Urothelial dysplasia

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Urothelial dysplasia
Diagnosis in short

Urothelial dysplasia. H&E stain.

Synonyms low-grade urothelial dysplasia

LM mild nuclear enlargement (~3x a resting lymphocyte) and hyperchromasia, mild disorganization of the architecture (some maturation), occasional mitotic figures - none atypical
LM DDx reactive changes, urothelial atypia of unknown significance, urothelial carcinoma in situ
IHC CK20 +ve/-ve (esp. non-umbrella cells), Ki-67 +ve/-ve (>10%), p53 +ve/-ve (>20%)
Site urothelium (renal pelvis, urinary bladder, ureters, urethra)

Prevalence common
Prognosis pre-malignant

Urothelial dysplasia, also low-grade (urothelial) dysplasia, is a lesion of the urothelium in the ISUP/WHO 2004 classification.[1]

It is precursor lesion to urothelial carcinoma that is less worrisome than urothelial carcinoma in situ (also known as high-grade (urothelial) dysplasia).


The ISUP/WHO classification of flat urothelial lesions is:[1]

  • Reactive urothelial atypia.
  • Flat urothelial hyperplasia.
  • Urothelial atypia of unknown significance.
  • Urothelial dysplasia (low-grade dysplasia).
  • Urothelial carcinoma in situ (high-grade dysplasia).
  • Invasive urothelial carcinoma.



  • Mild nuclear enlargement (~3x a resting lymphocyte) and hyperchromasia.
  • Slight disorganization of the architecture.
    • Some maturation to the surface - important.
  • Mitotic figures - occasional, none atypical.


  • It is probably not a good idea to make this diagnosis without immunohistochemistry.
  • This diagnosis not made on frozen section.





A comparison between benign, dysplasia and UCIS:[4]

Diagnosis CK20 Ki-67 p53 p63 ‡
Benign (reactive) umbrella cells +ve only -ve <=10% of cells (+/-rare basal cells) -ve <20% of cells (+/-weak staining) -ve surface cells
Urothelial dysplasia +ve non-umbrella cells +ve (~30% of cases) +ve >10% of cells (~40% of cases) +ve >=20% of cells (~70% of cases) -ve surface cells[5][6]
Urothelial carcinoma in situ (UCIS) +ve non-umbrella cells (~70% of cases) +ve >10% of cells (~95% of cases) +ve >=20% of cells (~80% of cases) +ve surface cells[5][6]


  • ‡ Morphology is considered the gold standard for UCIS versus urothelial dysplasia;[7] however, there is a small literature on p63 for dysplasia versus UCIS that is published in lesser known journals.

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Urinary Bladder, Biopsy:
     - Urothelial dysplasia, see comment.
     - Giant cell reaction and chronic inflammation.

The urothelium has moderate CK20 staining that extends to the basement membrane. A p53 stain is negative (<10% staining). A Ki-67 stain shows increased staining (marks 20% of urothelium). A p63 stain shows weak/negative surface staining. 

Block letters


There is focal non-umbrella cell CK20 staining, 10% (focal) urothelial 
p53 staining, and 30% (focal) urothelial Ki-67 staining. The findings 
are that of (low-grade) urothelial dysplasia.

See also


  1. 1.0 1.1 Hodges, KB.; Lopez-Beltran, A.; Davidson, DD.; Montironi, R.; Cheng, L. (Feb 2010). "Urothelial dysplasia and other flat lesions of the urinary bladder: clinicopathologic and molecular features.". Hum Pathol 41 (2): 155-62. doi:10.1016/j.humpath.2009.07.002. PMID 19762067.
  2. URL: http://pathology.jhu.edu/bladder/image1.cfm?case_number=10&image_number=1. Accessed on: 31 December 2013.
  3. McKenney, JK.; Gomez, JA.; Desai, S.; Lee, MW.; Amin, MB. (Mar 2001). "Morphologic expressions of urothelial carcinoma in situ: a detailed evaluation of its histologic patterns with emphasis on carcinoma in situ with microinvasion.". Am J Surg Pathol 25 (3): 356-62. PMID 11224606.
  4. Mallofré, C.; Castillo, M.; Morente, V.; Solé, M. (Mar 2003). "Immunohistochemical expression of CK20, p53, and Ki-67 as objective markers of urothelial dysplasia.". Mod Pathol 16 (3): 187-91. doi:10.1097/01.MP.0000056628.38714.5D. PMID 12640096.
  5. 5.0 5.1 Stepan, A.; Mărgăritescu, C.; Simionescu, C.; Ciurea, R. (2009). "E-cadherin and p63 immunoexpression in dysplastic lesions and urothelial carcinomas of the bladder.". Rom J Morphol Embryol 50 (3): 461-5. PMID 19690775.
  6. 6.0 6.1 Raheem, Sayad A.; Saied, Abdel N.; Al Shaer, Rabee; Mustafa, Osama; Ali, Ali H. (2014). "The Role of CK20, p53 and p63 in Differentiation of Some Urothelial Lesions of Urinary Bladder, Immunohistochemical Study". Open Journal of Pathology (4): 181-193. doi:10.4236/ojpathology.2014.44024.
  7. Amin MB, Trpkov K, Lopez-Beltran A, Grignon D (August 2014). "Best practices recommendations in the application of immunohistochemistry in the bladder lesions: report from the International Society of Urologic Pathology consensus conference". Am J Surg Pathol 38 (8): e20–34. doi:10.1097/PAS.0000000000000240. PMID 25029121.