The recent availability of molecular data on renal tumors has resulted in a clinically useful World Health Organization (WHO)-driven classification system including several new and intriguing subtypes such as translocation-associated renal cell carcinoma (t-RCC) and inherited renal neoplasms.
RCCs with melanogenesis-associated transcription factor (MITF) aberrations demonstrate a wide morphologic spectrum, highlighting the need to consider these entities within the differential diagnosis of renal tumors encountered in clinical practice. Although immunohistochemistry (IHC) for MITF family proteins TFE3 and TFEB is specific for t-RCC, there is poor reproducibility of TFE3 or TFEB IHC, and the sensitivity is not high enough to exclude the possibility of false-negative results. Fluorescence in situhybridization (FISH), however, has been robustly validated for the accurate diagnosis of these renal tumor subtypes and exhibits a high degree of sensitivity and specificity.
Dr. Rohit Mehra and colleagues have developed clinical FISH assays to detect TFE3 and TFEB translocations that are offered through UM genitourinary FISH service (at MLabs). Information about these tests can be found in the Pathology Handbook:
Additionally, Dr. Mehra recently led a study where they applied clinical FISH assays for the detection of TFE3 and TFEB gene aberrations in a large consecutive cohort of cases clinically, morphologically, and/or immunophenotypically suspicious for t-RCC. Results demonstrated that 37% of tumors were confirmed to demonstrate MITF aberrations (21 TFE3 translocation, 4 TFEB translocation, and 6 TFEB amplification cases). They described six new genotypically proven TFEB-amplified renal cell carcinoma cases and found morphologic features that may aid in the identification of renal cell carcinomas with MITF aberrations. Overall, FISH imaging of TFE3 and TFEB enabled accurate classification of renal cell carcinomas with MITF aberrations, including TFEB-amplified renal cell carcinoma, which may demonstrate aggressive behavior. The results of this study were published in Modern Pathology (Mod Pathol. 2017 Aug 25).