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This article deals with '''prostate cancer grading'''. It covers the '''Gleason System''' and the proposed '''Contemporary Prostate Cancer Grading System'''.
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==
==Gleason grading system==
*[[AKA]] ''modified 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===
===Overview===
*This system is only one any one talks about and there is consensus on how it is done.<ref name=pmid16096414>{{Cite journal  | last1 = Epstein | first1 = JI. | last2 = Allsbrook | first2 = WC. | last3 = Amin | first3 = MB. | last4 = Egevad | first4 = LL. | title = The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. | journal = Am J Surg Pathol | volume = 29 | issue = 9 | pages = 1228-42 | month = Sep | year = 2005 | doi =  | PMID = 16096414 }}</ref>
*There is consensus on how it is done.<ref name=pmid16096414>{{Cite journal  | last1 = Epstein | first1 = JI. | last2 = Allsbrook | first2 = WC. | last3 = Amin | first3 = MB. | last4 = Egevad | first4 = LL. | title = The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. | journal = Am J Surg Pathol | volume = 29 | issue = 9 | pages = 1228-42 | month = Sep | year = 2005 | doi =  | PMID = 16096414 }}</ref>
*Score range: 6-10.
*Score range: 6-10.
**Technically 2-10... but almost no one uses 2-5.
**Technically 2-10... but almost no one uses 2-5.
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**''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 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.
**''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)
*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.<ref name=Ref_GUP72>{{Ref GUP|72}}</ref>
====When to use/not to use====
**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).<ref name=Ref_GUP72>{{Ref GUP|72}}</ref>
The ''College of American Pathologist'' synoptic (''Cancer Protocol Template'') says:<ref>Srigley JR ''et al.'', "Protocol for the Examination of Specimens From Patients With Carcinoma of the Prostate Gland", College of American Pathologists, Version: 4.0.3.0. (June 2017), Accessed on: 10 October 2018.</ref>
*Grade all prostate specimens with adenocarcinoma except those with prior treatment changes (e.g. radiation therapy changes or anti-androgen changes).


Testing yourself:
====Tertiary Gleason pattern====
*There is a nice test-yourself quiz from Johns Hopkins: [http://162.129.103.34/prostate/ http://162.129.103.34/prostate/].
*Unfortunately there is no consensus definition for ''tertiary Gleason pattern''.<ref name=Koloffa>{{Cite journal | last1 = Koloffa | first1 = ZB | last2 = Hamstrab | first2 = DA | last3 = Weia | first3 = JT | last4 = Montgomerya | first4 = JS ''et al''| title = Impact of tertiary Gleason pattern 5 on prostate cancer aggressiveness: Lessons from a contemporary single institution radical prostatectomy series | journal = Asian Journal of Urology | volume = 2 | issue = 1| pages = 53–58 | month = | year = 2015 | doi = 10.1016/j.ajur.2015.04.007 | PMID = | PMC = | url = http://www.sciencedirect.com/science/article/pii/S2214388215000302 }}</ref>
**It was studied in a paper by Kronz et al.<ref name=pmid11014569>{{Cite journal | last1 = Kronz | first1 = JD. | last2 = Silberman | first2 = MA. | last3 = Allsbrook | first3 = WC. | last4 = Bastacky | first4 = SI. | last5 = Burks | first5 = RT. | last6 = Cina | first6 = SJ. | last7 = Mills | first7 = SE. | last8 = Ross | first8 = JS. | last9 = Sakr | first9 = WA. | last10 = Tomaszewski | first10 = JE. | last11 = True | first11 = LD. | last12 = Ulbright | first12 = TM. | last13 = Weinstein | first13 = MW. | last14 = Yantiss | first14 = RK. | last15 = Young | first15 = RH. | last16 = Epstein | first16 = JI. | title = Pathology residents' use of a Web-based tutorial to improve Gleason grading of prostate carcinoma on needle biopsies. | journal = Hum Pathol | volume = 31 | issue = 9 | pages = 1044-50 | month = Sep | year = 2000 | doi = 10.1053/hupa.2000.16278 | PMID = 11014569 }}</ref>
**The Foundation series GU book (1st Ed.) defines ''Tertiary Gleason pattern'' as:<ref name=Ref_GUP72>{{Ref GUP|72}}</ref> 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''<ref name=Koloffa/> 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).<ref name=Ref_GUP72>{{Ref GUP|72}}</ref>
 
Use:
*It is only used for prostatectomies.


====Examples====
====Examples====
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*A prostatectomy with 80% pattern 4, 16% pattern 3 and 4% pattern 5... would be reported as: 4+3=7 with tertiary pattern 5.
*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:<ref name=Koloffa/>
**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 patterns (modified)===
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Notes:
Notes:
*Gleason pattern 1 - probably represents what today would be called ''adenosis''.
*Gleason pattern 1 - probably represents what today would be called ''adenosis''.
**Should never be used.
**Should '''never''' be used.
*Gleason pattern 2 - used by few GU pathology experts occasionally.
*Gleason pattern 2 - used by few GU pathology experts occasionally.
**Generally, should '''not''' be diagnosed on core biopsies.<ref name=pmid20006878>{{Cite journal  | last1 = Epstein | first1 = JI. | title = An update of the Gleason grading system. | journal = J Urol | volume = 183 | issue = 2 | pages = 433-40 | month = Feb | year = 2010 | doi = 10.1016/j.juro.2009.10.046 | PMID = 20006878 }}</ref>
**Generally, should '''not''' be diagnosed on core biopsies.<ref name=pmid20006878>{{Cite journal  | last1 = Epstein | first1 = JI. | title = An update of the Gleason grading system. | journal = J Urol | volume = 183 | issue = 2 | pages = 433-40 | month = Feb | year = 2010 | doi = 10.1016/j.juro.2009.10.046 | PMID = 20006878 }}</ref>
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Notes:
Notes:
*Gland lumina should be seen.
*Gland lumina should be seen.
*All ''cribriform'' is now, generally, classified as Gleason pattern 4.<ref name=pmid20006878>{{cite journal |author=Epstein JI |title=An update of the Gleason grading system |journal=J. Urol. |volume=183 |issue=2 |pages=433–40 |year=2010 |month=February |pmid=20006878 |doi=10.1016/j.juro.2009.10.046 |url=}}</ref>
*All ''cribriform'' is now, generally, classified as Gleason pattern 4.<ref name=pmid20006878>{{Cite journal | last1 = Epstein | first1 = JI. | title = An update of the Gleason grading system. | journal = J Urol | volume = 183 | issue = 2 | pages = 433-40 | month = Feb | year = 2010 | doi = 10.1016/j.juro.2009.10.046 | PMID = 20006878 }}</ref>


====Gleason pattern 4====
====Gleason pattern 4====
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Image:Prostate_cancer_with_Gleason_pattern_4_low_mag.jpg | Gleason pattern 4 - cribriform. (WC)
Image:Prostate_cancer_with_Gleason_pattern_4_low_mag.jpg | Gleason pattern 4 - cribriform. (WC)
Image:Gleason_4_and_5_intermed_mag.jpg | Gleason pattern 4 - small glands & Gleason pattern 5 - single cells. (WC)
Image:Gleason_4_and_5_intermed_mag.jpg | Gleason pattern 4 - small glands & Gleason pattern 5 - single cells. (WC)
</gallery>
<gallery>
Image: Prostatic carcinoma - Gleason pattern 4 -- intermed mag.jpg | PC Gleason pattern 4 - intermed. mag.
Image: Prostatic carcinoma - Gleason pattern 4 -- high mag.jpg | PC Gleason pattern 4 - high mag.
</gallery>
</gallery>
www:
www:
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=====Images=====
=====Images=====
<gallery>
Image: Poorly differentiated prostate carcinoma -- intermed mag.jpg | PDPC (Gleason pattern 5) - intermed. mag. (WC/Nephron)
Image: Poorly differentiated prostate carcinoma -- high mag.jpg | PDPC (Gleason pattern 5) - high mag. (WC/Nephron)
Image: Poorly differentiated prostate carcinoma -- very high mag.jpg | PDPC (Gleason pattern 5) - very high mag. (WC/Nephron)
</gallery>
<gallery>  
<gallery>  
Image:Gleason_4_and_5_intermed_mag.jpg | Gleason pattern 4 - small glands (left) & Gleason pattern 5 - single cells (right). (WC)
Image:Gleason_4_and_5_intermed_mag.jpg | Gleason pattern 4 - small glands (left) & Gleason pattern 5 - single cells (right). (WC)
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| some advocate grade 4<ref name=pmid14976541/>
| some advocate grade 4<ref name=pmid14976541/>
|-
|-
|Sarcomatoid carcinoma
| [[Sarcomatoid carcinoma of the prostate|Sarcomatoid carcinoma]]
| 5
| 5
| glands graded separately
| glands graded separately
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|  
|  
|-
|-
|Small cell carcinoma
|[[Small cell carcinoma of the prostate gland|Small cell carcinoma]]
| not graded (ISUP 2005 consensus<ref name=pmid16096414>{{Cite journal  | last1 = Epstein | first1 = JI. | last2 = Allsbrook | first2 = WC. | last3 = Amin | first3 = MB. | last4 = Egevad | first4 = LL. | title = The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. | journal = Am J Surg Pathol | volume = 29 | issue = 9 | pages = 1228-42 | month = Sep | year = 2005 | doi =  | PMID = 16096414 }}</ref>)
| not graded (ISUP 2005 consensus<ref name=pmid16096414>{{Cite journal  | last1 = Epstein | first1 = JI. | last2 = Allsbrook | first2 = WC. | last3 = Amin | first3 = MB. | last4 = Egevad | first4 = LL. | title = The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. | journal = Am J Surg Pathol | volume = 29 | issue = 9 | pages = 1228-42 | month = Sep | year = 2005 | doi =  | PMID = 16096414 }}</ref>)
| may be graded 5<ref name=bostwicklabs/>
| may be graded 5<ref name=bostwicklabs/>
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</pre>
</pre>


==Grade groupings==
====Separate nodule upgrades prostatectomy====
<pre>
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. 
</pre>
 
==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]] ''prognostic Gleason grade groupings''.
*[[AKA]] ''a contemporary prostate cancer grading system'', abbreviated ''CPCGS''.
*[[AKA]] ''Gleason group''.<ref>URL: [http://www.cancer.net/cancer-types/prostate-cancer/stages-and-grades http://www.cancer.net/cancer-types/prostate-cancer/stages-and-grades]. Accessed on: May 1, 2017.</ref>
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.


Proposed new system and old (modified) Gleason score:<ref name=jhu2014>URL: [http://urology.jhu.edu/newsletter/2014/prostate_cancer_2014_19.php http://urology.jhu.edu/newsletter/2014/prostate_cancer_2014_19.php]. Accessed on: 28 March 2015.</ref><ref name=pmid26166626>{{Cite journal  | last1 = Epstein | first1 = JI. | last2 = Zelefsky | first2 = MJ. | last3 = Sjoberg | first3 = DD. | last4 = Nelson | first4 = JB. | last5 = Egevad | first5 = L. | last6 = Magi-Galluzzi | first6 = C. | last7 = Vickers | first7 = AJ. | last8 = Parwani | first8 = AV. | last9 = Reuter | first9 = VE. | title = A Contemporary Prostate Cancer Grading System: A Validated Alternative to the Gleason Score. | journal = Eur Urol | volume =  | issue =  | pages =  | month = Jul | year = 2015 | doi = 10.1016/j.eururo.2015.06.046 | PMID = 26166626 }}</ref>
===WHO prostate cancer grading system & Gleason score===
{| class="wikitable sortable"  style="margin-left:auto;margin-right:auto"
Proposed new system (endorsed by the WHO<ref name=pmid26492179>{{Cite journal  | last1 = Epstein | first1 = JI. | last2 = Egevad | first2 = L. | last3 = Amin | first3 = MB. | last4 = Delahunt | first4 = B. | last5 = Srigley | first5 = JR. | last6 = Humphrey | first6 = PA. | title = The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposal for a New Grading System. | journal = Am J Surg Pathol | volume = 40 | issue = 2 | pages = 244-52 | month = Feb | year = 2016 | doi = 10.1097/PAS.0000000000000530 | PMID = 26492179 }}</ref>) and old (modified) Gleason score:<ref name=jhu2014>URL: [http://urology.jhu.edu/newsletter/2014/prostate_cancer_2014_19.php http://urology.jhu.edu/newsletter/2014/prostate_cancer_2014_19.php]. Accessed on: 28 March 2015.</ref><ref name=pmid26166626>{{Cite journal  | last1 = Epstein | first1 = JI. | last2 = Zelefsky | first2 = MJ. | last3 = Sjoberg | first3 = DD. | last4 = Nelson | first4 = JB. | last5 = Egevad | first5 = L. | last6 = Magi-Galluzzi | first6 = C. | last7 = Vickers | first7 = AJ. | last8 = Parwani | first8 = AV. | last9 = Reuter | first9 = VE. | title = A Contemporary Prostate Cancer Grading System: A Validated Alternative to the Gleason Score. | journal = Eur Urol | volume =  | issue =  | pages =  | month = Jul | year = 2015 | doi = 10.1016/j.eururo.2015.06.046 | PMID = 26166626 }}</ref>
! Prognostic group
{| class="wikitable sortable"  style="text-align:center;margin-left:auto;margin-right:auto"
! WHO grade 
! Gleason score
! Gleason score
|-
|-
| I
| I
| 3+3
| 6 (3+3)
|-
|-
| II
| II
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Rationale:
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.<ref name=jhu2014>URL: [http://urology.jhu.edu/newsletter/2014/prostate_cancer_2014_19.php http://urology.jhu.edu/newsletter/2014/prostate_cancer_2014_19.php]. Accessed on: 28 March 2015.</ref>
*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.<ref name=jhu2014>URL: [http://urology.jhu.edu/newsletter/2014/prostate_cancer_2014_19.php http://urology.jhu.edu/newsletter/2014/prostate_cancer_2014_19.php]. Accessed on: 28 March 2015.</ref>
*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:<ref name=pmid26166626/>
{| class="wikitable sortable"  style="text-align:center;margin-left:auto;margin-right:auto"
! WHO grade
! Hazard ratio<br>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:
<pre>
Grade group: Grade Group 3, Gleason score 4+3=7.
</pre>
As a comment:
<pre>
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.
</pre>
=====Alternates=====
<pre>
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.
</pre>
<pre>
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.
</pre>


==See also==
==See also==
*[[Prostate cancer]].
*[[Prostate cancer]].
*[[Prostate cancer staging]].
*[[Cancer staging systems]].
*[[Cribriform pattern within invasive prostate carcinoma]].
*[[Apparent diffusion coefficient]].


==References==
==References==
{{Reflist|1}}
{{Reflist|1}}


[[Category:Prostate cancer]]
[[Category:Prostate carcinoma]]
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