Discussion:

Translocation renal cell carcinomas (RCC) are a rare variant of non-clear cell carcinomas and are predominantly found in young patients. This form of RCC arises due to chromosomal translocation to create transcription factor fusion proteins which become overexpressed. Translocation RCC primarily leads to the overexpression of the microphthalmia-associated transcription factor (MiTF) family of transcription factors, consisting of TFE3, TFEB, TFC, and MiTF. While the TFE3 transcription factor located on chromosomal region Xp11.2 is most commonly overexpressed due to a translocation of this region, other members of the MiTF family are occasionally affected by fusion protein formation.

Translocation RCCs may present as a painless abdominal mass or painless hematuria, but tumor development typically occurs unnoticed and are generally detected incidentally upon abdominal imaging. As a result, patients may not present for evaluation until late in the clinical course at advanced tumor stages.

Gross examination of translocation RCC typically reveal a tan-yellow colored mass that is commonly necrotic and hemorrhagic. Microscopically, due to their variable histological presentation, translocation RCC can resemble other forms of RCC such as clear cell RCC, multilocular cystic RCC, urothelial carcinoma, collecting duct carcinoma, mucinous tubular carcinoma, and epithelioid angiomyolipoma.

Fluorescent in situ hybridization analysis is the current gold standard to identify Xp11.2 translocation. Immunohistochemistry labeling for TFE3 can also be utilized as a marker for RCC. Although TFE3 is normally constitutively expressed in normal tissue, it is expressed at a low level undetectable on IHC. Therefore, TFE3 staining is observable via IHC only when it is overexpressed, conferring a strong nuclear stain. Translocation RCC also stains positively for PAX8 and is generally positive for CD10 and AMACR. Vimentin and cytokeratin 7, however, are not detectable.

Data supports initial treatment of translocation RCCs with a VEGFR inhibitor such as sunitinib. Alternatively, surgical intervention with partial nephrectomy is also an effective treatment.