REPRODUCIBILITY OF GLEASON GRADING SYSTEM FOR PROSTATIC ADENOCARCINOMA

Dr A. T Atanda, Consultant Pathologist, AKTH, kano

OUTLINE

IntroductionRationaleMethodologyResultsDiscussionConclusion

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

Methodology 10 H and E slides (Trucut Bx)

consensus 2 pathologists

11 participantsKappa statistics

Interpretation of kappa values

<0 Poor 0.01 – 0.2 slight reproducibility 0.21 – 0.40 fair reproducibility 0.41 – 0.60 moderate reproducibility 0.61 – 0.80 substantial reproducibility 0.81 – 0.99 almost perfect

reproducibility

Grade 2 round or oval closely arranged intermediate-sized glands with smooth ends and invasion into the surrounding non-neoplastic prostatic tissue.

Grade 3 rounded well circumscribed cribriform glands of the same size as normal glands and resembling high grade intra-epithelial neoplasm

Grade 4 large cribriform glands with irregular borders with ductal differentiation

Grade 5 solid sheets of cells and cribriform glands with comedonecrosis

Primary Gleason Pattern Rating 110 ratings Patterns

1 3 2.7% 2 38 34.5% 3 32 29.1% 4 18 16.4% 5 19 17.3

Compared to consensus Under-rating 54 49.1% Appropriate rating 52 47.3% Over-rating 4 3.6%

Primary Gleason Pattern Rating

Range of kappa 0.07 to 0.47

Performance (kappa distribution) 2 18.1% slight 5 45.5% fair 4 36.4% moderate

Overall kappa = 0.25 (fair agreement)

Primary Gleason Pattern Rating

Intra-rater consistency for Gleason pattern 3 0.29 – 0.78 3 27.3% fair 5 45.4% moderate 3 27.3% substantial

Intra-rater consistency for Gleason pattern 5 0.29 – 0.78 5 45.4% fair 4 36.4% moderate 2 18.2% substantial

Slide

No.

Consens

us

score

Gleaso

n

2 – 4

Gleason

5 – 6

Gleason

7

Gleason

8 – 10

1 8 2 2 4 3

2 5 8 3 0 0

3 8 1 1 5 4

4 5 6 5 0 0

5 10 0 1 1 9

6 9 3 6 2 0

7 5 1 6 3 1

8 10 0 0 1 10

9 6 2 9 0 0

10 7 1 6 1 3

Total   24 39 17 30

Gleason Score Rating

110 ratings Score groups

2 – 4 24 22% 5 – 6 39 36% 7 17 15% 8 – 10 30 27%

Compared to consensus Scores Under-grading 51.8% Appropriate grading 40.9% Over-grading 7.3%

Gleason Score Rating Group under-grading

5 – 6 38.6% 7 63.6% 8 – 10 45.5%

Kappa distribution for Gleason Scores 0 – 0.20 – to 0.54 6 54.5% slight 2 18.2% fair 2 18.2% poor 1 9.1% moderate

Overall kappa = 0.35 fair

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

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)

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

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

ISUP Recommendations Patterns 1 or 2 should

rarely be assignedGleason Scores 2 – 4 rarely in needle biopsies

Cribriform 3 now rendered 4

Need for immunohistochemistry (p63 staining)

Conditions for pattern 2

p63 demonstration of loss of basal staining

Perineural, glomeruloid features

Extra-prostatic extension

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

Cribriform carcinoma, Gleason 3

Cribriform carcinoma, Gleason 4

Cribriform carcinoma with ductal differentiation Gleason 4

Summary

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