Prostate cancer grading

This article deals with prostate cancer grading. It covers the Gleason System and the proposed Contemporary Prostate Cancer Grading System.

Gleason grading system

• AKA modified Gleason grading system.

Overview

• This system is only one any one talks about and there is consensus on how it is done.
• Score range: 6-10.
  • Technically 2-10... but almost no one uses 2-5.
• Reported on biopsy (and TURP) as: (primary pattern) + (highest non-primary pattern) = sum.
  • Gleason score 3+4=7 means: pattern 3 is present and dominant, pattern 4 is the remainder of the tumour - but present in a lesser amount than pattern 3.
  • Gleason score 4+5=9 means: pattern 4 is present and dominant, pattern 5 is present in a lesser amount that pattern 4. Pattern 3 may be present in a quantity less than pattern 4 or is absent.
• Reported as on prostatectomies as: (primary pattern) + (secondary pattern) = sum, (tertiary pattern)

• Tertiary Gleason pattern - definition: a pattern that is seen in less than 5% of the tumour (volume), that is higher grade than the two dominant patterns.
  • The presence of a tertiary patterns adversely affect the prognosis; however, the prognosis is not as bad as when the tertiary pattern is the secondary pattern, i.e. 3+4 tertiary 5 has a better prognosis than 3+5 (with some small amount of pattern 4).

Testing yourself:

• There is a nice test-yourself quiz from Johns Hopkins: http://162.129.103.34/prostate/.
  • It was studied in a paper by Kronz et al.

Examples

• A biopsy with 80% pattern 4, 16% pattern 3 and 4% pattern 5... would be reported as: 4+5=9.
• A biopsy with 92% pattern 4, and 8% pattern 3... would be reported as: 4+3=7.
• A biopsy with 98% pattern 4, and 2% pattern 3... would be reported as: 4+4=8.
• A prostatectomy with 80% pattern 4, 16% pattern 3 and 4% pattern 5... would be reported as: 4+3=7 with tertiary pattern 5.

Gleason patterns (modified)

Gleason pattern 1 & 2

• Use strongly discouraged by a number of GU pathology experts.

Notes:

• Gleason pattern 1 - probably represents what today would be called adenosis.
  • Should never be used.
• Gleason pattern 2 - used by few GU pathology experts occasionally.
  • Generally, should not be diagnosed on core biopsies.

Gleason pattern 3

• Glands smaller than normal prostate glands + loss of epithelial folding.
• Can draw a line around each gland.
• May have gland branching.
  • Glands have a X, U, V or Y shape.

Notes:

• Gland lumina should be seen.
• All cribriform is now, generally, classified as Gleason pattern 4.

Gleason pattern 4

• Loss of gland lumina.
• Gland fusion.
• Benign looking cords ('hypernephroid pattern').
• Cribriform.
• Glomeruloid pattern - resembles a glomerulus.

Notes:

• One gland is not enough to call Gleason 4.

Images

• 

  Gleason pattern 4 - cribriform. (WC)

• 

  Gleason pattern 4 - small glands & Gleason pattern 5 - single cells. (WC)

www:

• Glomeruloid pattern (nature.com).

Gleason pattern 5

• Sheets.
  • Must be differentiated from intraductal growth (which like in the breast are well circumscribed nests).
• Single cells.
  • May be confused with stromal/lymphocytic infiltration.
    • Look for nucleoli, cells should be round (prostatic stroma cells are spindle cells).
• Cords (strands).
  • Line of cells.
  • Should not be intermixed with clumps of cells (pattern 4).
• Nests of cells with necrosis (at the centre) (comedonecrosis) or (intraluminal) necrosis in a cribriform pattern.
  • Necrosis:
    • Nuclear changes:
      • Karyorrhexis (nuclear fragmentation).
      • Pynosis (nuclear shrinkage).
      • Karyolysis (nuclear dissolution).
    • Cell ghosts (cells without a nucleus).

Notes:

• Pattern 5 may be under-diagnosed.
• Single cells is the most commonly missed pattern.

Images

• 

  Gleason pattern 4 - small glands (left) & Gleason pattern 5 - single cells (right). (WC)

www:

• Gleason pattern 5 - sheeting (webpathology.com).

Special types

Special types of prostate cancer have suggested Gleason patterns:

Special type	Gleason pattern	Comment
Ductal carcinoma	4	may be graded 3 or 5
Mucinous carcinoma	3 or 4 - dependent on morphology	some advocate grade 4
Sarcomatoid carcinoma	5	glands graded separately
Signet ring cell carcinoma	5
Small cell carcinoma	not graded (ISUP 2005 consensus)	may be graded 5
Adenosquamous and squamous carcinoma	not graded
Lymphoepithelioma-like carcinoma	not graded
Adenoid cystic carcinoma	not graded
Urothelial carcinoma	not graded
Undifferentiated carcinoma, NOS	not graded

How to remember the ones that aren't graded - think of Ur Lung carcinomas (Urothelial carcinoma, Lymphoepithelioma-like carcinoma):

• Small cell carcinoma.
• Squamous cell carcinoma.
• Adenosquamous carcinoma.
• Adenoid cystic carcinoma.

Biopsy-prostatectomy concordance of Gleason score

• Discordance is common.
  • Upgrade on prostatectomy: 25-40%.
  • Downgrade on prostatectomy: 5-15%.

Selected studies on concordance:

Study	Upgrade	Downgrade	Notes
Sfoungaristos et al.	42.1%	13.7%	high volume of tumour predicts upgrade
Thomas et al.	38.1%	4.7%
Truesdale et al.	23%	11%

Upgrading

Gleason score upgrading on prostatectomy is considered relatively common; it is reported 
to occur in 23% to 42.1% of cases.[1][2]

1. BJU Int. 2011 107 (5): 749-54.
2. Can Urol Assoc J. 2012 Jan 24:1-5.

Downgrading

Gleason score downgrading on prostatectomy is considered uncommon; however, it is reported 
in 4.7% to 13.7% of cases.[1][2]

1. BJU Int. 2012 Jan; 109(2):214-9.
2. Can Urol Assoc J. 2012 Jan; 24;1-5.

Order of Gleason score components changed

COMMENT:
The change in the order of the Gleason score components (3+4 on prostatectomy 
versus 4+3 on core biopsy) may be explained by sampling.

Grade groupings

• AKA prognostic Gleason grade groupings.

Proposed new system and old (modified) Gleason score:

Prognostic group	Gleason score
I	3+3
II	3+4
III	4+3
IV	8 (4+4, 3+5, 5+3)
V	9 or 10 (4+5, 5+4, 5+5)

Rationale:

• Patients won't be told they have a 6 out of 10 cancer, and then think it is an intermediate grade cancer that is worrisome. Instead, they will be told they have a 1 out of 5 cancer.

See also

• Prostate cancer.