TFE/translocation Renal Cell Carcinoma (TFE RCC/tRCC) was formally recognized by the WHO in 2004 as a distinct, typically translocation-associated, RCC with characteristic morphology and immunohistochemical expression of TFE3 or TFEb. Cytogenetic translocations may include TFE3-ASPS, TFE3-PRCC, TFEb-alpha or other variants; mechanisms for TFE upregulation may be heterogenous. TFE3 and TFEB are members of the MiTF/TFE family of basic helix-loop–helix-leucine zipper transcription factors. (1-3)
TFE RCC tend to present at a younger age, but may present at any age. Approximately half of pediatric RCCs are TFE RCC, with a slight female predominance. (4-6) TFE RCC presents in all races, accounting for 1-5% of RCC overall. (4, 7-11) The dominant presentation pattern of TFE RCC is one of advanced stage and rapid fatality, pointing to an aggressive cancer (12, 13), though infrequent late recurrences (14) and prolonged stable disease (4, 15, 16) point to a less common indolent pattern. Overall, in pediatric series, 65% of tRCC cases present with TNM Stage 3 or 4 disease. (5)
Despite typical advance stage at presentation, often aggressive behavior, and apparent increasing awareness and diagnosis of TFE RCC, no formal treatment recommendations are available, as no dedicated adequately powered prospective therapeutic trials have been conducted. Study AREN1721 (Chair, Dr. James Geller) will be the first prospective ‘clinical’ study of TFE RCC in patients of all ages, studying PD1 inhibitor and antiangiogenic therapies, but will only accrue up to 75 patients with limited data collection, with enrollments limited to the United States. To more durably and rapidly advance clinical and biological insights, this TFE RCC consortium has now been created with a focus on clinical, biological, and tumor model/drug testing of TFE RCC.