Translocation Renal Cell Carcinoma

This is an Xp11 translocation renal cell carcinoma (RCC) with an ASPL-TFE3 gene fusion, resulting from a t(X;17) (p11;q25) chromosome translocation.  This tumor has nested and papillary architecture, and contains clear cells. This ASPL-TFE3 RCC demonstrates abundant, voluminous cytoplasm.  The tumor cells are enormous compared to the adjacent red blood cells. The ASPL-TFE3 RCC often contain extensive psammomatous calcifications, which can make these tumors evident on plain X-rays of the abdomen. Nuclear labeling for TFE3 protein is, when performed in the validated laboratory, a highly sensitive and specific marker for Xp11 translocation RCC when performed on properly-fixed tissue.  The gene fusions involving the TFE3 transcription factor result in overexpression of TFE3 protein, which is detected by immunohistochemistry as brown staining of the tumor cell nuclei.  Note that the adjacent blood vessels are negative (blue). These images demonstrate tumors with evidence of TFE3 rearrangement by TFE3 FISH.  Note the splitting of the red and green signals in the neoplastic cells. This is a t(6;11) (p21;q12) RCC.  The tumor demonstrates a distinctive biphasic appearance, with larger clear cells and smaller cells clustered around pink nodules of basement membrane material. The t(6;11) (p21;q12) translocation results in an Alpha- TFEB gene fusion, which results overexpression of native TFEB protein.  This can be detected by immunohistochemistry as overexpressed TFEB protein.  This is a highly sensitive and specific test these tumors when performed in a validated laboratory on properly fixed tissue.  Note that the tumor cells demonstrate strong nuclear staining for TFEB protein (brown) while the surrounding endothelial cells are negative (blue). Break-apart FISH assay for TFEB gene rearrangement, similar to that developed for TFE3 gene rearrangement, is now the performed method for confirming the diagnosis of the t(6;11) RCC.  As with the TFE3 FISH assay, one is looking for splitting of the red and green signals, which are normally fused to make a single yellow signal.

This site is dedicated to patients with a subgroup of renal cell carcinoma and other cancers that involve chromosome translocations involving TFE3 or TFEB genes. Other names for these neoplasms in the literature include Xp11 translocation renal cell carcinoma, TFE3 rearranged renal cell carcinoma, Xp11 translocation PEComa, melanotic Xp11 translocation cancer, t(6;11) translocation renal cell carcinoma, and TFEB rearranged renal cell carcinoma, and MiT family translocation carcinoma. These neoplasms were originally described at Johns Hopkins by Dr. Pedram Argani, M.D., Professor of Pathology and Oncology, who maintains this site. The purpose of this site is to provide a resource to these patients and their families. Included in this site are educational materials, links to the latest research on these neoplasms, and opportunities to contribute to the understanding of these neoplasms. We hope this site is useful to these patients and their families.