eMedicine Specialties > Pediatrics: General Medicine > Oncology

Clear Cell Sarcoma of the Kidney

Author: Nita Seibel, MD, Senior Investigator, Pediatric Section, Clinical Investigations Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute; Adjunct Professor of Pediatrics, George Washington University School of Medicine and Public Health; Attending Physician, Center for Cancer and Blood Disorders, Children's National Medical Center
Contributor Information and Disclosures

Updated: Feb 11, 2009

Introduction

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.¹ In 1970, Kidd initially recognized clear cell sarcoma of the kidney as a distinct clinicopathologic entity, noting its propensity to metastasize to bone. The distinctive histopathologic features of clear cell sarcoma of the kidney were reported simultaneously in 1978 by Morgan and Kidd,² Marsden et al,³ and Beckwith and Palmer.¹ 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, clear cell sarcoma of the kidney has not been associated with intralobar nephrogenic rests. In a series of 351 cases from the NWTSG that was reviewed by Argani et al, only one case of clear cell sarcoma of the kidney was associated with a perilobar nephrogenic rest.⁴ Gene expression profiles of clear cell sarcomas of the kidney suggest the cell of origin to be a renal mesenchymal cell with neural markers. Only one case has been associated with renal dysplasia, and no familial cases or syndromes have been identified in association with clear cell sarcoma of the kidney. 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).⁵

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 clear cell sarcoma of the kidney is the ipsilateral renal hilar lymph nodes. Skip metastases to periaortic lymph nodes have been reported in patients with clear cell sarcoma of the kidney 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 clear cell sarcoma of the kidney metastases occurred at least 3 years after diagnosis; some occurred as long as 10 years later.

Frequency

United States

Clear cell sarcoma of the kidney represents less than 3% of pediatric renal tumors. Approximately 20 new cases are diagnosed each year in the United States. Clear cell sarcoma of the kidney is extremely rare in infants younger than 6 months and in young adults. Most patients are aged 1-4 years. A male predominance is observed. Fifty percent of cases are diagnosed in children aged 2-3 years. Around 5% of patients have metastatic disease at presentation.

Mortality/Morbidity

In the fourth National Wilms Tumor Study (NWTS-4), patients were randomized between 6 months of chemotherapy and 15 months of chemotherapy.⁶  Patients randomized to 15 months of therapy had a better outcome compared with patients who received the shorter course of chemotherapy. The 8-year relapse-free survival and overall survival were 87.8% and 87.5%, respectively, for patients receiving 15 months of chemotherapy.

Race

Whites and blacks 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 clear cell sarcoma of the kidney 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. Clear cell sarcoma of the kidney 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

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 is usually identified by a caregiver or family relative who has not seen the child in some time.

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 clear cell sarcoma of the kidney have been reported.

Causes

The histogenesis of clear cell sarcoma of the kidney is unknown and appears to be unrelated to Wilms tumor. No specific chromosomal translocation has been associated with clear cell sarcoma of the kidney; a finding that generally indicates a normal karyotype. 

The origin of clear cell sarcoma of the kidney has not been established. Dysregulation of the EGFR pathway has been observed at multiple levels in clear cell sarcoma of the kidney. The proto-oncogene c-kit is overexpressed in clear cell sarcoma of the kidney but is not accompanied by gene amplification or activating mutations. The t(10;17)(q22;p13) and deletion 14q have been described. Cells that have been suggested as the origin for clear cell sarcoma of the kidney include 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.⁷

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