Difference between revisions of "Urothelial carcinoma"

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{{ Infobox diagnosis
{{ Infobox diagnosis
| Name      = {{PAGENAME}}
| Name      = {{PAGENAME}}
| Image      =  
| Image      = Urothelial carcinoma positive margin -- high mag.jpg
| Width      =
| Width      =
| Caption    =  
| Caption    = Urothelial carcinoma at a [[surgical margin]]. [[H&E stain]].
| Synonyms  = urothelial cell carcinoma
| Synonyms  = urothelial cell carcinoma
| Micro      =
| Micro      =
| Subtypes  = microcystic, glandular, inverted (growth pattern), nested. papillary (dealt with separately in ''[[high-grade papillary urothelial carcinoma]]'' and ''[[low-grade papillary urothelial carcinoma]]''), others
| Subtypes  = [[microcystic urothelial carcinoma|microcystic]], [[micropapillary urothelial carcinoma|micropapillary]], glandular, inverted (growth pattern), [[nested urothelial carcinoma|nested]], papillary (dealt with separately in ''[[high-grade papillary urothelial carcinoma]]'' and ''[[low-grade papillary urothelial carcinoma]]''), [[plasmacytoid urothelial carcinoma]], others
| LMDDx      = [[urothelial carcinoma in situ]], metastatic carcinoma ([[prostate carcinoma]], [[colorectal carcinoma]]), [[inverted urothelial papilloma]] (for UCC with inverted growth pattern)
| LMDDx      = [[urothelial carcinoma in situ]], metastatic carcinoma ([[prostate carcinoma]], [[colorectal carcinoma]]), [[inverted urothelial papilloma]] (for UCC with inverted growth pattern), [[epithelioid angiosarcoma]]
| Stains    =
| Stains    =
| IHC        = GATA3 +ve, p63 +ve, CK5/6 +ve, CK34betaE12 +ve, PSA -ve
| IHC        = [[GATA3]] +ve, p63 +ve, CK5/6 +ve, CK34betaE12 +ve, PSA -ve
| EM        =
| EM        =
| Molecular  = not used for diagnosis; typically: 9p deletions, 17p deletions
| Molecular  = not used for diagnosis; typically: 9p deletions, 17p deletions; can be [[Classification of urothelial carcinoma by immunohistochemistry|subclassified with IHC]]; [[FGFR2/FGFR3]] mutations
| IF        =
| IF        =
| Gross      =
| Gross      =
| Grossing  =
| Grossing  = [[radical cystectomy grossing]], [[cystoprostatectomy grossing]], [[nephroureterectomy grossing]]
| Site      = [[urothelium]] - [[ureter]], [[urinary bladder]], proximal urethra (males), renal pelvis
| Staging    = [[bladder cancer staging]]
| Site      = [[urothelium]] - [[ureter]], [[urinary bladder]], proximal [[urethra]] (see [[urothelial carcinoma of the urethra]], renal pelvis
| Assdx      =
| Assdx      =
| Syndromes  = [[Lynch syndrome]] - esp. ureters
| Syndromes  = [[Lynch syndrome]] - esp. ureters
| Clinicalhx =
| Clinicalhx = typically [[smoking|smokers]]
| Signs      = hematuria
| Signs      = hematuria
| Symptoms  =
| Symptoms  =
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See ''[[Urine_cytopathology#Urothelial_cell_carcinoma|urine cytology]]'' for the [[cytopathology]].
See ''[[Urine_cytopathology#Urothelial_cell_carcinoma|urine cytology]]'' for the [[cytopathology]].


==General==
=General=
*These lesions lack papillae and are typical flat.
*These lesions lack papillae and are typical flat.
*Clinically, it may not be possible to differentiate renal pelvis urothelial carcinoma and [[renal cell carcinoma]].
*Clinically, it may not be possible to differentiate renal pelvis urothelial carcinoma and [[renal cell carcinoma]].
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*Women often have worse outcomes as they present with more advanced tumours.<ref name=pmid24239476>{{Cite journal  | last1 = Mitra | first1 = AP. | last2 = Skinner | first2 = EC. | last3 = Schuckman | first3 = AK. | last4 = Quinn | first4 = DI. | last5 = Dorff | first5 = TB. | last6 = Daneshmand | first6 = S. | title = Effect of gender on outcomes following radical cystectomy for urothelial carcinoma of the bladder: a critical analysis of 1,994 patients. | journal = Urol Oncol | volume = 32 | issue = 1 | pages = 52.e1-9 | month = Jan | year = 2014 | doi = 10.1016/j.urolonc.2013.08.007 | PMID = 24239476 }}</ref>
*Women often have worse outcomes as they present with more advanced tumours.<ref name=pmid24239476>{{Cite journal  | last1 = Mitra | first1 = AP. | last2 = Skinner | first2 = EC. | last3 = Schuckman | first3 = AK. | last4 = Quinn | first4 = DI. | last5 = Dorff | first5 = TB. | last6 = Daneshmand | first6 = S. | title = Effect of gender on outcomes following radical cystectomy for urothelial carcinoma of the bladder: a critical analysis of 1,994 patients. | journal = Urol Oncol | volume = 32 | issue = 1 | pages = 52.e1-9 | month = Jan | year = 2014 | doi = 10.1016/j.urolonc.2013.08.007 | PMID = 24239476 }}</ref>
*Positive soft tissue [[margin status|margin]].<ref  name=pmid17936804>{{Cite journal  | last1 = Dotan | first1 = ZA. | last2 = Kavanagh | first2 = K. | last3 = Yossepowitch | first3 = O. | last4 = Kaag | first4 = M. | last5 = Olgac | first5 = S. | last6 = Donat | first6 = M. | last7 = Herr | first7 = HW. | title = Positive surgical margins in soft tissue following radical cystectomy for bladder cancer and cancer specific survival. | journal = J Urol | volume = 178 | issue = 6 | pages = 2308-12; discussion 2313 | month = Dec | year = 2007 | doi = 10.1016/j.juro.2007.08.023 | PMID = 17936804 }}</ref>
*Positive soft tissue [[margin status|margin]].<ref  name=pmid17936804>{{Cite journal  | last1 = Dotan | first1 = ZA. | last2 = Kavanagh | first2 = K. | last3 = Yossepowitch | first3 = O. | last4 = Kaag | first4 = M. | last5 = Olgac | first5 = S. | last6 = Donat | first6 = M. | last7 = Herr | first7 = HW. | title = Positive surgical margins in soft tissue following radical cystectomy for bladder cancer and cancer specific survival. | journal = J Urol | volume = 178 | issue = 6 | pages = 2308-12; discussion 2313 | month = Dec | year = 2007 | doi = 10.1016/j.juro.2007.08.023 | PMID = 17936804 }}</ref>
**Definition (radical cystectomy): tumour touching ink.
**Definition (radical cystectomy): tumour touching [[ink]].


==Microscopic==
Risk factors:
*[[Smoking]].
*Toxins.
*Drugs, e.g. cyclophosphamide.
*Others.
 
=Microscopic=
Features:
Features:
*Nuclear pleomorphism - '''key feature'''.
*Nuclear pleomorphism - '''key feature'''.
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*[[High-grade papillary urothelial carcinoma]].
*[[High-grade papillary urothelial carcinoma]].
*[[Low-grade papillary urothelial carcinoma]].
*[[Low-grade papillary urothelial carcinoma]].
*[[Prostate carcinoma]].
*[[Prostate carcinoma]] - may have pseudopapillae<ref name=pmid24503758>{{cite journal |author=Gordetsky J, Epstein JI |title=Pseudopapillary features in prostatic adenocarcinoma mimicking urothelial carcinoma: a diagnostic pitfall |journal=Am. J. Surg. Pathol. |volume=38 |issue=7 |pages=941–5 |year=2014 |month=July |pmid=24503758 |doi=10.1097/PAS.0000000000000178 |url=}}</ref> - see ''[[urothelial carcinoma-like prostatic carcinoma]]''.
*[[Epithelioid angiosarcoma]] - have intracytoplasmic lumens and interspersed red blood cells, usually have a history radiation treatment.<ref name=pmid25929352>{{cite journal |authors=Matoso A, Epstein JI |title=Epithelioid Angiosarcoma of the Bladder: A Series of 9 Cases |journal=Am J Surg Pathol |volume=39 |issue=10 |pages=1377–82 |date=October 2015 |pmid=25929352 |doi=10.1097/PAS.0000000000000444 |url=}}</ref>


===Staging===
==Staging==
{{Main|Bladder cancer staging}}
*T1 - lamina propria.
*T1 - lamina propria.
**Several subdivisions of T1 exist:
**Several subdivisions of T1 exist:
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**In approximately 15% of cases it is pT0 (no primary tumour identified).
**In approximately 15% of cases it is pT0 (no primary tumour identified).


====Muscularis propria invasion====
===Muscularis propria invasion===
The presence or absence of muscularis propria invasion is a '''very important''' determination, as the clinical management changes between T1 and T2:
{{Main|Muscularis propria invasion in the urinary bladder}}
*T1: usually conservative treatment (local excision).
*T2: radical treatment (cystectomy or cystoprostatectomy).
 
A thin layer of discontinous muscularis mucuosae (MM) is present and, especially if hypertrophic, may be confused with muscuaris propria (MP).
 
=====Comparing MM and MP=====
A comparison between muscularis propria and muscularis mucosae - adapted from Paner ''et al.'':<ref name=pmid17721199>{{Cite journal  | last1 = Paner | first1 = GP. | last2 = Ro | first2 = JY. | last3 = Wojcik | first3 = EM. | last4 = Venkataraman | first4 = G. | last5 = Datta | first5 = MW. | last6 = Amin | first6 = MB. | title = Further characterization of the muscle layers and lamina propria of the urinary bladder by systematic histologic mapping: implications for pathologic staging of invasive urothelial carcinoma. | journal = Am J Surg Pathol | volume = 31 | issue = 9 | pages = 1420-9 | month = Sep | year = 2007 | doi = 10.1097/PAS.0b013e3180588283 | PMID = 17721199 }}</ref>
{| class="wikitable sortable"
! Feature
! Muscularis mucosae
! Muscularis propria
|-
| Outline/border
| typically irregular (frayed edges)
| usually regular (circumscribed)
|-
| Size of bundles ‡
| classically "small", often "large" (hypertrophic)
| usually "large"
|-
| Isolated fibres
| yes
| no
|-
| Location in bladder
| less common in trigone, dome very common
| everywhere
|-
| Depth †
| superficial, occ. deep
| deep
|}
 
Notes:
*† The lamina propria thickness varies with location. It is thinnest in the trigone (0.5-1.6 mm) and thickest in the dome (1.0-3.1 mm).
*‡ Small is defined as <4 muscle fibres; large >= 4 muscle fibres.
**The presence of hyperplastic bundles ranges from ~20% in the trigone to ~70% in the dome.
 
=====Rational assessment of muscularis propria invasion=====
To call muscularis propria invasion:
#Definite tumour must be between muscle.
#Muscle bundles must be thick.
#Multiple bundles must be adjacent to one another.
#Should '''not''' be superficial - surface epithelium if present should be distant.
 
===Subtypes of urothelial carcinoma===
There are numerous subtypes:<ref>URL: [http://www.nature.com/modpathol/journal/v22/n2s/full/modpathol200926a.html http://www.nature.com/modpathol/journal/v22/n2s/full/modpathol200926a.html]. Accessed on: 19 August 2011.</ref>
*Squamous differentiation.
*Clear cell.
*Plasmacytoid.
*Micropapillary.
**Small nests (< ~10 cells/nest).
*Sarcomatoid.
**Images: [http://path.upmc.edu/cases/case615.html UCC with sarcomatoid differentiation (upmc.edu)].
*Many others...
 
Benign patterns - mnemonic ''Much GIN'':
*'''M'''icrocystic.
*Small tubular/'''g'''landular.
*'''I'''nverted.
*'''N'''ested.
 
====Plasmacytoid urothelial cell carcinoma====
Features:
*Abundant gray cytoplasm, eccentric nucleus.
 
Images:
*[http://path.upmc.edu/cases/case267.html Plasmacytoid UCC - several images (upmc.edu)].
 
====Nested urothelial cell carcinoma====
*[[AKA]] ''nested variant urothelial cell carcinoma''.
 
Features:<ref name=pmid2712189>{{Cite journal  | last1 = Talbert | first1 = ML. | last2 = Young | first2 = RH. | title = Carcinomas of the urinary bladder with deceptively benign-appearing foci. A report of three cases. | journal = Am J Surg Pathol | volume = 13 | issue = 5 | pages = 374-81 | month = May | year = 1989 | doi =  | PMID = 2712189 }}</ref>
*High density of well-circumscribed nests.
*Mild-to-moderate nuclear atypia.
*+/-Foci of unequivocal conventional urothelial carcinoma.
**Focally solid or gland fusion.
**Moderate-to-severe nuclear atypia +/- abundant mitoses.
*+/-Extension into the muscularis propria.
 
DDx:
*[[von Brunn nests]].
*[[Low grade papillary urothelial carcinoma]] with lamina propria invasion.


===Images===
==Images==
<gallery>
<gallery>
Image:Nested_variant_of_urothelial_carcinoma_-_intermed_mag.jpg | Nested variant of urothelial carcinoma - intermed. mag. (WC/Nephron)
Image: Urothelial carcinoma positive margin -- intermed mag.jpg | Typical UCC pos. margin - intermed. mag.
Image:Nested_variant_of_urothelial_carcinoma_-_high_mag.jpg | Nested variant of urothelial carcinoma - high mag. (WC/Nephron)
Image: Urothelial carcinoma positive margin -- high mag.jpg | Typical UCC pos. margin - high mag.
Image:Nested_variant_of_urothelial_carcinoma_-_very_high_mag.jpg | Nested variant of urothelial carcinoma - very high mag. (WC/Nephron)
Image: Urothelial carcinoma positive margin -- very high mag.jpg |Typical UCC pos. margin - very high mag.
Image: Urothelial carcinoma positive margin - alt -- intermed mag.jpg | Typical UCC pos. margin - intermed. mag.
Image: Urothelial carcinoma positive margin - alt -- high mag.jpg | Typical UCC pos. margin - high mag.
</gallery>
</gallery>
www:
www:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282447/figure/F2/ Several images of NUCC (nih.gov)].<ref name=pmid22355497>{{Cite journal  | last1 = Terada | first1 = T. | title = Nested variant of urothelial carcinoma of the urinary bladder. | journal = Rare Tumors | volume = 3 | issue = 4 | pages = e42 | month = Oct | year = 2011 | doi = 10.4081/rt.2011.e42 | PMID = 22355497 | PMC = 3282447 }}</ref>
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282447/figure/F2/ Several images of NUCC (nih.gov)].<ref name=pmid22355497>{{Cite journal  | last1 = Terada | first1 = T. | title = Nested variant of urothelial carcinoma of the urinary bladder. | journal = Rare Tumors | volume = 3 | issue = 4 | pages = e42 | month = Oct | year = 2011 | doi = 10.4081/rt.2011.e42 | PMID = 22355497 | PMC = 3282447 }}</ref>


==[[IHC]]==
[[File:5 410253052 sl 1.png| High grade urothelial carcinoma]]
Recommended by ISUP consensus panel:<ref name=pmid25025364 >{{cite journal |author=Amin MB, Epstein JI, Ulbright TM, ''et al.'' |title=Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference |journal=Am. J. Surg. Pathol. |volume=38 |issue=8 |pages=1017–22 |year=2014 |month=August |pmid=25025364 |doi=10.1097/PAS.0000000000000254 |url=}}</ref>
[[File:5 410253052 sl 2.png| High grade urothelial carcinoma]]
[[File:5 410253052 sl 3.png| High grade urothelial carcinoma]]
[[File:5 410253052 sl 4.png| High grade urothelial carcinoma]]
[[File:5 410253052 sl 5.png| High grade urothelial carcinoma]]
[[File:5 410253052 sl 6.png| High grade urothelial carcinoma]]
[[File:5 410253052 sl 7.png| High grade urothelial carcinoma]]
[[File:5 410253052 sl 8.png| High grade urothelial carcinoma]]<br>
High grade urothelial carcinoma in a 43 year old man. A. At low power, necrosis is seen, luminal, with viable invasive tumor elsewhere. B. Tumor partly fills right ureteral orifice. C.  Tumor cells sometimes form Indian files (black arrows), appear to have nuclei that mold (red arrows), and have granular chromatin (cyan arrows), raising possibility of neuroendocrine carcinoma. D. Tumor invades lymphatic spaces. E. Urothelial carcinoma in situ is present. F,G,H.  Tumor cells are diffusely positive for CK7, focally positive for CDX2, and diffusely positive for P40, with no positivity for chromogranin or synaptophysin.
 
=[[IHC]]=
Recommended by [[ISUP]] consensus panel:<ref name=pmid25025364 >{{cite journal |author=Amin MB, Epstein JI, Ulbright TM, ''et al.'' |title=Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference |journal=Am. J. Surg. Pathol. |volume=38 |issue=8 |pages=1017–22 |year=2014 |month=August |pmid=25025364 |doi=10.1097/PAS.0000000000000254 |url=}}</ref>
*GATA3 +ve, CK20 +ve, p63 +ve, CK5/6, HMWCK (e.g. CK34betaE12) +ve.  
*GATA3 +ve, CK20 +ve, p63 +ve, CK5/6, HMWCK (e.g. CK34betaE12) +ve.  


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:''See [[urothelial carcinoma in situ]]''.
:''See [[urothelial carcinoma in situ]]''.


===UCC versus other===
===UCC versus other cancers===
UCC vs. [[Prostate cancer|prostate]]:
UCC vs. [[Prostate cancer|prostate]]:
*UCC: GATA3 +ve, p63 +ve, CK20 +ve.
*UCC: GATA3 +ve, PSA -ve, [[p63]] +ve, [[CK20]] +ve.
*Prostate: PSA +ve, PSAP +ve, CK7 -ve, CK20 -ve, p63 -ve, GATA3 -ve.
*Prostate: [[PSA]] +ve, [[GATA3]] -ve, [[PSAP]] +ve, CK7 -ve, CK20 -ve, p63 -ve.  


UCC vs. [[renal cell carcinoma|RCC]]:
UCC vs. [[renal cell carcinoma|renal cell carcinoma]]:
*UCC: p63+.<ref>{{Cite journal  | last1 = Langner | first1 = C. | last2 = Ratschek | first2 = M. | last3 = Tsybrovskyy | first3 = O. | last4 = Schips | first4 = L. | last5 = Zigeuner | first5 = R. | title = P63 immunoreactivity distinguishes upper urinary tract transitional-cell carcinoma and renal-cell carcinoma even in poorly differentiated tumors. | journal = J Histochem Cytochem | volume = 51 | issue = 8 | pages = 1097-9 | month = Aug | year = 2003 | doi =  | PMID = 12871991 }}
*UCC: p63 +ve.<ref>{{Cite journal  | last1 = Langner | first1 = C. | last2 = Ratschek | first2 = M. | last3 = Tsybrovskyy | first3 = O. | last4 = Schips | first4 = L. | last5 = Zigeuner | first5 = R. | title = P63 immunoreactivity distinguishes upper urinary tract transitional-cell carcinoma and renal-cell carcinoma even in poorly differentiated tumors. | journal = J Histochem Cytochem | volume = 51 | issue = 8 | pages = 1097-9 | month = Aug | year = 2003 | doi =  | PMID = 12871991 }}
</ref>
</ref>


===Staging===
Metastatic UCC versus primary lung squamous cell carcinoma:
Staging - muscularis propria invasion versus muscularis mucosae invasion ''smoothelin'' stain:<ref>{{Cite journal  | last1 = Paner | first1 = GP. | last2 = Shen | first2 = SS. | last3 = Lapetino | first3 = S. | last4 = Venkataraman | first4 = G. | last5 = Barkan | first5 = GA. | last6 = Quek | first6 = ML. | last7 = Ro | first7 = JY. | last8 = Amin | first8 = MB. | title = Diagnostic utility of antibody to smoothelin in the distinction of muscularis propria from muscularis mucosae of the urinary bladder: a potential ancillary tool in the pathologic staging of invasive urothelial carcinoma. | journal = Am J Surg Pathol | volume = 33 | issue = 1 | pages = 91-8 | month = Jan | year = 2009 | doi = 10.1097/PAS.0b013e3181804727 | PMID = 18936687 }}</ref>
:See ''[[Squamous_cell_carcinoma_of_the_lung#Lung_SCC_versus_metastatic_bladder_urothelial_carcinoma]]''.
*Muscularis propria - usu. strong. †
*Muscularis mucosae - negative/weak. †


Note:
Note:
*† Overlap between the patterns is described,<ref>{{Cite journal  | last1 = Miyamoto | first1 = H. | last2 = Sharma | first2 = RB. | last3 = Illei | first3 = PB. | last4 = Epstein | first4 = JI. | title = Pitfalls in the use of smoothelin to identify muscularis propria invasion by urothelial carcinoma. | journal = Am J Surg Pathol | volume = 34 | issue = 3 | pages = 418-22 | month = Mar | year = 2010 | doi = 10.1097/PAS.0b013e3181ce5066 | PMID = 20154589 }}</ref> this limits the utility of the stain.
*In a large series, PSA positivity is reported in 1.4% bladder UCC.<ref name=pmid19192675>{{Cite journal  | last1 = Chen | first1 = JC. | last2 = Ho | first2 = CL. | last3 = Tsai | first3 = HW. | last4 = Tzai | first4 = TS. | last5 = Liu | first5 = HS. | last6 = Chow | first6 = NH. | last7 = Yang | first7 = WH. | last8 = Cheng | first8 = HL. | title = Immunohistochemical detection of prostate-specific antigen expression in primary urothelial carcinoma of the urinary bladder. | journal = Anticancer Res | volume = 28 | issue = 6B | pages = 4149-54 | month = | year = | doi = | PMID = 19192675 }}
</ref>
**In half the cases the staining is weak and in the other half it is strong.<ref name=pmid19192675/>


==Molecular==
===IHC for staging===
Not used for diagnosis.
*''Smoothelin'' immunostain for [[bladder muscularis propria invasion|muscularis propria invasion]] versus muscularis mucosae invasion - see ''[[Muscularis_propria_invasion_in_the_urinary_bladder#IHC]]''.
 
=Molecular=
*Molecular testing usually ''not'' used for diagnosis.
**Molecular subtyping can be approximated with immunostaining - see ''[[Classification of urothelial carcinoma by immunohistochemistry]]''.


Changes:
Changes:
Line 217: Line 159:
*17p deletion -- site of PT53 (AKA p53).
*17p deletion -- site of PT53 (AKA p53).


==Sign out==
=Sign out=
===High grade UC===
==High grade UC==
<pre>
<pre>
URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION URINARY BLADDER TUMOUR (TURBT):  
URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION URINARY BLADDER TUMOUR (TURBT):  
Line 226: Line 168:
</pre>
</pre>


===Nested variant===
==UCC with some suspicion for muscularis propria invasion==
<pre>
URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION OF BLADDER TUMOUR (TURBT):
- INVASIVE LOW-GRADE UROTHELIAL CARCINOMA, NESTED VARIANT.
- TUMOUR PRESENT AT EDGE OF TISSUE.
- NO MUSCULARIS PROPRIA IDENTIFIED.
</pre>
 
===UCC with some suspicion for muscularis propria invasion===
<pre>
<pre>
URINARY BLADDER LESION ("TUMOUR"), DEEP, RE-RESECTION (TURBT):
URINARY BLADDER LESION ("TUMOUR"), DEEP, RE-RESECTION (TURBT):
Line 249: Line 183:
</pre>
</pre>


====Alternate comment====
===Alternate comment===
<pre>
<pre>
The sections shows thickened muscle bundles with frayed edges between the  
The sections shows thickened muscle bundles with frayed edges between the  
Line 257: Line 191:
</pre>
</pre>


==See also==
=Subtypes of urothelial carcinoma=
There are numerous subtypes:<ref>URL: [http://www.nature.com/modpathol/journal/v22/n2s/full/modpathol200926a.html http://www.nature.com/modpathol/journal/v22/n2s/full/modpathol200926a.html]. Accessed on: 19 August 2011.</ref>
*Squamous differentiation.
*Clear cell.
*[[Plasmacytoid urothelial carcinoma|Plasmacytoid]].
*[[Micropapillary urothelial carcinoma|Micropapillary]].
**Small nests (< ~10 cells/nest).
*Sarcomatoid.
**Images: [http://path.upmc.edu/cases/case615.html UCC with sarcomatoid differentiation (upmc.edu)].
*Many others...
 
Benign patterns - mnemonic ''Much GIN'':
*'''M'''icrocystic.
*Small tubular/'''g'''landular.
*'''I'''nverted.
*'''N'''ested.
 
==Plasmacytoid urothelial cell carcinoma==
{{Main|Plasmacytoid urothelial carcinoma}}
 
==Microcystic urothelial carcinoma==
{{Main|Microcystic urothelial carcinoma}}
 
==Micropapillary urothelial carcinoma==
{{Main|Micropapillary urothelial carcinoma}}
 
==Lymphoepithelioma-like carcinoma==
{{Main|Lymphoepithelioma-like carcinoma of the urinary bladder}}
 
==Nested urothelial cell carcinoma==
*[[AKA]] ''nested variant of urothelial cell carcinoma''.
{{Main|Nested urothelial carcinoma}}
 
=See also=
*[[Urothelium]].
*[[Urothelium]].
*[[Urothelial dysplasia]].
*[[Urothelial dysplasia]].
Line 263: Line 230:
*[[Prostatic urothelial carcinoma]].
*[[Prostatic urothelial carcinoma]].


==References==
=References=
{{Reflist|2}}
{{Reflist|2}}


[[Category:Urothelium]]
[[Category:Urothelium]]
[[Category:Diagnosis]]
[[Category:Diagnosis]]

Latest revision as of 16:10, 8 March 2024

Urothelial carcinoma
Diagnosis in short

Urothelial carcinoma at a surgical margin. H&E stain.
Synonyms urothelial cell carcinoma
Subtypes microcystic, micropapillary, glandular, inverted (growth pattern), nested, papillary (dealt with separately in high-grade papillary urothelial carcinoma and low-grade papillary urothelial carcinoma), plasmacytoid urothelial carcinoma, others
LM DDx urothelial carcinoma in situ, metastatic carcinoma (prostate carcinoma, colorectal carcinoma), inverted urothelial papilloma (for UCC with inverted growth pattern), epithelioid angiosarcoma
IHC GATA3 +ve, p63 +ve, CK5/6 +ve, CK34betaE12 +ve, PSA -ve
Molecular not used for diagnosis; typically: 9p deletions, 17p deletions; can be subclassified with IHC; FGFR2/FGFR3 mutations
Grossing notes radical cystectomy grossing, cystoprostatectomy grossing, nephroureterectomy grossing
Staging bladder cancer staging
Site urothelium - ureter, urinary bladder, proximal urethra (see urothelial carcinoma of the urethra, renal pelvis
Syndromes Lynch syndrome - esp. ureters
Clinical history typically smokers
Signs hematuria
Prevalence common
Prognosis dependent on grade and stage
Treatment dependent on grade and stage

Urothelial carcinoma, also urothelial cell carcinoma, is a malignancy that arises from the urothelium. Urothelial carcinoma is abbreviated UC and urothelial cell carcinoma is abbreviated UCC.

This article deals with flat invasive urothelial carcinoma. The direct precursor is dealt with in urothelial carcinoma in situ.

Papillary urothelial carcinomas are dealt with in low-grade papillary urothelial carcinoma and high-grade papillary urothelial carcinoma.

See urine cytology for the cytopathology.

General

  • These lesions lack papillae and are typical flat.
  • Clinically, it may not be possible to differentiate renal pelvis urothelial carcinoma and renal cell carcinoma.
  • May be a part of Lynch syndrome.

Prognosis:

  • Women often have worse outcomes as they present with more advanced tumours.[1]
  • Positive soft tissue margin.[2]
    • Definition (radical cystectomy): tumour touching ink.

Risk factors:

  • Smoking.
  • Toxins.
  • Drugs, e.g. cyclophosphamide.
  • Others.

Microscopic

Features:

  • Nuclear pleomorphism - key feature.
    • Compare nuclei to one another.
  • Increased N/C ratio.
  • Lack of maturation to surface (important).
  • Cells become dyscohesive.

Invasion vs. in situ: Useful features - present in invasion:[3]

  • Thin-walled vessels.
  • Stromal reaction (hypercellularity).
  • Retraction artefact around the tumour cell nests.

Note:

  • The presence/absence of muscle should be commented on in biopsy specimens.
  • Adipose tissue may be seen in the lamina propria; tumour adjacent to adipose tissue on a biopsy does not imply invasion deep to the muscularis propria.[4]

DDx:

Staging

Main article: Bladder cancer staging
  • T1 - lamina propria.
    • Several subdivisions of T1 exist:
      • T1a - superficial or in muscularis mucosae.
      • T1b - beyond muscularis mucosae - into submucosa.
  • T2 - muscularis propria.

Note:

  • Approximately 25% of muscle invasive urothelial carcinoma on biopsy is a lower stage in the cystectomy specimen.[7]
    • In approximately 15% of cases it is pT0 (no primary tumour identified).

Muscularis propria invasion

Main article: Muscularis propria invasion in the urinary bladder

Images

  • Typical UCC pos. margin - intermed. mag.

  • Typical UCC pos. margin - high mag.

  • Typical UCC pos. margin - very high mag.

  • Typical UCC pos. margin - intermed. mag.

  • Typical UCC pos. margin - high mag.

www:

High grade urothelial carcinoma High grade urothelial carcinoma High grade urothelial carcinoma High grade urothelial carcinoma High grade urothelial carcinoma High grade urothelial carcinoma High grade urothelial carcinoma High grade urothelial carcinoma
High grade urothelial carcinoma in a 43 year old man. A. At low power, necrosis is seen, luminal, with viable invasive tumor elsewhere. B. Tumor partly fills right ureteral orifice. C. Tumor cells sometimes form Indian files (black arrows), appear to have nuclei that mold (red arrows), and have granular chromatin (cyan arrows), raising possibility of neuroendocrine carcinoma. D. Tumor invades lymphatic spaces. E. Urothelial carcinoma in situ is present. F,G,H. Tumor cells are diffusely positive for CK7, focally positive for CDX2, and diffusely positive for P40, with no positivity for chromogranin or synaptophysin.

IHC

Recommended by ISUP consensus panel:[9]

  • GATA3 +ve, CK20 +ve, p63 +ve, CK5/6, HMWCK (e.g. CK34betaE12) +ve.

Others:

  • CK7 +ve.
  • PSA -ve.

Notes:

  • CK20 negative in over 50% of cases with metastases.[10]

Reactive changes versus UCIS

See urothelial carcinoma in situ.

UCC versus other cancers

UCC vs. prostate:

  • UCC: GATA3 +ve, PSA -ve, p63 +ve, CK20 +ve.
  • Prostate: PSA +ve, GATA3 -ve, PSAP +ve, CK7 -ve, CK20 -ve, p63 -ve.

UCC vs. renal cell carcinoma:

Metastatic UCC versus primary lung squamous cell carcinoma:

See Squamous_cell_carcinoma_of_the_lung#Lung_SCC_versus_metastatic_bladder_urothelial_carcinoma.

Note:

  • In a large series, PSA positivity is reported in 1.4% bladder UCC.[12]
    • In half the cases the staining is weak and in the other half it is strong.[12]

IHC for staging

Molecular

Changes:

  • 9p deletion -- site of CDKN2A[13] (AKA p16).
  • 17p deletion -- site of PT53 (AKA p53).

Sign out

High grade UC

URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION URINARY BLADDER TUMOUR (TURBT): 
- INVASIVE HIGH-GRADE PAPILLARY UROTHELIAL CARCINOMA WITH SQUAMOUS DIFFERENTIATION AT LEAST 
  INTO MUSCULARIS PROPRIA.
- LYMPHOVASCULAR INVASION PRESENT.

UCC with some suspicion for muscularis propria invasion

URINARY BLADDER LESION ("TUMOUR"), DEEP, RE-RESECTION (TURBT):
- INVASIVE HIGH-GRADE UROTHELIAL CARCINOMA WITH SQUAMOUS DIFFERENTIATION AT
  LEAST INTO THE LAMINA PROPRIA, SEE COMMENT.
- NO DEFINITE LYMPHOVASCULAR INVASION.

COMMENT:
Tumour is seen adjacent to smooth muscle fibres of intermediate thickness. This is
interpreted as thick muscularis mucosae. The tissue orientation is suboptimal. 
Definite muscularis propria is not apparent. Levels were cut. 

Tumour is abundant in the lamina propria.

Alternate comment

The sections shows thickened muscle bundles with frayed edges between the 
tumour cells. The muscle is thought to represent hypertrophic muscularis 
mucosae. The large extent of lamina propria invasion raises the possibility 
of a higher stage lesion that may not have been sampled.

Subtypes of urothelial carcinoma

There are numerous subtypes:[14]

Benign patterns - mnemonic Much GIN:

  • Microcystic.
  • Small tubular/glandular.
  • Inverted.
  • Nested.

Plasmacytoid urothelial cell carcinoma

Main article: Plasmacytoid urothelial carcinoma

Microcystic urothelial carcinoma

Main article: Microcystic urothelial carcinoma

Micropapillary urothelial carcinoma

Main article: Micropapillary urothelial carcinoma

Lymphoepithelioma-like carcinoma

Main article: Lymphoepithelioma-like carcinoma of the urinary bladder

Nested urothelial cell carcinoma

  • AKA nested variant of urothelial cell carcinoma.
Main article: Nested urothelial carcinoma

See also

References

  1. ↑ Mitra, AP.; Skinner, EC.; Schuckman, AK.; Quinn, DI.; Dorff, TB.; Daneshmand, S. (Jan 2014). "Effect of gender on outcomes following radical cystectomy for urothelial carcinoma of the bladder: a critical analysis of 1,994 patients.". Urol Oncol 32 (1): 52.e1-9. doi:10.1016/j.urolonc.2013.08.007. PMID 24239476.
  2. ↑ Dotan, ZA.; Kavanagh, K.; Yossepowitch, O.; Kaag, M.; Olgac, S.; Donat, M.; Herr, HW. (Dec 2007). "Positive surgical margins in soft tissue following radical cystectomy for bladder cancer and cancer specific survival.". J Urol 178 (6): 2308-12; discussion 2313. doi:10.1016/j.juro.2007.08.023. PMID 17936804.
  3. ↑ Sternberg, SE. Histology for Pathologists. P.2047.
  4. ↑ Bochner, BH.; Nichols, PW.; Skinner, DG. (Mar 1995). "Overstaging of transitional cell carcinoma: clinical significance of lamina propria fat within the urinary bladder.". Urology 45 (3): 528-31. doi:10.1016/S0090-4295(99)80030-2. PMID 7879346.
  5. ↑ Gordetsky J, Epstein JI (July 2014). "Pseudopapillary features in prostatic adenocarcinoma mimicking urothelial carcinoma: a diagnostic pitfall". Am. J. Surg. Pathol. 38 (7): 941–5. doi:10.1097/PAS.0000000000000178. PMID 24503758.
  6. ↑ Matoso A, Epstein JI (October 2015). "Epithelioid Angiosarcoma of the Bladder: A Series of 9 Cases". Am J Surg Pathol 39 (10): 1377–82. doi:10.1097/PAS.0000000000000444. PMID 25929352.
  7. ↑ D'Souza, AM.; Pohar, KS.; Arif, T.; Geyer, S.; Zynger, DL. (Oct 2012). "Retrospective analysis of survival in muscle-invasive bladder cancer: impact of pT classification, node status, lymphovascular invasion, and neoadjuvant chemotherapy.". Virchows Arch 461 (4): 467-74. doi:10.1007/s00428-012-1249-4. PMID 22915241.
  8. ↑ Terada, T. (Oct 2011). "Nested variant of urothelial carcinoma of the urinary bladder.". Rare Tumors 3 (4): e42. doi:10.4081/rt.2011.e42. PMC 3282447. PMID 22355497. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282447/.
  9. ↑ Amin MB, Epstein JI, Ulbright TM, et al. (August 2014). "Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference". Am. J. Surg. Pathol. 38 (8): 1017–22. doi:10.1097/PAS.0000000000000254. PMID 25025364.
  10. ↑ Jiang, J.; Ulbright, TM.; Younger, C.; Sanchez, K.; Bostwick, DG.; Koch, MO.; Eble, JN.; Cheng, L. (Jul 2001). "Cytokeratin 7 and cytokeratin 20 in primary urinary bladder carcinoma and matched lymph node metastasis.". Arch Pathol Lab Med 125 (7): 921-3. doi:10.1043/0003-9985(2001)1250921:CACIPU2.0.CO;2. PMID 11419977.
  11. ↑ Langner, C.; Ratschek, M.; Tsybrovskyy, O.; Schips, L.; Zigeuner, R. (Aug 2003). "P63 immunoreactivity distinguishes upper urinary tract transitional-cell carcinoma and renal-cell carcinoma even in poorly differentiated tumors.". J Histochem Cytochem 51 (8): 1097-9. PMID 12871991.
  12. ↑ 12.0 12.1 Chen, JC.; Ho, CL.; Tsai, HW.; Tzai, TS.; Liu, HS.; Chow, NH.; Yang, WH.; Cheng, HL.. "Immunohistochemical detection of prostate-specific antigen expression in primary urothelial carcinoma of the urinary bladder.". Anticancer Res 28 (6B): 4149-54. PMID 19192675.
  13. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 600160
  14. ↑ URL: http://www.nature.com/modpathol/journal/v22/n2s/full/modpathol200926a.html. Accessed on: 19 August 2011.
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