Diagnostic approach in TFE3-rearranged renal cell carcinoma: a multi-institutional international survey. Issue 5 (29th January 2021)

• Record Type: Journal Article
• Authors: Akgul, Mahmut; Williamson, Sean R; Ertoy, Dilek; Argani, Pedram; Gupta, Sounak; Caliò, Anna; Reuter, Victor; Tickoo, Satish; Al-Ahmadie, Hikmat A; Netto, George J; Hes, Ondrej; Hirsch, Michelle S; Delahunt, Brett; Mehra, Rohit; Skala, Stephanie; Osunkoya, Adeboye O; Harik, Lara; Rao, Priya; Sangoi, Ankur R; Nourieh, Maya; Zynger, Debra L; Smith, Steven Cristopher; Nazeer, Tipu; Gumuskaya, Berrak; Kulac, Ibrahim; Khani, Francesca; Tretiakova, Maria S; Vakar-Lopez, Funda; Barkan, Guliz; Molinié, Vincent; Verkarre, Virginie; Rao, Qiu; Kis, Lorand; Panizo, Angel; Farzaneh, Ted; Magers, Martin J; Sanfrancesco, Joseph; Perrino, Carmen; Gondim, Dibson; Araneta, Ronald; So, Jeffrey S; Ro, Jae Y; Wasco, Matthew; Hameed, Omar; Lopez-Beltran, Antonio; Samaratunga, Hemamali; Wobker, Sara E; Melamed, Jonathan; Cheng, Liang; Idrees, Muhammad T;
• Is Part Of: Journal of clinical pathology. Volume 74:Issue 5(2021)
• Page Start: 291
• Page End: 299
• Publication Date: 2021-01-29
• Subjects: immunohistochemistry -- genitourinary pathology -- kidney neoplasms; Pathology -- Periodicals; Pathology, Molecular -- Periodicals; 616.0705
• DOI: 10.1136/jclinpath-2020-207372
• Languages: English
• ISSNs: 0021-9746

Abstract

Abstract : 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.