Approximately 20% of paediatric and adolescent/young adult patients with renal tumours are diagnosed with non-Wilms tumour, a broad heterogeneous group of tumours that includes clear-cell sarcoma of the kidney, congenital mesoblastic nephroma, malignant rhabdoid tumour of the kidney, renal-cell carcinoma, renal medullary carcinoma and other rare histologies. The differential diagnosis of these tumours dates back many decades, when these pathologies were identified initially through clinicopathological observation of entities with outcomes that diverged from Wilms tumour, corroborated with immunohistochemistry and molecular cytogenetics and, subsequently, through next-generation sequencing. These advances enabled near-definitive recognition of different tumours and risk stratification of patients. In parallel, the generation of new renal-tumour models of some of these pathologies including cell lines, organoids, xenografts and genetically engineered mouse models improved our understanding of the development of these tumours and have facilitated the identification of new therapeutic targets. Despite these many achievements, paediatric and adolescent/young adult patients continue to die from such rare cancers at higher rates than patients with Wilms tumour. Thus, international coordinated efforts are needed to answer unresolved questions and improve outcomes.
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