Xp11 translocation renal cell carcinoma

Xp11 translocation renal cell carcinoma (RCC) is a group of neoplasms characterised by translocations involving a breakpoint at Xp11.2. The resulting gene fusions involve the TFE3 transcription factor gene and multiple reported genes, including the same one (ASPL) found in the characteristic gene fusion of alveolar soft part sarcoma. Xp11 translocation RCCs likely comprise a significant proportion of paediatric RCCs. While uncommon on a percentage basis in adults, adult cases may outnumber paediatric cases due to the much higher overall incidence of RCC in the adult population. The only known risk factor for its development is prior exposure to chemotherapy. The most distinctive histological pattern is a neoplasm with both clear cells and papillary architecture, often with abundant psammoma bodies. Immunohistochemistry typically reveals minimal reactivity to cytokeratins, epithelial membrane antigen (EMA) or vimentin. The most sensitive and specific immunohistochemical markers for these neoplasms are TFE3 protein and cathepsin-K. Clinical outcome data are still premature at this time. However, children with regional nodal metastases but without haematogenous spread have a favourable short-term prognosis. Adults often present with aggressive tumours with widespread systemic metastases and these patients have a poor clinical outcome. Regardless, the tumour can metastasise decades after its initial presentation, so long-term follow-up is necessary. A recently reported melanotic neoplasm with overt melanin pigment may represent a new subset of TFE3 related cancers.