Xp11.2 Translocation Renal Cell Carcinoma

Abstract Xp11.2 translocation renal cell carcinomas (RCCs), a recently recognized distinct subtype, are rare tumors predominantly reported in young patients. They comprise at least one-third of pediatric RCCs, and only few adult cases have been reported. They are characterized by various translocations involving chromosome Xp11.2, all resulting in gene fusions involving the transcription factor E3 ( TFE3 ) gene. In recent years, at least 6 different Xp11.2 translocation RCCs have been identified and characterized at the molecular level. These include a distinctive RCC that bears a translocation with the identical chromosomal breakpoints (Xp11.2, 17q25) and identical resulting ASPL-TFE3 gene fusion as alveolar soft part sarcoma. They typically have papillary or nested architecture and are composed of cells with voluminous, clear, or eosinophilic cytoplasm. Their most distinctive immunohistochemical feature is nuclear labeling for TFE3 protein. Although only limited data are available so far, they are believed to be rather indolent, but there have been increasing, recent reports of an aggressive clinical course in adult cases. The consistent immunohistochemical staining for TFE3 in all RCC with unusual histology, regardless of patient age, is likely to expand the spectrum of Xp11.2 translocation RCC with respect to age, clinical behavior, and molecular abnormalities.