title: Molecular Genetic Alterations in Renal Cell Carcinomas With Tubulocystic Pattern: Tubulocystic Renal Cell Carcinoma, Tubulocystic Renal Cell Carcinoma With Heterogenous Component and Familial Leiomyomatosis-associated Renal Cell Carcinoma. Clinicopathologic and Molecular Genetic Analysis of 15 Cases.
abstract: The characteristic morphologic spectrum of tubulocystic renal cell carcinoma (TC-RCC) may include areas resembling papillary RCC (PRCC). Our study includes 15 RCCs with tubulocystic pattern: 6 TC-RCCs, 1 RCC-high grade with tubulocystic architecture, 5 TC-RCCs with foci of PRCC, 2 with high-grade RCC (HGRCC) not otherwise specified, and 1 with a clear cell papillary RCC/renal angiomyoadenomatous tumor-like component. We analyzed aberrations of chromosomes 7, 17, and Y; mutations of VHL and FH genes; and loss of heterozygosity at chromosome 3p. Genetic analysis was performed separately in areas of classic TC-RCC and in those with other histologic patterns. The TC-RCC component demonstrated disomy of chromosome 7 in 9/15 cases, polysomy of chromosome 17 in 7/15 cases, and loss of Y in 1 case. In the PRCC component, 2/3 analyzable cases showed disomy of chromosome 7 and polysomy of chromosome 17 with normal Y. One case with focal HGRCC exhibited only disomy 7, whereas the case with clear cell papillary RCC/renal angiomyoadenomatous tumor-like pattern showed polysomies of 7 and 17, mutation of VHL, and loss of heterozygosity 3p. FH gene mutation was identified in a single case with an aggressive clinical course and predominant TC-RCC pattern. The following conclusions were drawn: (1) TC-RCC demonstrates variable status of chromosomes 7, 17, and Y even in cases with typical/uniform morphology. (2) The biological nature of PRCC/HGRCC-like areas within TC-RCC remains unclear. Our data suggest that heterogenous TC-RCCs may be associated with an adverse clinical outcome. (3) Hereditary leiomyomatosis-associated RCC can be morphologically indistinguishable from "high-grade" TC-RCC; therefore, in TC-RCC with high-grade features FH gene status should be tested.
authors.affiliation: *Ljudevit Jurak Department of Pathology, Sestre milosrdnice Clinical Hospital Center †Department of Pathology, School of Medicine, University of Zagreb, Zagreb, Croatia ‡Department of Pathology and Cytology, Clinical Center of the University of Sarajevo, Sarajevo, Bosnia and Hercegovina §Department of Pathology, New York School of Medicine, NYU Langone Medical Center, New York, NY ‡‡Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS Departments of ∥Pathology #Urology **Otorhinolaryngology, Charles University, Medical Faculty and Charles University Hospital Plzen ¶¶Biomedical Centre, Faculty of Medicine in Plzen, Charles University in Prague, Plzen, Czech Republic ¶Department of Pathology, Centro Medico ∥∥Department of Pathology, Institute Nacional de Cancerologia, Mexico City, Mexico ††Department of Pathology, East University, Riga, Latvia §§Department of Pathology, Cytopathos, Bratislava, Slovakia.
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authors.forename: Ming
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authors.lastname: Zhou
authors.forename: Božo
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authors.lastname: Krušlin
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authors.lastname: Martínek
authors.forename: Petr
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authors.lastname: Grossmann
authors.forename: Kvetoslava
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authors.lastname: Peckova
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authors.initials: I
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authors.forename: Kristyna
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authors.lastname: Kalusova
authors.forename: Bohuslava
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authors.lastname: Kokoskova
authors.forename: Pavla
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authors.lastname: Rotterova
authors.forename: Milan
authors.initials: M
authors.lastname: Hora
authors.forename: Ondrej
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authors.lastname: Daum
authors.forename: Magdalena
authors.initials: M
authors.lastname: Dubova
authors.forename: Kevin
authors.initials: K
authors.lastname: Bauleth
authors.forename: David
authors.initials: D
authors.lastname: Slouka
authors.forename: Maris
authors.initials: M
authors.lastname: Sperga
authors.forename: Whitney
authors.initials: W
authors.lastname: Davidson
authors.forename: Boris
authors.initials: B
authors.lastname: Rychly
authors.forename: Delia
authors.initials: D
authors.lastname: Perez Montiel
authors.forename: Michal
authors.initials: M
authors.lastname: Michal
authors.forename: Ondrej
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authors.lastname: Hes
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D041322:Chromosomes, Human, Y / Q000235:genetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007680:Kidney Neoplasms / Q000235:genetics*; D018231:Leiomyomatosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics
chemical_list: D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human