Atlas of Genetics and Cytogenetics in Oncology and Haematology


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Kidney: Renal Oncocytoma

Identity

Phylum Urinary system:Kidney:Adult:Oncocytoma/oncocytosis

Classification

Note Renal Oncocytoma (RO) is a benign renal epithelial neoplasm that comprises approximately 5% of renal tubular epithelial tumors.

Clinics and Pathology

Note The first case of renal oncocytoma was reported by Zippel in 1942. Since then this tumor have been described as proximal tubular adenoma with oncocytic features and later oncocytoma became the generally accepted term.
Embryonic origin Many investigators have suggested that these tumors originate from intercalated cells of the collecting system.
Etiology Renal oncocytomas can present in familial or sporadic forms. Oncocytomas are the most frequent renal tumors in patients with Birt-Hogg-Dube syndrome (BHD). BHD is caused by mutations in the folliculin gene (FLCN). The etiology of sporadic RO is not known.
Epidemiology Renal oncocytomas account for about 3-7% of all renal tumors and shows 2.5:1 male to female ratio. More than 50% of patients with RO are asymptomatic. Some patients have been reported in association with angiomyolipoma and/or tuberous sclerosis .
Pathology Macroscopically, renal oncocytomas are solitary, well-circumscribed, slightly lobulated solid tumors with generally mahogany brown or dark red cut surface. A central scar is frequently observed. Necrosis and hemorrhage are uncommon. Microscopically, tumor cells with abundant, granular cytoplasm are arranged in nests, tubulocystic, solid, or trabecular patterns within edematous, myxomatous or hyalinized stroma. On low power, the epithelial cell nests surrounded by myxomatous stroma gives the appearance of an island archipelago, which is a characteristic feature of oncocytomas. The nucleus is homogenous, round and centrally located, but large bizarre nuclei are frequently observed. Ultrastructurally, tumor cells contain many mitochondria with predominantly lamellar cristae.
Some special stains are helpful for differential diagnosis with the eosinophilic or granular form of clear cell carcinoma: most RO show negative vimentin and RCC antigen staining, although positive staining for vimentin in up to 72% has been reported in some series. The immunohistochemical patterns of oncocytoma and chromophobe carcinoma are virtually identical, which often makes distinctions of these tumors with overlapping morphologic features quite difficult. Recently, claudin 8 positivity in oncocytomas has been reported as tool to differentiate these two neoplasms since chromophobe carcinomas are negative for claudin 8 and positive for claudin 7.
Some authors have suggested that oncocytoma can progress to chromophobe carcinoma, based on shared abnormalities in chromosome 1, although the occurrence of this transformation has not been conclusively proven.
Treatment Most patients with RO are treated with nephrectomy. Nephrectomy (radical or partial), enucleation or wedge resection may be performed.
Prognosis Almost all cases of oncocytoma behave in a benign fashion with no recurrence, metastasis or mortality. Some atypical features, such as nuclear pleomorphism, perinephric fat involvement and focal necrosis do not seem influence prognosis. Rarely few cases of RO have simulated malignant behavior showing extension to branches of renal vein however this does not correlate with poor outcome. A case of metastatic oncocytoma has been reported.

Cytogenetics

Note Complete or partial loss of chromosome 1 is the most common cytogenetic abnormality reported in approximately 40% of cases. Other frequent changes include loss of Y (15%) and monosomy 14 (15%). Trisomy 7 has been reported as the most common chromosomal gain in up to 5% of patients. Structural rearrangements involving 11q12-13 have been reported. Approximately 50% of tumors show no chromosomal abnormalities.
The incidence of chromosome 1 abnormalities in bilateral tumors seems to be higher than single tumors. Chromosomal abnormalities seem to be more frequent in sporadic tumors, while familial RO has a higher frequency of cytogenetically normal tumors.
One of the diagnostic pitfalls in renal epithelial tumors is distinguishing between benign RO from the eosinophillic variant of chromophobe RCC. Many studies have reported that chromophobe RCC shows complex simultaneous losses of chromosomes 1, 2, 6, 10, 13, 17, and 21. Although occasional losses of all these chromosomes have been reported in RO, the simultaneous loss of all these chromosomes has not been seen in oncocytomas.

Genes involved and Proteins

Note RO is characterized by dense accumulation of mitochondria and deficient in electron transport chain complex I (CI). CI or NADP-ubiquinone oxidoreductase is the main gateway to the electron transport chain. Mitochondrial proliferation in oncocytic cells could be regulatory response attempting to restore a defective respiratory function since defective oxygen consumption makes mitochondrial proliferation. CI is encoded in part by nuclear genome and in part by the mitochondrial genome for 7 genes (MT-ND1, MT-ND2, MT-ND3, MT-ND4, MD4L, MD5, MD6) yielding 45 subunits. Mitochondrial DNA point mutations are found in all ROs studied (9/9 cases), especially in complex I and none of chromophobe RCC.
Mutations in folliculin (FLCN, 17p11.2) cause Birt-Hogg-Dube (BHD) syndrome which is a rare inherited genodermatosis characterized by hair follicle hamartomas, kidney tumors, and spontaneous pneumothorax. RO is the most common renal tumor seen in patients with BHD. The FLCN protein contains a conserved SLS potential phosphorylation site, and shows a highly conserved sequence between human and homologs in mice, Drosophila, and C. elegans. It is believed that FLCN may be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways.

Other genes implicated (Data extracted from papers in the Atlas)

Genes CDC73 FLCN LOX NNMT NRF1 PRSS8 EPCAM

Translocations implicated (Data extracted from papers in the Atlas)

External links

3031 Oncocytoma;Onc
Mitelman databaseTopo ( Kidney ) - Morpho ( Onc ) - Mitelman database (CGAP - NCBI)
COSMICHisto = - Site = kidney (COSMIC)
Other databaseoncocytomafiles/bhd/index.html
Other databasehttp://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=135150
Other databasehttp://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=610594

Bibliography

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Toro JR, Glenn G, Duray P, Darling T, Weirich G, Zbar B, Linehan M, Turner ML.
Arch Dermatol. 1999 Oct;135(10):1195-202.
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Familial and sporadic renal oncocytomas--a comparative molecular-genetic analysis.
Junker K, Weirich G, Moravek P, Podhola M, Ilse B, Hartmann A, Schubert J.
Eur Urol. 2001 Sep;40(3):330-6.
PMID 11684851
 
Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dube syndrome.
Nickerson ML, Warren MB, Toro JR, Matrosova V, Glenn G, Turner ML, Duray P, Merino M, Choyke P, Pavlovich CP, Sharma N, Walther M, Munroe D, Hill R, Maher E, Greenberg C, Lerman MI, Linehan WM, Zbar B, Schmidt LS.
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Review of renal oncocytoma with focus on clinical and pathobiological aspects.
Kuroda N, Toi M, Hiroi M, Shuin T, Enzan H.
Histol Histopathol. 2003 Jul;18(3):935-42.
PMID 12792905
 
Pathology and Genetics of Tumors of the Urinary System and Male Genital Organs.
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Microsatellite allelotyping differentiates chromophobe renal cell carcinomas from renal oncocytomas and identifies new genetic changes.
Nagy A, Buzogany I, Kovacs G.
Histopathology. 2004 Jun;44(6):542-6.
PMID 15186268
 
Losses of 1p and chromosome 14 in renal oncocytomas.
Fuzesi L, Frank D, Nguyen C, Ringert RH, Bartels H, Gunawan B.
Cancer Genet Cytogenet. 2005 Jul 15;160(2):120-5.
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Insertion (8;11) in a renal oncocytoma with multifocal transformation to chromophobe renal cell carcinoma.
Salido M, Lloreta J, Melero C, García M, Placer J, Espinet B, Villa O, Bielsa O, Gelabert-Mas A, Serrano S, Sole F.
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Classification of renal neoplasms based on molecular signatures.
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Metastatic renal oncocytoma.
Oxley JD, Sullivan J, Mitchelmore A, Gillatt DA.
J Clin Pathol. 2007 Jun;60(6):720-2.
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High incidence of chromosome 1 abnormalities in a series of 27 renal oncocytomas: cytogenetic and fluorescence in situ hybridization studies.
Paner GP, Lindgren V, Jacobson K, Harrison K, Cao Y, Campbell SC, Flanigan RC, Picken MM.
Arch Pathol Lab Med. 2007 Jan;131(1):81-5.
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Clonal expansion of mutated mitochondrial DNA is associated with tumor formation and complex I deficiency in the benign renal oncocytoma.
Gasparre G, Hervouet E, de Laplanche E, Demont J, Pennisi LF, Colombel M, Mege-Lechevallier F, Scoazec JY, Bonora E, Smeets R, Smeitink J, Lazar V, Lespinasse J, Giraud S, Godinot C, Romeo G, Simonnet H.
Hum Mol Genet. 2008 Apr 1;17(7):986-95.
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Renal oncocytoma with and without intravascular extension into the branches of renal vein have the same morphological, immunohistochemical, and genetic features.
Hes O, Michal M, Síma R, Vanecek T, Brunelli M, Martignoni G, Kuroda N, Alvarado Cabrero I, Perez-Montiel D, Hora M, Urge T, Dvorak M, Jarosova M, Yang X.
Virchows Arch. 2008 Feb;452(2):193-200.
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Oncocytic papillary renal cell carcinoma with solid architecture: mimic of renal oncocytoma.
Mai KT, Kohler DM, Robertson SJ, Belanger EC, Marginean EC.
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Progesterone receptor reactivity in renal oncocytoma and chromophobe renal cell carcinoma.
Mai KT, Teo I, Belanger EC, Robertson SJ, Marginean EC, Islam S.
Histopathology. 2008 Feb;52(3):277-82.
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Loss of complex I due to mitochondrial DNA mutations in renal oncocytoma.
Mayr JA, Meierhofer D, Zimmermann F, Feichtinger R, Kogler C, Ratschek M, Schmeller N, Sperl W, Kofler B.
Clin Cancer Res. 2008 Apr 15;14(8):2270-5.
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Chromosome 1 Analysis in Chromophobe Renal Cell Carcinomas With Tissue Microarray (TMA)-facilitated Fluorescence In Situ Hybridization (FISH) Demonstrates Loss of 1p/1 Which is Also Present in Renal Oncocytomas.
Meyer PN, Cao Y, Jacobson K, Krausz T, Flanigan RC, Picken MM.
Diagn Mol Pathol. 2008 Mar 28. Epub ahead of print.
PMID 18382368
 
Whole genome SNP arrays as a potential diagnostic tool for the detection of characteristic chromosomal aberrations in renal epithelial tumors.
Monzon FA, Hagenkord JM, Lyons-Weiler MA, Balani JP, Parwani AV, Sciulli CM, Li J, Chandran UR, Bastacky SI, Dhir R.
Mod Pathol. 2008 May;21(5):599-608.
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Analysis of chromosome 1p abnormalities in renal oncocytomas by loss of heterozygosity studies: correlation with conventional cytogenetics and fluorescence in situ hybridization.
Picken MM, Chyna B, Flanigan RC, Lee JM.
Am J Clin Pathol. 2008 Mar;129(3):377-82.
PMID 18285259
 
Claudins 7 and 8 Expression Separate Chromophobe Renal Cell Carcinoma from Oncocytoma.
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REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed

Contributor(s)

Written04-2008Hyun-Jung Kim, Federico A Monzon
Inje University, Sanggye Paik Hospital, Seoul, Korea (HJK); The Methodist Hospital and The Methodist Hospital Research Institute, Houston, TX, USA (FAM)

Citation

This paper should be referenced as such :
Kim, HJ ; Monzon, FA
Kidney: Renal Oncocytoma
Atlas Genet Cytogenet Oncol Haematol. 2009;13(4):316-318.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Tumors/RenalOncocytomaID5132.html

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indexed on : Fri Jul 11 13:11:17 CEST 2014


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