Transitional cell carcinoma pathophysiology: Difference between revisions

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==Pathogenesis==
==Pathogenesis==
*The surface epithelium (urothelium) that lines the mucosal surfaces of the entire urinary tract is exposed to potential carcinogens that are either excreted in the urine or activated from precursors in the urine by hydrolyzing enzymes.
*This "field cancerization" effect is one hypothesis to explain the multifocal occurrence that is a characteristic feature of urothelial carcinomas of both the urinary bladder and the upper urinary tract.<ref name="pmid11134200">{{cite journal |vauthors=Rabbani F, Perrotti M, Russo P, Herr HW |title=Upper-tract tumors after an initial diagnosis of bladder cancer: argument for long-term surveillance |journal=J. Clin. Oncol. |volume=19 |issue=1 |pages=94–100 |date=January 2001 |pmid=11134200 |doi=10.1200/JCO.2001.19.1.94 |url=}}</ref>
*In the majority of cases, multifocal urothelial carcinomas are monoclonal which supports their presumed origin from a single genetically altered cell,referred to as the monoclonality hypothesis.
*Under normal conditions, the [[bladder]], the lower part of the [[kidneys]], the [[ureters]], and the proximal [[urethra]] are lined with a specialized mucous membrane referred to as transitional epithelium (also called [[urothelium]]).
*Under normal conditions, the [[bladder]], the lower part of the [[kidneys]], the [[ureters]], and the proximal [[urethra]] are lined with a specialized mucous membrane referred to as transitional epithelium (also called [[urothelium]]).
*Most [[cancers]] that form in the bladder, the lower part of the kidneys, the ureters, and the proximal urethra are transitional cell carcinomas (also called urothelial carcinomas) that derive from transitional epithelium.
*Most [[cancers]] that form in the bladder, the lower part of the kidneys, the ureters, and the proximal urethra are transitional cell carcinomas (also called urothelial carcinomas) that derive from transitional epithelium.
===Genetics===
===Genetics===
* Genetic [[mutations]] involved in the pathogenesis of bladder cancer include:<ref name=”cancergov”>National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/types/bladder/hp/bladder-treatment-pdq#link/_359_toc  Accessed on February 19, 2016</ref>
* Genetic [[mutations]] involved in the pathogenesis of bladder cancer include:<ref name="”cancergov”">National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/types/bladder/hp/bladder-treatment-pdq#link/_359_toc  Accessed on February 19, 2016</ref>
:* [[HRAS]] mutation  
:* [[HRAS]] mutation  
:* [[Retinoblastoma protein|Rb1]] mutation
:* [[Retinoblastoma protein|Rb1]] mutation
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| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
Non-invasive urothelial carcinoma
Non-invasive urothelial carcinoma
| style="padding: 5px 5px; background: #F5F5F5;" align=left |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Flat [[lesions]] or papillary lesions
*Flat [[lesions]] or papillary lesions
|-  
|-  
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| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
Invasive urothelial carcinoma
Invasive urothelial carcinoma
| style="padding: 5px 5px; background: #F5F5F5;" align=left |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Large infiltrative [[mass]] or a multifocal, flat to papillary lesion with delicate fronds
*Large infiltrative [[mass]] or a multifocal, flat to papillary lesion with delicate fronds
|}
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! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|'''Subtype'''}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|'''Subtype'''}}
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Urothelial carcinomas with squamous differentiation  
Urothelial carcinomas with squamous differentiation  
| style="padding: 5px 5px; background: #F5F5F5;" align=left |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Presence of urothelial and [[Squamous cell|squamous cells]]
*Presence of urothelial and [[Squamous cell|squamous cells]]
*Observed in 44% of renal pelvis tumors
*Observed in 44% of renal pelvis tumors
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| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
Urothelial carcinomas with glandular differentiation  
Urothelial carcinomas with glandular differentiation  
| style="padding: 5px 5px; background: #F5F5F5;" align=left |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Presence of gland cells and true glandular spaces
*Presence of gland cells and true glandular spaces
*[[Mucin]] production
*[[Mucin]] production
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| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
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Micropapillary urothelial carcinomas  
Micropapillary urothelial carcinomas  
| style="padding: 5px 5px; background: #F5F5F5;" align=left |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Presence of micropapillae
*Presence of micropapillae
*High grade [[neoplasm]]
*High grade [[neoplasm]]
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Sarcomatoid urothelial carcinomas  
Sarcomatoid urothelial carcinomas  
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| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Presence of cells that look like sarcoma
*Presence of cells that look like sarcoma
*This aggressive carcinoma has often spread to [[lymph nodes]] and organs other than the renal pelvis or ureter when it is diagnosed
*This aggressive carcinoma has often spread to [[lymph nodes]] and organs other than the renal pelvis or ureter when it is diagnosed
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Nested variant of urothelial carcinomas  
Nested variant of urothelial carcinomas  
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*Irregular and confluent small nests and abortive tubules are composed of urothelial cells
*Irregular and confluent small nests and abortive tubules are composed of urothelial cells
*Very rare but aggressive
*Very rare but aggressive
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Microcystic urothelial carcinomas  
Microcystic urothelial carcinomas  
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| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Cysts in them that can range in size from microscopic to 2 mm
*Cysts in them that can range in size from microscopic to 2 mm
*Very rare
*Very rare
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Lymphoepithelioma-like urothelial carcinomas
Lymphoepithelioma-like urothelial carcinomas
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*Lymphatic tissue mixed with urothelial cells, or transitional cells
*Lymphatic tissue mixed with urothelial cells, or transitional cells
*Very rare carcinoma
*Very rare carcinoma
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Plasmacytoid and lymphoma-like urothelial carcinomas
Plasmacytoid and lymphoma-like urothelial carcinomas
| style="padding: 5px 5px; background: #F5F5F5;" align=left |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Tumor cells that look like [[lymphoma]] or [[plasmacytoma]]  
*Tumor cells that look like [[lymphoma]] or [[plasmacytoma]]  
|-  
|-  
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[[Giant cell]] urothelial carcinomas  
[[Giant cell]] urothelial carcinomas  
| style="padding: 5px 5px; background: #F5F5F5;" align=left |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Abnormally large cells with more than one [[nucleus]]
*Abnormally large cells with more than one [[nucleus]]
|-  
|-  
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
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Clear cell urothelial carcinomas  
Clear cell urothelial carcinomas  
| style="padding: 5px 5px; background: #F5F5F5;" align=left |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*[[Clear cell|Clear cells]] (cells with clear cytoplasm and a large nucleus)
*[[Clear cell|Clear cells]] (cells with clear cytoplasm and a large nucleus)
|-  
|-  
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| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
Lipid cell variant of urothelial carcinomas  
Lipid cell variant of urothelial carcinomas  
| style="padding: 5px 5px; background: #F5F5F5;" align=left |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Cells that are filled with fat
*Cells that are filled with fat
|-  
|-  
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Undifferentiated variant of urothelial carcinomas  
Undifferentiated variant of urothelial carcinomas  
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| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Cells that don’t have any clear features and don’t look like any other type of cell (they are undifferentiated).  
*Cells that don’t have any clear features and don’t look like any other type of cell (they are undifferentiated).  
|-  
|-  
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Urothelial carcinomas with trophoblastic differentiation  
Urothelial carcinomas with trophoblastic differentiation  
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| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Presence of cells that look like [[Trophoblast|trophoblasts]]
*Presence of cells that look like [[Trophoblast|trophoblasts]]
*[[Human chorionic gonadotropin]] production within the cells
*[[Human chorionic gonadotropin]] production within the cells
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According to the WHO grading criteria, there are two grades of transitional cell carcinoma based on the degree of cellular differentiation:  
According to the WHO grading criteria, there are two grades of transitional cell carcinoma based on the degree of cellular differentiation:  
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Low grade
Low grade
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| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Tumors with the least degree of cellular anaplasia
*Tumors with the least degree of cellular anaplasia
*Rarely invades the muscular wall of the bladder or spreads to other parts of the body
*Rarely invades the muscular wall of the bladder or spreads to other parts of the body
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High grade
High grade
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*Tumors with the most severe degrees of cellular anaplasia
*Tumors with the most severe degrees of cellular anaplasia
*Commonly recurs and also has a strong tendency to invade the muscular wall of the bladder and spread to other parts of the body.
*Commonly recurs and also has a st [[Category:Disease]]  [[Category:Up-To-Date]] [[Category:Oncology]] [[Category:Medicine]] rong tendency to invade the muscular wall of the bladder and spread to other parts of the body.
*High grade transitional cell carcinoma is much more likely to result in death
*High grade transitional cell carcinoma is much more likely to result in death
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Following table illustrates the cancers that may be associated with transitional cell carcinoma of urinary tract:<ref name="KirkaliTuzel2003">{{cite journal|last1=Kirkali|first1=Ziya|last2=Tuzel|first2=Emre|title=Transitional cell carcinoma of the ureter and renal pelvis|journal=Critical Reviews in Oncology/Hematology|volume=47|issue=2|year=2003|pages=155–169|issn=10408428|doi=10.1016/S1040-8428(03)00079-9}}</ref>
Following table illustrates the cancers that may be associated with transitional cell carcinoma of urinary tract:<ref name="KirkaliTuzel2003">{{cite journal|last1=Kirkali|first1=Ziya|last2=Tuzel|first2=Emre|title=Transitional cell carcinoma of the ureter and renal pelvis|journal=Critical Reviews in Oncology/Hematology|volume=47|issue=2|year=2003|pages=155–169|issn=10408428|doi=10.1016/S1040-8428(03)00079-9}}</ref>
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Bladder cancer after the diagnosis of upper urinary tract transitional cell cancer
Bladder cancer after the diagnosis of upper urinary tract transitional cell cancer
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20 - 50%
20 - 50%
|-  
|-  
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Upper urinary tract transitional cell cancer after the diagnosis of bladder cancer
Upper urinary tract transitional cell cancer after the diagnosis of bladder cancer
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0.74 - 4%
0.74 - 4%
|-  
|-  
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Upper urinary tract transitional cell cancer after cystectomy
Upper urinary tract transitional cell cancer after cystectomy
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2 - 9%
2 - 9%
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[[Category:Disease]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]

Revision as of 16:21, 18 June 2019

https://https://www.youtube.com/watch?v=zv-vOLDOcRE%7C350}}

Transitional cell carcinoma Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Suveenkrishna Pothuru, M.B,B.S. [2]

Overview

Genes involved in the pathogenesis of transitional cell carcinoma of bladder include HRAS, Rb1, PTEN/MMAC1, NAT2, and GSTM1. On gross pathology, flat lesions or papillary lesions are characteristic findings of non-invasive transitional cell carcinomas; a large infiltrative mass or a multifocal, flat to papillary lesion with delicate fronds are characteristic findings of invasive transitional cell carcinomas. On microscopic histopathological analysis, loss of cell polarity, nuclear crowding, and cytologic atypia are characteristic findings of flat lesion; fibrovascular stalks, umbrella cells, and eosinophilic cytoplasm are characteristic findings of papillary lesion; invasion beyond the basement membrane is the characteristic finding of invasive transitional cell carcinomas.

Pathogenesis

  • The surface epithelium (urothelium) that lines the mucosal surfaces of the entire urinary tract is exposed to potential carcinogens that are either excreted in the urine or activated from precursors in the urine by hydrolyzing enzymes.
  • This "field cancerization" effect is one hypothesis to explain the multifocal occurrence that is a characteristic feature of urothelial carcinomas of both the urinary bladder and the upper urinary tract.[1]
  • In the majority of cases, multifocal urothelial carcinomas are monoclonal which supports their presumed origin from a single genetically altered cell,referred to as the monoclonality hypothesis.
  • Under normal conditions, the bladder, the lower part of the kidneys, the ureters, and the proximal urethra are lined with a specialized mucous membrane referred to as transitional epithelium (also called urothelium).
  • Most cancers that form in the bladder, the lower part of the kidneys, the ureters, and the proximal urethra are transitional cell carcinomas (also called urothelial carcinomas) that derive from transitional epithelium.

Genetics

  • Genetic mutations involved in the pathogenesis of bladder cancer include:[2]
  • HRAS mutation
  • Rb1 mutation
  • PTEN/MMAC1 mutation
  • NAT2 slow acetylator phenotype
  • GSTM1 null phenotype

Pathology

Gross Pathology

The following table illustrates the findings on gross pathology for the subtypes of transitional cell carcinoma:[3][4][5]

Type Description

Non-invasive urothelial carcinoma

Invasive urothelial carcinoma

  • Large infiltrative mass or a multifocal, flat to papillary lesion with delicate fronds

Microscopic Pathology

Non-invasive urothelial carcinoma

  • On microscopic histopathological analysis, loss of cell polarity, nuclear crowding, and cytologic atypia are characteristic findings.
  • On microscopic histopathological analysis, fibrovascular stalks, umbrella cells, and eosinophilic cytoplasm are characteristic findings.

Invasive urothelial carcinoma

  • Invasive urothelial carcinomas grow from the lining of the renal pelvis or ureter into the deeper layers of the renal pelvis or ureter wall, such as lamina propria and muscularis.[5]
  • Transitional cell carcinomas with mixed epithelial features are invasive tumors that have different types of cells mixed with the cancer cells.
  • They occur less often than typical invasive transitional cell carcinomas and are generally considered to be more aggressive.
  • The following table illustrates the findings on microscopic analysis for invasive transitional cell carcinomas with mixed epithelial features:
Subtype Features on Histopathological Microscopic Analysis

Urothelial carcinomas with squamous differentiation

  • Presence of urothelial and squamous cells
  • Observed in 44% of renal pelvis tumors

Urothelial carcinomas with glandular differentiation

  • Presence of gland cells and true glandular spaces
  • Mucin production
  • Floating signet ring cells within the mucinous material

Micropapillary urothelial carcinomas

  • Presence of micropapillae
  • High grade neoplasm

Sarcomatoid urothelial carcinomas

  • Presence of cells that look like sarcoma
  • This aggressive carcinoma has often spread to lymph nodes and organs other than the renal pelvis or ureter when it is diagnosed

Nested variant of urothelial carcinomas

  • Irregular and confluent small nests and abortive tubules are composed of urothelial cells
  • Very rare but aggressive

Microcystic urothelial carcinomas

  • Cysts in them that can range in size from microscopic to 2 mm
  • Very rare

Lymphoepithelioma-like urothelial carcinomas

  • Lymphatic tissue mixed with urothelial cells, or transitional cells
  • Very rare carcinoma
  • More common in men than women

Plasmacytoid and lymphoma-like urothelial carcinomas

Giant cell urothelial carcinomas

  • Abnormally large cells with more than one nucleus

Clear cell urothelial carcinomas

  • Clear cells (cells with clear cytoplasm and a large nucleus)

Lipid cell variant of urothelial carcinomas

  • Cells that are filled with fat

Undifferentiated variant of urothelial carcinomas

  • Cells that don’t have any clear features and don’t look like any other type of cell (they are undifferentiated).

Urothelial carcinomas with trophoblastic differentiation

Grading

According to the WHO grading criteria, there are two grades of transitional cell carcinoma based on the degree of cellular differentiation:

Grade Description

Low grade

  • Tumors with the least degree of cellular anaplasia
  • Rarely invades the muscular wall of the bladder or spreads to other parts of the body
  • Often recurs after treatment

High grade

  • Tumors with the most severe degrees of cellular anaplasia
  • Commonly recurs and also has a st rong tendency to invade the muscular wall of the bladder and spread to other parts of the body.
  • High grade transitional cell carcinoma is much more likely to result in death

Associated Conditions

Following table illustrates the cancers that may be associated with transitional cell carcinoma of urinary tract:[8]

Association Percentage of cases

Bladder cancer after the diagnosis of upper urinary tract transitional cell cancer

20 - 50%

Upper urinary tract transitional cell cancer after the diagnosis of bladder cancer

0.74 - 4%

Upper urinary tract transitional cell cancer after cystectomy

2 - 9%

References

  1. Rabbani F, Perrotti M, Russo P, Herr HW (January 2001). "Upper-tract tumors after an initial diagnosis of bladder cancer: argument for long-term surveillance". J. Clin. Oncol. 19 (1): 94–100. doi:10.1200/JCO.2001.19.1.94. PMID 11134200.
  2. National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/types/bladder/hp/bladder-treatment-pdq#link/_359_toc Accessed on February 19, 2016
  3. 3.0 3.1 Cheng L, Cheville JC, Neumann RM, Bostwick DG (2000). "Flat intraepithelial lesions of the urinary bladder". Cancer. 88 (3): 625–31. PMID 10649257.
  4. Cheng L, Cheville JC, Neumann RM, Bostwick DG (1999). "Natural history of urothelial dysplasia of the bladder". Am J Surg Pathol. 23 (4): 443–7. PMID 10199474.
  5. 5.0 5.1 Pons F, Orsola A, Morote J, Bellmunt J (2011). "Variant forms of bladder cancer: basic considerations on treatment approaches". Curr Oncol Rep. 13 (3): 216–21. doi:10.1007/s11912-011-0161-4. PMID 21360040.
  6. McKenney JK, Amin MB, Young RH (2003). "Urothelial (transitional cell) papilloma of the urinary bladder: a clinicopathologic study of 26 cases". Mod Pathol. 16 (7): 623–9. doi:10.1097/01.MP.0000073973.74228.1E. PMID 12861056.
  7. Picozzi S, Casellato S, Bozzini G, Ratti D, Macchi A, Rubino B; et al. (2013). "Inverted papilloma of the bladder: a review and an analysis of the recent literature of 365 patients". Urol Oncol. 31 (8): 1584–90. doi:10.1016/j.urolonc.2012.03.009. PMID 22520573.
  8. Kirkali, Ziya; Tuzel, Emre (2003). "Transitional cell carcinoma of the ureter and renal pelvis". Critical Reviews in Oncology/Hematology. 47 (2): 155–169. doi:10.1016/S1040-8428(03)00079-9. ISSN 1040-8428.

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