Transitional cell carcinoma pathophysiology: Difference between revisions

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Latest revision as of 12:39, 28 October 2019

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Suveenkrishna Pothuru, M.B,B.S. [2] Ramyar Ghandriz MD [3]

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

There has been a small increase in risk in relatives of those with bladder cancer, and the risk appears to be greatest in those whose affected relatives were diagnosed before age 60 years^[2]^[3]^[4]
Genetic mutations involved in the pathogenesis of bladder cancer include:^[5]

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:^[6]^[7]^[8]


Type	Description

Non-invasive urothelial carcinoma	Flat lesions or papillary lesions
Invasive urothelial carcinoma	Large infiltrative mass or a multifocal, flat to papillary lesion with delicate fronds

Microscopic Pathology

Non-invasive urothelial carcinoma

Flat lesions^[6]^[9]^[10]

On microscopic histopathological analysis, loss of cell polarity, nuclear crowding, and cytologic atypia are characteristic findings.

Papillary lesions

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.^[8]
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	Tumor cells that look like lymphoma or plasmacytoma
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	Presence of cells that look like trophoblasts Human chorionic gonadotropin production within the cells

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:^[11]


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

↑ 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.
↑ Plna K, Hemminki K (2001). "Familial bladder cancer in the National Swedish Family Cancer Database". J Urol. 166 (6): 2129–33. PMID 11696721.
↑ Lin J, Spitz MR, Dinney CP, Etzel CJ, Grossman HB, Wu X (2006). "Bladder cancer risk as modified by family history and smoking". Cancer. 107 (4): 705–11. doi:10.1002/cncr.22071. PMID 16845665.
↑ Martin C, Leiser CL, O'Neil B, Gupta S, Lowrance WT, Kohlmann W; et al. (2018). "Familial Cancer Clustering in Urothelial Cancer: A Population-Based Case-Control Study". J Natl Cancer Inst. 110 (5): 527–533. doi:10.1093/jnci/djx237. PMC 5946951. PMID 29228305.
↑ 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
↑ ^6.0 ^6.1 Cheng L, Cheville JC, Neumann RM, Bostwick DG (2000). "Flat intraepithelial lesions of the urinary bladder". Cancer. 88 (3): 625–31. PMID 10649257.
↑ 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.
↑ ^8.0 ^8.1 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.
↑ 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.
↑ 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.
↑ 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.

Template:WH Template:WS

[pmid11134200-1] 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.

[pmid11696721-2] Plna K, Hemminki K (2001). "Familial bladder cancer in the National Swedish Family Cancer Database". J Urol. 166 (6): 2129–33. PMID 11696721.

[pmid16845665-3] Lin J, Spitz MR, Dinney CP, Etzel CJ, Grossman HB, Wu X (2006). "Bladder cancer risk as modified by family history and smoking". Cancer. 107 (4): 705–11. doi:10.1002/cncr.22071. PMID 16845665.

[pmid29228305-4] Martin C, Leiser CL, O'Neil B, Gupta S, Lowrance WT, Kohlmann W; et al. (2018). "Familial Cancer Clustering in Urothelial Cancer: A Population-Based Case-Control Study". J Natl Cancer Inst. 110 (5): 527–533. doi:10.1093/jnci/djx237. PMC 5946951. PMID 29228305.

[”cancergov”-5] 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

[pmid10649257-6] 6.0 ^6.1 Cheng L, Cheville JC, Neumann RM, Bostwick DG (2000). "Flat intraepithelial lesions of the urinary bladder". Cancer. 88 (3): 625–31. PMID 10649257.

[pmid10199474-7] 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.

[pmid21360040-8] 8.0 ^8.1 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.

[pmid12861056-9] 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.

[pmid22520573-10] 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.

[KirkaliTuzel2003-11] 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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[4]

[5]

[6]

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@@ Line 1: / Line 1: @@
 __NOTOC__
 {{Transitional cell carcinoma}}
-{{CMG}};{{AE}} {{PSK}}
+{{CMG}};{{AE}} {{PSK}} {{RG}}
 ==Overview==
 [[Genes]] involved in the [[pathogenesis]] of transitional cell carcinoma of bladder include [[HRAS]], [[Retinoblastoma protein|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.<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]]).
 *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:<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>
+* There has been a small increase in risk in relatives of those with bladder cancer, and the risk appears to be greatest in those whose affected relatives were diagnosed before age 60 years<ref name="pmid11696721">{{cite journal| author=Plna K, Hemminki K| title=Familial bladder cancer in the National Swedish Family Cancer Database. | journal=J Urol | year= 2001 | volume= 166 | issue= 6 | pages= 2129-33 | pmid=11696721 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11696721  }} </ref><ref name="pmid16845665">{{cite journal| author=Lin J, Spitz MR, Dinney CP, Etzel CJ, Grossman HB, Wu X| title=Bladder cancer risk as modified by family history and smoking. | journal=Cancer | year= 2006 | volume= 107 | issue= 4 | pages= 705-11 | pmid=16845665 | doi=10.1002/cncr.22071 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16845665  }} </ref><ref name="pmid29228305">{{cite journal| author=Martin C, Leiser CL, O'Neil B, Gupta S, Lowrance WT, Kohlmann W et al.| title=Familial Cancer Clustering in Urothelial Cancer: A Population-Based Case-Control Study. | journal=J Natl Cancer Inst | year= 2018 | volume= 110 | issue= 5 | pages= 527-533 | pmid=29228305 | doi=10.1093/jnci/djx237 | pmc=5946951 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29228305  }} </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
 :* [[Retinoblastoma protein|Rb1]] mutation
@@ Line 21: / Line 25: @@
 {| style="border: 0px; font-size: 90%; margin: 3px; width: 800px"
-|valign=top|
+| valign="top" |
 |+
 ! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|'''Type'''}}
@@ Line 28: / Line 32: @@
 | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
 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
 |-
 | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
 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
 |}
@@ Line 39: / Line 43: @@
 ===Microscopic Pathology===
 ====Non-invasive urothelial carcinoma====
 :* Flat lesions<ref name="pmid10649257">{{cite journal| author=Cheng L, Cheville JC, Neumann RM, Bostwick DG| title=Flat intraepithelial lesions of the urinary bladder. | journal=Cancer | year= 2000 | volume= 88 | issue= 3 | pages= 625-31 | pmid=10649257 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10649257  }} </ref><ref name="pmid12861056">{{cite journal| author=McKenney JK, Amin MB, Young RH| title=Urothelial (transitional cell) papilloma of the urinary bladder: a clinicopathologic study of 26 cases. | journal=Mod Pathol | year= 2003 | volume= 16 | issue= 7 | pages= 623-9 | pmid=12861056 | doi=10.1097/01.MP.0000073973.74228.1E | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12861056  }} </ref><ref name="pmid22520573">{{cite journal| author=Picozzi S, Casellato S, Bozzini G, Ratti D, Macchi A, Rubino B et al.| title=Inverted papilloma of the bladder: a review and an analysis of the recent literature of 365 patients. | journal=Urol Oncol | year= 2013 | volume= 31 | issue= 8 | pages= 1584-90 | pmid=22520573 | doi=10.1016/j.urolonc.2012.03.009 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22520573  }} </ref>
 ::* On microscopic histopathological analysis, loss of [[cell]] polarity, [[nuclear]] crowding, and cytologic [[atypia]] are characteristic findings.
@@ Line 45: / Line 50: @@
 ====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]].<ref name="pmid21360040">{{cite journal| author=Pons F, Orsola A, Morote J, Bellmunt J| title=Variant forms of bladder cancer: basic considerations on treatment approaches. | journal=Curr Oncol Rep | year= 2011 | volume= 13 | issue= 3 | pages= 216-21 | pmid=21360040 | doi=10.1007/s11912-011-0161-4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21360040  }} </ref>
+*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]].<ref name="pmid21360040">{{cite journal| author=Pons F, Orsola A, Morote J, Bellmunt J| title=Variant forms of bladder cancer: basic considerations on treatment approaches. | journal=Curr Oncol Rep | year= 2011 | volume= 13 | issue= 3 | pages= 216-21 | pmid=21360040 | doi=10.1007/s11912-011-0161-4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21360040  }} </ref>
 *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 urothelial carcinomas and are generally considered to be more aggressive.
+*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 the subtypes of invasive transitional cell carcinoma:
+*The following table illustrates the findings on microscopic analysis for invasive transitional cell carcinomas with mixed epithelial features:
 {| style="border: 0px; font-size: 90%; margin: 3px; width: 800px"
-|valign=top|
+| valign="top" |
 |+
 ! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|'''Subtype'''}}
@@ Line 58: / Line 63: @@
 | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
 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]]
 *Observed in 44% of renal pelvis tumors
@@ Line 64: / Line 69: @@
 | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
 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
 *[[Mucin]] production
@@ Line 71: / Line 76: @@
 | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
 Micropapillary urothelial carcinomas
-| style="padding: 5px 5px; background: #F5F5F5;" align=left |
+| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
 *Presence of micropapillae
 *High grade [[neoplasm]]
@@ Line 77: / Line 82: @@
 | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
 Sarcomatoid urothelial carcinomas
-| style="padding: 5px 5px; background: #F5F5F5;" align=left |
+| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
 *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
@@ Line 83: / Line 88: @@
 | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
 Nested variant of urothelial carcinomas
-| style="padding: 5px 5px; background: #F5F5F5;" align=left |
+| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
 *Irregular and confluent small nests and abortive tubules are composed of urothelial cells
 *Very rare but aggressive
@@ Line 89: / Line 94: @@
 | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
 Microcystic urothelial carcinomas
-| style="padding: 5px 5px; background: #F5F5F5;" align=left |
+| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
 *Cysts in them that can range in size from microscopic to 2 mm
 *Very rare
@@ Line 95: / Line 100: @@
 | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
 Lymphoepithelioma-like urothelial carcinomas
-| style="padding: 5px 5px; background: #F5F5F5;" align=left |
+| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
 *Lymphatic tissue mixed with urothelial cells, or transitional cells
 *Very rare carcinoma
@@ Line 102: / Line 107: @@
 | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
 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]]
 |-
 | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
 [[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]]
 |-
 | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
 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)
 |-
 | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
 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
 |-
 | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
 Undifferentiated variant of urothelial carcinomas
-| style="padding: 5px 5px; background: #F5F5F5;" align=left |
+| 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).
 |-
 | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
 Urothelial carcinomas with trophoblastic differentiation
-| style="padding: 5px 5px; background: #F5F5F5;" align=left |
+| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
 *Presence of cells that look like [[Trophoblast|trophoblasts]]
 *[[Human chorionic gonadotropin]] production within the cells
@@ Line 135: / Line 140: @@
 According to the WHO grading criteria, there are two grades of transitional cell carcinoma based on the degree of cellular differentiation:
 {| style="border: 0px; font-size: 90%; margin: 3px; width: 800px"
-|valign=top|
+| valign="top" |
 |+
 ! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|'''Grade'''}}
@@ Line 142: / Line 147: @@
 | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
 Low grade
-| style="padding: 5px 5px; background: #F5F5F5;" align=left |
+| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
 *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 in the after treatment
+*Often recurs after treatment
 |-
 | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
 High grade
-| style="padding: 5px 5px; background: #F5F5F5;" align=left |
+| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
 *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
 |}
@@ Line 158: / Line 163: @@
 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>
 {| style="border: 0px; font-size: 90%; margin: 3px; width: 800px"
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+| valign="top" |
 |+
 ! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|'''Association'''}}
@@ Line 165: / Line 170: @@
 | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
 Bladder cancer after the diagnosis of upper urinary tract transitional cell cancer
-| style="padding: 5px 5px; background: #F5F5F5;" align=left |
+| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
 - 50%
 |-
 | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
 Upper urinary tract transitional cell cancer after the diagnosis of bladder cancer
-| style="padding: 5px 5px; background: #F5F5F5;" align=left |
+| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
 .74 - 4%
 |-
 | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; align=left" |
 Upper urinary tract transitional cell cancer after cystectomy
-| style="padding: 5px 5px; background: #F5F5F5;" align=left |
+| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
 - 9%
 |}
@@ Line 184: / Line 189: @@
 {{WH}}
 {{WS}}
-[[Category:Disease]]