Bladder, ureter & renal pelvis
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Grading-bladder


Minor changes: 19 November 2020

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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. http://www.pathologyoutlines.com/topic/bladdergrading.html. Accessed November 23rd, 2020.
Definition / general
  • Nonmuscle invasive urothelial carcinomas are graded following the 2 tier WHO 2004 (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 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 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) cannot be translated directly into each other due to overlapping grades (Eur Urol 2010;57:1052)
  • WHO 1973 but not WHO 2004 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 PUNLMP
  • Clinical description
    • Frequency: < 5% of noninvasive papillary neoplasms with controversy regarding use of this designation; some experts advise elimination of this category (Urol Oncol 2020;38:440, Histopathology 2020;77:525)
    • Manifestation by micro or gross hematuria
    • Urine cytology negative
    • Cystoscopy shows exophytic sea anemone-like tumor
  • Microscopic description
    • Increased thickness of papillary structures with slender fibrovascular cores
    • Ordered layering (streaming) of uniform nuclei with preserved polarity
    • Inconspicuous nucleoli
    • No variation in nuclear size, contour or shape
    • No nuclear hyperchromasia
    • Minimal mitotic activity confined to basal layers
    • Presence of umbrella cell layer
WHO 2004 low grade
  • Clinical description
    • Frequency: 60% in pTa, 10% 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 of somewhat enlarged nuclei with variation in polarity
    • Mild variation in nuclear size, contour or shape
    • Limited mitotic activity may extend to suprabasal layers
    • Presence of umbrella cell layer
  • Reference: Pathol Int 2010;60:1
WHO 2004 high grade
  • Clinical description
    • Frequency: 40% in pTa, 90% in pT1
    • Manifestation by gross or microscopic hematuria
    • Urine cytology often positive
    • Cystoscopy shows exophytic sessile, solid or polypoid lesion
  • Microscopic description
    • Papillary structures of variable thickness with fibrovascular cores
    • Disordered layering with loss of polarity
    • Variably enlarged nuclei and nuclear crowding
    • Variation in nuclear size, contour or shape
    • Nuclear hyperchromasia may be present
    • Mitotic activity may extend to upper layers
    • Umbrella cell layer generally indiscernible
  • Reference: Pathol Int 2010;60:1
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
  • Reference: WHO: Histological Typing of Urinary Bladder Tumours [Accessed 8 September 2020]
WHO 1973 grade 2
WHO 1973 grade 3
  • Clinical description
    • Frequency: 12% in pTa, 55% in pT1 (World J Urol 2019;37:41)
    • Manifestation by gross or microscopic hematuria
    • Positive urine cytology
    • Cystoscopy shows exophytic sessile, solid or polypoid lesion
  • Microscopic description
    • Papillary structures of variable thickness with fibrovascular cores
    • Disordered layering with variability in polarity and nuclear crowding
    • Substantially increased nuclear size
    • Strong variation in nuclear size, contour or shape
    • Marked nuclear hyperchromasia
    • Prominent mitotic activity extending into upper layers
    • Umbrella cell layer absent
  • Reference: WHO: Histological Typing of Urinary Bladder Tumours [Accessed 8 September 2020]
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, PUNLMP

WHO 2004, PUNLMP

WHO 2004, low grade

WHO 2004, low grade

WHO 2004, high grade

WHO 2004, 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 answer #1
D. Variation in nuclear size

Comment Here

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