Difference between revisions of "Urothelial carcinoma"

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Urothelial carcinoma (view source)

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| Image      = Urothelial carcinoma positive margin -- high mag.jpg
| Image      = Urothelial carcinoma positive margin -- high mag.jpg
| Width      =
| Width      =
| Caption    = Urothelial carcinoma at a surgical margin. [[H&E stain]].
| Caption    = Urothelial carcinoma at a [[surgical margin]]. [[H&E stain]].
| Synonyms  = urothelial cell carcinoma
| Synonyms  = urothelial cell carcinoma
| Micro      =
| Micro      =
| 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
| 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  = [[radical cystectomy grossing]], [[cystoprostatectomy grossing]], [[nephroureterectomy grossing]]
| Grossing  = [[transurethral resection of bladder tumour 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
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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]].


Risk factors:
Risk factors:
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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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===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.
 
=====Images=====
<gallery>
Image: Urinary bladder muscularis mucosae -- intermed mag.jpg | MM - intermed. mag. (wc)
Image: Urinary bladder muscularis mucosae -- high mag.jpg | MM - high mag. (WC)
Image: Urinary bladder muscularis mucosae -- very high mag.jpg | MM - very high mag. (WC)
</gallery>
 
====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.


==Images==
==Images==
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Image: Urothelial carcinoma positive margin - alt -- intermed mag.jpg | Typical UCC pos. margin - intermed. 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.
Image: Urothelial carcinoma positive margin - alt -- high mag.jpg | Typical UCC pos. margin - high mag.
</gallery>
<gallery>
Image:Nested_variant_of_urothelial_carcinoma_-_intermed_mag.jpg | Nested variant of urothelial carcinoma - intermed. mag. (WC/Nephron)
Image:Nested_variant_of_urothelial_carcinoma_-_high_mag.jpg | Nested variant of urothelial carcinoma - high mag. (WC/Nephron)
Image:Nested_variant_of_urothelial_carcinoma_-_very_high_mag.jpg | Nested variant of urothelial carcinoma - very high mag. (WC/Nephron)
</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>
[[File:5 410253052 sl 1.png| High grade urothelial carcinoma]]
[[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]]=
=[[IHC]]=
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*CK20 negative in over 50% of cases with metastases.<ref name=pmid11419977>{{Cite journal  | last1 = Jiang | first1 = J. | last2 = Ulbright | first2 = TM. | last3 = Younger | first3 = C. | last4 = Sanchez | first4 = K. | last5 = Bostwick | first5 = DG. | last6 = Koch | first6 = MO. | last7 = Eble | first7 = JN. | last8 = Cheng | first8 = L. | title = Cytokeratin 7 and cytokeratin 20 in primary urinary bladder carcinoma and matched lymph node metastasis. | journal = Arch Pathol Lab Med | volume = 125 | issue = 7 | pages = 921-3 | month = Jul | year = 2001 | doi = 10.1043/0003-9985(2001)1250921:CACIPU2.0.CO;2 | PMID = 11419977 }}</ref>
*CK20 negative in over 50% of cases with metastases.<ref name=pmid11419977>{{Cite journal  | last1 = Jiang | first1 = J. | last2 = Ulbright | first2 = TM. | last3 = Younger | first3 = C. | last4 = Sanchez | first4 = K. | last5 = Bostwick | first5 = DG. | last6 = Koch | first6 = MO. | last7 = Eble | first7 = JN. | last8 = Cheng | first8 = L. | title = Cytokeratin 7 and cytokeratin 20 in primary urinary bladder carcinoma and matched lymph node metastasis. | journal = Arch Pathol Lab Med | volume = 125 | issue = 7 | pages = 921-3 | month = Jul | year = 2001 | doi = 10.1043/0003-9985(2001)1250921:CACIPU2.0.CO;2 | PMID = 11419977 }}</ref>


==Reactive changes versus UCIS==
===Reactive changes versus UCIS===
:''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, PSA -ve, p63 +ve, CK20 +ve.
*UCC: GATA3 +ve, PSA -ve, [[p63]] +ve, [[CK20]] +ve.
*Prostate: PSA +ve, GATA3 -ve, PSAP +ve, CK7 -ve, CK20 -ve, p63 -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 +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 }}
*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>
Metastatic UCC versus primary lung squamous cell carcinoma:
:See ''[[Squamous_cell_carcinoma_of_the_lung#Lung_SCC_versus_metastatic_bladder_urothelial_carcinoma]]''.


Note:
Note:
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**In half the cases the staining is weak and in the other half it is strong.<ref name=pmid19192675/>
**In half the cases the staining is weak and in the other half it is strong.<ref name=pmid19192675/>


==Staging==
===IHC for staging===
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>
*''Smoothelin'' immunostain for [[bladder muscularis propria invasion|muscularis propria invasion]] versus muscularis mucosae invasion - see ''[[Muscularis_propria_invasion_in_the_urinary_bladder#IHC]]''.
*Muscularis propria - usu. strong. †
*Muscularis mucosae - negative/weak. †
 
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.


=Molecular=
=Molecular=
Not used for diagnosis.
*Molecular testing usually ''not'' used for diagnosis.
**Molecular subtyping can be approximated with immunostaining - see ''[[Classification of urothelial carcinoma by immunohistochemistry]]''.


Changes:
Changes:
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   INTO MUSCULARIS PROPRIA.
   INTO MUSCULARIS PROPRIA.
- LYMPHOVASCULAR INVASION PRESENT.
- LYMPHOVASCULAR INVASION PRESENT.
</pre>
==Nested variant==
<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>
</pre>


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==Nested urothelial cell carcinoma==
==Nested urothelial cell carcinoma==
*[[AKA]] ''nested variant urothelial cell carcinoma''.
*[[AKA]] ''nested variant of urothelial cell carcinoma''.
 
{{Main|Nested urothelial carcinoma}}
===General===
*Aggressive behaviour despite bland histomorphology.<ref name=pmid14681330>{{Cite journal  | last1 = Lin | first1 = O. | last2 = Cardillo | first2 = M. | last3 = Dalbagni | first3 = G. | last4 = Linkov | first4 = I. | last5 = Hutchinson | first5 = B. | last6 = Reuter | first6 = VE. | title = Nested variant of urothelial carcinoma: a clinicopathologic and immunohistochemical study of 12 cases. | journal = Mod Pathol | volume = 16 | issue = 12 | pages = 1289-98 | month = Dec | year = 2003 | doi = 10.1097/01.MP.0000094091.04541.FC | PMID = 14681330 }}</ref>
 
===Microscopic===
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]].<ref name=pmid21836490>{{Cite journal  | last1 = Cox | first1 = R. | last2 = Epstein | first2 = JI. | title = Large nested variant of urothelial carcinoma: 23 cases mimicking von Brunn nests and inverted growth pattern of noninvasive papillary urothelial carcinoma. | journal = Am J Surg Pathol | volume = 35 | issue = 9 | pages = 1337-42 | month = Sep | year = 2011 | doi = 10.1097/PAS.0b013e318222a653 | PMID = 21836490 }}</ref>
*[[Low grade papillary urothelial carcinoma]] with lamina propria invasion.
 
===IHC===
*MIB-1 typically >15%.<ref name=pmid14681330/>


=See also=
=See also=
Michael
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