title: Molecular-genetic analysis is essential for accurate classification of renal carcinoma resembling Xp11.2 translocation carcinoma.
abstract: Xp11.2-translocation renal carcinoma (TRCC) is suspected when a renal carcinoma occurs in young patients, patients with a prior history of exposure to chemotherapy and when the neoplasm has morphological features suggestive of that entity. We retrieved 20 renal tumours (from 17,500 archival cases) of which morphology arose suspicion for TRCC. In nine cases, TFE3 translocation was confirmed by fluorescence in situ hybridisation analysis. In 9 of the remaining 11 TRCC-like cases (7 male, 4 female, aged 22-84 years), material was available for further study. The morphological spectrum was diverse. Six tumours showed a mixture of cells with eosinophilic or clear cytoplasm in tubular, acinar and papillary architecture. One case was high grade with epithelioid, spindle cell and sarcomatoid areas. Another showed tubular, solid, and papillary areas and foci containing spindle cells reminiscent of mucinous tubular and spindle cell carcinoma. The third showed dyscohesive nests of large epithelioid and histiocytoid cells in a background of dense lymphoplasmacytic infiltrate. By immunohistochemistry, keratin AE1/AE3 was diffusely positive in three tumours, while CK7 strongly stained one tumour and another focally and weakly. CD10 and Pax8 were expressed by eight, AMACR and vimentin by seven, CA-IX by four and TFE3 and cathepsin K by two tumours. Of the two TFE3-positive tumours, one showed polysomy of chromosome 7 and the other of 17; they were VHL normal and diagnosed as unclassifiable RCC. Of the seven TFE3-negative tumours, three showed polysomy of 7/17 and VHL abnormality and were diagnosed as combined clear cell RCC/papillary RCC. One TFE3-negative tumour with normal 7/17 but LOH 3p (VHL abnormality) was diagnosed as clear cell RCC. One TFE3-negative tumour with polysomy 7/17 but normal VHL was diagnosed as papillary RCC, and two with normal chromosomes 7/17 and VHL gene were considered unclassifiable. As morphological features and IHC are heterogeneous, TRCC-like renal tumours can only be sub-classified accurately by multi-parameter molecular-genetic analysis.
authors.affiliation: Department of Pathology, BC Cancer Agency and Clinical Professor of Pathology, University of British Columbia, Vancouver, Canada.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Hayes
authors.forename: Kvetoslava
authors.initials: K
authors.lastname: Peckova
authors.forename: Petr
authors.initials: P
authors.lastname: Martinek
authors.forename: Milan
authors.initials: M
authors.lastname: Hora
authors.forename: Kristyna
authors.initials: K
authors.lastname: Kalusova
authors.forename: Lubomir
authors.initials: L
authors.lastname: Straka
authors.forename: Ondrej
authors.initials: O
authors.lastname: Daum
authors.forename: Bohuslava
authors.initials: B
authors.lastname: Kokoskova
authors.forename: Pavla
authors.initials: P
authors.lastname: Rotterova
authors.forename: Kristyna
authors.initials: K
authors.lastname: Pivovarčikova
authors.forename: Jindrich
authors.initials: J
authors.lastname: Branzovsky
authors.forename: Magdalena
authors.initials: M
authors.lastname: Dubova
authors.forename: Pavla
authors.initials: P
authors.lastname: Vesela
authors.forename: Michal
authors.initials: M
authors.lastname: Michal
authors.forename: Ondrej
authors.initials: O
authors.lastname: Hes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000145:classification* / Q000175:diagnosis / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007680:Kidney Neoplasms / Q000145:classification* / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D012189:Retrospective Studies; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C069203:TFE3 protein, human