Perotti Daniela, O'Sullivan Maureen J, Walz Amy L, Davick Jonathan, Al-Saadi Reem, Benedetti Daniel J, Brzezinski Jack, Ciceri Sara, Cost Nicholas G, Dome Jeffrey S, Drost Jarno, Evageliou Nicholas, Furtwängler Rhoikos, Graf Norbert, Maschietto Mariana, Mullen Elizabeth A, Murphy Andrew J, Ortiz Michael V, van der Beek Justine N, Verschuur Arnauld, Wegert Jenny, Williams Richard, Spreafico Filippo, Geller James I, van den Heuvel-Eibrink Marry M, Hong Andrew L
Predictive Medicine: Molecular Bases of Genetic Risk, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
Histology Laboratory, Children's Health Ireland at Crumlin, Dublin, Ireland.
Nat Rev Urol. 2025 Jan 29. doi: 10.1038/s41585-024-00993-6.
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.
约20%的儿童及青少年/青年肾肿瘤患者被诊断为非威尔姆斯瘤，这是一组广泛的异质性肿瘤，包括肾透明细胞肉瘤、先天性中胚层肾瘤、肾恶性横纹肌样瘤、肾细胞癌、肾髓质癌及其他罕见组织学类型。这些肿瘤的鉴别诊断可追溯到几十年前，当时这些病理类型最初是通过对预后与威尔姆斯瘤不同的实体进行临床病理观察来确定的，免疫组织化学和分子细胞遗传学进一步证实了这一点，随后又通过新一代测序得以确认。这些进展使得能够近乎明确地识别不同肿瘤并对患者进行风险分层。与此同时，一些此类病理类型的新肾肿瘤模型的建立，包括细胞系、类器官、异种移植和基因工程小鼠模型，增进了我们对这些肿瘤发生发展的理解，并有助于确定新的治疗靶点。尽管取得了这些诸多成就，但儿童及青少年/青年患者死于这类罕见癌症的比例仍高于威尔姆斯瘤患者。因此，需要国际间的协同努力来解答尚未解决的问题并改善治疗结果。
