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{{ Infobox diagnosis | |||
| Name = {{PAGENAME}} | |||
| Image = Urothelial carcinoma positive margin -- high mag.jpg | |||
| Width = | |||
| Caption = Urothelial carcinoma at a [[surgical margin]]. [[H&E stain]]. | |||
| Synonyms = urothelial cell carcinoma | |||
| 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 | |||
| LMDDx = [[urothelial carcinoma in situ]], metastatic carcinoma ([[prostate carcinoma]], [[colorectal carcinoma]]), [[inverted urothelial papilloma]] (for UCC with inverted growth pattern), [[epithelioid angiosarcoma]] | |||
| Stains = | |||
| IHC = [[GATA3]] +ve, p63 +ve, CK5/6 +ve, CK34betaE12 +ve, PSA -ve | |||
| EM = | |||
| 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 = | |||
| Gross = | |||
| Grossing = [[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 | |||
| Assdx = | |||
| Syndromes = [[Lynch syndrome]] - esp. ureters | |||
| Clinicalhx = typically [[smoking|smokers]] | |||
| Signs = hematuria | |||
| Symptoms = | |||
| Prevalence = common | |||
| Bloodwork = | |||
| Rads = | |||
| Endoscopy = | |||
| Prognosis = dependent on grade and stage | |||
| Other = | |||
| ClinDDx = | |||
| Tx = 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'''. | '''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'''. | ||
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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= | |||
*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]]. | ||
*May be a part of [[Lynch syndrome]]. | |||
Prognosis: | Prognosis: | ||
*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: | |||
*[[Smoking]]. | |||
*Toxins. | |||
*Drugs, e.g. cyclophosphamide. | |||
*Others. | |||
=Microscopic= | |||
Features: | Features: | ||
*Nuclear pleomorphism - '''key feature'''. | *Nuclear pleomorphism - '''key feature'''. | ||
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*Increased N/C ratio. | *Increased N/C ratio. | ||
*Lack of maturation to surface (important). | *Lack of maturation to surface (important). | ||
*Cells become dyscohesive. | *Cells become dyscohesive. | ||
Invasion vs. in situ: | Invasion vs. in situ: | ||
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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]] - 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== | |||
{{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=== | |||
{{Main|Muscularis propria invasion in the urinary bladder}} | |||
==Images== | |||
<gallery> | |||
Image: Urothelial carcinoma positive margin -- intermed mag.jpg | Typical UCC pos. margin - intermed. mag. | |||
Image: Urothelial carcinoma positive margin -- high mag.jpg | Typical UCC pos. margin - high mag. | |||
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> | |||
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> | |||
[[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]]= | |||
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. | |||
* | |||
Others: | |||
*CK7 +ve. | |||
*PSA -ve. | |||
Notes: | |||
*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=== | ||
:''See [[urothelial carcinoma in situ]]''. | |||
===UCC versus other cancers=== | |||
UCC vs. [[Prostate cancer|prostate]]: | UCC vs. [[Prostate cancer|prostate]]: | ||
*UCC: | *UCC: GATA3 +ve, PSA -ve, [[p63]] +ve, [[CK20]] +ve. | ||
*Prostate: | *Prostate: [[PSA]] +ve, [[GATA3]] -ve, [[PSAP]] +ve, CK7 -ve, CK20 -ve, p63 -ve. | ||
UCC vs. [[renal cell carcinoma| | 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> | ||
Metastatic UCC versus primary lung squamous cell carcinoma: | |||
:See ''[[Squamous_cell_carcinoma_of_the_lung#Lung_SCC_versus_metastatic_bladder_urothelial_carcinoma]]''. | |||
Note: | Note: | ||
* | *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/> | |||
===IHC for staging=== | |||
*''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: | ||
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*17p deletion -- site of PT53 (AKA p53). | *17p deletion -- site of PT53 (AKA p53). | ||
=Sign out= | |||
==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): | ||
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</pre> | </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): | ||
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</pre> | </pre> | ||
===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 | ||
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</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]]. | ||
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*[[Prostatic urothelial carcinoma]]. | *[[Prostatic urothelial carcinoma]]. | ||
=References= | |||
{{Reflist|2}} | {{Reflist|2}} | ||
[[Category:Urothelium]] | [[Category:Urothelium]] | ||
[[Category:Diagnosis]] | [[Category:Diagnosis]] |
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