Clinical management of children with clear cell sarcoma of the kidney according to the uMbreLLa SIoP rTSG 2016 protocol

Clear cell sarcoma of the kidney (CCSK) is an uncommon childhood renal tumor that comprises 2-5% of all primary renal malignancies in children 1-4. CCSK is observed most often in children between two and four years of age, shows a slight male predominance and is characterized by a high malignant potential 3, 5. The majority of the patients presents with localized disease, while metastatic disease is identified in only 6-7% of the patients at diagnosis (most frequent sites: bone, lungs and liver) 2, 3, 5. Histologically, CCSKs show a remarkable morphologic diversity (ie classic, myxoid, sclerosing, cellular, epithelioid and other histological patterns) 3. This often renders difficulties in distinguishing CCSK from other pediatric renal tumors, including blastemal type nephroblastoma, mesoblastic nephroma, primitive neuroectodermal tumor and rhabdoid tumor of the kidney 2. The histogenesis of CCSK is uncertain. Tumor cells are positive for vimentin 3. In addition, recent studies showed diffuse and strong reactivity of CCSKs after immunohistochemical staining with cyclin D1, NGFR and BCOR 6-8. CCSKs are genetically relatively quiescent renal tumors, even at RNA/DNA deep sequencing levels 9-12. A subgroup of CCSKs has been shown to carry the translocation t (10; 17)(q22; p13), leading to a fusion of the genes YWHAE and NUTM2B/E 13. Recently, a somatic internal tandem duplication (ITD) in the X-linked BCOR gene affecting the 3’part of the exon 16 coding sequence has been discovered in the majority of CCSKs 10, 12, 14. It has been shown that these BCOR ITDs and t (10; 17)(q22; p13) are mutually exclusive events in CCSK 15-17 …