Pediatric Renal Cell Carcinoma

Kiersten M. Craig; Dix P. Poppas; Ardavan Akhavan


Curr Opin Urol. 2019;29(5):500-504. 

In This Article


Although the most common form of RCC documented in adults is clear cell carcinoma, in children, a unique subtype of RCC not otherwise specified (NOS) predominates.[3,4] This is likely secondary to the frequency of translocation tumors. In 1998, Carcao et al. published an article on their evaluation of 16 children with renal cell carcinoma between 1979 and 1996. Eleven (68.8%) of the patients were girls and 56% of the tumors were characterized as clear cell. They performed cytogenetic analysis of four of those tumors and found two tumors with translocations involving the X chromosome.[20] The specific area of the X chromosome was later identified to involve a translocation of the transcription factor E3 (TFE3) located on the short arm of the X chromosome (Xp11.23).[21] Although numerous translocation partners have been identified, a fusion protein involving the Alveolar soft part sarcoma (ASPSCR1) gene on the long arm of chromosome 17 (17q25.3) is most common. This fusion protein disrupts lysosomal mediated apoptosis, which promotes tumorigenesis via the MET tyrosine receptor kinase pathway.[22] Therapeutic strategies targeting this pathway have been investigated (see therapeutic section). These translocation tumors were formally recognized by the WHO in 2004 as Xp11 translocation tumors and later reclassified in 2016 as Micropthlamia family of transcription factor (MiTF) translocation tumors when more related transcription factors were identified, all leading to RCC or in the case of the ASPSCR1, fusion gene sarcoma.[23] These tumors are characterized by large high-grade clear cells with papillary architecture and a true fibrovascular core. Psammoma bodies can also be found. The similarity to clear cell carcinoma, papillary architecture and previously unrecognized specific category likely led to translocation tumors being previously classified into RCC NOS, clear cell, or papillary RCC, which is a confounding factor in historical literature on these patients.[24–26]