Basics of TFE RCC

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.

  1. Argani P, Ladanyi M: Translocation carcinomas of the kidney. Clin Lab Med 25:363-78, 2005
  2. Argani P, Ladanyi M: The evolving story of renal translocation carcinomas. Am J Clin Pathol 126:332-4, 2006
  3. Ramphal R, Pappo A, Zielenska M, et al: Pediatric renal cell carcinoma: clinical, pathologic, and molecular abnormalities associated with the members of the mit transcription factor family. Am J Clin Pathol 126:349-64, 2006
  4. Geller JI, Argani P, Adeniran A, et al: Translocation renal cell carcinoma. Cancer 112:1607-1616, 2008
  5. Geller JI, Ehrlich PF, Cost NG, et al: Characterization of adolescent and pediatric renal cell carcinoma: A report from the Children's Oncology Group study AREN03B2. Cancer 121:2457-64, 2015
  6. PF E, NG C, G K, et al: A Description of the Surgical Experience in Children, Adolescents and Young Adults with Renal Cell Carcinoma: A Report from the Children's Oncology Group Study AREN 03B2. BJU International 110:18, 2012
  7. Zhong M, De Angelo P, Osborne L, et al: Translocation renal cell carcinomas in adults: a single-institution experience. Am J Surg Pathol 36:654-62, 2012
  8. Kauffman E, Gupta G, Cecchi F, et al: Characterization of the Akt-mTOR pathway in TFE3-Fusion Renal Cell Cancers and Implications for Targeted Therapy. The Journal of Urology 187:e183-e184, 2012
  9. Choueiri TK, Lim ZD, Hirsch MS, et al: Vascular endothelial growth factor-targeted therapy for the treatment of adult metastatic Xp11.2 translocation renal cell carcinoma. Cancer 116:5219-25, 2010
  10. Malouf GG, Camparo P, Molinie V, et al: Transcription factor E3 and transcription factor EB renal cell carcinomas: clinical features, biological behavior and prognostic factors. J Urol 185:24-9, 2011
  11. Camparo P, Vasiliu V, Molinie V, et al: Renal translocation carcinomas: clinicopathologic, immunohistochemical, and gene expression profiling analysis of 31 cases with a review of the literature. Am J Surg Pathol 32:656-70, 2008
  12. Meyer PN, Clark JI, Flanigan RC, et al: Xp11.2 translocation renal cell carcinoma with very aggressive course in five adults. Am J Clin Pathol 128:70-9, 2007
  13. Hung CC, Pan CC, Lin CC, et al: XP11.2 translocation renal cell carcinoma: clinical experience of Taipei Veterans General Hospital. J Chin Med Assoc 74:500-4, 2011
  14. Dal Cin P, Stas M, Sciot R, et al: Translocation (X;1) reveals metastasis 31 years after renal cell carcinoma. Cancer Genet Cytogenet 101:58-61, 1998
  15. Arnoux V, Long JA, Fiard G, et al: [Xp11.2 translocation renal carcinoma in adults over 50 years of age: about four cases]. Prog Urol 22:932-7, 2012
  16. Geller JI, Khoury JD, Dome JS: Author’s Reply re: Letter to the Editor re: ‘Geller J and Dome J. Lymph Node Involvement Does Not Predict Poor Outcome in Pediatric Renal Cell Carcinoma, Cancer, 101:1575-1583, October 1, 2004. Cancer 103:1318-1318, 2005