Bladder, ureter & renal pelvis

General

Grading-bladder


Editorial Board Member: Maria Tretiakova, M.D., Ph.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Theodorus van der Kwast, M.D., Ph.D.

Topic Completed: 17 June 2021

Minor changes: 23 June 2021

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Theodorus van der Kwast, M.D., Ph.D.
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Cite this page: van der Kwast T. Grading-bladder. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bladdergrading.html. Accessed December 7th, 2021.
Definition / general
  • Nonmuscle invasive urothelial carcinomas are graded following the 2 tier WHO 2004 / 2016 (endorsed by the American Urologic Association and European Association of Urology) or the 3 tier WHO 1973 grading systems (endorsed by the European Association of Urology)
  • WHO 2004 / 2016 classification of urothelial neoplasms includes papillary urothelial neoplasm of unknown malignant potential (PUNLMP)
  • Grading of nonmuscle invasive papillary urothelial carcinomas determines the risk of stage progression in recurrent bladder cancer
  • Invasive urothelial carcinomas, independent of the degree of invasion, are generally graded as WHO 2004 / 2016 high grade (World J Urol 2019;37:41)
Essential features
  • Grading of (papillary) urothelial carcinomas is based on the level of orderedness of the urothelial lining at intermediate power and nuclear atypia
  • Orderedness represents a continuum, varying from very well ordered to chaotic with increasing nuclear atypia (see Diagrams / tables)
  • Substantial interobserver variation due to lack of landmarks separating the different grades
  • 2 grading systems (WHO 1973 and 2004 / 2016) cannot be translated directly into each other due to overlapping grades (Eur Urol 2010;57:1052)
  • WHO 1973 but not WHO 2004 / 2016 grading of pT1 bladder cancer is prognostic for stage progression (BJU Int 2011;107:404)
  • In urothelial carcinomas with grade heterogeneity, the highest grade is reported
Diagrams / tables

Contributed by Theodorus van der Kwast, M.D., Ph.D.
WHO 1973 versus WHO 2004

WHO 1973 versus WHO 2004

WHO 2004 / 2016 PUNLMP
WHO 2004 / 2016 low grade
WHO 2004 / 2016 high grade
WHO 1973 grade 1
  • Clinical description
    • Frequency: 35% in pTa, < 5% in pT1
    • Manifestation by micro or gross hematuria
    • Urine cytology almost always negative
    • Cystoscopy shows exophytic sessile or polypoid lesion
  • Microscopic description
    • Increased thickness of papillary structures with slender fibrovascular cores
    • Ordered layering with streaming of uniform nuclei
    • No or minimal nuclear enlargement
    • No or mild variation in nuclear size, contour or shape
    • Nuclear grooves
    • No nuclear hyperchromasia
    • Limited mitotic activity may extend to suprabasal cell layers
    • Presence of umbrella cell layer
  • References: WHO: Histological Typing of Urinary Bladder Tumours [Accessed 14 June 2021], Eur Urol Focus 2021 Mar 23 [Epub ahead of print]
WHO 1973 grade 2
WHO 1973 grade 3
Grade heterogeneity
  • Clinical description
    • Frequency: up to 30% (Cancer 2000;88:1663)
    • Manifestation by microscopic or gross hematuria
    • Occasionally positive urine cytology
    • Cystoscopy shows exophytic sessile, solid or polypoid lesion
  • Microscopic description
    • Distinct areas of low and high grade urothelial carcinoma
    • Clear demarcation of separate areas
  • Reporting
    • By convention, the highest grade is reported if comprising > 5% of the carcinoma
    • If < 5%, a comment on its presence is made
Microscopic (histologic) images

Contributed by Theodorus van der Kwast, M.D., Ph.D.
WHO 2004 / 2016, PUNLMP

WHO 2004 / 2016, PUNLMP

WHO 2004 / 2016, low grade

WHO 2004 / 2016, low grade

WHO 2004 / 2016, high grade

WHO 2004 / 2016, high grade

WHO 1973, grade 1

WHO 1973, grade 1


WHO 1973, grade 2

WHO 1973, grade 2

WHO 1973, grade 3

WHO 1973, grade 3

Grade heterogeneity

Board review style question #1

Low grade papillary urothelial carcinoma can be distinguished from high grade papillary urothelial carcinoma microscopically by

  1. Absence of suprabasal mitoses
  2. Number of cell layers of the urothelial lining
  3. Presence of umbrella cells
  4. Variation in nuclear size
Board review style answer #1
D. Variation in nuclear size

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