title: Aggressive and nonaggressive translocation t(6;11) renal cell carcinoma: comparative study of 6 cases and review of the literature.
abstract: t(6;11) renal cell carcinoma (RCC) has been recognized as a rare and mostly nonaggressive tumor (NAT). The criteria for distinguishing aggressive tumors (AT) from NATs are not well established. A total of 6 cases were selected for the study. Five cases of t(6;11) RCCs behaved nonaggressively, and 1 was carcinoma with aggressive behavior. The tumors were analyzed morphologically using immunohistochemistry and by molecular-genetic methods. The specimen of aggressive t(6;11) RCC was from a 77-year-old woman who died of the disease 2.5 months after diagnosis. The specimens of nonaggressive t(6;11) RCCs were from 3 women and 2 men whose ages range between 15 and 54 years. Follow-up was available in all cases (2.5 months-8 years). The tumor size ranged from 3 to 14 cm in nonaggressive t(6;11) RCC. In the aggressive carcinoma, the tumor size was 12 cm. All tumors (6/6) were well circumscribed. Aggressive t(6;11) RCC was widely necrotic. Six (100%) of 6 all tumors displayed a solid/alveolar architecture with occasional tubules and pseudorosettes. Pseudopapillary formations lined by bizarre polymorphic cells were found focally in the aggressive t(6;11) RCC case. Mitoses, though rare, were found as well. All cases (AT and NAT) were positive for HMB-45, Melan-A, Cathepsin K, and cytokeratins. CD117 positivity was seen in 4 of 5 NATs, as well as in the primary and metastatic lesions of the AT. mTOR was positive in 2 of 5 NATs and vimentin in 4 of 5 NATs. Vimentin was negative in the primary lesion of the AT, as well as in the metastasis found in the adrenal gland. Translocation t(6;11)(Alpha-TFEB) or TFEB break was detected in 4 of 5 NATs and in the AT case. Aggressive tumor showed amplification of TFEB locus. Losses of part of chromosome 1 and chromosome 22 were found in 1 of 5 NATs and in the AT.
  
  
  CONCLUSIONS
  (1) Aggressive t(6;11) RCCs generally occur in the older population in comparison with their indolent counterparts. (2) In regard to the histologic findings in ATs, 3 of 5 so far published cases were morphologically not typical for t(6;11) RCC. Of the 3 cases, 2 cases lacked a small cell component and 1 closely mimicked clear cell-type RCC. (3) Necroses were only present in aggressive t(6;11) RCC. (4) Amplification of TFEB locus was also found only in the aggressive t(6;11) RCC.
authors.affiliation: Department of Pathology, Faculty of Medicine, University Hospital Plzeň, Charles University, Pilsen, Czech Republic.
authors.forename: Kvetoslava
authors.initials: K
authors.lastname: Peckova
authors.affiliation: Department of Pathology, Faculty of Medicine, University Hospital Plzeň, Charles University, Pilsen, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Vanecek
authors.affiliation: Department of Pathology, Faculty of Medicine, University Hospital Plzeň, Charles University, Pilsen, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Martinek
authors.affiliation: Department of Pathology, PathWest Laboratory Medicine WA, Nedlands, Australia.
authors.forename: Dominic
authors.initials: D
authors.lastname: Spagnolo
authors.affiliation: Department of Diagnostic Pathology, Kochi Red Cross Hospital, Kochi, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Kuroda
authors.affiliation: Department of Pathology and Diagnostic, University of Verona, Verona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
authors.affiliation: Department of Pathology, Clinical Center of the University of Sarajevo, Sarajevo, Bosnia and Herzegovina.
authors.forename: Semir
authors.initials: S
authors.lastname: Vranic
authors.affiliation: Department of Pathology, Mother and Child Health Institute of Serbia, Belgrade, Serbia.
authors.forename: Slavisa
authors.initials: S
authors.lastname: Djuricic
authors.affiliation: Department of Pathology, Faculty of Medicine, University Hospital Plzeň, Charles University, Pilsen, Czech Republic.
authors.forename: Pavla
authors.initials: P
authors.lastname: Rotterova
authors.affiliation: Department of Pathology, Faculty of Medicine, University Hospital Plzeň, Charles University, Pilsen, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Daum
authors.affiliation: Department of Pathology, Faculty of Medicine, University Hospital Plzeň, Charles University, Pilsen, Czech Republic.
authors.forename: Bohuslava
authors.initials: B
authors.lastname: Kokoskova
authors.affiliation: Department of Pathology, Faculty of Medicine, University Hospital Plzeň, Charles University, Pilsen, Czech Republic.
authors.forename: Pavla
authors.initials: P
authors.lastname: Vesela
authors.affiliation: Department of Pathology, Faculty of Medicine, University Hospital Plzeň, Charles University, Pilsen, Czech Republic.
authors.forename: Kristyna
authors.initials: K
authors.lastname: Pivovarcikova
authors.affiliation: Department of Pathology, Faculty of Medicine, University Hospital Plzeň, Charles University, Pilsen, Czech Republic.
authors.forename: Kevin
authors.initials: K
authors.lastname: Bauleth
authors.affiliation: Department of Pathology, Faculty of Medicine, University Hospital Plzeň, Charles University, Pilsen, Czech Republic.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Dubova
authors.affiliation: Department of Urology, Faculty of Medicine in Plzeň, Charles University in Prague, Pilsen, Czech Republic.
authors.forename: Kristyna
authors.initials: K
authors.lastname: Kalusova
authors.affiliation: Department of Urology, Faculty of Medicine in Plzeň, Charles University in Prague, Pilsen, Czech Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Hora
authors.affiliation: Department of Pathology, Faculty of Medicine, University Hospital Plzeň, Charles University, Pilsen, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Michal
authors.affiliation: Department of Pathology, Faculty of Medicine, University Hospital Plzeň, Charles University, Pilsen, Czech Republic; Biomedical Centre, Faculty of Medicine in Plzen, Charles University in Prague, Pilsen, Czech Republic. Electronic address: hes@medima.cz.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Hes
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C064972:TFEB protein, human
keywords: Aggressive; Immunohistochemistry; Kidney; Molecular biology; Nonaggressive; Translocation renal cell carcinoma; t(6;11)