{Reference Type}: Journal Article {Title}: Diagnostic approach in TFE3-rearranged renal cell carcinoma: a multi-institutional international survey. {Author}: Akgul M;Williamson SR;Ertoy D;Argani P;Gupta S;CaliĆ² A;Reuter V;Tickoo S;Al-Ahmadie HA;Netto GJ;Hes O;Hirsch MS;Delahunt B;Mehra R;Skala S;Osunkoya AO;Harik L;Rao P;Sangoi AR;Nourieh M;Zynger DL;Smith SC;Nazeer T;Gumuskaya B;Kulac I;Khani F;Tretiakova MS;Vakar-Lopez F;Barkan G;MoliniĆ© V;Verkarre V;Rao Q;Kis L;Panizo A;Farzaneh T;Magers MJ;Sanfrancesco J;Perrino C;Gondim D;Araneta R;So JS;Ro JY;Wasco M;Hameed O;Lopez-Beltran A;Samaratunga H;Wobker SE;Melamed J;Cheng L;Idrees MT; {Journal}: J Clin Pathol {Volume}: 74 {Issue}: 5 {Year}: May 2021 {Factor}: 4.463 {DOI}: 10.1136/jclinpath-2020-207372 {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.