Urothelial carcinoma

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Author: Mikael Häggström [note 1]
95% of bladder cancers are urothelial carcinoma (also called transitional cell carcinoma).[1]


On this resource, the following formatting is used for comprehensiveness:

  • Minimal depth
  • (Moderate depth)
  • ((Comprehensive))
Other legend

<< Decision needed between alternatives separated by / signs >>
{{Common findings / In case of findings}}
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Gross processing

Further information: Urinary bladder

Microscopic examination

Low grade urothelial carcinoma.[2]
In contrast, an inverted urothelial papilloma has smooth surface with minimal to absent exophytic component, is well circumscribed with smooth base, and has no obvious infiltration and no/minimal cytologic atypia.[3]

Urothelial carcinoma displays more crowding and layering, and more hyperchromasia and mitoses, than papillomas and papillary urothelial neoplasm of low malignant potential (also included in grading table below for comparison).[4]


Also consider non-urothelial cancer types (together constituting 5% of urinary bladder cancers): squamous cell carcinomas (Further information: Urothelial versus squamous cell carcinoma ), adenocarcinomas, sarcomas, small cell carcinomas, and secondary deposits from cancers elsewhere in the body.[1]

If urothelial carcinoma, perform grading and staging. Also report any intraepithelial neoplasia of any surrounding urothelium.


Urothelial carcinomas are classified as papillary when they have projections with fibrovascular cores.


By grade, urothelial neoplasms are classified as either:

  • Papillary urothelial neoplasm of low malignant potential (PUNLMP)
  • Low-grade urothelial carcinoma
  • High-grade urothelial carcinoma


Papillary urothelial neoplasm of low malignant potential (PUNLMP)
Low grade

Overexpression of p53 is seen in 75% of low-grade urothelial carcinomas and only 10% of PUNLMP.[7]

High grade

There should be at least 5% of high grade areas to call the tumor high grade.[notes 1] High-grade areas less than 5% confers a report addition of "focal high-grade features".


Papillary urothelial neoplasms[8]
Papillary urothelial neoplasm of low malignant potential Low grade High grade
Architecture Papillae
  • Delicate
  • Rarely fused
  • Delicate
  • Occasionally fused
  • Delicate
  • Fused and branching
  • Normal polarity
  • Cohesive cells
  • Minimal crowding and loss of polarity
  • Cohesive cells
  • Crowding
  • Overlapping cells
  • Loss of polarity
  • Often discohesive cells
Nuclei Size and nuclear/cytoplasmic ratio Mildly increased Increased
Nuclear size variability No Some Marked
  • Elongated
  • Uniform
  • Elongated—oval—round
  • Slight variability
  • Pleomorphic
  • Fine
  • Fine with some variability
  • Frequently coarse with marked variability
  • Absent to inconspicuous
  • Usually inconspicuous
  • Prominent
  • Single to multiple
  • Rare
  • Basal if present
  • Infrequent
  • Mostly basal if present
  • Frequent
  • At any level
Invasion Non-invasive Rarely invasive Invasive



In the TNM staging system (AJCC 8th Ed.) for bladder cancer:[9][10][11]

T (Primary tumor)

  • TX Primary tumor cannot be assessed
  • T0 No evidence of primary tumor
  • Ta Non-invasive papillary carcinoma
  • Tis Carcinoma in situ ('flat tumor')
  • T1 Tumor invades subepithelial connective tissue
High grade papillary urothelial carcinoma, with early invasion, showing single cells and irregularly shaped nests of tumor cells infiltrating the underlying stroma (T1).[2] Pointy rather than smooth edges indicate a true invasion rather than a tangential cut of the basal part of carcinoma in situ.

To detect subepithelial invasion, scroll through all areas of subepithelial connective tissue. Distinguish the following:

Tangentially cut non-invasive tumor Subepithelial invasion
Nest shapes Rounded Irregular
Cells Similar to non-invasive Larger and more eosinophilic
At adjacent levels Fused with non-invasive tumor Persistently isolated nests
  • T2 Tumor invades the detrusor muscle (muscularis propria). In biopsies, muscle areas smaller than 2 mm in size may be regarded as muscularis mucosae (subepithelial connective tissue) whereas areas larger than 4 mm can be regarded as detrusor muscle.
  • T2a Tumor invades superficial muscle (inner half of the detrusor muscle)[12]
  • T2b Tumor invades deep muscle (outer half of the detrusor muscle)[12]
  • T3 Tumor invades perivesical tissue:
    • T3a Microscopically
    • T3b Macroscopically (extravesical mass)
  • T4a Tumor invades prostate, uterus or vagina
  • T4b Tumor invades pelvic wall or abdominal wall

N (Lymph nodes)

  • NX Regional lymph nodes cannot be assessed
  • N0 No regional lymph node metastasis
  • N1 Metastasis in a single lymph node in true pelvis (hypogastric, obturator, external iliac, or presacral nodes)
  • N2 Metastasis in multiple lymph nodes in true pelvis (hypogastric, obturator, external iliac, or presacral nodes)
  • N3 Metastasis in common iliac lymph nodes

M (Distant metastasis) Can be performed if tissues have been submitted from distant sites.

  • MX Distant metastasis cannot be assessed
  • M0 No distant metastasis
  • M1 Distant metastasis.
    • M1a: The cancer has spread only to lymph nodes outside of the pelvis.
    • M1b: The cancer has spread other parts of the body.

Microscopy report

  • Histopathologic type of cancer
  • Grade
  • Stage. For biopsies, there should be a mention of the presence or absence of the muscularis propria in the sample, and if it is involved.
(Right bladder neck, transurethral resection:)
<<Invasive / Non-invasive>> <<Low / high>>-grade {{papillary}} urothelial carcinoma. <<Negative for lamina propria invasion / Carcinoma invades the ___ [[Deepest layer involved]]>>. Muscularis propria is <<present / absent>>. See synoptic report.
Synoptic report

Procedure: Transurethral resection of bladder (TURBT)

  • Tumor site: <<Right / left >> bladder <<neck, floor, wall>>
  • Histologic type: Papillary urothelial carcinoma, noninvasive
  • Histologic grade: <<Low / high>>-grade
  • Tumor extension: Noninvasive
  • Muscularis propria presence: Muscularis propria (detrusor muscle) is <<abdent / present in ___ [[location]]
  • Lymphovascular invasion: <<Present / Not identified>>
  • TNM Histopathologic summary: pT__, pN__
Papillary urothelial carcinoma with early invasion, high mag.jpg
High-grade papillary urothelial carcinoma with invasion into subepithelial connective tissue.[2]
Synoptic report
  • Procedure:tumor site(s): posterior dome
  • Histologic type: papillary urothelial carcinoma
  • Histologic grade: high-grade
  • TNM tumor stage:
  • Primary tumor (pt): pT1: tumor invading lamina propria
  • Lymph node staging (pN): pNx: lymph nodes not sampled
  • Muscularis propria sampled: present
  • Lymphovascular invasion: absent

  See also: General notes on reporting


  1. The 5% volume for classifying as high-grade is not universally accepted.
  1. For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.

Main page


  1. 1.0 1.1 . Types of Bladder Cancer: TCC & Other Variants. CTCA.
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22 2.23 Image(s) provided by CoRus13, Public Domain.
  3. Monika Roychowdhury. Bladder, ureter & renal pelvis - Urothelial neoplasms - noninvasive - Inverted urothelial papilloma. Pathology Outlines. Topic Completed: 1 December 2014. Minor changes: 3 December 2020
  4. Rugvedita Parakh. Bladder, ureter & renal pelvis - Urothelial neoplasms-noninvasive - Noninvasive papillary urothelial carcinoma low grade. Pathology Outlines. Topic Completed: 1 December 2014. Minor changes: 30 March 2020
  5. 5.0 5.1 5.2 Maxwell, Jay P; Wang, Cheng; Wiebe, Nicholas; Yilmaz, Asli; Trpkov, Kiril (2015). "Long-term outcome of primary Papillary Urothelial Neoplasm of Low Malignant Potential (PUNLMP) including PUNLMP with inverted growth ". Diagnostic Pathology 10 (1). doi:10.1186/s13000-015-0234-z. ISSN 1746-1596. 
    - Figure 1- available via license: Creative Commons Attribution 4.0 International license
    - Figure 2- available via license: Creative Commons Attribution 4.0 International license
  6. Image is taken from following source, with some modification by Mikael Häggström, MD:
    - Schallenberg S, Plage H, Hofbauer S, Furlano K, Weinberger S, Bruch PG (2023). "Altered p53/p16 expression is linked to urothelial carcinoma progression but largely unrelated to prognosis in muscle-invasive tumors. ". Acta Oncol: 1-10. doi:10.1080/0284186X.2023.2277344. PMID 37938166. Archived from the original. . 
  7. Kalantari MR, Ahmadnia H (2007). "P53 overexpression in bladder urothelial neoplasms: new aspect of World Health Organization/International Society of Urological Pathology classification. ". Urol J 4 (4): 230-3. PMID 18270948. Archived from the original. . 
  8. Grignon, David J (2009). "The current classification of urothelial neoplasms ". Modern Pathology 22 (S2): S60–S69. doi:10.1038/modpathol.2008.235. ISSN 0893-3952. 
  9. Amin, Mahul (2017). AJCC cancer staging manual (8 ed.). Switzerland: Springer. ISBN 978-3-319-40617-6. OCLC 961218414. 
    - For access, see the Secrets chapter of Patholines.
    - Copyright note: The AJCC, 8th Ed. is published by a company in Switzerland, and the tables presented therein are Public Domain because they consist of tabular information without literary or artistic innovation, and therefore do not fulfil the inclusion criterion of the Swiss Copyright Act (CopA) which applies to "literary and artistic intellectual creations with individual character" (see Federal Act on Copyright and Related Rights (Copyright Act, CopA) of 9 October 1992 (Status as of 1 January 2022)). edit
  11. "Staging of bladder cancer ". Histopathology 74 (1): 112–134. January 2019. doi:10.1111/his.13734. PMID 30565300. 
  12. 12.0 12.1 . Bladder Cancer: Stages and Grades. Cancer.net. Approved by the Cancer.Net Editorial Board 05/2019

Image sources