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Prostate Pathology: Prostate Carcinoma, variants and Gleason Grading
(Part 1)
June 7, 2012
Jae Y. Ro, MD, PhD
Ten Leading Cancer Types for the Estimated New Cancer
Cases and Deaths By Sex, United States, 2012.
CA Cancer J Clin 2012; 62(1):10-29
Cancers in Men, 2012Incidence (41%)
• Prostate 241,740 29% 1st
• Urinary Bladder 55,600 7% 4th
• Kidney & renal pelvis 40,250 5% 6th
Estimated deaths (15%)
• Prostate 28,170 9% 2nd
• Urinary Bladder 10,510 3% 8th
• Kidney & renal pelvis 8,650 3% 10th
CA Cancer J Clin 2012;62 (1):10-29
Prostate Cancers
• Most frequently diagnosed cancer in
men (total = 241,740; 29%)
• 2nd cause of cancer mortality in men
(total = 28,170; 9%)
Reference: Siegel R et al: Cancer Statistics, 2012
CA Cancer J Clin 2012;62:10–29
American Cancer Society
Do your BeST!
• B represents Basic.
• e (effort)
• S represents Study.
• T represents Think.
• E represents Enjoy.
Do your BeST!
1. Basic
• Prostate anatomy
• Prostate histology
Disease of Prostate
P. Zone (70%) T. Zone (5-10%) C. Zone (20%)
CA (70%) CA (25%) CA (<5%)
PIN BPH
AAH
BCH
CCCH
SA
2. Study• Prostate cancers
Microacinar carcinoma
Gleason grading
Variants
• Precancerous conditions
Prostatic intraepithelial neoplasia
Atypical adenomatous hyperplasia
ASAP
• Stromal lesions
You have to look for 3 things!
In biopsies, TURP and radical
prostatectomies
• Small glands
• Medium/Large glands with atypia
• Stromal abnormalities
Prostate Carcinoma
Well-diff. and poorly diff. adenocarcinoma
well-diff. adenocarcinoma
- For screening: three “Too”
(too small, too crowded, and too clear)
- For confirmation: nuclear enlargement,
prominent nucleoli and lack of basal cells
poorly diff. adenocarcinoma
- Uniformity, p. nucleolus, no or low mitoses
Adenocarcinoma
Other helpful features:
• Acid mucin
• Crystalloids
• Rigid luminal border
• Collagenous micronodules
(mucinous fibroplasia)
• Glomerulation
• Perineural circumferential invasion
• Glands in fat
High grade prostatic carcinoma
vs. Non-prostatic carcinoma
Prostate Non-prostate
N. monotony + -
Nucleolus prominent variable
Mitoses rare frequent
Gleason Grading, 1974
Pattern 1
Pattern 2
Pattern 3
Pattern 4
Pattern 5
Revision, 2005Original , 1977
Gleason Grade, Revisited
2005 ISUP consensus (AJSP 29:1228, 2005)
• Gleason pattern 1, 2 (score 2-4 cancer)
• Cribriform form
• Isolated cells
Variants of prostate cancers and
special features seen in prostate
cancers: Grading for variants of adenocarcinoma of prostate
Vacuoles, collagenous micronodules, glomerulation
Gleason Grading, Revisited
• Original Gleason grade 1+1, most likely AAH (adenosis): Gleason score 1+1 should not be diagnosed in any specimens
• Gleason score 3-4: rarely seen in TURP, radical prostatectomy, and possibly biopsy from transition zone or at apex
• Gleason score 3-4 in needle biopsy should not make without consultation: 1) poor reproducibility, 2) poor correlation with prostatectomy, 3) misguide clinicians and patients into believing that the patient has an indolent cancer
• Possible very low-grade on needle biopsy: score 5 (2+3 or 3+2)
Gleason Grading, Revisited
• Cribriform Gleason pattern 2/3, most likely high grade PIN
• No cribriform pattern 2 cancers
• Cribriform 3, rounded, well-circumscribed glands of similar size of normal glands (no basal cells)
• Individual cells are Gleason pattern 5, not allowed for Gleason pattern 3
Cribriform, new revision, 4 or 5
Cribriform pattern, 2011
• 2005 revision
No pattern 2
May be pattern 3
• 2010-2011 revision
No pattern 3
All pattern 4/5
No pattern 3,
cribriform
Special features and variants of Ca (I)
• Vacuoles: can be seen in any patterns and
should be distinguished from signet ring cell
carcinoma
Tumors should be graded, as if vacuoles were
not present (by evaluating underlying
architectural pattern)
• Adenoca with focal mucin extravasation: ignore
mucin extravasation, grade based on the
underlying architecture: distinguished from
colloid (mucinous) carcinoma, Gleason score
4+4
Gleason Grading, Revisited
• Mucinous fibroplasia (collagenous
micronodules)
- Resembling cribriform structures
- Subtract away mucinous fibroplasia, grade
based on the underlying glandular architecture
- Gleason score 3+3
• Glomeruloid structures
- Cribriform proliferation that is not transmural
- Prognostic significance unknown
- Lack of consensus, pattern 3 vs. 4
- Either approach is acceptable until future data
Variants of Prostate Ca
• Mucinous adenocarcinoma: Gleason pattern 4
may be 3
• Ductal-endometrioid ca: 4 to 5
• Sarcomatoid ca: 5
• Signet ring cell ca: 5
• LELC: 5 and oncocytic ca: 5
• Foamy gland carcinoma: 3, may be higher
• Ca with atrophic & hyperplastic features: 3
• Transition zone ca: 2
• Small cell, TCC, squamous and adenosq ca: not be assigned GG
Revision, 2005Original , 1974, 1977
New Revision, 2010, cribriform, 4 or 5
Gleason 3 vs. 4
Grade 3
Discrete units
Can draw a circle
around individual
glands
Presence of a few
poorly formed
glands under a
high power is still
O.K. for pattern 3
Grade 4
Fused glands
Ill-defined
papillary/cribriform
glands
solid nests with
clear cells
NOTE: any difficulty in
small sample,
conservative grading
3 is recommended
Mucinous Adenoca of Prostate
• Boyd first described a case of
mucinous adenocarcinoma of
the prostate in 1881
• A rare variant of
adenocarcinoma
(Gleason pattern 4)
• Accounts for <0.5% of prostatic
adenocarcinoma
Mucinous Adenoca of Prostate
Criteria:
• At least 25% of total tumor volume
• Extracellular mucin pool with single
or clusters of tumor cells floating in
mucin lakes (nondilated glands
containing mucin do not quality)
• Extraprostatic origin should be
excluded: PSA and PAP positive in
tumor cells
Mucinous Adenoca of Prostate
• In the past, most pathologists and
clinicians believed
1) less aggressive
2) not likely to metastasize to bone
3) serum PSA and PAP not elevated
4) arose from “female” portion of gland
• Recent studies demonstrate as a
variant of prostatic ca; prognosis not
differ stage by stage
• Should exclude metastasis from other sites
or direct extension
• Helpful features for 1st prostate mucinous ca.
1) Association with other histologic types of
prostatic ca
2) Cuboidal or oval round tumor cells (not
columnar)
3) Signet ring cells, goblet cells not present
4) Tumor cells floating in mucin lakes
5) PSA and PAP positivity in tumor cells.
Mucinous Adenoca of Prostate
• Age & symptoms not different
from acinar carcinoma
• Elevated serum PSA & PAP
• LN and bone metastases with
osteoblastic nature
Mucinous Adenoca of Prostate
• Mucin confined within glandular
lumina should not be classified as
mucinous carcinoma
• Mucinous areas occupy small
portion of tumor designate as
prostatic carcinoma with focal
mucinous component
(particularly in needle biopsies)
Mucinous Adenoca of Prostate
• Normal and benign glands usually contain
neutral mucin
• Prostatic ca. contains neutral and acid
mucins
• Intraluminal acid mucin in 70% of prostatic ca
• However, intracellular mucin not common in
prostatic carcinoma
• Associated with intraluminal crystalloids
• Seen in benign conditions, such as SA
• Useful aids in diagnosing prostatic ca
Intraluminal Acid Mucin
Mucinous Adenoca of Prostate
Management and Prognosis:
• Same as microacinar carcinoma
(depends on clinical presentation and
stage)
• Prognosis not different from other
prostate carcinoma, stage by stage
• Neither grade of nonmucinous
component nor proportion of mucinous
component is associated with
prognosis
Differential Diagnosis
Prostate Non-prostate
Cells Cuboidal Columnar
Goblet cells - +
Signet ring cells - +
Intracytoplasmic mucin Usually absent Present
Immuno PSA, PAP + CEA +
CK 20 - CK 20 +
Mucinous Adenoca of Prostate
Mucinous Adenoca of Prostate
Summaries:
• A variant of prostatic carcinoma
• Accounts for < 0.5% of prostatic ca
• Symptoms, signs, Rx and prognosis
not different from other prostatic ca
• Diagnostic criteria
Prostate Pathology: Prostate Carcinoma, variants and Gleason Grading
(Part 2)
June 7, 2012
Jae Y. Ro, MD, PhD
