TY - JOUR
T1 - Diagnostic approach in TFE3-rearranged renal cell carcinoma
T2 - A multi-institutional international survey
AU - Akgul, Mahmut
AU - Williamson, Sean R.
AU - Ertoy, DIlek
AU - Argani, Pedram
AU - Gupta, Sounak
AU - Caliò, Anna
AU - Reuter, Victor
AU - Tickoo, Satish
AU - Al-Ahmadie, Hikmat A.
AU - Netto, George J.
AU - Hes, Ondrej
AU - Hirsch, Michelle S.
AU - Delahunt, Brett
AU - Mehra, Rohit
AU - Skala, Stephanie
AU - Osunkoya, Adeboye O.
AU - Harik, Lara
AU - Rao, Priya
AU - Sangoi, Ankur R.
AU - Nourieh, Maya
AU - Zynger, Debra L.
AU - Smith, Steven Cristopher
AU - Nazeer, Tipu
AU - Gumuskaya, Berrak
AU - Kulac, Ibrahim
AU - Khani, Francesca
AU - Tretiakova, Maria S.
AU - Vakar-Lopez, Funda
AU - Barkan, Guliz
AU - Molinié, Vincent
AU - Verkarre, Virginie
AU - Rao, Qiu
AU - Kis, Lorand
AU - Panizo, Angel
AU - Farzaneh, Ted
AU - Magers, Martin J.
AU - Sanfrancesco, Joseph
AU - Perrino, Carmen
AU - Gondim, DIbson
AU - Araneta, Ronald
AU - So, Jeffrey S.
AU - Ro, Jae Y.
AU - Wasco, Matthew
AU - Hameed, Omar
AU - Lopez-Beltran, Antonio
AU - Samaratunga, Hemamali
AU - Wobker, Sara E.
AU - Melamed, Jonathan
AU - Cheng, Liang
AU - Idrees, Muhammad T.
N1 - © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2021/5/1
Y1 - 2021/5/1
N2 - 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.
AB - 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.
KW - genitourinary pathology
KW - immunohistochemistry
KW - kidney neoplasms
KW - Immunohistochemistry
KW - Predictive Value of Tests
KW - Humans
KW - Middle Aged
KW - Child, Preschool
KW - Infant
KW - Male
KW - Kidney Neoplasms/chemistry
KW - Biomarkers, Tumor/genetics
KW - Young Adult
KW - Carcinoma, Renal Cell/chemistry
KW - Aged, 80 and over
KW - Adult
KW - Female
KW - Child
KW - Genetic Predisposition to Disease
KW - In Situ Hybridization, Fluorescence
KW - Pathologists
KW - Practice Patterns, Physicians'
KW - Phenotype
KW - Gene Rearrangement
KW - Adolescent
KW - Aged
KW - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics
KW - Health Care Surveys
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U2 - 10.1136/jclinpath-2020-207372
DO - 10.1136/jclinpath-2020-207372
M3 - Article
C2 - 33514585
AN - SCOPUS:85100602241
SN - 0021-9746
VL - 74
SP - 291
EP - 299
JO - Journal of Clinical Pathology
JF - Journal of Clinical Pathology
IS - 5
ER -