bone-metastasizing
renal tumor, renal sarcoma, clear cell cancer, kidney cancer, kidney sarcoma, renal cancer
INTRODUCTION Section 2 of 11
Authors and Editors Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Multimedia References
Background Clear cell sarcoma of the kidney (CCSK), an uncommon renal neoplasm of childhood, represents one of the most common tumors with "unfavorable histology" listed in the National Wilms Tumor Study Group (NWTSG) clinical protocols. In 1970, Kidd initially recognized CCSK as a distinct clinicopathologic entity, noting its propensity to metastasize to bone. The distinctive histopathologic features of CCSK were reported simultaneously in 1978 by Morgan and Kidd, Marsden et al, and Beckwith and Palmer. These reports confirmed the propensity of the tumor to metastasize to bone, poor clinical outcome, and the sarcomatous nonepithelial nature of the tumor. Pathophysiology Unlike Wilms tumor, CCSK has not been associated with intralobar nephrogenic rests, and, in a series of 351 cases from the NWTSG that was reviewed by Argani et al, only one case of CCSK was associated with a perilobar nephrogenic rest. Gene expression profiles of CCSKs suggest the cell of origin to be a renal mesenchymal cell with neural markers. Only one case of CCSK has been associated with renal dysplasia, and no familial cases or syndromes have been identified in
association with CCSK. Using the fifth National Wilms Tumor Study (NWTS-5) criteria for tumor staging, 25% of patients had localized stage I tumors, most patients presented with stage II (37%) or stage III (34%) disease, and only 4% of patients presented with distant metastases (see Wilms Tumor for staging information). No true bilateral primary tumors have been identified. One patient with widespread disseminated disease was noted to have a 1-cm tumor in the contralateral kidney, which was believed to be a metastasis. The most common site of metastasis at the time of presentation in patients with CCSK is the ipsilateral renal hilar lymph nodes. Skip metastases to periaortic lymph nodes have been reported in patients with CCSK in the presence of hilar lymph nodes that were histologically confirmed with negative results. Only 4% of patients present with distant metastases. Bone is the most common site of metastases (15%), followed closely by lung, abdomen, retroperitoneum, brain, and liver. Unusual soft tissue sites (scalp, epidural, nasopharynx, neck, paraspinal, ovary, abdominal wall, axilla) and other sites (orbit) have been reported. Approximately 20% of documented CCSK metastases occurred at least 3 years after diagnosis; some occurred as long as 10 years later. Frequency United States Approximately 20 new cases of CCSK are diagnosed each year in the United States. CCSK is extremely rare in infants younger than 6 months and in young adults. Most patients are aged 1-4 years. A male predominance exists. Fifty percent of cases are diagnosed in children aged 2-3 years. Mortality/Morbidity The 4-year survival rate was 75% in a group of 50 patients treated during the third National Wilms Tumor Study (NWTS-3). The 6-year survival rate for patients with stage I disease was 97.6%, stage II disease was 75%, stage III disease was 77.4%, and stage IV disease was 50%. Race Whites and African Americans are affected in equal numbers. Sex A male predominance has been noted, with a male-to-female ratio of 2.04:1. Age Age of presentation ranges from 2 months to 14 years, with a mean age of 36 months. The highest incidence of CCSK is in children aged 2-3 years, in which 50% of the cases are diagnosed. A sharp decline in incidence occurs in children older than 3 years. CCSK is
extremely rare in infants younger than 6 months and in young adults, although it has been reported. The oldest reported patient was aged 57 years.
CLINICAL Section 3 of 11
Authors and Editors Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Multimedia References
History Manifestations in patients with clear cell sarcoma of the kidney (CCSK) are similar to those in patients with Wilms tumor. Patients present with an abdominal mass, which usually is identified by a caregiver or family relative who has not seen the child for a while. Often, abdominal swelling or the presence of an abdominal mass is noticed by a parent while bathing or dressing the child. Abdominal pain, gross hematuria, fever, and hypertension are other frequent findings. Physical
Physical findings include a large palpable unilateral abdominal mass. Patients may have accompanying findings, such as hypertension and/or hematuria (gross or microscopic), depending on the size of the tumor. Extrarenal tumors with histologic features identical to those of CCSK have been reported.
Causes
The histogenesis of CCSK is unknown and appears to be unrelated to Wilms tumor. No specific chromosomal translocation has been associated with CCSK; a finding that generally indicates a normal karyotype. Two reports identify a balanced translocation, t(10;17)(q22;p13), in patients with CCSK. Cells that have been suggested as the origin for CCSK are renomedullary interstitial cells, nonorgan specific mesenchymal cells, blastemal cap cells, primitive mesenchymal cells, and the cells that form the lower limbs of S-bodies. Cutcliffe et al have suggested that the cell of origin is within a renal mesenchymal cell that possesses neural markers. http://www.emedicine.com/PED/topic3018.htm eneral Information About Wilms Tumor and Other Childhood Kidney Tumors Key Points for This Section
Wilms tumor and other childhood kidney tumors are diseases in which malignant (cancer) cells form in the tissues of the kidney. Having certain genetic syndromes or birth defects can increase the risk of developing Wilms tumor. Having certain conditions may be associated with renal cell carcinoma. Possible signs of Wilms tumor and other childhood kidney tumors include a lump in the abdomen and blood in the urine. Tests that examine the kidney and the blood are used to detect (find) Wilms tumor and other childhood kidney tumors. Wilms tumor and other childhood kidney tumors are usually diagnosed and removed in surgery. Certain factors affect prognosis (chance of recovery) and treatment options.
Wilms tumor and other childhood kidney tumors are diseases in which malignant (cancer) cells form in the tissues of the kidney. Wilms tumor Wilms tumor and other kidney tumors are diseases in which malignant (cancer) cells are found in the kidney. In Wilms tumor, one or more tumors may be found in one or both kidneys. There are two kidneys, one on each side of the backbone, above the waist. Tiny tubules in the kidneys filter and clean the blood, taking out waste products and making urine. The urine passes from each kidney through a long tube called a ureter into the bladder. The bladder holds the urine until it is passed from the body.
Wilms tumor may spread to the lungs, liver, or nearby lymph nodes. Diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) is a condition in which abnormal tissue grows on the outer part of one or both kidneys. Children with DHPLN are at risk for developing a type of Wilms tumor that grows quickly. Frequent follow-up testing is important for at least 7 years after the child is diagnosed with DHPLN. Other kidney tumors Clear cell sarcoma of the kidney, rhabdoid tumor of the kidney, neuroepithelial tumor of the kidney, renal cell cancer (RCC), and mesoblastic nephroma are also childhood kidney tumors, but they are not related to Wilms tumor.
Clear cell sarcoma of the kidney is a type of kidney tumor that may spread to the lung, bone, brain, and soft tissue. Rhabdoid tumor of the kidney is a type of cancer that occurs mostly in children under age 2. It grows and spreads quickly, often to the lungs and brain. Neuroepithelial tumors of the kidney are rare and usually occur in young adults. They grow and spread quickly. Renal cell carcinoma occurs rarely in children. The tumor can spread to the lungs, bones, liver, and lymph nodes. Mesoblastic nephroma is a tumor of the kidney that is usually diagnosed within the first 3 months of life. It may also be found during an ultrasound before birth. Mesoblastic nephroma occurs more often in males than females.
Having certain genetic syndromes or birth defects can increase the risk of developing Wilms tumor. Anything that increases your risk of getting a disease is called a risk factor. Wilms tumor may be part of a genetic syndrome that affects growth or development. A genetic syndrome is a set of symptoms or conditions that occur together and is usually caused by abnormal genes. Certain birth defects can also increase a child's risk for developing Wilms tumor. The following genetic syndromes and birth defects have been linked to Wilms tumor:
WAGR (Wilms tumor, aniridia, ambiguous genitalia, and mental retardation) syndrome. Beckwith-Wiedemann syndrome. Hemihypertrophy. Denys-Drash syndrome. Cryptorchidism. Hypospadias.
Children with these genetic syndromes and birth defects should be screened for Wilms tumor every three months until age 8. An ultrasound test may be used for screening.
Having certain conditions may be associated with renal cell carcinoma. Renal cell carcinoma may be related to the following conditions:
Von Hippel-Lindau disease (an inherited condition that causes abnormal growth of blood vessels). Tuberous sclerosis (an inherited disease marked by noncancerous fatty cysts in the kidney). Neuroblastoma and/ or sickle cell disease.
Possible signs of Wilms tumor and other childhood kidney tumors include a lump in the abdomen and blood in the urine. These and other symptoms may be caused by kidney tumors. Other conditions may cause the same symptoms. A doctor should be consulted if any of the following problems occur in the child:
A lump, swelling, or pain in the abdomen. Blood in the urine. Fever for no known reason.
Tests that examine the kidney and the blood are used to detect (find) Wilms tumor and other childhood kidney tumors. The following tests and procedures may be used:
Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken. Complete blood count (CBC): A procedure in which a sample of blood is drawn and checked for the following: o The number of red blood cells, white blood cells, and platelets. o The amount of hemoglobin (the protein that carries oxygen) in the red blood cells. o The portion of the blood sample made up of red blood cells. Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it. Liver function test: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by the liver. A higher than normal amount of a substance can be a sign that the liver is not working as it should. Renal function test: A procedure in which blood or urine samples are checked to measure the amounts of certain substances released into the blood or urine by the
kidneys. A higher or lower than normal amount of a substance can be a sign that the kidneys are not working as they should. Urinalysis: A test to check the color of urine and its contents, such as sugar, protein, blood, and bacteria. Ultrasound exam: A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. An ultrasound of the abdomen is done to diagnose a kidney tumor. CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography. Abdominal x-ray: An x-ray of the organs inside the abdomen. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body. Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer.
Wilms tumor and other childhood kidney tumors are usually diagnosed and removed in surgery. Once a kidney tumor is found, surgery is done to find out whether or not the tumor is cancer. If the tumor is only in the kidney, the surgeon will remove the whole kidney (nephrectomy). If there are tumors in both kidneys or if the tumor has spread outside the kidney, a piece of the tumor will be removed. In any case, a sample of tissue from the tumor is sent to a pathologist, who looks at it under a microscope to check for signs of cancer. Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery) and treatment options depend on the following:
How different the tumor cells are from normal kidney cells. The stage of the cancer. The type and size of the tumor. The age of the child. Whether the tumor can be completely removed in surgery. Whether the cancer has just been diagnosed or has recurred (come back). Whether there are any abnormal chromosomes or genes. Whether the patient is treated by pediatric experts with experience in treating patients with Wilms tumor.
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