Wilms Tumor and Other Childhood Kidney Tumors Treatment (PDQ®)–Health Professional Version

Clear Cell Sarcoma of the Kidney

General Information About Clear Cell Sarcoma of the Kidney

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 is favorable histology (FH) Wilms tumor.[1] 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.[1] (Refer to the Clinical Features of Wilms Tumor and Diagnostic and Staging Evaluation for Wilms Tumor sections of this summary for more information about the clinical features and diagnostic evaluation of childhood kidney tumors.)

Younger age and stage IV disease have been identified as adverse prognostic factors for event-free survival (EFS).[2]

Historically, relapses have occurred in long intervals after the completion of chemotherapy (up to 14 years); however, with current therapy, relapses after 3 years are uncommon.[3] 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.[2-5] 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.

Genomics of Clear Cell Sarcoma of the Kidney

Clear cell sarcoma of the kidney is an uncommon renal tumor that comprises approximately 5% of all primary renal malignancies in children, accounts for approximately 20 new cases per year in the United States, and is observed most often before age 3 years.[1] The molecular background of clear cell sarcoma of the kidney is poorly understood because of its rarity and lack of experimental models.

Several biological features of clear cell sarcoma of the kidney have been described, including the following:

Internal tandem duplications in exon 15 of the BCOR gene (BCL6 corepressor) have been reported in 90% of cases of clear cell sarcoma of the kidney, with a smaller subset harboring YWHAE-NUTM2B/E or BCOR-CCNB3 gene fusions.[6-11] All of these genetic abnormalities result in a transcriptional signature characterized by high BCOR mRNA expression.[12]
Diffuse strong immunoreactivity for BCOR is highly sensitive and specific for the diagnosis of clear cell sarcoma of the kidney. In a series of 79 neoplasms—including Wilms tumors, congenital mesoblastic nephromas, clear cell sarcoma of the kidney, metanephric stromal tumors, rhabdoid tumors of the kidney, renal primitive neuroectodermal tumor (PNET), and sclerosing epithelioid fibrosarcomas—all of the clear cell sarcomas of the kidney samples that were tested demonstrated diffuse, strong nuclear labeling for BCOR. Most of the other pediatric renal neoplasms were completely negative for BCOR.[13]

Treatment of 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 optimal 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 National Wilms Tumor Study (NWTS)-3 trial (NWTS-3), 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.[1]
The NWTS-4 trial used regimen DD-4A, which consisted of vincristine, dactinomycin, and doxorubicin for 15 months, and radiation therapy.[14]
- NWTS-4 reported that patients who were treated with vincristine, doxorubicin, and dactinomycin for 15 months had an improved relapse-free survival rate 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.[3]
- With this treatment, the 5-year EFS rate was 79%, and the OS rate was 90%.
- Stage I patients had 5-year EFS and OS rates of 100%.
- Stage II patients had a 5-year EFS rate of 88% and a 5-year OS rate of 98%.
- Stage III patients had a 5-year EFS rate of 73% and a 5-year OS rate of 89%.
- Stage IV patients had a 5-year EFS rate of 29% and a 5-year OS rate of 36%.
A review of patients with stage I clear cell sarcoma of the kidney treated on the NWTS-1, NWTS-2, NWTS-3, NWTS-4, and NWTS-5 trials showed an excellent OS rate of 100% with a wide variety of chemotherapy and radiation therapy regimens.[15]

(Refer to the Treatment of Recurrent Clear Cell Sarcoma of the Kidney section of this summary for information about recurrent disease.)

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References

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. [PUBMED Abstract]
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. [PUBMED Abstract]
Seibel NL, Chi YY, Perlman EJ, et al.: Impact of cyclophosphamide and etoposide on outcome of clear cell sarcoma of the kidney treated on the National Wilms Tumor Study-5 (NWTS-5). Pediatr Blood Cancer 66 (1): e27450, 2019. [PUBMED Abstract]
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. [PUBMED Abstract]
Gooskens SL, Furtwängler R, Spreafico F, et al.: Treatment and outcome of patients with relapsed clear cell sarcoma of the kidney: a combined SIOP and AIEOP study. Br J Cancer 111 (2): 227-33, 2014. [PUBMED Abstract]
Ueno-Yokohata H, Okita H, Nakasato K, et al.: Consistent in-frame internal tandem duplications of BCOR characterize clear cell sarcoma of the kidney. Nat Genet 47 (8): 861-3, 2015. [PUBMED Abstract]
Argani P, Kao YC, Zhang L, et al.: Primary Renal Sarcomas With BCOR-CCNB3 Gene Fusion: A Report of 2 Cases Showing Histologic Overlap With Clear Cell Sarcoma of Kidney, Suggesting Further Link Between BCOR-related Sarcomas of the Kidney and Soft Tissues. Am J Surg Pathol 41 (12): 1702-1712, 2017. [PUBMED Abstract]
Karlsson J, Valind A, Gisselsson D: BCOR internal tandem duplication and YWHAE-NUTM2B/E fusion are mutually exclusive events in clear cell sarcoma of the kidney. Genes Chromosomes Cancer 55 (2): 120-3, 2016. [PUBMED Abstract]
Astolfi A, Melchionda F, Perotti D, et al.: Whole transcriptome sequencing identifies BCOR internal tandem duplication as a common feature of clear cell sarcoma of the kidney. Oncotarget 6 (38): 40934-9, 2015. [PUBMED Abstract]
Roy A, Kumar V, Zorman B, et al.: Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney. Nat Commun 6: 8891, 2015. [PUBMED Abstract]
Wong MK, Ng CCY, Kuick CH, et al.: Clear cell sarcomas of the kidney are characterised by BCOR gene abnormalities, including exon 15 internal tandem duplications and BCOR-CCNB3 gene fusion. Histopathology 72 (2): 320-329, 2018. [PUBMED Abstract]
Kao YC, Sung YS, Zhang L, et al.: Recurrent BCOR Internal Tandem Duplication and YWHAE-NUTM2B Fusions in Soft Tissue Undifferentiated Round Cell Sarcoma of Infancy: Overlapping Genetic Features With Clear Cell Sarcoma of Kidney. Am J Surg Pathol 40 (8): 1009-20, 2016. [PUBMED Abstract]
Argani P, Pawel B, Szabo S, et al.: Diffuse Strong BCOR Immunoreactivity Is a Sensitive and Specific Marker for Clear Cell Sarcoma of the Kidney (CCSK) in Pediatric Renal Neoplasia. Am J Surg Pathol 42 (8): 1128-1131, 2018. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]