title: MiT Family Translocation-Associated Renal Cell Carcinoma: A Contemporary Update With Emphasis on Morphologic, Immunophenotypic, and Molecular Mimics.
abstract: Translocation-associated renal cell carcinoma (t-RCC) is a relatively uncommon subtype of renal cell carcinoma characterized by recurrent gene rearrangements involving the TFE3 or TFEB loci. TFE3 and TFEB are members of the microphthalmia transcription factor (MiT) family, which regulates differentiation in melanocytes and osteoclasts, and MiT family gene fusions activate unique molecular programs that can be detected immunohistochemically. Although the overall clinical behavior of t-RCC is variable, emerging molecular data suggest the possibility of targeted approaches to advanced disease. Thus, distinguishing t-RCC from its morphologic, immunophenotypic, and molecular mimics may have important clinical implications. The differential diagnosis for t-RCC includes a variety of common renal neoplasms, particularly those demonstrating clear cell and papillary features; in addition, because of immunophenotypic overlap and/or shared molecular abnormalities (ie, TFE3 gene rearrangement), a distinctive set of nonepithelial renal tumors may also warrant consideration. Directed ancillary testing is an essential aspect to the workup of t-RCC cases and may include a panel of immunohistochemical stains, such as PAX8, pancytokeratins, epithelial membrane antigen, carbonic anhydrase IX, HMB-45, and Melan-A. Dual-color, break-apart fluorescent in situ hybridization for TFE3 or TFEB gene rearrangement may be helpful in diagnostically challenging cases or when molecular confirmation is needed.
authors.affiliation: From the Department of Pathology (Drs Magers, Udager, and Mehra), and the Comprehensive Cancer Center (Dr Mehra), University of Michigan Health System, Ann Arbor; and the Michigan Center for Translational Pathology, Ann Arbor (Dr Mehra).
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Magers
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Udager
authors.forename: Rohit
authors.initials: R
authors.lastname: Mehra
mesh_terms: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D003937:Diagnosis, Differential; D015321:Gene Rearrangement; D006801:Humans; D016130:Immunophenotyping; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051739:Microphthalmia-Associated Transcription Factor; C069203:TFE3 protein, human; C064972:TFEB protein, human