diseases of the prostate - 2009erspc 2009 and plco •!erspc - >160,000 men – 20% risk...
TRANSCRIPT
Diseases of the Prostate
Dr Jon Oxley
Southmead Hospital, Bristol
13th May 2009
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
Incidence of prostate cancer
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)
Age related incidence
Crude Incidence Rates 2002
Source: ONS, WCISU
Why has incidence increased?
•!PSA testing
•!Better reporting
•!Biopsy rate increasing
•!Greater patient awareness
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
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
Treatment options
Radical prostatectomy (open,laparoscopic,robotic)
Radiotherapy – including brachiotherapy +/- HDR boost
Active monitoring
Hormones
HIFU
Cryotherapy
Screening for prostate cancer
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
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
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
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
Prostatectomies by Age Band and Year
Includes radical prostatectomies (OPCS Codes M611-619) England only Source: HES 6
Pathology
Look at a prostate for normal histology Anterior
Posterior
Right Left
A
B
Area A
Area B
Ejaculatory ducts
Ejaculatory ducts
Seminal vesicle
Benign mimicking cancer
1.! Seminal / ejaculatory duct epithelium
2.! Basal cell hyperplasia
3.! Clear cell adenosis (variants)
4.! Atrophy
Seminal vesicle / ejaculatory duct
•!Lipofuscin granules
•!Nuclear pleomorphism
•!Tufting of cytoplasm
Basal cell hyperplasia •!Dark staining
cytoplasm
•!Antler shaped glands with little cytoplasm
•!High molecular weight keratin positive
Clear cell adenosis •!Various
entities described
•!Clear cytoplasm with small nuclei
•!Crowded glands
•!Report as atypical but not HG PIN
Clear cell adenosis – 34Beta
Atrophy
•!Pale cytoplasm
•!Dilated glands
•!Occasional small nucleoli
•!Loss of basal layer
Atrophy contd.
Small nucleoli
Atrophy – 34Beta
Multidisciplinary team meeting
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?
High grade prostatic intraepithelial neoplasia (HG PIN)
HG PIN
HG PIN
•! 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
Small volume on core
High molecular weight cytokeratin (34BetaE12)
34BetaE12
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
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?
Gleason Score
•!Based on architecture
•!Nomogram devised by Gleason in 1975
•!Two grades
•!First number is predominant pattern
•!Second number is next commonest
Gleason score
grade 3 + grade 4
= GLEASON SCORE 7
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)
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)
Major pitfalls
•!Cribriform Gleason grade 3 versus glandular fusion in grade 4
Reference: Current diagnostic pathology
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: ………+………=………
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
Extracapsular invasion
•!Tumour in fat
•!Tumour in Ganglion
•! 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
Radical prostatectomy cut up
Apex and Base
•!Shave or perpendicular?
Seminal vesicles
•!Various techniques
•!Vertical cut
•!Embed in total
Whole mounts
•!Advantages
•!Orientation
•!Less blocks / slides
•!Easier to demonstrate
•!Disadvantages
•!Technically difficult (esp. immuno)
•!Storage
Whole mount
Extracapsular extension
Ganglion with perineural invasion
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
Surgical margins Base
Apex
Circumferential
(intra or extraprostatic)
Intraprostatic positive (pT2+)
Volume calculation - estimate
Volume calculation
•!Width x Length x thickness of block
•!…ml = ….cm x ….cm x 0.5cm
Maximum length
•! Either width or length
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
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
Stage
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
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.
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
Case 1 Gleason grading
•!Gleason grade this area
PSA
Case 2 •!Gleason grade this area
Case 3 •!Gleason grade this area
Case 4 •!Gleason grade this area
Case 5 •!Gleason grade this area
Case 6 •!Gleason grade this area
Case 7 •!What feature should you comment on?
Case 8
•!Benign or malignant?
Case 8 contd.
Case 9 •!Estimate the volume (%core)
Case 9 – contd. •!Measure or field?
Case 10 •!Estimate the volume (% of core)
Case 11
•!What feature should you comment on?
Case 12
•!Gleason grade this area?
LP34
Case 13 •!Benign or malignant?
Case 14
•!Benign or malignant?
Note mitosis
Case 14 – 34beta immuno
Case 15
•!Benign or malignant?
Case 15 – 34beta immuno
Case 16 •!Benign or malignant?
Case 17 •!Benign or malignant?
Case 17 – 34beta immuno
Case 18 •!Benign or malignant?
Case 18 – 34beta immuno
Case 19
•!Benign or malignant?
Case 19 – 34beta immuno
Case 20 – Bonus case!! •!Large renal clear cell carcinoma Fuhrman
grade 4 with renal vein invasion.
•!Adrenal gland- ?diagnosis
Case 20 contd
Vimentin
Synaptophysin
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