title: Clear cell papillary renal cell carcinoma and renal angiomyoadenomatous tumor: two variants of a morphologic, immunohistochemical, and genetic distinct entity of renal cell carcinoma.
abstract: Clear cell papillary renal cell carcinoma (ccpRCC) and renal angiomyoadenomatous tumor (RAT) share morphologic similarities with clear cell (ccRCC) and papillary RCC (pRCC). It is a matter of controversy whether their morphologic, immunophenotypic, and molecular features allow the definition of a separate renal carcinoma entity. The aim of our project was to investigate specific renal immunohistochemical biomarkers involved in the hypoxia-inducible factor pathway and mutations in the VHL gene to clarify the relationship between ccpRCC and RAT. We investigated 28 ccpRCC and 9 RAT samples by immunohistochemistry using 25 markers. VHL gene mutations and allele losses were investigated by Sanger sequencing and fluorescence in situ hybridization. Clinical follow-up data were obtained for a subset of the patients. No tumor recurrence or tumor-related death was observed in any of the patients. Immunohistochemistry and molecular analyses led to the reclassification of 3 tumors as ccRCC and TFE3 translocation carcinomas. The immunohistochemical profile of ccpRCC and RAT samples was very similar but not identical, differing from both ccRCC and pRCC. Especially, the parafibromin and hKIM-1 expression exhibited differences in ccpRCC/RAT compared with ccRCC and pRCC. Genetic analysis revealed VHL mutations in 2/27 (7%) and 1/7 (14%) ccpRCC and RAT samples, respectively. Fluorescence in situ hybridization analysis disclosed a 3p loss in 2/20 (10%) ccpRCC samples. ccpRCC and RAT have a specific morphologic and immunohistochemical profile, but they share similarities with the more aggressive renal tumors. On the basis of our results, we regard ccpRCC/RAT as a distinct entity of RCCs.
authors.affiliation: *Institute of Surgical Pathology, University Hospital Zurich, Zurich ‡‡Cantonal Hospital Aarau §§Institute of Histological and Cytological Diagnostics, Aarau ¶¶University Institute of Pathology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland †Institute of Pathology, University Medicine Göttingen (UMG), Göttingen ∥Institute of Pathology, University Hospital Tübingen, Tübingen ¶Institute of Pathology, HELIOS Hospital Berlin-Buch, Berlin #Institute of Pathology Bogenhausen, Städtisches Klinikum München GmbH, Munich **Institute of Pathology, Heinrich Heine University Hospital, Dusseldorf ††Institute of Pathology, RWTH University, Aachen ∥∥Institute of Pathology, HELIOS Hospital Schwerin, Schwerin ***Institute of Pathology, Städtisches Klinikum Karlsruhe gGmbH, Karlsruhe †††Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany ‡Service d'Anatomie et Cytologie Pathologiques 1, Groupe Hospitalier Pitié-Salpêtrière, Paris, France §Department of Medicine, Renal Division, Brigham and Women's Hospital, Boston, MA ##Institute of Pathology, University of Florence, Florence, Italy.
authors.forename: Karl-Friedrich
authors.initials: KF
authors.lastname: Deml
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Schildhaus
authors.forename: Eva
authors.initials: E
authors.lastname: Compérat
authors.forename: Adriana
authors.initials: A
authors.lastname: von Teichman
authors.forename: Martina
authors.initials: M
authors.lastname: Storz
authors.forename: Peter
authors.initials: P
authors.lastname: Schraml
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Bonventre
authors.forename: Falko
authors.initials: F
authors.lastname: Fend
authors.forename: Barbara
authors.initials: B
authors.lastname: Fleige
authors.forename: Andreas
authors.initials: A
authors.lastname: Nerlich
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Gabbert
authors.forename: Nikolaus
authors.initials: N
authors.lastname: GaBler
authors.forename: Rainer
authors.initials: R
authors.lastname: Grobholz
authors.forename: Seife
authors.initials: S
authors.lastname: Hailemariam
authors.forename: Raoul
authors.initials: R
authors.lastname: Hinze
authors.forename: Ruth
authors.initials: R
authors.lastname: Knüchel
authors.forename: Benoit
authors.initials: B
authors.lastname: Lhermitte
authors.forename: Gabriella
authors.initials: G
authors.lastname: Nesi
authors.forename: Thomas
authors.initials: T
authors.lastname: Rüdiger
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000145:classification / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged