1. REPRODUCIBILITY OF GLEASON GRADING SYSTEM FOR PROSTATIC ADENOCARCINOMA Dr A. T Atanda, Consultant Pathologist, AKTH, kano

2. OUTLINE  Introduction  Rationale  Methodology  Results  Discussion  Conclusion

3. Introduction  Qualitative versus Quantitative data  Grading in histopathology  Why Carcinoma of the Prostate  Grading is important (Gleason System)  Epidemiological significance of Ca Prostate  Role in determining treatment option  Role in determining prognosis  Inappropriate Treatment

4. Methodology  10 H and E slides (Trucut Bx)  consensus  2 pathologists  11 participants  Kappa statistics

5. Interpretation of kappa values  <0Poor  0.01 – 0.2slight reproducibility  0.21 – 0.40fair reproducibility  0.41 – 0.60moderate reproducibility  0.61 – 0.80substantial reproducibility  0.81 – 0.99almost perfect reproducibility

6.  Grade 2round or oval closely arranged intermediate- sized glands with smooth ends and invasion into the surrounding non-neoplastic prostatic tissue.  Grade 3rounded well circumscribed cribriform glands of the same size as normal glands and resembling high grade intra-epithelial neoplasm  Grade 4large cribriform glands with irregular borders with ductal differentiation  Grade 5solid sheets of cells and cribriform glands with comedonecrosis

7. Primary Gleason Pattern Rating  110 ratings  Patterns  132.7%  23834.5%  33229.1%  41816.4%  51917.3  Compared to consensus  Under-rating5449.1%  Appropriate rating5247.3%  Over-rating43.6%

8. Primary Gleason Pattern Rating  Range of kappa0.07 to 0.47  Performance (kappa distribution)  218.1%slight  545.5%fair  436.4%moderate  Overall kappa = 0.25 (fair agreement)

9. Primary Gleason Pattern Rating  Intra-rater consistency for Gleason pattern 3  0.29 – 0.78  327.3%fair  545.4%moderate  327.3%substantial  Intra-rater consistency for Gleason pattern 5  0.29 – 0.78  545.4%fair  436.4%moderate  218.2%substantial

10. Slide No. Consensus score Gleason 2 – 4 Gleason 5 – 6 Gleason 7 Gleason 8 – 10 182243 258300 381154 456500 5100119 693620 751631 8 001 962900 71613 Total 24391730

11. Gleason Score Rating  110 ratings  Score groups  2 – 424 22%  5 – 6 3936%  71715%  8 – 10 3027%  Compared to consensus Scores  Under-grading51.8%  Appropriate grading40.9%  Over-grading7.3%

12. Gleason Score Rating  Group under-grading  5 – 6 38.6%  763.6%  8 – 10 45.5%  Kappa distribution for Gleason Scores  0 – 0.20 – to 0.54  654.5%slight  218.2%fair  218.2%poor  19.1%moderate  Overall kappa = 0.35fair

13. Summary  Pattern recognition was only fair (kappa = 0.25)  Underrating of primary Gleason pattern occurred in 49.1% of ratings  Intra-rater consistency was higher for Gleason pattern 3 than for pattern 5  There was no statistically significant difference between participants

14. Summary ctd  Inter-rater agreement for Gleason score was fair (kappa = 0.35)  Under-grading occurred in 51.8 % of ratings overall  Grade 7 was most under-graded (63.6% of ratings)

15. Authors Kappa for GS Our study kappa McLean et al (1997)0.16 – 0.29– 0.20 – 0.54 Djavan et al (1998)0.148 – 328– 0.20 – 0.54 Allsbrook et al (2001)0.56 – 0.70– 0.20 – 0.54 Melia et al (2005)0.08 – 0.58– 0.20 – 0.54 Singh et al (2011)– 0.11 – 0.82– 0.20 – 0.54

16. Factors identified for imperfect inter- and intra-rater agreement  Underscoring  Dearth of expertise in uropathology  Low awareness of current reviewed Gleason grading system (ISUP, 2005)  Infrequent refresher tutoring

17. ISUP Recommendations  Patterns 1 or 2 should rarely be assigned  Gleason Scores 2 – 4 rarely in needle biopsies  Cribriform 3 now rendered 4  Need for immunohistochemistry (p63 staining)

18. Conditions for pattern 2  p63 demonstration of loss of basal staining  Perineural, glomeruloid features  Extra-prostatic extension

19. Cribirform pattern 3 conditions  p63 demonstration of loss of basal cells  Presence of extra-prostatic extension  Perineural invasion  rounded well circumscribed cribriform glands of the same size as normal glands and resembling high grade intra- epithelial neoplasm

21. Cribriform carcinoma, Gleason 3

22. Cribriform carcinoma, Gleason 4

23. Cribriform carcinoma with ductal differentiation Gleason 4

24.  Summary  Thank you for your time