Renal oncocytoma pathophysiology: Difference between revisions

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==Overview==
==Overview==
The exact pathogenesis of [disease name] is not fully understood.
The exact [[pathogenesis]] of renal oncocytoma is not completely understood. Although some mechanisms are suggested in the [[pathogenesis]] of this disease that include, lossing of [[chromosome 1]] and [[dysfunction]] of [[mitochondrial]] [[enzymes]] which is caused by alterations in the [[mitochondrial DNA]]. [[DNA]] [[Diploid|diploidy]] is seen in 96% of [[patients]] with renal oncocytomas. The development of renal oncocytoma is the result of multiple [[genetic mutations]] such as deletion of [[chromosome 1]], deletion of the [[sex chromosome]], [[Translocations|translocation]] of [[chromosome]] 11q13, sporadic or no [[chromosomal]] alteration. Renal oncocytoma can be associated with familial renal oncocytoma or Birt-Hogg-Dube [[syndrome]]. On [[gross]] [[pathology]],  tan to brown surface color , well-encapsulated with a thick, well-defined, [[fibrous]] [[capsule]], central scar, and [[homogeneous]] appearance without any [[hemorrhage]] or [[necrosis]] inside it in the [[tumor]] cut are characteristic findings of renal oncocytoma. On [[microscopic]] [[histopathological]] [[analysis]], renal oncocytoma characterized by "oncocytes". They are large, round to polygonal [[neoplastic]] cells accompanied by [[eosinophilic]] granular [[cytoplasm]] and are organized in nested or organoid pattern. Although, renal oncocytoma is [[benign]], [[atypia]], prominent [[nucleoli]], and [[pleomorphism]] may seen in [[microscopic examination]].
 
OR
 
It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
 
OR
 
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
 
OR
 
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
 
OR
 
 
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
 
OR
 
The progression to [disease name] usually involves the [molecular pathway].
 
OR
 
The pathophysiology of [disease/malignancy] depends on the histological subtype.


==Pathophysiology==
==Pathophysiology==
===Physiology===
The normal physiology of [name of process] can be understood as follows:
===Pathogenesis===
===Pathogenesis===
*The exact pathogenesis of [disease name] is not completely understood.
*The exact [[pathogenesis]] of renal oncocytoma is not completely understood.
OR
*The mechanisms which are suggested in the [[pathogenesis]] of renal oncocytoma include:<ref name="Thrash-BinghamSalazar1996">{{cite journal|last1=Thrash-Bingham|first1=Catherine A.|last2=Salazar|first2=Hernando|last3=Greenberg|first3=Richard E.|last4=Tartof|first4=Kenneth D.|title=Loss of heterozygosity studies indicate that chromosome arm 1p harbors a tumor suppressor gene for renal oncocytomas|journal=Genes, Chromosomes and Cancer|volume=16|issue=1|year=1996|pages=64–67|issn=10452257|doi=10.1002/(SICI)1098-2264(199605)16:1<64::AID-GCC9>3.0.CO;2-1}}</ref><ref name="Dijkhuizenvan den Berg1997">{{cite journal|last1=Dijkhuizen|first1=T.|last2=van den Berg|first2=E.|last3=Störkel|first3=S.|last4=de Vries|first4=B.|last5=van der Veen|first5=A.Y.|last6=Wilbrink|first6=M.|last7=Geurts van Kessel|first7=A.|last8=de Jong|first8=B.|title=Renal oncocytoma with t(5;12;11), der(1)t(1;8) and add(19): “true” oncocytoma or chromophobe adenoma?|journal=International Journal of Cancer|volume=73|issue=4|year=1997|pages=521–524|issn=00207136|doi=10.1002/(SICI)1097-0215(19971114)73:4<521::AID-IJC11>3.0.CO;2-C}}</ref><ref name="NeuhausDijkhuizen1997">{{cite journal|last1=Neuhaus|first1=Christine|last2=Dijkhuizen|first2=T.|last3=van den Berg|first3=E.|last4=Störkel|first4=S.|last5=Stöckle|first5=M.|last6=Mensch|first6=B.|last7=Huber|first7=C.|last8=Decker|first8=H.-J.|title=Involvement of the chromosomal region 11q13 in renal oncocytoma: Case report and literature review|journal=Cancer Genetics and Cytogenetics|volume=94|issue=2|year=1997|pages=95–98|issn=01654608|doi=10.1016/S0165-4608(96)00205-1}}</ref><ref>{{Cite journal
*It is understood that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
| author = [[C. Welter]], [[G. Kovacs]], [[G. Seitz]] & [[N. Blin]]
*[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
| title = Alteration of mitochondrial DNA in human oncocytomas
*Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
| journal = [[Genes, chromosomes & cancer]]
*[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
| volume = 1
*The progression to [disease name] usually involves the [molecular pathway].
| issue = 1
*The pathophysiology of [disease/malignancy] depends on the histological subtype.
| pages = 79–82
| year = 1989
| month = September
| pmid = 2487148
}}</ref>
**Lossing of [[chromosome 1]]
** [[Dysfunction]] of [[mitochondrial]] [[enzymes]] which is caused by alterations in the [[mitochondrial DNA]]


==Genetics==
==Genetics==
DNA diploidy is seen in 96% of patients with renal oncocytomas.<ref>{{Cite journal
[[DNA]] [[Diploid|diploidy]] is seen in 96% of [[patients]] with renal oncocytomas.<ref>{{Cite journal
  | author = [[M. R. Licht]], [[A. C. Novick]], [[R. R. Tubbs]], [[E. A. Klein]], [[H. S. Levin]] & [[S. B. Streem]]
  | author = [[M. R. Licht]], [[A. C. Novick]], [[R. R. Tubbs]], [[E. A. Klein]], [[H. S. Levin]] & [[S. B. Streem]]
  | title = Renal oncocytoma: clinical and biological correlates
  | title = Renal oncocytoma: clinical and biological correlates
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  | month = November
  | month = November
  | pmid = 8411404
  | pmid = 8411404
}}</ref><ref name="J. HartwickEl-Naggar1992">{{cite journal|last1=J. Hartwick|first1=R. Warren|last2=El-Naggar|first2=Adel K.|last3=Ro|first3=Jae Y.|last4=Srigley|first4=John R.|last5=Mclemore|first5=Donia D.|last6=Jones|first6=Edward C.|last7=Grignon|first7=David J.|last8=Thomas|first8=M. Jane|last9=Ayala|first9=Alberto G.|title=Renal Oncocytoma and Granular Renal Cell Carcinoma: A Comparative Clinicopathologic and DNA Flow Cytometric Study|journal=American Journal of Clinical Pathology|volume=98|issue=6|year=1992|pages=587–593|issn=1943-7722|doi=10.1093/ajcp/98.6.587}}</ref>
}}</ref><ref name="J. HartwickEl-Naggar1992">{{cite journal|last1=J. Hartwick|first1=R. Warren|last2=El-Naggar|first2=Adel K.|last3=Ro|first3=Jae Y.|last4=Srigley|first4=John R.|last5=Mclemore|first5=Donia D.|last6=Jones|first6=Edward C.|last7=Grignon|first7=David J.|last8=Thomas|first8=M. Jane|last9=Ayala|first9=Alberto G.|title=Renal Oncocytoma and Granular Renal Cell Carcinoma: A Comparative Clinicopathologic and DNA Flow Cytometric Study|journal=American Journal of Clinical Pathology|volume=98|issue=6|year=1992|pages=587–593|issn=1943-7722|doi=10.1093/ajcp/98.6.587}}</ref><ref>{{Cite journal
<ref>{{Cite journal
  | author = [[L. Fuzesi]], [[B. Gunawan]], [[S. Braun]], [[F. Bergmann]], [[A. Brauers]], [[P. Effert]] & [[C. Mittermayer]]
  | author = [[L. Fuzesi]], [[B. Gunawan]], [[S. Braun]], [[F. Bergmann]], [[A. Brauers]], [[P. Effert]] & [[C. Mittermayer]]
  | title = Cytogenetic analysis of 11 renal oncocytomas: further evidence of structural rearrangements of 11q13 as a characteristic chromosomal anomaly
  | title = Cytogenetic analysis of 11 renal oncocytomas: further evidence of structural rearrangements of 11q13 as a characteristic chromosomal anomaly
Line 69: Line 46:
}}</ref>
}}</ref>
      
      
The development of renal oncocytoma is the result of multiple genetic mutations such as:
The development of renal oncocytoma is the result of multiple [[genetic mutations]] such as:<ref>{{Cite journal
<ref>{{Cite journal
  | author = [[L. Fuzesi]], [[B. Gunawan]], [[S. Braun]], [[F. Bergmann]], [[A. Brauers]], [[P. Effert]] & [[C. Mittermayer]]
  | author = [[L. Fuzesi]], [[B. Gunawan]], [[S. Braun]], [[F. Bergmann]], [[A. Brauers]], [[P. Effert]] & [[C. Mittermayer]]
  | title = Cytogenetic analysis of 11 renal oncocytomas: further evidence of structural rearrangements of 11q13 as a characteristic chromosomal anomaly
  | title = Cytogenetic analysis of 11 renal oncocytomas: further evidence of structural rearrangements of 11q13 as a characteristic chromosomal anomaly
Line 91: Line 67:
  | pmid = 9216713
  | pmid = 9216713
}}</ref>
}}</ref>
*Loss of chromosome 1  
*Deletion of [[chromosome 1]]
*Loss of the sex chromosome
*Deletion of the [[sex chromosome]]
*Translocation of chromosome 11q13
*[[Translocations|Translocation]] of [[chromosome]] 11q13
*Sporadic or no chromosomal alteration
*Sporadic or no [[chromosomal]] alteration


==Associated Conditions==
==Associated Conditions==
Line 107: Line 83:
  | month = August
  | month = August
  | pmid = 9679872
  | pmid = 9679872
}}</ref>
}}</ref><ref>{{Cite journal
<ref>{{Cite journal
  | author = [[J. R. Toro]], [[G. Glenn]], [[P. Duray]], [[T. Darling]], [[G. Weirich]], [[B. Zbar]], [[M. Linehan]] & [[M. L. Turner]]
  | author = [[J. R. Toro]], [[G. Glenn]], [[P. Duray]], [[T. Darling]], [[G. Weirich]], [[B. Zbar]], [[M. Linehan]] & [[M. L. Turner]]
  | title = Birt-Hogg-Dube syndrome: a novel marker of kidney neoplasia
  | title = Birt-Hogg-Dube syndrome: a novel marker of kidney neoplasia
Line 120: Line 95:
}}</ref>
}}</ref>


*Familial renal oncocytoma and Birt-Hogg-Dube syndrome.
*[[Familial]] renal oncocytoma
*Birt-Hogg-Dube syndrome
*Birt-Hogg-Dube [[syndrome]]


'''Note:''' Renal oncocytoma can be associated with is called Birt-Hogg-Dube syndrome. This syndrome is an autosomal dominant syndrome which is presented with different types of dermatologic diseases and renal epithelial tumors such as renal oncocytoma and RCCs.
'''Note:''' Birt-Hogg-Dube [[syndrome]] is an [[autosomal dominant]] [[syndrome]] which is presented with different types of [[Dermatology|dermatologic]] [[diseases]] and [[renal]] [[epithelial]] [[tumors]] such as renal oncocytoma and [[Renal cell carcinoma|RCC]]<nowiki/>s.
 
Grossly renal oncocytomas are well-circumscribed, tan-brown or mahogany-colored masses with a central stellate scar.[2] The central scar is characteristic of renal oncocytoma, but it is not specific for this entity and is not always present.[2] Grossly, oncocytoma can occasionally interdigitate with perinephric fat. When it does this, there does not appear to be any stromal reaction or response in the fat. This does not change benign behavior.[2] Similarly,  a small portion of tumors may have vascular invasion.
 
Microscopically, renal oncocytomas appear well-circumscribed. The mass is composed of nests and tubular structures line by round to polygonal cells with abundant granular eosinophilic cytoplasm. The cells have uniform nuclei with prominent central nucleoli.[1] The background stroma is edematous, myxomatous, or hyalinized.[6] Other possible architectural patterns include compact nesting, solid, focal rare abortive papillary structures, and cystic spaces.[2] One variation is a small cell oncocytoma, which occurs when there are areas with scant cytoplasm.
 
It is well established that oncocytomas may contain a degree of cytologic atypia, which is thought to be degenerative. This atypia may include increased nuclear size, irregular nuclear contours, and smudged chromatin.[2] Mitosis is extremely rare in oncocytoma, and more than one mitotic figure should not be found.[2]
 
Clinicians can confirm the diagnosis of oncocytoma with immunohistochemistry. The most common stain used is cytokeratin 7, which is minimally positive and limited to scattered individual cells or small clusters. AMACR may be positive in low intensity. Oncocytoma should have membranous positivity for CD117. Other positive stains include cyclin D1, kidney-specific cadherin, S100A1, and E-cadherin.[7][2] Colloidal iron staining is often described as helpful in diagnosis, but there is wide variation in staining techniques that can make interpretation challenging. If used, colloidal iron staining should be negative.[2] Vimentin may be focally positive at the edge of the central scar but should not be diffusely positive.[2] Oncocytoma will be negative for melanocytic markers.
 
If evaluated on a cytology specimen, oncocytoma will have large cells with granular cytoplasm, regular nuclei with tiny nucleoli, and minimal atypia.[8]


==Gross Pathology==
==Gross Pathology==
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
On gross pathology, tan to brown surface color , well-encapsulated with a thick, well-defined, [[fibrous]] [[capsule]], central scar, and [[homogeneous]] appearance without any [[hemorrhage]] or [[necrosis]] inside it in the [[tumor]] cut are characteristic findings of renal oncocytoma.<ref name="MochCubilla2016">{{cite journal|last1=Moch|first1=Holger|last2=Cubilla|first2=Antonio L.|last3=Humphrey|first3=Peter A.|last4=Reuter|first4=Victor E.|last5=Ulbright|first5=Thomas M.|title=The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs—Part A: Renal, Penile, and Testicular Tumours|journal=European Urology|volume=70|issue=1|year=2016|pages=93–105|issn=03022838|doi=10.1016/j.eururo.2016.02.029}}</ref><ref name="AminCrotty1997">{{cite journal|last1=Amin|first1=Mahul B.|last2=Crotty|first2=Thomas B.|last3=Tickoo|first3=Satish K.|last4=Farrow|first4=George M.|title=Renal Oncocytoma: A Reappraisal of Morphologic Features with Clinicopathologic Findings in 80 Cases|journal=The American Journal of Surgical Pathology|volume=21|issue=1|year=1997|pages=1–12|issn=0147-5185|doi=10.1097/00000478-199701000-00001}}</ref><ref name="Perez-OrdonezHamed1997">{{cite journal|last1=Perez-Ordonez|first1=Bayardo|last2=Hamed|first2=Ghiath|last3=Campbell|first3=Steve|last4=Erlandson|first4=Robert|last5=Russo|first5=Paul|last6=Gaudin|first6=Paul|last7=Reuter|first7=Victor|journal=American Journal of Surgical Pathology|volume=21|issue=8|year=1997|pages=871–883|issn=01475185|doi=10.1097/00000478-199708000-00001}}</ref><ref name="TrpkovYilmaz2010">{{cite journal|last1=Trpkov|first1=Kiril|last2=Yilmaz|first2=Asli|last3=Uzer|first3=Dina|last4=Dishongh|first4=Kristin M|last5=Quick|first5=Charles M|last6=Bismar|first6=Tarek A|last7=Gokden|first7=Neriman|title=Renal oncocytoma revisited: a clinicopathological study of 109 cases with emphasis on problematic diagnostic features|journal=Histopathology|volume=57|issue=6|year=2010|pages=893–906|issn=03090167|doi=10.1111/j.1365-2559.2010.03726.x}}</ref><ref>{{Cite journal
 
| author = [[B. Perez-Ordonez]], [[G. Hamed]], [[S. Campbell]], [[R. A. Erlandson]], [[P. Russo]], [[P. B. Gaudin]] & [[V. E. Reuter]]
| title = Renal oncocytoma: a clinicopathologic study of 70 cases
| journal = [[The American journal of surgical pathology]]
| volume = 21
| issue = 8
| pages = 871–883
| year = 1997
| month = August
| pmid = 9255250
}}</ref><ref>{{Cite journal
| author = [[F. Bertoni]], [[C. Ferri]], [[P. Bacchini]], [[G. Corrado]], [[A. Benati]], [[D. Mannini]] & [[F. Corrado]]
| title = Oncocytoma and low-grade oncocytic carcinoma of the kidney
| journal = [[European urology]]
| volume = 16
| issue = 2
| pages = 101–109
| year = 1989
| month =
| pmid = 2714326
}}</ref>
[[File:Gross pathology of renal oncocytoma.jpg|350px|none|thumb|https://radiopaedia.org/cases/renal-oncocytoma-gross-pathology-2?lang=us]]
[[File:Gross pathology- coronal section.jpg|350px|none|thumb|https://radiopaedia.org/cases/renal-oncocytoma-pathology-2?lang=us]]
==Microscopic Pathology==
==Microscopic Pathology==
On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
On [[microscopic]] [[histopathological]] [[analysis]], renal oncocytoma characterized by "oncocytes". They are large, round to polygonal [[neoplastic]] cells accompanied by [[eosinophilic]] granular [[cytoplasm]] and are organized in nested or organoid pattern. Although, renal oncocytoma is [[benign]], [[atypia]], prominent [[nucleoli]], and [[pleomorphism]] may seen in [[microscopic examination]].<ref>{{Cite journal
 
| author = [[B. Perez-Ordonez]], [[G. Hamed]], [[S. Campbell]], [[R. A. Erlandson]], [[P. Russo]], [[P. B. Gaudin]] & [[V. E. Reuter]]
==Overview==
| title = Renal oncocytoma: a clinicopathologic study of 70 cases
On gross pathology, tan or mahogany brown, well circumscribed [[tumor]], and central scar are characteristic findings of renal oncocytoma. On microscopic histopathological analysis, oncocytes and large [[eosinophilic]] cells are characteristic findings of renal oncocytoma.<ref name="pmid2028856">{{cite journal |vauthors=Palmer WE, Chew FS |title=Renal oncocytoma |journal=AJR Am J Roentgenol |volume=156 |issue=6 |pages=1144 |year=1991 |pmid=2028856 |doi=10.2214/ajr.156.6.2028856 |url=http://www.ajronline.org/doi/abs/10.2214/ajr.156.6.2028856}}</ref>
| journal = [[The American journal of surgical pathology]]
 
| volume = 21
==Pathogenesis==
| issue = 8
* Renal oncocytoma is thought to arise from the [[intercalated cells]] of [[collecting ducts]] of the [[kidney]].<ref name="pmid6606945">{{cite journal |vauthors=Velasquez G, Glass TA, D'Souza VJ, Formanek AG |title=Multiple oncocytomas and renal carcinoma |journal=AJR Am J Roentgenol |volume=142 |issue=1 |pages=123–4 |year=1984 |pmid=6606945 |doi=10.2214/ajr.142.1.123 |url=http://www.ajronline.org/doi/abs/10.2214/ajr.142.1.123}}</ref>
| pages = 871–883
 
| year = 1997
==Gross Pathology==
| month = August
* The [[tumors]] are tan or mahogany brown, well circumscribed, and contain a central scar. They may achieve a large size (up to 12 cm in diameter).<ref name="pmid6606945">{{cite journal |vauthors=Velasquez G, Glass TA, D'Souza VJ, Formanek AG |title=Multiple oncocytomas and renal carcinoma |journal=AJR Am J Roentgenol |volume=142 |issue=1 |pages=123–4 |year=1984 |pmid=6606945 |doi=10.2214/ajr.142.1.123 |url=http://www.ajronline.org/doi/abs/10.2214/ajr.142.1.123}}</ref>
| pmid = 9255250
 
}}</ref><ref name="BarnesBeckman1983">{{cite journal|last1=Barnes|first1=C. Allan|last2=Beckman|first2=Edwin N.|title=Renal Oncocytoma and Its Congeners|journal=American Journal of Clinical Pathology|volume=79|issue=3|year=1983|pages=312–318|issn=1943-7722|doi=10.1093/ajcp/79.3.312}}</ref><ref>{{Cite journal
<gallery>
| author = [[H. Choi]], [[U. A. Almagro]], [[J. T. McManus]], [[D. H. Norback]] & [[S. C. Jacobs]]
Image:
| title = Renal oncocytoma. A clinicopathologic study
Renal oncocytoma1.jpg|Renal oncocytoma<ref>Renal oncocytoma. Libre Pathology 2015. http://librepathology.org/wiki/index.php/Renal_oncocytoma Accessed on October, 29 2015 </ref>
| journal = [[Cancer]]
</gallery>
| volume = 51
 
| issue = 10
==Microscopic Pathology==
| pages = 1887–1896
* An epithelial tumor composed of oncocytes, large [[eosinophilic]] cells having small, round, benign-appearing [[nuclei]] with large [[nucleoli]] and excessive amounts of [[mitochondria]].<ref name="pmid2028856">{{cite journal |vauthors=Palmer WE, Chew FS |title=Renal oncocytoma |journal=AJR Am J Roentgenol |volume=156 |issue=6 |pages=1144 |year=1991 |pmid=2028856 |doi=10.2214/ajr.156.6.2028856 |url=http://www.ajronline.org/doi/abs/10.2214/ajr.156.6.2028856}}</ref>
| year = 1983
 
| month = May
<gallery>
| pmid = 6831354
Image:
}}</ref><ref>{{Cite journal
Renal oncocytoma2.jpg|Renal oncocytoma<ref>Renal oncocytoma. Libre Pathology 2015. http://librepathology.org/wiki/index.php/Renal_oncocytoma Accessed on October, 29 2015 </ref>
| author = [[M. B. Amin]], [[T. B. Crotty]], [[S. K. Tickoo]] & [[G. M. Farrow]]
</gallery>
| title = Renal oncocytoma: a reappraisal of morphologic features with clinicopathologic findings in 80 cases
 
| journal = [[The American journal of surgical pathology]]
==Genetics==
| volume = 21
* Genes involved in the pathogenesis of renal concocytoma may include mtDNA MTND6 and [[FLCN]].<ref name="pmid21555623">{{cite journal |vauthors=Bartoletti-Stella A, Salfi NC, Ceccarelli C, Attimonelli M, Romeo G, Gasparre G |title=Mitochondrial DNA mutations in oncocytic adnexal lacrimal glands of the conjunctiva |journal=[[Archives of Ophthalmology (Chicago, Ill. : 1960)]] |volume=129 |issue=5 |pages=664–6 |year=2011 |pmid=21555623 |doi=10.1001/archophthalmol.2011.95 |url=http://archopht.jamanetwork.com/article.aspx?doi=10.1001/archophthalmol.2011.95 |issn=}}</ref>
| issue = 1
 
| pages = 1–12
| year = 1997
| month = January
| pmid = 8990136
}}</ref><ref>{{Cite journal
| author = [[J. N. Eble]] & [[M. T. Hull]]
| title = Morphologic features of renal oncocytoma: a light and electron microscopic study
| journal = [[Human pathology]]
| volume = 15
| issue = 11
| pages = 1054–1061
| year = 1984
| month = November
| pmid = 6490001
}}</ref>
[[File:Renal oncocytoma HE.png|350px|none|thumb|https://openi.nlm.nih.gov/detailedresult?img=PMC3557568_rt-2012-4-e54-g003&query=renal%20oncocytoma&it=xg&req=4&npos=61]][[File:Renal oncocytoma.png|350px|none|thumb|https://openi.nlm.nih.gov/detailedresult?img=PMC3306738_1471-2369-13-9-1&query=renal%20oncocytoma&it=xg&req=4&npos=41]]


Renal oncocytomas are usually tan to brown and
well demarcated. A “pseudocapsule” is often seen
where the tumor compresses the adjacent renal parenchyma.
1,13,14 Although hemorrhage is typically
absent, focal areas can be detected in some tumors.
1,6,7,12–16 Most cases of oncocytoma are confined
within the renal parenchyma, and gross evidence
of capsular or vascular invasion is
rare.1,2,12,16 One distinctive feature of oncocytomas
is the presence of a prominent central scar in an
otherwise homogenous tumor, seen in 33% to 80%
of cases.1,12,17,18 The average size of oncocytomas
with central scars is slightly less than that of tumors
without scars,18 indicating a limited correlation
between tumor size and the presence of central
scars. Thus, the diagnosis of oncocytoma
cannot be made on the basis of the tumor size or
the absence or presence of a central scar.
MICROSCOPIC FEATURES
Microscopic examination of oncocytomas reveals
characteristic features of the cellular architecture,
cytoplasm, and nucleus. Uniformity in
cellular size and color, round to polygonal
shape, and abundant fine granular cytoplasm are
consistent findings.1,6,13–15,17 Clear cells are not
present, but foci of cytoplasmic clearing can be
seen within the granular cells, distinctive from
the clear cells seen in RCC.1,2,19 The typical nuclei
appear small, uniform, and round, contain
fine evenly dispersed chromatin, and show no
evidence of mitosis.1,2,7,13–15,17,19,20 A minority of
cells can have nuclear atypia and there may be
focal presence of large nucleoli, moderate to
marked pleomorphism, hyperchromasia, and
binucleation or multinucleation.1,2,10,15,17,20 The
degree of nuclear atypia is not correlated with
the tumor size2 and does not affect the benign
nature of the tumor. Accordingly, nuclear grading
for oncocytomas has been abandoned.1,2
Three cellular architectural patterns are commonly
seen (Fig. 1). The first type is described as
“organoid,”2,6 with nests of cells surrounded by a
reticulin framework of thin blood vessels and
strands of delicate fibrous stroma. The nests can be
loosely arranged or packed tightly into a sheet-like
appearance.1,2,6,15,17 The second pattern is tubulocystic
or alveolar, with cells arranged as tubular
and cystic structures separated in a loose edematous
stroma.1,2,15,17 The third type consists of a mixture of the organoid and tubulocystic patterns.
2,17
Lymphovascular invasion, perinephric extension,
and necrosis are usually not present.1,2,15 Because
such findings are so uncommon, the impact
on patient prognosis is inconclusive. Such tumors
are best considered “atypical oncocytomas.”
Examination using Hale’s colloidal iron staining
is often used to distinguish oncocytomas from
CRCC, and the results are either negative or focally
positive at perinuclear, perimembranous, or apical
regions of the cell (Fig. 2). In CRCC, a correlation
has been found between positive Hale’s colloidal
iron staining and the presence of cytoplasmic mi-crovesicles.3 The pattern of Hale’s colloidal iron
staining seen in oncocytomas also parallels the microvesicular
distribution.
Despite the well-characterized cytologic features
of renal oncocytomas and the obvious benefits of
the preoperative diagnosis of a benign tumor, the
role of tumor biopsy for definitive diagnosis has
been studied only retrospectively on samples taken
from surgical specimens21,22 and remains questionable.
Moreover, the overall sensitivity of renal biopsy
ranges from 40% to 90%,23–25 and many tumors
that are read as “nondiagnostic” on biopsy
are often found to be malignant after complete surgical
extirpation and thorough histologic examination.
24,25 Until the techniques and interpretations
of biopsies become more consistent, its utility for
the preoperative diagnosis of renal oncocytomas
will remain limited.
ULTRASTRUCTURE AND
IMMUNOHISTOCHEMISTRY
The most striking feature on electron microscopic
examination is the diffuse distribution of
round and uniform mitochondria, with a scarcity
of all other cytoplasmic organelles1,13,17,20,26 (Fig.
3). Most mitochondria contain long lamellar cristae
arranged in parallel arrays.1,26 Small amounts of
microvesicles can usually be identified in the cytoplasm.
20,26 The presence of these microvesicles
supports the conclusion that oncocytomas originate
from the intercalated cells of the collecting
duct, which normally demonstrate numerous apically
located microvesicles.27
Immunohistochemical studies have shown that
oncocytomas express various cytokeratins typical
to epidermal neoplasms. But unlike most RCCs,
which diffusely express vimentin, oncocytomas
will show only sporadic vimentin expression.28
Immunohistochemical staining for cathepsin H
can also distinguish oncocytomas from RCC,29
with negative or weakly positive staining for cathepsin
H in RCC and strong and diffuse staining
in oncocytomas.
GENETIC ALTERATIONS
DNA ploidy studies and chromosomal analyses
have demonstrated important differences between
oncocytomas and RCC. DNA diploidy occurs in up
to 96% of oncocytomas.10,16,30 In comparison,
more than 60% of RCC tumors demonstrating
granular cytoplasm have some ploidy anomaly.16
Oncocytomas average two genetic alterations per
tumor and locally advanced RCC averages 4.6.31
The most common abnormalities associated with
RCC variants, including loss of heterozygosity of
chromosome 3p in nonpapillary RCC, specific trisomies
of chromosomes 3q, 7, 8, 12, 16, 17, and 20
in papillary RCC, and the combined loss of heterozygosity
at chromosomes 1, 2, 6, 10, 13, 17, and
21 in chromophobe RCC, are not detected in oncocytomas.
31–34
The chromosomal alterations that are associated
with oncocytomas can be placed in three categories:
loss of chromosome 1 and the sex chromosome,
balanced translocations involving chromosome
11q13, and a third group consisting of
apparently sporadic, still ill-defined, chromosomal
changes or no detectable chromosomal changes.
30,31,35–39 Table I summarizes the most common
genetic alterations associated with the various tumor
types.
Chromosome 1p is thought to harbor a tumor suppressor gene that is involved in the development
of oncocytomas.36 Others believe that oncocytomas
and CRCC reside on a common “morphologic
spectrum”40 on the basis of their loss of
chromosome 1. One hypothesis suggests that oncocytomas
with loss of chromosome 1 have the
potential to progress to CRCC after subsequent
loss of chromosomes 2, 6, 10, 13, 17, and 21.37
Others speculate that the two tumors actually arise
from a common precursor with the potential to
differentiate either in the benign or malignant direction.
40 It is also notable that oncocytomas are
marked by alterations in their mitochondrial
DNA.39 Mitochondrial proteins are encoded on
chromosomes 1, 11, and 20, suggesting that mitochondrial
enzymes may have some role in the development
of oncocytomas.41 Despite these interesting
findings, most oncocytomas fall into the
third category of sporadic, ill-defined, genetic aberrations.
Clearly, the genetic changes resulting in
the pathogenesis of oncocytomas remain largely
unknown.
Associations between a subset of patients with
multifocal renal oncocytomas and heritable syndromes
have been described, including familial renal
oncocytoma42 and Birt-Hogg-Dube syndrome.
43,44 Birt-Hogg-Dube syndrome is an
autosomal dominant syndrome characterized by
various dermatologic disorders and the development
of renal epithelial tumors, including oncocytomas
and RCCs. The clinicopathologic impact of
these heritable syndromes is unclear.
==References==
==References==
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{{reflist|2}}
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[[Category:Oncology]]
[[Category:Oncology]]
[[Category:Nephrology]]
[[Category:Nephrology]]
[[Category: Primary care]]

Latest revision as of 23:57, 29 July 2020

Renal oncocytoma Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Homa Najafi, M.D.[2] Shanshan Cen, M.D. [3]

Overview

The exact pathogenesis of renal oncocytoma is not completely understood. Although some mechanisms are suggested in the pathogenesis of this disease that include, lossing of chromosome 1 and dysfunction of mitochondrial enzymes which is caused by alterations in the mitochondrial DNA. DNA diploidy is seen in 96% of patients with renal oncocytomas. The development of renal oncocytoma is the result of multiple genetic mutations such as deletion of chromosome 1, deletion of the sex chromosome, translocation of chromosome 11q13, sporadic or no chromosomal alteration. Renal oncocytoma can be associated with familial renal oncocytoma or Birt-Hogg-Dube syndrome. On gross pathology, tan to brown surface color , well-encapsulated with a thick, well-defined, fibrous capsule, central scar, and homogeneous appearance without any hemorrhage or necrosis inside it in the tumor cut are characteristic findings of renal oncocytoma. On microscopic histopathological analysis, renal oncocytoma characterized by "oncocytes". They are large, round to polygonal neoplastic cells accompanied by eosinophilic granular cytoplasm and are organized in nested or organoid pattern. Although, renal oncocytoma is benign, atypia, prominent nucleoli, and pleomorphism may seen in microscopic examination.

Pathophysiology

Pathogenesis

Genetics

DNA diploidy is seen in 96% of patients with renal oncocytomas.[5][6][7]

The development of renal oncocytoma is the result of multiple genetic mutations such as:[8][9][10][1][2][11]

Associated Conditions

Conditions associated with renal oncocytoma include:[12][13]

Note: Birt-Hogg-Dube syndrome is an autosomal dominant syndrome which is presented with different types of dermatologic diseases and renal epithelial tumors such as renal oncocytoma and RCCs.

Gross Pathology

On gross pathology, tan to brown surface color , well-encapsulated with a thick, well-defined, fibrous capsule, central scar, and homogeneous appearance without any hemorrhage or necrosis inside it in the tumor cut are characteristic findings of renal oncocytoma.[14][15][16][17][18][19]

https://radiopaedia.org/cases/renal-oncocytoma-gross-pathology-2?lang=us
https://radiopaedia.org/cases/renal-oncocytoma-pathology-2?lang=us

Microscopic Pathology

On microscopic histopathological analysis, renal oncocytoma characterized by "oncocytes". They are large, round to polygonal neoplastic cells accompanied by eosinophilic granular cytoplasm and are organized in nested or organoid pattern. Although, renal oncocytoma is benign, atypia, prominent nucleoli, and pleomorphism may seen in microscopic examination.[20][21][22][23][24]

https://openi.nlm.nih.gov/detailedresult?img=PMC3557568_rt-2012-4-e54-g003&query=renal%20oncocytoma&it=xg&req=4&npos=61
https://openi.nlm.nih.gov/detailedresult?img=PMC3306738_1471-2369-13-9-1&query=renal%20oncocytoma&it=xg&req=4&npos=41

References

  1. ↑ 1.0 1.1 Thrash-Bingham, Catherine A.; Salazar, Hernando; Greenberg, Richard E.; Tartof, Kenneth D. (1996). "Loss of heterozygosity studies indicate that chromosome arm 1p harbors a tumor suppressor gene for renal oncocytomas". Genes, Chromosomes and Cancer. 16 (1): 64–67. doi:10.1002/(SICI)1098-2264(199605)16:1<64::AID-GCC9>3.0.CO;2-1. ISSN 1045-2257.
  2. ↑ 2.0 2.1 Dijkhuizen, T.; van den Berg, E.; Störkel, S.; de Vries, B.; van der Veen, A.Y.; Wilbrink, M.; Geurts van Kessel, A.; de Jong, B. (1997). "Renal oncocytoma with t(5;12;11), der(1)t(1;8) and add(19): "true" oncocytoma or chromophobe adenoma?". International Journal of Cancer. 73 (4): 521–524. doi:10.1002/(SICI)1097-0215(19971114)73:4<521::AID-IJC11>3.0.CO;2-C. ISSN 0020-7136.
  3. ↑ Neuhaus, Christine; Dijkhuizen, T.; van den Berg, E.; Störkel, S.; Stöckle, M.; Mensch, B.; Huber, C.; Decker, H.-J. (1997). "Involvement of the chromosomal region 11q13 in renal oncocytoma: Case report and literature review". Cancer Genetics and Cytogenetics. 94 (2): 95–98. doi:10.1016/S0165-4608(96)00205-1. ISSN 0165-4608.
  4. ↑ C. Welter, G. Kovacs, G. Seitz & N. Blin (1989). "Alteration of mitochondrial DNA in human oncocytomas". Genes, chromosomes & cancer. 1 (1): 79–82. PMID 2487148. Unknown parameter |month= ignored (help)
  5. ↑ M. R. Licht, A. C. Novick, R. R. Tubbs, E. A. Klein, H. S. Levin & S. B. Streem (1993). "Renal oncocytoma: clinical and biological correlates". The Journal of urology. 150 (5 Pt 1): 1380–1383. PMID 8411404. Unknown parameter |month= ignored (help)
  6. ↑ J. Hartwick, R. Warren; El-Naggar, Adel K.; Ro, Jae Y.; Srigley, John R.; Mclemore, Donia D.; Jones, Edward C.; Grignon, David J.; Thomas, M. Jane; Ayala, Alberto G. (1992). "Renal Oncocytoma and Granular Renal Cell Carcinoma: A Comparative Clinicopathologic and DNA Flow Cytometric Study". American Journal of Clinical Pathology. 98 (6): 587–593. doi:10.1093/ajcp/98.6.587. ISSN 1943-7722.
  7. ↑ L. Fuzesi, B. Gunawan, S. Braun, F. Bergmann, A. Brauers, P. Effert & C. Mittermayer (1998). "Cytogenetic analysis of 11 renal oncocytomas: further evidence of structural rearrangements of 11q13 as a characteristic chromosomal anomaly". Cancer genetics and cytogenetics. 107 (1): 1–6. PMID 9809026. Unknown parameter |month= ignored (help)
  8. ↑ L. Fuzesi, B. Gunawan, S. Braun, F. Bergmann, A. Brauers, P. Effert & C. Mittermayer (1998). "Cytogenetic analysis of 11 renal oncocytomas: further evidence of structural rearrangements of 11q13 as a characteristic chromosomal anomaly". Cancer genetics and cytogenetics. 107 (1): 1–6. PMID 9809026. Unknown parameter |month= ignored (help)
  9. ↑ Presti, Joseph C.; Moch, Holger; Reuter, Victor E.; Huynh, Danh; Waldman, Frederic M. (1996). "Comparative genomic hybridization for genetic analysis of renal oncocytomas". Genes, Chromosomes and Cancer. 17 (4): 199–204. doi:10.1002/(SICI)1098-2264(199612)17:4<199::AID-GCC1>3.0.CO;2-Z. ISSN 1045-2257.
  10. ↑ van den Berg, E.; Dijkhuizen, T.; Störkel, S.; Brutel de la Rivière, G.; Dam, A.; Mensink, H.J.A.; Oosterhuis, J.W.; de Jong, B. (1995). "Chromosomal changes in renal oncocytomas Evidence that t(5;11)(q35;q13) may characterize a second subgroup of oncocytomas". Cancer Genetics and Cytogenetics. 79 (2): 164–168. doi:10.1016/0165-4608(94)00142-X. ISSN 0165-4608.
  11. ↑ R. J. Sinke, T. Dijkhuizen, B. Janssen, D. Olde Weghuis, G. Merkx, E. van den Berg, E. Schuuring, A. M. Meloni, B. de Jong & A. Geurts van Kessel (1997). "Fine mapping of the human renal oncocytoma-associated translocation (5;11)(q35;q13) breakpoint". Cancer genetics and cytogenetics. 96 (2): 95–101. PMID 9216713. Unknown parameter |month= ignored (help)
  12. ↑ G. Weirich, G. Glenn, K. Junker, M. Merino, S. Storkel, I. Lubensky, P. Choyke, S. Pack, M. Amin, M. M. Walther, W. M. Linehan & B. Zbar (1998). "Familial renal oncocytoma: clinicopathological study of 5 families". The Journal of urology. 160 (2): 335–340. PMID 9679872. Unknown parameter |month= ignored (help)
  13. ↑ J. R. Toro, G. Glenn, P. Duray, T. Darling, G. Weirich, B. Zbar, M. Linehan & M. L. Turner (1999). "Birt-Hogg-Dube syndrome: a novel marker of kidney neoplasia". Archives of dermatology. 135 (10): 1195–1202. PMID 10522666. Unknown parameter |month= ignored (help)
  14. ↑ Moch, Holger; Cubilla, Antonio L.; Humphrey, Peter A.; Reuter, Victor E.; Ulbright, Thomas M. (2016). "The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs—Part A: Renal, Penile, and Testicular Tumours". European Urology. 70 (1): 93–105. doi:10.1016/j.eururo.2016.02.029. ISSN 0302-2838.
  15. ↑ Amin, Mahul B.; Crotty, Thomas B.; Tickoo, Satish K.; Farrow, George M. (1997). "Renal Oncocytoma: A Reappraisal of Morphologic Features with Clinicopathologic Findings in 80 Cases". The American Journal of Surgical Pathology. 21 (1): 1–12. doi:10.1097/00000478-199701000-00001. ISSN 0147-5185.
  16. ↑ Perez-Ordonez, Bayardo; Hamed, Ghiath; Campbell, Steve; Erlandson, Robert; Russo, Paul; Gaudin, Paul; Reuter, Victor (1997). American Journal of Surgical Pathology. 21 (8): 871–883. doi:10.1097/00000478-199708000-00001. ISSN 0147-5185. Missing or empty |title= (help)
  17. ↑ Trpkov, Kiril; Yilmaz, Asli; Uzer, Dina; Dishongh, Kristin M; Quick, Charles M; Bismar, Tarek A; Gokden, Neriman (2010). "Renal oncocytoma revisited: a clinicopathological study of 109 cases with emphasis on problematic diagnostic features". Histopathology. 57 (6): 893–906. doi:10.1111/j.1365-2559.2010.03726.x. ISSN 0309-0167.
  18. ↑ B. Perez-Ordonez, G. Hamed, S. Campbell, R. A. Erlandson, P. Russo, P. B. Gaudin & V. E. Reuter (1997). "Renal oncocytoma: a clinicopathologic study of 70 cases". The American journal of surgical pathology. 21 (8): 871–883. PMID 9255250. Unknown parameter |month= ignored (help)
  19. ↑ F. Bertoni, C. Ferri, P. Bacchini, G. Corrado, A. Benati, D. Mannini & F. Corrado (1989). "Oncocytoma and low-grade oncocytic carcinoma of the kidney". European urology. 16 (2): 101–109. PMID 2714326.
  20. ↑ B. Perez-Ordonez, G. Hamed, S. Campbell, R. A. Erlandson, P. Russo, P. B. Gaudin & V. E. Reuter (1997). "Renal oncocytoma: a clinicopathologic study of 70 cases". The American journal of surgical pathology. 21 (8): 871–883. PMID 9255250. Unknown parameter |month= ignored (help)
  21. ↑ Barnes, C. Allan; Beckman, Edwin N. (1983). "Renal Oncocytoma and Its Congeners". American Journal of Clinical Pathology. 79 (3): 312–318. doi:10.1093/ajcp/79.3.312. ISSN 1943-7722.
  22. ↑ H. Choi, U. A. Almagro, J. T. McManus, D. H. Norback & S. C. Jacobs (1983). "Renal oncocytoma. A clinicopathologic study". Cancer. 51 (10): 1887–1896. PMID 6831354. Unknown parameter |month= ignored (help)
  23. ↑ M. B. Amin, T. B. Crotty, S. K. Tickoo & G. M. Farrow (1997). "Renal oncocytoma: a reappraisal of morphologic features with clinicopathologic findings in 80 cases". The American journal of surgical pathology. 21 (1): 1–12. PMID 8990136. Unknown parameter |month= ignored (help)
  24. ↑ J. N. Eble & M. T. Hull (1984). "Morphologic features of renal oncocytoma: a light and electron microscopic study". Human pathology. 15 (11): 1054–1061. PMID 6490001. Unknown parameter |month= ignored (help)

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