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Diagnostic approach in TFE3-rearranged renal cell carcinoma: a multi-institutional international survey
  1. Mahmut Akgul1,
  2. Sean R Williamson2,
  3. Dilek Ertoy3,
  4. Pedram Argani4,
  5. Sounak Gupta5,
  6. Anna Caliò6,
  7. Victor Reuter7,
  8. Satish Tickoo7,
  9. Hikmat A Al-Ahmadie8,
  10. George J Netto9,
  11. Ondrej Hes10,11,
  12. Michelle S Hirsch12,
  13. Brett Delahunt13,
  14. Rohit Mehra14,
  15. Stephanie Skala14,
  16. Adeboye O Osunkoya15,
  17. Lara Harik15,
  18. Priya Rao16,
  19. Ankur R Sangoi17,
  20. Maya Nourieh18,
  21. Debra L Zynger19,
  22. Steven Cristopher Smith20,
  23. Tipu Nazeer1,
  24. Berrak Gumuskaya21,
  25. Ibrahim Kulac3,
  26. Francesca Khani22,
  27. Maria S Tretiakova23,
  28. Funda Vakar-Lopez23,
  29. Guliz Barkan24,
  30. Vincent Molinié25,
  31. Virginie Verkarre26,
  32. Qiu Rao27,
  33. Lorand Kis28,
  34. Angel Panizo29,
  35. Ted Farzaneh30,
  36. Martin J Magers31,
  37. Joseph Sanfrancesco32,
  38. Carmen Perrino33,
  39. Dibson Gondim34,
  40. Ronald Araneta35,
  41. Jeffrey S So36,
  42. Jae Y Ro37,
  43. Matthew Wasco38,
  44. Omar Hameed39,
  45. Antonio Lopez-Beltran40,
  46. Hemamali Samaratunga41,
  47. Sara E Wobker42,
  48. Jonathan Melamed43,
  49. Liang Cheng44,
  50. Muhammad T Idrees44
  1. 1Pathology, Albany Medical Center, Albany, New York, USA
  2. 2Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA
  3. 3Department of Pathology, Koc University School of Medicine, Istanbul, Turkey
  4. 4Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland, USA
  5. 5Department of Pathology, Mayo Clinic, Rochester, Minnesota, USA
  6. 6Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Veneto, Italy
  7. 7Pathology, Memorial Sloan Kettering Cancer Center, New York City, New York, USA
  8. 8Department of Pathology, Memorial Sloan Kettering Cancer Center, New York City, New York, USA
  9. 9Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA
  10. 10Faculty of Medicine in Plzen, Charles University, Plzen, Czech Republic
  11. 11Medical Teaching School, University Hospital, Charles University, Plzen, Czech Republic
  12. 12Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
  13. 13Pathology and Molecular Medicine, Wellington School of Medicine and Health Sciences, Wellington South, New Zealand
  14. 14Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
  15. 15Department of Pathology, Emory University School of Medicine, Atlanta, Georgia, USA
  16. 16Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  17. 17Department of Pathology, El Camino Hospital, Mountain View, California, USA
  18. 18Department of Pathology, Institut Curie, Paris, France
  19. 19Department of Pathology, The Ohio State University Medical Center, Columbus, Ohio, USA
  20. 20Department of Pathology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
  21. 21Department of Pathology, Yildirim Beyazit University School of Medicine, Ankara, Turkey
  22. 22Department of Pathology, Cornell University Joan and Sanford I Weill Medical College, New York City, New York, USA
  23. 23Department of Pathology, University of Washington, Seattle, Washington, USA
  24. 24Department of Pathology, Loyola University Health System, Maywood, Illinois, USA
  25. 25Pathology, University Hospital Center of Martinique, Fort-de-France, Martinique
  26. 26Department of Pathology, Hôpital Européen Georges Pompidou Anatomie Pathologie, Paris, Île-de-France, France
  27. 27Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China
  28. 28Department of Pathology, Karolinska Institute, Stockholm, Sweden
  29. 29Department of Pathology, Complejo Hospitalario de Navarra Servicio de Cardiologia, Pamplona, Navarra, Spain
  30. 30Department of Pathology, Univer Irvine Healthcare, Orange County, California, USA
  31. 31IHA Pathology and Laboratory Medicine, Ann Arbor, Michigan, USA
  32. 32Department of Pathology, Charleston Area Medical Center, Charleston, South Carolina, USA
  33. 33Department of Pathology, Mount Auburn Hospital, Cambridge, Massachusetts, USA
  34. 34Department of Pathology, University of Louisville, Louisville, Kentucky, USA
  35. 35Department of Pathology, Hartford Hospital, Hartford, Connecticut, USA
  36. 36Department of Pathology, St Luke's Hospital, Manila, Philippines
  37. 37Department of Pathology, Houston Methodist Hospital, Houston, Texas, USA
  38. 38Department of Pathology, St Joseph Mercy Hospital, Ann Arbor, Michigan, USA
  39. 39Forward Pathology Solutions, Vanderbilt University, Kansas City, Montana, USA
  40. 40Department of Pathology and Surgery, Cordoba University Medical School, Cordoba, Spain
  41. 41Aquesta Pathology, Brisbane, Queensland, Australia
  42. 42Department of Pathology, University of North Carolina System, Chapel Hill, North Carolina, USA
  43. 43Department of Pathology, New York University Langone Medical Center, New York City, New York, USA
  44. 44Department of Pathology & Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
  1. Correspondence to Dr Mahmut Akgul, Pathology, Albany Medical Center, Albany, NY 12206, USA; mahmut.akgulmd{at}


Transcription factor E3-rearranged renal cell carcinoma (TFE3-RCC) has heterogenous morphologic and immunohistochemical (IHC) features.

131 pathologists with genitourinary expertise were invited in an online survey containing 23 questions assessing their experience on TFE3-RCC diagnostic work-up.

Fifty (38%) participants completed the survey. 46 of 50 participants reported multiple patterns, most commonly papillary pattern (almost always 9/46, 19.5%; frequently 29/46, 63%). Large epithelioid cells with abundant cytoplasm were the most encountered cytologic feature, with either clear (almost always 10/50, 20%; frequently 34/50, 68%) or eosinophilic (almost always 4/49, 8%; frequently 28/49, 57%) cytology. Strong (3+) or diffuse (>75% of tumour cells) nuclear TFE3 IHC expression was considered diagnostic by 13/46 (28%) and 12/47 (26%) participants, respectively. Main TFE3 IHC issues were the low specificity (16/42, 38%), unreliable staining performance (15/42, 36%) and background staining (12/42, 29%). Most preferred IHC assays other than TFE3, cathepsin K and pancytokeratin were melan A (44/50, 88%), HMB45 (43/50, 86%), carbonic anhydrase IX (41/50, 82%) and CK7 (32/50, 64%). Cut-off for positive TFE3 fluorescent in situ hybridisation (FISH) was preferably 10% (9/50, 18%), although significant variation in cut-off values was present. 23/48 (48%) participants required TFE3 FISH testing to confirm TFE3-RCC regardless of the histomorphologic and IHC assessment. 28/50 (56%) participants would request additional molecular studies other than FISH assay in selected cases, whereas 3/50 participants use additional molecular cases in all cases when TFE3-RCC is in the differential.

Optimal diagnostic approach on TFE3-RCC is impacted by IHC and/or FISH assay preferences as well as their conflicting interpretation methods.

  • immunohistochemistry
  • genitourinary pathology
  • kidney neoplasms

Statistics from


  • Handling editor Runjan Chetty.

  • Twitter @akgulmd, @mayanourieh, @RonAraneta, @gleason4plus5

  • Contributors MA, MTI, SRW and DE designed the survey. All other authors were direct participants of the survey and successfully completed the questionnaire with significant contribution.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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