diseases of the prostate - 2009erspc 2009 and plco •!erspc - >160,000 men – 20% risk...
TRANSCRIPT
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Diseases of the Prostate
Dr Jon Oxley
Southmead Hospital, Bristol
13th May 2009
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Topics
•!Background and screening
•!Normal histology
•!Benign conditions mimicking cancer
•!Multidisciplinary team meeting
•!Small volume disease
•!High Grade PIN
•!Gleason grading
•!Radical prostatectomy
•!Slide seminar
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Incidence of prostate cancer
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Trends in Prostate Cancer Incidence and Mortality in England and Wales, 92-04
European age-standardised rates Source: ONS (Office for National Statistics) and WCISU (Wales Cancer Intelligence and Surveillance Unit)
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Age related incidence
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Crude Incidence Rates 2002
Source: ONS, WCISU
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Why has incidence increased?
•!PSA testing
•!Better reporting
•!Biopsy rate increasing
•!Greater patient awareness
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PSA
•!First described in 1979
•!Sensitive but lacks specificity
•!Age dependent normal ranges
•!6th decade <2.5ng/ml
•!8th decade <6 ng/ml
•!Affected by UTI, prostate size, iatrogenic
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Transrectal ultrasound
•!US abnormalities associated with cancer uncommon
•!Hypoechoic areas may be benign
•!Increased numbers of biopsies from 4 to 10 in recent years to overcome these problems
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Treatment options
Radical prostatectomy (open,laparoscopic,robotic)
Radiotherapy – including brachiotherapy +/- HDR boost
Active monitoring
Hormones
HIFU
Cryotherapy
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Screening for prostate cancer
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General Principles of Screening
•!The condition should be a significant health problem
•!The natural history should be understood
•!There should be an early or latent stage
•!Treatment at an early stage should be of more benefit than started at a later stage
•!There should be a suitable test
•!Test should be acceptable to the population
•!Screening should be repeated at intervals
•!Facilities available for diagnosis & treatment
•!Chance of harm should be less than chance of benefit
•!Cost effective
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ERSPC 2009 and PLCO
•!ERSPC - >160,000 men – 20% risk reduction in deaths from prostate cancer in screened group. N Engl J Med. 2009 Mar 26;360(13):1320-8
•!PLCO – USA – 76693 men – no risk reduction if screened. N Engl J Med. 2009 Mar 26;360(13):1310-9.
•!48 men treated for prostate cancer for every life saved
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ProtecT Study flowchart up to April 2009
226,716
Invitations
111,091 (49%)
Prostate check clinic attenders
10,274 (11.1%)
Raised PSA
2,618 (82%) Localised
324 (10%) Advanced
232 (7%) Excluded
3,174 (31%) Total cancer
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ProtecT randomisation
2618
Eligible cases
1651 (63%)
Randomised
967(37%)
Preference
540
A Monitoring
546 Surgery
541 Radiotherapy
Annual follow-up
263
Surgery
506
A Monitoring
130
Radiotherapy
& 57 Brachy
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Prostatectomies by Age Band and Year
Includes radical prostatectomies (OPCS Codes M611-619) England only Source: HES 6
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Pathology
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Look at a prostate for normal histology Anterior
Posterior
Right Left
A
B
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Area A
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Area B
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Ejaculatory ducts
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Ejaculatory ducts
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Seminal vesicle
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Benign mimicking cancer
1.! Seminal / ejaculatory duct epithelium
2.! Basal cell hyperplasia
3.! Clear cell adenosis (variants)
4.! Atrophy
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Seminal vesicle / ejaculatory duct
•!Lipofuscin granules
•!Nuclear pleomorphism
•!Tufting of cytoplasm
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Basal cell hyperplasia •!Dark staining
cytoplasm
•!Antler shaped glands with little cytoplasm
•!High molecular weight keratin positive
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Clear cell adenosis •!Various
entities described
•!Clear cytoplasm with small nuclei
•!Crowded glands
•!Report as atypical but not HG PIN
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Clear cell adenosis – 34Beta
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Atrophy
•!Pale cytoplasm
•!Dilated glands
•!Occasional small nucleoli
•!Loss of basal layer
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Atrophy contd.
Small nucleoli
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Atrophy – 34Beta
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Multidisciplinary team meeting
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Patient A
•! 48 year man, asymptomatic. No comorbidity
•!PSA 4.1 ng/ml
•!TRUSS guided biopsies
- 4/8 biopsies show high grade
intraepithelial neoplasia
•!Significance?
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High grade prostatic intraepithelial neoplasia (HG PIN)
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HG PIN
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HG PIN
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•! 55yr old, asymptomatic. No comorbidity
•!PSA 7.5 ng/ml
•!TRUSS guided biopsies
- 1/8 biopsies show a few acini with
well differentiated cancer
•!Significance?
•!What next?
Patient B
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Small volume on core
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High molecular weight cytokeratin (34BetaE12)
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34BetaE12
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Interpreting immunohistochemistry
•!At the periphery of benign nodules loose staining
•!Attenuated in PIN and benign nodules
•!Negative gland surrounded by strongly positive glands is very suspicious
•! Reference: Cytokeratin 34BetaE-12 immunoreactivity in benign
prostatic acini. Goldstein et al, Am J Clin Pathol 1999;112:69-74
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Patient C
•! 59 year old, asymptomatic. No comorbidity
•!PSA 7.1 ng/ml
•!TRUSS guided biopsies
- Gleason 7 adenocarcinoma
in 3/8 biopsies, all on right side
•!Management?
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Gleason Score
•!Based on architecture
•!Nomogram devised by Gleason in 1975
•!Two grades
•!First number is predominant pattern
•!Second number is next commonest
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Gleason score
grade 3 + grade 4
= GLEASON SCORE 7
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Tips to grading 1 – Jelly bean grading
•!Grade 1 – Jelly bean crosssection
– NEVER in core
•!Grade 2 – Jelly bean – rarely in core
•!Grade 3 – Bent jelly bean – commonest
•!Grade 4 – Melted jelly bean (gland fusion)
•!Grade 5 – Blended jelly bean (single cells)
or small cell (often PSA -ve)
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Tips to grading 2
•!Start at Gleason grade 3 and go up or down
•!If only one pattern – double it
•!If any high grade area put in score
•!NEVER GRADE IN HORMONE TREATED
•!If a score of 4 or below is reported needs review (only acceptable in TURPs)
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Major pitfalls
•!Cribriform Gleason grade 3 versus glandular fusion in grade 4
Reference: Current diagnostic pathology
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Minimum dataset RIGHT (+ RIGHT APEX)* Cores:
Number of cores involved: (Apex is positive / negative)*
Total percentage of tumour:
Adenocarcinoma Gleason score=……+……=
! Perineural invasion yes no
Extraprostatic invasion yes no not assessable
Seminal vesicle invasion yes no not assessable
Vascular invasion yes no
!
LEFT (+ LEFT APEX)* Cores: [as above]
CONCLUSION
! Prostatic adenocarcinoma
! Type of tumour : microacinar other(state)
!OVERALL GLEASON SCORE: ………+………=………
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Volume in cores
•!Shown to reflect stage in radical prostatectomy (ref: Grossklaus J Urol 2002)
•!Large volume in core = more advanced stage
•!BUT converse is not true.
•!Several methods
•!Number of cores involved
•!Length in mm
•!% of each core
•!% of total cores
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Extracapsular invasion
•!Tumour in fat
•!Tumour in Ganglion
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•! 58 year old, asymptomatic. No comorbidity
•!PSA 8.2 ng/ml
•!TRUSS guided biopsies
- 3/6 show Gleason 7 adenocarcinoma
•!Underwent radical prostatectomy
•!Lymph nodes clear. Capsular penetration
at base on right. Perineural infiltration
•!Further management?
Patient D
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Radical prostatectomy cut up
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Apex and Base
•!Shave or perpendicular?
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Seminal vesicles
•!Various techniques
•!Vertical cut
•!Embed in total
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Whole mounts
•!Advantages
•!Orientation
•!Less blocks / slides
•!Easier to demonstrate
•!Disadvantages
•!Technically difficult (esp. immuno)
•!Storage
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Whole mount
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Extracapsular extension
Ganglion with perineural invasion
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Surgical margins
•!Intracapsular positive – the surgical margin is inside the prostate and tumour is present at this margin.
•!Extracapsular positive – the surgical margin is outside the prostate but tumour has breached the capsule and extends to this margin.
•!Apex positive – tumour is present at the apical margin
•!Base positive - tumour is present at the base margin
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Surgical margins Base
Apex
Circumferential
(intra or extraprostatic)
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Intraprostatic positive (pT2+)
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Volume calculation - estimate
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Volume calculation
•!Width x Length x thickness of block
•!…ml = ….cm x ….cm x 0.5cm
Maximum length
•! Either width or length
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Minimum dataset PSA (if known) :
Weight (g) :
Tumour present (Yes/No) :
Urothelium (Normal/Other) :
Type of tumour (microacinar, ductal, other) :
Number of Foci (1,2,3,4+) :
SITE of TUMOUR – Largest :
2nd :
MAXIMUM LENGTH (mm) :
TOTAL VOLUME (ml) :
High Grade PIN (Yes/No) :
PERINEURAL INVASION (Yes/No) :
VASCULAR INVASION (Yes/No) :
CAPSULAR BREACH (Yes/No) :
EXTRAPROSTATIC SURGICAL MARGIN : Positive Negative
INTRAPROSTATIC SURGICAL MARGIN : Positive Negative
APEX MARGIN : Positive Negative
BASE MARGIN : Positive Negative
SEMINAL VESICLES : Positive(R) Positive(L) Negative
Lymph Nodes : Yes (R) (L) None
OVERALL GLEASON SCORE : + =
STAGE : pT N
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Stage
Stages (2002 – TNM):
pT2 confined
pT2a one lobe
pT2b more than half one lobe
pT2c both lobes
pT2+ +ve intraprostatic margin
pT3 extracapsular
pT3a extracapsular,
pT3b seminal vesicle
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Stage
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Takehome message
•!Never Gleason score below 5
•!Recognise Grade 4 fusion as clinically affects management
•!Spot extracapsular invasion on cores
•!Use 34BetaE12 with a low threshold
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References •! Cytokeratin 34BetaE-12 immunoreactivity in benign prostatic acini. Goldstein et
al, Am J Clin Pathol 1999;112:69-74
•! Percent of cancer in the biopsy set predicts pathological findings after prostatectomy. Grossklaus et al, J Urol 2002;167:2032-2036
•! Gleason scores of prostate biopsy and radical prostatectomy specimens over
the past 10 years. Smith et al, Cancer 2002;94:2282-7
•! The pathological interpretation and significance prostate needle biopsy findings: implications and current controversies. Epstein & Potter, J Urol 2001;166:402-410
•! Problems in grading and staging prostatic carcinoma. McWilliam et al, Curr Diag Path 2002;8:65-75
•! The 2005 International Society of Urological disease (ISUP) Consensus
conference on Gleason grading of prostatic carcinoma. Epstein et al. Am J Surg Pathol 2005 29:1228-1242
•! What’s new in prostate cancer disease assessment in 2006? J Epstein Curr Opin
Urol 16:146-151
•! Andriole GL, Crawford ED, Grubb RL III, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009;360:1310-1319.
•! Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009;360:1320-1328.
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Slide seminar •!Study the pictures and complete the answer
sheet.
•!We will examine the interobserver variation when we review the answers – so please complete on your own.
•!Useful reference:
Problems in grading and staging prostatic carcinoma.
McWilliam et al, Curr Diag Path 2002;8:65-75
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Case 1 Gleason grading
•!Gleason grade this area
PSA
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Case 2 •!Gleason grade this area
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Case 3 •!Gleason grade this area
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Case 4 •!Gleason grade this area
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Case 5 •!Gleason grade this area
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Case 6 •!Gleason grade this area
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Case 7 •!What feature should you comment on?
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Case 8
•!Benign or malignant?
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Case 8 contd.
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Case 9 •!Estimate the volume (%core)
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Case 9 – contd. •!Measure or field?
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Case 10 •!Estimate the volume (% of core)
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Case 11
•!What feature should you comment on?
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Case 12
•!Gleason grade this area?
LP34
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Case 13 •!Benign or malignant?
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Case 14
•!Benign or malignant?
Note mitosis
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Case 14 – 34beta immuno
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Case 15
•!Benign or malignant?
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Case 15 – 34beta immuno
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Case 16 •!Benign or malignant?
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Case 17 •!Benign or malignant?
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Case 17 – 34beta immuno
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Case 18 •!Benign or malignant?
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Case 18 – 34beta immuno
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Case 19
•!Benign or malignant?
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Case 19 – 34beta immuno
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Case 20 – Bonus case!! •!Large renal clear cell carcinoma Fuhrman
grade 4 with renal vein invasion.
•!Adrenal gland- ?diagnosis
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Case 20 contd
Vimentin
Synaptophysin
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Answer sheet
1 Gl. grade 5 11 Extracapsular
2 Gl. grade 3 12 Gl. grade 2
3 Cribriform
Gl.grade 3
13 Gl. grade 2
4 Gl. grade 2 or 3 14 Basal hyperplasia
5 Gl. grade 3 15 Suspicious/HG PIN
6 Gl. Grade 4 16 Malignant
7 Perineural 17 Gl. grade 2 or 3
8 HG PIN 18 Suspicious
9 33% 19 Basal hyperplasia
10 66% 20 Normal adrenal