Renal oncocytoma pathophysiology: Difference between revisions

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==Gross Pathology==
==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.
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>


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.
Renal oncocytomas often have a typical macroscopic
appearance, which differs significantly from the typical
gross appearance of RCCs. They are solitary, in rare
instances multiple, generally well-encapsulated with a thick,
well-defined, fibrous capsule.12 The surface on sectioning is
usually mahogany-brown and less often tan in color. Large
oncocytomas occasionally have a characteristic central stellate
fibrous scar, which is composed of loose or dense
hyalinized connective tissue containing occasional
entrapped tumor cells and represents a sign of slow growth
of this renal epithelial neoplasm.13 On the cut section, renal
oncocytomas generally have a homogeneous appearance
with no hemorrhage or necrosis within the tumor. Cases of
histologically typical renal oncocytoma with calcification in
the tumor center,14 necrosis,14,15 a liquid center,16 or a large central cyst,17 and numerous cysts18 have been described.


==Microscopic Pathology==
==Microscopic Pathology==
Line 179: Line 165:




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==
{{reflist|2}}
{{reflist|2}}

Revision as of 15:42, 12 June 2019

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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 [disease name] is not fully understood.

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

Physiology

The normal physiology of [name of process] can be understood as follows:

Pathogenesis

  • The exact pathogenesis of [disease name] is not completely understood.

OR

  • 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].
  • [Pathogen name] is usually transmitted via the [transmission route] route to the human host.
  • Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
  • [Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
  • The progression to [disease name] usually involves the [molecular pathway].
  • The pathophysiology of [disease/malignancy] depends on the histological subtype.

Genetics

DNA diploidy is seen in 96% of patients with renal oncocytomas.[1][2][3]

The development of renal oncocytoma is the result of multiple genetic mutations such as:[4][5][6][7][8][9]

Associated Conditions

Conditions associated with renal oncocytoma include:[10][11]

  • Familial renal oncocytoma
  • Birt-Hogg-Dube syndrome

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.[12][13][14][15][16][17]


Microscopic Pathology

On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Overview

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.[18]

Pathogenesis

Gross Pathology

  • 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).[19]


Microscopic Pathology



References

  1. ↑ 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)
  2. ↑ 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.
  3. ↑ 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)
  4. ↑ 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)
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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)
  10. ↑ 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)
  11. ↑ 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)
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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)
  15. ↑ 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.
  16. ↑ 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)
  17. ↑ 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.
  18. ↑ 18.0 18.1 Palmer WE, Chew FS (1991). "Renal oncocytoma". AJR Am J Roentgenol. 156 (6): 1144. doi:10.2214/ajr.156.6.2028856. PMID 2028856.
  19. ↑ 19.0 19.1 Velasquez G, Glass TA, D'Souza VJ, Formanek AG (1984). "Multiple oncocytomas and renal carcinoma". AJR Am J Roentgenol. 142 (1): 123–4. doi:10.2214/ajr.142.1.123. PMID 6606945.

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