Clear cell sarcoma of the kidney is not a Wilms tumor variant, but it is an important primary renal tumor associated with a higher rate of relapse and death than favorable-histology (FH) Wilms tumor. The classic pattern of clear cell sarcoma of the kidney is defined by nests or cords of cells separated by regularly spaced fibrovascular septa. In addition to pulmonary metastases, clear cell sarcoma also spreads to bone, brain, and soft tissue. (Refer to the Wilms tumor Clinical Features and Diagnostic and Staging Evaluation sections of this summary for more information about the clinical features and diagnostic evaluation of childhood kidney tumors.)
While little is known about the biology of clear cell sarcoma of the kidney, the t(10;17)(q22;p13) translocation has been reported. As a result of the translocation, the YWHAE-FAM22 fusion transcript is formed; this transcript was detected in 12% of cases of clear cell sarcoma of the kidney in one series. 17p13 is the site of the P53 gene; however, this gene does not show abnormal expression and most likely is not involved. Gene expression studies revealed the upregulation of neural markers, with ensuing activation of the sonic hedgehog and Akt pathways. When DNA methylation profiling was used, the epigenetic characteristics of clear cell sarcoma of the kidney, rhabdoid tumor of the kidney, and Ewing sarcoma of the kidney, in comparison with those of the non-neoplastic kidney, exhibited distinct DNA methylation profiles in a tumor type-specific manner. The DNA methylation pattern of the THBS1 CpG site is sufficient for distinction of clear cell sarcoma of the kidney from other pediatric renal tumors.
Younger age and stage IV disease have been identified as adverse prognostic factors for event-free survival (EFS).
Historically, relapses have occurred in long intervals after the completion of chemotherapy (up to 10 years); however, with current therapy, relapses after 3 years are uncommon. The brain is a frequent site of recurrent disease, suggesting that it is a sanctuary site for cells that are protected from the intensive chemotherapy that patients currently receive.[5,7,8] An awareness of the clinical signs of recurrent disease in the brain is important during regular follow-up. There are no standard recommendations for the frequency of brain imaging during follow-up.
Standard Treatment Options for Clear Cell Sarcoma of the Kidney
Because of the relative rarity of this tumor, all patients with clear cell sarcoma of the kidney should be considered for entry into a clinical trial. Treatment planning by a multidisciplinary team of cancer specialists (pediatric surgeon or pediatric urologist, pediatric radiation oncologist, and pediatric oncologist) with experience treating renal tumors is required to determine and implement optimum treatment.
The approach for treating clear cell sarcoma of the kidney is different from the approach for treating Wilms tumor because the overall survival (OS) of children with clear cell sarcoma of the kidney remains lower than that for patients with FH Wilms tumor. All patients undergo postoperative radiation to the tumor bed and receive doxorubicin as part of their chemotherapy regimen.
The standard treatment option for clear cell sarcoma of the kidney is the following:
- Surgery, chemotherapy, and radiation therapy.
Surgery, chemotherapy, and radiation therapy
Evidence (surgery, chemotherapy, and radiation therapy):
- In the NWTS-3 trial, the addition of doxorubicin to the combination of vincristine, dactinomycin, and radiation therapy resulted in an improvement in disease-free survival for patients with clear cell sarcoma of the kidney.
- The NWTS-4 trial used regimen DD-4A, which consisted of vincristine, dactinomycin, and doxorubicin for 15 months and radiation therapy.
- NWTS-4 reported that patients who were treated with vincristine, doxorubicin, and dactinomycin for 15 months had an improved relapse-free survival compared with patients who were treated for 6 months (88% vs. 61% at 8 years).
- In the NWTS-5 (COG-Q9401/NCT00002611) trial, children with stages I to IV clear cell sarcoma of the kidney were treated with a new chemotherapeutic regimen combining vincristine, doxorubicin, cyclophosphamide, and etoposide in an attempt to further improve the survival of these high-risk groups. All patients received radiation therapy to the tumor bed.
- With this treatment, the 5-year EFS was approximately 79%, and the OS was approximately 89%.
- Stage I patients had 5-year EFS and OS rates of 100%.
- Stage II patients had a 5-year EFS of approximately 87% and a 5-year OS of approximately 97%.
- Stage III patients had a 5-year EFS of approximately 74% and a 5-year OS of approximately 87%.
- Stage IV patients had a 5-year EFS of approximately 36% and a 5-year OS of 45%.
- A review of stage I clear cell sarcoma of the kidney treated on the NWTS-1 through NWTS-5 trials showed an excellent 100% OS with a wide variety of chemotherapy and radiation therapy regimens.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with clear cell sarcoma of the kidney. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
- Argani P, Perlman EJ, Breslow NE, et al.: Clear cell sarcoma of the kidney: a review of 351 cases from the National Wilms Tumor Study Group Pathology Center. Am J Surg Pathol 24 (1): 4-18, 2000.
- O'Meara E, Stack D, Lee CH, et al.: Characterization of the chromosomal translocation t(10;17)(q22;p13) in clear cell sarcoma of kidney. J Pathol 227 (1): 72-80, 2012.
- Cutcliffe C, Kersey D, Huang CC, et al.: Clear cell sarcoma of the kidney: up-regulation of neural markers with activation of the sonic hedgehog and Akt pathways. Clin Cancer Res 11 (22): 7986-94, 2005.
- Ueno H, Okita H, Akimoto S, et al.: DNA methylation profile distinguishes clear cell sarcoma of the kidney from other pediatric renal tumors. PLoS One 8 (4): e62233, 2013.
- Furtwängler R, Gooskens SL, van Tinteren H, et al.: Clear cell sarcomas of the kidney registered on International Society of Pediatric Oncology (SIOP) 93-01 and SIOP 2001 protocols: a report of the SIOP Renal Tumour Study Group. Eur J Cancer 49 (16): 3497-506, 2013.
- Seibel NL, Li S, Breslow NE, et al.: Effect of duration of treatment on treatment outcome for patients with clear-cell sarcoma of the kidney: a report from the National Wilms' Tumor Study Group. J Clin Oncol 22 (3): 468-73, 2004.
- Seibel NL, Sun J, Anderson JR, et al.: Outcome of clear cell sarcoma of the kidney (CCSK) treated on the National Wilms Tumor Study-5 (NWTS). [Abstract] J Clin Oncol 24 (Suppl 18): A-9000, 502s, 2006.
- Radulescu VC, Gerrard M, Moertel C, et al.: Treatment of recurrent clear cell sarcoma of the kidney with brain metastasis. Pediatr Blood Cancer 50 (2): 246-9, 2008.
- Kalapurakal JA, Perlman EJ, Seibel NL, et al.: Outcomes of patients with revised stage I clear cell sarcoma of kidney treated in National Wilms Tumor Studies 1-5. Int J Radiat Oncol Biol Phys 85 (2): 428-31, 2013.