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

Primary Renal Sarcomas With BCOR-CCNB3 Gene Fusion

“…As such, BCOR-CCNB3 sarcomas are typically treated as Ewing sarcomas at most centers today. Given the overlapping morphology of BCOR-CCNB3 sarcomas which CCSK and their overlapping transcriptional profile, and given that patients with CCSK have been shown to benefit from specific doxorubicin-based chemotherapy 1, 29 , it seems logical to consider treating the BCOR-CCNB3 soft tissue sarcomas with CCSK-based therapy regimens (which emphasize Doxorubicin and do not include Ifosfamide) rather than Ewing sarcoma-based regimens (which include both Doxorubicin and Ifosfamide). The former chemotherapy regimen is overall less toxic, and at least in CCSK has demonstrated significant clinical benefit.…”

Rationale for the treatment of children with CCSK in the UMBRELLA SIOP–RTSG 2016 protocol

“…The morphology of CCSK shows a remarkable diversity, which can result in considerable diagnostic difficulty 2,3 . In the SIOP 93-01 and SIOP 2001 studies, 27% of CCSKs were initially diagnosed as other renal tumours by local pathologists 2 .…”

“…Once the diagnosis of CCSK is made, brain MRI is advised as a complementary baseline investigation, as observational studies of the AIEOP, SIOP, and COG renal tumour study groups have identified the brain to be a preferential site for CCSK meta stasis, especially in the relapse setting (approximately 40% of relapses are located in the brain) 20,21 . Furthermore, whole-body FDG-PET (sensitivity ± 90%), whole-body MRI (sensitivity ± 82%), or 99m Tc bone scan (sensitivity ± 71%) is recommended as bone is one of the most common metastatic sites at diagnosis (in SIOP 93-01 and SIOP 2001, 69% of metastases at diagnosis occurred in the bone, and in NWTS 5 22% of metastasis at diagnosis occurred in the bone) 2,20,38 .…”

“…minority of patients do not have a favourable prognostic clinical signature (especially patients with stage IV disease, young patients, and patients with relapsed disease), and a plateau in survival seems to have been reached as current treatment protocols already contain the maximum tolerated intensity of traditional cytotoxic agents that can cause consequential serious toxicity 2,3,21 . Thus, the development of new (targeted) therapies is necessary for this group of patients.…”

Clear Cell Sarcoma of the Kidney in a Child with Fanconi Anemia

“…The fact that heterozygous loss-of-function mutations predispose to early onset breast and ovarian cancer underlines the significant role these genes have in oncogenesis [10], While patients in this complementation group have an increased risk of solid tumors, CCSK has not been reported previously to our knowledge. In the general population, CCSK is extremely rare, representing be tween 3 and 5% of pediatric renal tumors [11,12], The CCSK was recognized as a clinical entity distinct from WT (which is associated more frequently with FA), nearly 30 years ago, with a tendency to metastasize to bone [13]. Its pathogenesis also appears to be distinct from WT, and its resistance to conventional therapy makes proper distinction between these two renal neoplasms essential [14].…”