Prostate cancer grading

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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.[1]
  • 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.[2]
    • 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).[2]

Testing yourself:

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.[4]

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.[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:

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.[1]
    • 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.[5]
Images

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

www:

Special types

Special types of prostate cancer have suggested Gleason patterns:[6]

Special type Gleason pattern Comment
Ductal carcinoma 4 may be graded 3 or 5[7]
Mucinous carcinoma 3 or 4 - dependent on morphology[8][9] some advocate grade 4[6]
Sarcomatoid carcinoma 5 glands graded separately
Signet ring cell carcinoma 5
Small cell carcinoma not graded (ISUP 2005 consensus[1]) may be graded 5[7]
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.[10] 42.1% 13.7% high volume of tumour predicts upgrade
Thomas et al.[11] 38.1% 4.7%
Truesdale et al.[12] 23% 11%

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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:[13][14]

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.[13]

See also

References

  1. ↑ 1.0 1.1 1.2 Epstein, JI.; Allsbrook, WC.; Amin, MB.; Egevad, LL. (Sep 2005). "The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma.". Am J Surg Pathol 29 (9): 1228-42. PMID 16096414.
  2. ↑ 2.0 2.1 Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 72. ISBN 978-0443066771.
  3. ↑ Kronz, JD.; Silberman, MA.; Allsbrook, WC.; Bastacky, SI.; Burks, RT.; Cina, SJ.; Mills, SE.; Ross, JS. et al. (Sep 2000). "Pathology residents' use of a Web-based tutorial to improve Gleason grading of prostate carcinoma on needle biopsies.". Hum Pathol 31 (9): 1044-50. doi:10.1053/hupa.2000.16278. PMID 11014569.
  4. ↑ 4.0 4.1 Epstein, JI. (Feb 2010). "An update of the Gleason grading system.". J Urol 183 (2): 433-40. doi:10.1016/j.juro.2009.10.046. PMID 20006878. Cite error: Invalid <ref> tag; name "pmid20006878" defined multiple times with different content
  5. ↑ Fajardo, DA.; Miyamoto, H.; Miller, JS.; Lee, TK.; Epstein, JI. (Nov 2011). "Identification of Gleason pattern 5 on prostatic needle core biopsy: frequency of underdiagnosis and relation to morphology.". Am J Surg Pathol 35 (11): 1706-11. doi:10.1097/PAS.0b013e318228571d. PMID 21997691.
  6. ↑ 6.0 6.1 Grignon DJ (March 2004). "Unusual subtypes of prostate cancer". Mod. Pathol. 17 (3): 316–27. doi:10.1038/modpathol.3800052. PMID 14976541.
  7. ↑ 7.0 7.1 URL: https://www.bostwicklaboratories.com/global/physicians/medical-library/articles/gleason-grading.aspx. Accessed on: 26 November 2011.
  8. ↑ Osunkoya, AO.; Adsay, NV.; Cohen, C.; Epstein, JI.; Smith, SL. (Jul 2008). "MUC2 expression in primary mucinous and nonmucinous adenocarcinoma of the prostate: an analysis of 50 cases on radical prostatectomy.". Mod Pathol 21 (7): 789-94. doi:10.1038/modpathol.2008.47. PMID 18487999.
  9. ↑ Osunkoya, AO.; Nielsen, ME.; Epstein, JI. (Mar 2008). "Prognosis of mucinous adenocarcinoma of the prostate treated by radical prostatectomy: a study of 47 cases.". Am J Surg Pathol 32 (3): 468-72. doi:10.1097/PAS.0b013e3181589f72. PMID 18300802.
  10. ↑ Sfoungaristos, S.; Perimenis, P. (Jan 2012). "Clinical and pathological variables that predict changes in tumour grade after radical prostatectomy in patients with prostate cancer.". Can Urol Assoc J: 1-5. doi:10.5489/cuaj.11067. PMID 22277633.
  11. ↑ Thomas, C.; Pfirrmann, K.; Pieles, F.; Bogumil, A.; Gillitzer, R.; Wiesner, C.; Thüroff, JW.; Melchior, SW. (Jan 2012). "Predictors for clinically relevant Gleason score upgrade in patients undergoing radical prostatectomy.". BJU Int 109 (2): 214-9. doi:10.1111/j.1464-410X.2011.10187.x. PMID 21592293.
  12. ↑ Truesdale, MD.; Cheetham, PJ.; Turk, AT.; Sartori, S.; Hruby, GW.; Dinneen, EP.; Benson, MC.; Badani, KK. (Mar 2011). "Gleason score concordance on biopsy-confirmed prostate cancer: is pathological re-evaluation necessary prior to radical prostatectomy?". BJU Int 107 (5): 749-54. doi:10.1111/j.1464-410X.2010.09570.x. PMID 20840549.
  13. ↑ 13.0 13.1 URL: http://urology.jhu.edu/newsletter/2014/prostate_cancer_2014_19.php. Accessed on: 28 March 2015.
  14. ↑ Epstein, JI.; Zelefsky, MJ.; Sjoberg, DD.; Nelson, JB.; Egevad, L.; Magi-Galluzzi, C.; Vickers, AJ.; Parwani, AV. et al. (Jul 2015). "A Contemporary Prostate Cancer Grading System: A Validated Alternative to the Gleason Score.". Eur Urol. doi:10.1016/j.eururo.2015.06.046. PMID 26166626.
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