Renal oncocytoma pathophysiology: Difference between revisions
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==Pathophysiology== | ==Pathophysiology== | ||
===Pathogenesis=== | ===Pathogenesis=== | ||
*The exact pathogenesis of [disease name] is not completely understood. | *The exact pathogenesis of [disease name] is not completely understood. | ||
| Line 146: | Line 143: | ||
==Microscopic Pathology== | ==Microscopic Pathology== | ||
On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name]. | On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name]. | ||
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 microvesicles.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. | |||
The “oncocyte” is the basic component of large oncocytoma. | |||
It is a large, round, or polygonal neoplastic cell with | |||
a granular eosinophilic cytoplasm. Oncocytic tumors were | |||
reported outside the kidney in the thyroid, parathyroid, | |||
salivary glands, and other tissues. With electron microscopy, | |||
it was demonstrated that oncocytes are abundant with | |||
mitochondria, which gives them the characteristic staining | |||
features. Oncocytomas are arranged in nested or organoid | |||
growth pattern [12]. Microscopic features of oncocytomas | |||
may include cellular atypia, prominent nucleoli, and pleomorphism. | |||
These are clearly manifestations of malignancy. | |||
However, oncocytomas with these features maintain benign | |||
behavior. Within the oncocytoma tumor it is possible to find | |||
a small population of cells that exhibit cytoplasmic clearing. | |||
This cytoplasmic clearing may also coexist in chromophobe | |||
type RCC [6]. | |||
Histopathological examination carried out for hematoxylin | |||
and eosin (HE) stained sections of tumor tissue is the first | |||
and the most important step in the diagnostic approach to | |||
epithelial renal neoplasms. It gives the information about | |||
cellular, nuclear, cytoplasmic, stromal and vascular network | |||
features as well as about growth pattern. | |||
Renal oncocytomas are histopatologically characterized | |||
by “oncocytes”, which by definition are large neoplastic | |||
cells with intensely eosinophilic granular cytoplasm that | |||
results from the large number of mitochondria. This term | |||
was coined by Hamperl from Greek “onkousthai” and | |||
“cyte”, to swell and cell or swelling cytoplasm.20 Oncocytomas | |||
are found in a number of organs and have been | |||
described previously in the thyroid gland, salivary gland, | |||
parathyroid gland, adrenal gland and other anatomical | |||
sites.8 The exact cell type that gives rise to an oncocytoma in | |||
the kidney or other organs is unknown. Most pathologists | |||
suggest a distal tubular origin for renal oncocytomas,21,22 | |||
although a proximal tubular origin was first proposed.2,23 | |||
In general, renal oncocytoma has a variable morphological | |||
appearance. The cells are usually arranged in solid | |||
compact nests/alveoli (acinar growth exemplar) and/or in | |||
cords, tubules and sheets of trabeculae (tubulocystic | |||
arrangement) that are separated by loose edematous fibrous | |||
or hyalinised stroma (Fig. 1a). However, papillary and cystic | |||
architecture might occur in renal oncocytomas, which might | |||
be composed of regularly large oncocytes or small “basophilic” | |||
cells (Fig. 1b). Recently, another aspect of two cell | |||
types of renal oncocytoma has been discussed.24 The predominant | |||
classic form of cells (so-called “oncocyte”) corresponds | |||
to round-to-polygonal cells with densely granular | |||
eosinophilic cytoplasm, round and uniform nuclei with | |||
finely distributed chromatin, and a centrally placed prominent | |||
nucleolus. A smaller population of cells (called | |||
oncoblasts) has less conspicuous, paler, scanty, granular | |||
cytoplasm, a high nuclear/cytoplasmic ratio, and dense dark | |||
hyperchromatic, markedly pleomorphic nuclei. Bizarre, | |||
polyploidy, enlarged nuclei, which are characteristic for | |||
endocrine adenomas, might be scattered throughout the | |||
renal oncocytomas, but mitoses are absent. | |||
Summarizing the histological data, although the diagnosis | |||
of renal oncocytoma is relatively easy in experienced hands, | |||
difficulties might arise when this neoplasm has atypical | |||
morphology. Additional studies, such as electron microscopy, | |||
chromosomal analysis and immunohistochemistry, | |||
might help in achieving a correct diagnosis. | |||
==Pathogenesis== | ==Pathogenesis== | ||
Revision as of 15:52, 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
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]
- Deletion of chromosome 1
- Deletion of the sex chromosome
- Translocation of chromosome 11q13
- Sporadic or no chromosomal alteration
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].
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 microvesicles.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.
The “oncocyte” is the basic component of large oncocytoma. It is a large, round, or polygonal neoplastic cell with a granular eosinophilic cytoplasm. Oncocytic tumors were reported outside the kidney in the thyroid, parathyroid, salivary glands, and other tissues. With electron microscopy, it was demonstrated that oncocytes are abundant with mitochondria, which gives them the characteristic staining features. Oncocytomas are arranged in nested or organoid growth pattern [12]. Microscopic features of oncocytomas may include cellular atypia, prominent nucleoli, and pleomorphism. These are clearly manifestations of malignancy. However, oncocytomas with these features maintain benign behavior. Within the oncocytoma tumor it is possible to find a small population of cells that exhibit cytoplasmic clearing. This cytoplasmic clearing may also coexist in chromophobe type RCC [6].
Histopathological examination carried out for hematoxylin and eosin (HE) stained sections of tumor tissue is the first and the most important step in the diagnostic approach to epithelial renal neoplasms. It gives the information about cellular, nuclear, cytoplasmic, stromal and vascular network features as well as about growth pattern. Renal oncocytomas are histopatologically characterized by “oncocytes”, which by definition are large neoplastic cells with intensely eosinophilic granular cytoplasm that results from the large number of mitochondria. This term was coined by Hamperl from Greek “onkousthai” and “cyte”, to swell and cell or swelling cytoplasm.20 Oncocytomas are found in a number of organs and have been described previously in the thyroid gland, salivary gland, parathyroid gland, adrenal gland and other anatomical sites.8 The exact cell type that gives rise to an oncocytoma in the kidney or other organs is unknown. Most pathologists suggest a distal tubular origin for renal oncocytomas,21,22 although a proximal tubular origin was first proposed.2,23 In general, renal oncocytoma has a variable morphological appearance. The cells are usually arranged in solid compact nests/alveoli (acinar growth exemplar) and/or in cords, tubules and sheets of trabeculae (tubulocystic arrangement) that are separated by loose edematous fibrous or hyalinised stroma (Fig. 1a). However, papillary and cystic architecture might occur in renal oncocytomas, which might be composed of regularly large oncocytes or small “basophilic” cells (Fig. 1b). Recently, another aspect of two cell types of renal oncocytoma has been discussed.24 The predominant classic form of cells (so-called “oncocyte”) corresponds to round-to-polygonal cells with densely granular eosinophilic cytoplasm, round and uniform nuclei with finely distributed chromatin, and a centrally placed prominent nucleolus. A smaller population of cells (called oncoblasts) has less conspicuous, paler, scanty, granular cytoplasm, a high nuclear/cytoplasmic ratio, and dense dark hyperchromatic, markedly pleomorphic nuclei. Bizarre, polyploidy, enlarged nuclei, which are characteristic for endocrine adenomas, might be scattered throughout the renal oncocytomas, but mitoses are absent. Summarizing the histological data, although the diagnosis of renal oncocytoma is relatively easy in experienced hands, difficulties might arise when this neoplasm has atypical morphology. Additional studies, such as electron microscopy, chromosomal analysis and immunohistochemistry, might help in achieving a correct diagnosis.
Pathogenesis
- Renal oncocytoma is thought to arise from the intercalated cells of collecting ducts of the kidney.[18]
Microscopic Pathology
- An epithelial tumor composed of oncocytes, large eosinophilic cells having small, round, benign-appearing nuclei with large nucleoli and excessive amounts of mitochondria.[19]
References
- ↑ 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) - ↑ 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.
- ↑ 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) - ↑ 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) - ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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) - ↑ 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) - ↑ 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) - ↑ 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.
- ↑ 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.
- ↑ 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) - ↑ 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.
- ↑ 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) - ↑ 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.
- ↑ 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.
- ↑ Palmer WE, Chew FS (1991). "Renal oncocytoma". AJR Am J Roentgenol. 156 (6): 1144. doi:10.2214/ajr.156.6.2028856. PMID 2028856.