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Prostate

Prostatic carcinoma

Grading (Gleason)


Reviewers: Komal Arora, M.D., (see Reviewers page)
Revised: 7 August 2012, last major update February 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
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● Grade / pattern is 1 to 5, based on glandular differentiation at low power
● Score is 2 to 10, based on Gleason grade for first and second most predominant patterns
● If only one pattern present, primary and secondary patterns are given the same grade
● Score 2-4 (well differentiated) almost never develop aggressive disease, 8-10 usually die of disease
● Clinically important distinctions are Gleason scores 2-6, 7, 8, 9-10
● Upgrading is seen in 1/3 of prostatectomy specimens after biopsy, down grading in 5%
● 1/3 of Gleason 8 at biopsy are Gleason 7 at radical prostatectomy
● If minimal tumor on biopsy (1 mm or less), Gleason score does not predict tumor stage; perhaps should note this on report (Am J Surg Pathol 2000;24:1634)
● Do NOT report secondary patterns of lower grade if <5% of tumor area and if high-grade cancer is present
● DO report secondary patterns of higher grade, even if limited, and include within the Gleason score
● Reference: 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading (Am J Surg Pathol 2005;29:1228)

Tertiary Gleason patterns
Needle Biopsy: primary pattern and the highest grade should be recorded. Secondary pattern should be ignored
Radical Prostatectomy: Gleason score should be based on the primary and secondary patterns with a comment on the tertiary pattern (J Urol 2010;183:433)

Gleason grade 1
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● Single, separate, closely packed, uniform round glands arranged in a circumscribed nodule with pushing borders
● Separation of glands at the periphery from the main collection by more than one gland diameter indicates a component of at least grade 2
● Uncommon pattern except in transitional zone adenocarcinomas; almost never seen in needle biopsies
● Gleason score of 1+1=2 is extremely rare
● Most cases that were diagnosed as Gleason score 1 + 1 = 2 in the era of Gleason would today be referred to as adenosis/atypical adenomatous hyperplasia

Gleason grade 2
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● Like grade 1 but more variability in gland shape and more stroma separating glands
● Most glands are separated by less than one average gland diameter
● Less circumscribed at periphery, although no infiltration into stroma or between benign glands
● More common in transitional zone adenocarcinoma, less frequent in peripheral zone adenocarcinomas
● Presence of even a few well-formed malignant glands in a needle biopsy (often interspersed among benign elements) indicates a grade 3 pattern
● Tends to be periurethral and not sampled

Note: don't diagnose Gleason grades 1 or 2 on prostate needle biopsies since
● (a) are uncommon in peripheral zone
● (b) there is marked inter-pathologist variability
● (c) usually reflects undergrading compared to experts
● (d) doesn't correlate with radical prostatectomy

       
Various grade 2 tumors

Gleason grade 3
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● Single, separate, much more variable glands, may be closely packed but usually irregularly separated, ragged, poorly defined edge, but still in circumscribed structure, looser than nodule, slightly infiltrative, but can draw a circle around each gland
● Tangentially cut glands may be poorly formed

Patterns of Gleason grade 3 prostatic adenocarcinoma::
● (a) Most common pattern is well-formed, relatively uniform glands infiltrating between benign glands; glands may be angulated or compressed, separated by > 1 gland diameter, tend to have basophilic cytoplasm and larger nucleoli than grades 1 or 2

           
Gleason pattern 3(a)

● (b) Small glands with inconspicuous or absent lumina, glands still separate


Gleason pattern 3(b)

● (c) Papillary or cribriform patterns, with smooth, rounded, pushing type edges without stromal infiltration; uncommon; cribriform unit should be small (size of normal prostate gland), and well circumscribed without a ragged or infiltrative border; difficult to differentiate from cribriform PIN
● Note: many cases previously diagnosed as cribriform prostate carcinoma would today be diagnosed as cribriform high grade PIN, if basal cell markers were used
● Most cancer in prostate with cribriform architecture is Gleason pattern 4 rather than 3 by consensus conference criteria
● Extremely stringent criteria for the diagnosis of cribriform pattern 3 is that the glands should be rounded, well circumscribed and within the same size range of normal glands
● Even slight irregularities oí the outer border of cribriform glands typically results in upgrading as pattern 4 (Am J Surg Pathol 2001;25:147)

● (d) large gland variant


   
Gleason pattern 3(d)

Gleason grade 4
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● Chopped up fused glands
● Either all glands without stroma or small fragments of glands

Patterns of Gleason grade 4 prostatic adenocarcinoma::
● (a) Most common is small acinar structures, some with well-formed lumina, fusing into cords or chains; may be undergraded as Gleason 3

           
Gleason pattern 4(a)

● (b) Papillary-cribriform tumors with irregular / invasive edges; includes many but not all endometrioid carcinomas; nodule of cribriform gland should be larger than normal prostate gland; large nodules of cribriform Gleason 4 lack supporting stroma and tend to fragment; thus large fragments of cribriform glands on needle biopsy represents Gleason 4
● Note: patients with Gleason 8 at biopsy may have Gleason 7 at prostatectomy due to unsampled Gleason 3

● (c) Hypernephroid pattern, with nests of clear cells resembling renal cell carcinoma; small, hyperchromatic nuclei; fusion of acini into more solid sheets with the appearance of back to back glands without intervening stroma


Gleason pattern 4(c)

Gleason grade 5
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Grade 5 - two patterns
● 5a: Comedocarcinoma-papillary / cribriform carcinomas with central necrosis (must have intraluminal necrotic cells or karyorrhexis)
● 5b: Carcinomas with minimal glandular differentiation, ranging from infiltrating single cells (including signet ring cells) to solid sheets of tumor cells

           
Gleason pattern 5(b)

● The presence of Gleason grade 5 and high percent carcinoma at prostatectomy predicts early death (Am J Clin Pathol 2001;116:864)

Diagram
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Dr. Gleason's drawing of the five Gleason grades

End of Prostate > Prostatic carcinoma > Grading (Gleason)


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