Prostate cancer grading

This article deals with prostate cancer grading.

It covers the Gleason system and the proposed Prostate cancer grading system endorsed by the WHO.

Prostate cancer is dealt with in the prostate cancer article.

Gleason grading system

• AKA modified Gleason grading system.
  • It could be called the modified modified Gleason grading system, as it has been changed twice.

Overview

• 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.
  • If a lower grade pattern is present and less than 5% it is ignored.
    • A biopsy with 98% Gleason pattern 4 and 2% Gleason pattern 3 would be graded as 8/10 (4+4).
• Reported as on prostatectomies as: (primary pattern) + (secondary pattern) = sum, (tertiary pattern)

When to use/not to use

The College of American Pathologist synoptic (Cancer Protocol Template) says:

• Grade all prostate specimens with adenocarcinoma except those with prior treatment changes (e.g. radiation therapy changes or anti-androgen changes).

Tertiary Gleason pattern

• Unfortunately there is no consensus definition for tertiary Gleason pattern.
  • The Foundation series GU book (1st Ed.) defines Tertiary Gleason pattern as: a pattern that is seen in less than 5% of the tumour that is of a higher grade than the two dominant patterns.
  • Koloffa et al notes that some define it as: the third most prevalent pattern and most require that it is a higher grade than the two dominant patterns.
    • Parsed with the all the subtleties a working definition could be: The third most prevalent pattern and a higher grade than the two dominant patterns or a pattern that is seen in less than 5% of the tumour and of higher grade than one pattern that comprises >95% of the tumour.

Significance:

• 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).

Use:

• It is only used for prostatectomies.

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.

Note:

• Based on the various definitions of tertiary pattern:
  • A prostatectomy with 75% pattern 4, 15% pattern 3 and 10% pattern 5 could be reported as: 4+3=7 with tertiary pattern 5 or 4+5=9.
    • As there is no consensus on this, it is probably best to report the percentages of the various patterns if this situation arises.

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)

• 

  PC Gleason pattern 4 - intermed. mag.

• 

  PC Gleason pattern 4 - high mag.

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

• 

  PDPC (Gleason pattern 5) - intermed. mag. (WC/Nephron)

• 

  PDPC (Gleason pattern 5) - high mag. (WC/Nephron)

• 

  PDPC (Gleason pattern 5) - very high mag. (WC/Nephron)

• 

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

www:

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

Gleason pattern for 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.

Separate nodule upgrades prostatectomy

A tumour nodule in the left mid portion of the gland (1.2 cm) is predominantly 4+3; the Gleason score for the case is assigned on the basis of the tumour nodule as Gleason score 7/10 (4+3).

Overall, Gleason pattern 3 represents 65% of the cancer in the prostate, and Gleason pattern 4 represents 35% of the cancer in the prostate.  

Prostate cancer grading system endorsed by the WHO

• AKA WHO prostate cancer grading system or WHO system.
• AKA ISUP prostate grading.
• AKA grade groupings.
• AKA prognostic Gleason grade groupings.
• AKA a contemporary prostate cancer grading system, abbreviated CPCGS.
• AKA Gleason group.

This system has been proposed. Currently, it is not widely used. The name of the system is not completely settled. This system has been proposed. Currently, it is not widely used. The name of the system is not completely settled.

WHO prostate cancer grading system & Gleason score

Proposed new system (endorsed by the WHO) and old (modified) Gleason score:

WHO grade	Gleason score
I	6 (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.
• Gleason score 7 is split into two separate groups, as the follow-up data suggests they should be.

Prognostication

Recurrence free progression stratified by the system endorsed by the WHO:

WHO grade	Hazard ratio compared to Group I
I	(1.0)
II	1.9
III	5.1
IV	8.0
V	11.7

Sign out

• The language is still evolving as this is relatively new.
• As of 2017, many pathologists continue to predominantly use (modified) Gleason grading, and add a comment about (the equivalent grade in) the new grading system.

Reporting examples

Within a synoptic report:

Grade group: Grade Group 3, Gleason score 4+3=7.

As a comment:

The World Health Organization (WHO) grade is: 3 out of 5. Gleason pattern 3 represents 30% of the tumour, and Gleason pattern 4 represents 70% of the tumour.

Alternates

The World Health Organization (WHO) prostate cancer grade is: 3 out of 5. Gleason pattern 3 represents 30% of the tumour, and Gleason pattern 4 represents 70% of the tumour.

Gleason pattern 3 represents 30% of the tumour, and Gleason pattern 4 represents 70% of the tumour.
The World Health Organization (WHO) endorsed prostate cancer grade grouping is: 3 out of 5.

See also

• Prostate cancer.
• Prostate cancer staging.
• Cancer staging systems.
• Cribriform pattern within invasive prostate carcinoma.
• Apparent diffusion coefficient.