Difference between revisions of "Prostate gland"

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The '''prostate''' adds juice to the sperm.  In old men it creates lotsa problems... nodular hyperplasia (commonly called BPH or benign prostatic hypertrophy) and cancer (adenocarcinoma).
[[Image:Prostatelead.jpg|thumb|right|200px|The prostate gland and its surrounding structures. (WC/NCI)]]
The '''prostate gland''' adds juice to the sperm.  In old men it creates a lot of problems... [[nodular hyperplasia]] (commonly called BPH or [[benign prostatic hyperplasia]]) and cancer (usually adenocarcinoma).


==Normal==  
[[Prostate cancer]] is such a big topic it is dealt with in its own article. 
===Prostate===
 
The female homologue of the prostate gland is considered to be Skene's gland.<ref name=pmid8522254>{{Cite journal  | last1 = Dodson | first1 = MK. | last2 = Cliby | first2 = WA. | last3 = Pettavel | first3 = PP. | last4 = Keeney | first4 = GL. | last5 = Podratz | first5 = KC. | title = Female urethral adenocarcinoma: evidence for more than one tissue of origin? | journal = Gynecol Oncol | volume = 59 | issue = 3 | pages = 352-7 | month = Dec | year = 1995 | doi = 10.1006/gyno.1995.9963 | PMID = 8522254 }}</ref>
 
=Normal prostate gland=
==Anatomy==
Divided into three zones:<ref name=pmid2456702>{{Cite journal  | last1 = McNeal | first1 = JE. | title = Normal histology of the prostate. | journal = Am J Surg Pathol | volume = 12 | issue = 8 | pages = 619-33 | month = Aug | year = 1988 | doi =  | PMID = 2456702 }}
</ref>
#Peripheral zone - posterior aspect, palpable with digit.
#*Classic location for [[prostate cancer|cancer]].
#Central zone - considered resistant to disease.
#Transition zone - usual location for [[nodular hyperplasia of the prostate|nodular hyperplasia]].
 
==Histology==
*Glands have two cell layers (similar to glands in breast).
*Glands have two cell layers (similar to glands in breast).
**Second cell layer may be difficult to see (like in breast).
**Second cell layer may be difficult to see (like in breast).
*Epithelium in glands fold.
*Epithelium in glands is "folded" or "tufted".
**Very important - helps on differentiate from Gleason pattern 3.
**Very important - helps to differentiate from Gleason pattern 3.
*Luminal epithelium often clear.
*Luminal epithelium often clear cytoplasm.
*Single nucleus.
*Single nucleus.
Negatives:
*No nucleoli present (if you see nuclei think: cancer, HGPIN, reactive changes, basal cell hyperplasia).
*No mitoses - these are uncommon... even in high grade prostate cancer.


Benign normal:
Benign normal:
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**These should be differentiated from ''eosinophilic proteinaceous debris'' - which is associated with cancer.
**These should be differentiated from ''eosinophilic proteinaceous debris'' - which is associated with cancer.


Male accessory glands:
Negatives:
*Mucinous glands at the apex of the prostate = ''Cowper's gland'' (AKA ''bulbourethral gland''), resemble (mucinous) [[salivary gland]]s.<ref>PR. September 2009.</ref>
*No nucleoli present (if you see nuclei think: cancer, HGPIN, reactive changes, basal cell hyperplasia).
*No mitoses - these are uncommon... even in high grade prostate cancer.
 
Notes:
*Tufted epithelium is a strong indicator of benignancy; however two uncommon prostate cancer variants typically have tufted epithelium:
**[[Pseudohyperplastic adenocarcinoma]].
**[[Foamy gland carcinoma]].
 
====Images====
<gallery>  
Image:Corpora_amylacea_low_mag.jpg | Benign prostate with corpora amylacea - low mag. (WC/Nephron)
Image:Corpora_amylacea_high_mag.jpg | Benign prostate with corpora amylacea - high mag. (WC/Nephron)
</gallery>


====IHC of normal prostate====
==IHC of normal prostate==
Normal prostate:  
Normal prostate:  
*AMACR-, p63+, HMWCK+, PSA+, PSAP+.
*[[AMACR]] -ve (mark epithelial cells).
*[[CK5/6]] +ve,<ref name=pmid19605815>{{Cite journal  | last1 = Trpkov | first1 = K. | last2 = Bartczak-McKay | first2 = J. | last3 = Yilmaz | first3 = A. | title = Usefulness of cytokeratin 5/6 and AMACR applied as double sequential immunostains for diagnostic assessment of problematic prostate specimens. | journal = Am J Clin Pathol | volume = 132 | issue = 2 | pages = 211-20; quiz 307 | month = Aug | year = 2009 | doi = 10.1309/AJCPGFJP83IXZEUR | PMID = 19605815 }}</ref> p63 +ve, HMWCK +ve (mark basal cells).
*PSA ([[prostate-specific antigen]]) +ve, PSAP ([[prostatic-specific acid phosphatase]]) +ve.
 
==Sign out==
===Staining slightly abnormal - morphology not definitely abnormal===
<pre>
COMMENT:
Very focal AMACR staining is seen; this is interpreted as negative, in the
context of no definite cytologic changes.  The basal cells appear to be
preserved in all of the tissue sampled.
</pre>


===Seminal vesicles===
===Compatible with previous biopsy===
*Leaf-like architecture - epithelial component clustered closely, looks like it connects.
<pre>
**Epithelium surrounded by a thick layer of muscle (>10 cells across ~80 microns).
COMMENT:
*Lipofuscin (coarse cytoplasmic yellow granules approximately 1-2 micrometers).
Siderophages are seen in several cores; this is compatible with the history
*Nucleoli - common.
of a previous biopsy.
</pre>


Images:
=Other accessory glands=
*[http://dspace.udel.edu:8080/dspace/bitstream/19716/2016/1/cmrsvlm3.GIF SV (udel.edu)].
==Bulbourethral gland==
*[[AKA]] ''Cowper's gland''.
{{Main|Bulbourethral gland}}
 
==Seminal vesicles==
{{Main|Seminal vesicles}}
 
=Specimens=
*[[Prostate core biopsy]] - done transrectal.
*[[Prostate chips]] (from a ''transurethral resection of the prostate'', abbreviated ''TURP'') - usu. done for [[nodular hyperplasia of the prostate gland]]; may be done in the context of obstructing cancer.
*[[Radical prostatectomy]] - includes the [[seminal vesicles]].
*[[Radical cystoprostatectomy]] - includes the [[urinary bladder]] and [[seminal vesicles]].<ref>URL: [http://www.cancer.gov/dictionary?cdrid=446218 http://www.cancer.gov/dictionary?cdrid=446218]. Accessed on: 23 February 2012.</ref>
 
=Approach=
*Know the common diagnoses well.
*Core biopsies - scan the slides with the 10x objective.


==Common diagnoses==
==Common diagnoses==
*Benign.
*Benign.
**Atrophy (may be resemble adenocarcinoma).
**[[Atrophy of the prostate|Atrophy]] - may resemble adenocarcinoma - typically not reported.
*Prostate adenocarcinoma.  
**[[Adenosis of the prostate|Adenosis]] - may resemble adenocarcinoma - typically not reported.
**Most common Grade is 3+3=6.
*[[Prostate adenocarcinoma]].  
*HGPIN (high-grade prostatic intraepithelial neoplasia).
*[[HGPIN]] (high-grade prostatic intraepithelial neoplasia) - prostate adenocarcinoma precursor lesion.
*ASAP (atypical small acinar proliferation) - used if you have a few abnormal appearing glands... but can't decide between prostate adenocarcinoma & benign.
*[[ASAP]] (atypical small acinar proliferation) - used if you have a few abnormal appearing glands... but can't decide between prostate adenocarcinoma & benign.
*Chronic inflammation.
*Chronic inflammation.
*Acute inflammation - can result in an elevated PSA and may have prompted the biopsy you're looking at.
*Acute inflammation - can result in an elevated PSA and may have prompted the biopsy you're looking at.
*Nodular hyperplasia of the prostate; AKA ''benign prostatic hypertrophy'' (BPH).
*[[Nodular hyperplasia of the prostate]]; [[AKA]] ''benign prostatic hypertrophy'' (BPH).
**Not diagnosed on needle biopsies.
**Not diagnosed on needle biopsies.
**''BPH'' is technically incorrect -- the process is a hyperplasia.
**''BPH'' is technically incorrect -- the process is a hyperplasia.
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****How to remember? A. '''P'''rostate... hyper'''P'''lasia.
****How to remember? A. '''P'''rostate... hyper'''P'''lasia.


==Cancer==
=Clinical history=
===Criteria as a list===
{{Main|Prostate specific antigen}}
Major criteria (the ABCs of prostate pathology):<ref name=pmid17213347>{{cite journal |author=Humphrey PA |title=Diagnosis of adenocarcinoma in prostate needle biopsy tissue |journal=J. Clin. Pathol. |volume=60 |issue=1 |pages=35–42 |year=2007 |month=January |pmid=17213347 |pmc=1860598 |doi=10.1136/jcp.2005.036442 |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860598/?tool=pubmed}}</ref>
*[[PSA]] (serum).
#Architecture - "infiltrative growth" pattern.
** >10 ng/mL worrisome for prostate cancer.
#Basal cells lacking.
** Normal is age dependent - increases with age, usu. cut-off ~ 4 ng/mL.
#Cytological abnormalities:
*HIFU = ''High Intensity Focused Ultrasound'' - an ablation procedure for prostate cancer.<ref>URL: [http://www.internationalhifu.com/what-is-hifu-mainmenu-132.html http://www.internationalhifu.com/what-is-hifu-mainmenu-132.html]. Accessed on: 15 June 2010.</ref>
#*Nuclear enlargement.
#*Nucleoli.


Minor criteria:<ref name=pmid17213347/>
=Benign changes and remnants=
#Nuclear hyperchromasia.
==Adenosis of the prostate gland==
#Wispy blue mucin.
*[[AKA]] ''atypical adenomatous hyperplasia of the prostate gland'' (or ''atypical adenomatous hyperplasia'').
#*Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f3.html#figure-title Wispy blue mucin (nature.com)] - from Epstein.<ref name=pmid14739905>{{cite journal |author=Epstein JI |title=Diagnosis and reporting of limited adenocarcinoma of the prostate on needle biopsy |journal=Mod. Pathol. |volume=17 |issue=3 |pages=307–15 |year=2004 |month=March |pmid=14739905 |doi=10.1038/modpathol.3800050 |url=http://www.nature.com/modpathol/journal/v17/n3/full/3800050a.html}}</ref>
{{Main|Adenosis of the prostate gland}}
#Pink amorphous secretions.
#*Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f11.html Pink amorphous secretions (nature.com)] - from Epstein.<ref name=pmid14739905>{{cite journal |author=Epstein JI |title=Diagnosis and reporting of limited adenocarcinoma of the prostate on needle biopsy |journal=Mod. Pathol. |volume=17 |issue=3 |pages=307–15 |year=2004 |month=March |pmid=14739905 |doi=10.1038/modpathol.3800050 |url=http://www.nature.com/modpathol/journal/v17/n3/full/3800050a.html}}</ref>
#Intraluminal crystalloid.
#*Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f4.html#figure-title Intraluminal crystalloid (nature.com)] - from Epstein.<ref name=pmid14739905/>
#Amphophilic cytoplasm.
#*Amphopilic is said to be ''bluish-red''<ref>URL: [http://pancreaticcancer2000.com/page1.htm http://pancreaticcancer2000.com/page1.htm]. Accessed on: 3 June 2010.</ref> -- though might also be described as ''blue-grey''.  
#**Image: [http://www.webpathology.com/image.asp?n=4&Case=20 Amphophilic cytoplasm is prostate carcinoma].
#Adjacent HGPIN.
#Mitoses - quite rare.


===Low power features===
==Basal cell hyperplasia of the prostate==
*Architecture is the '''key''' to diagnosing low grade cancer.
{{Main|Basal cell hyperplasia of the prostate}}
**Back-to-back glands or crowding of glands -- think low grade cancer (Gleason pattern 3).
**Sharp transition between gland border and lumen.
***Loss of epithelial folding at the epithelium-gland lumen interface - "punched-out" appearance.
**Eosinophilic debris within the gland lumen (pink amorphous secretions, intraluminal crystalloid).
**Blue-tinged acellular material within the gland lumen (mucin) -- uncommon.
**"Infiltrative": small round/oval (malignant) glands (approx. 5 cells across) interspersed with larger (benign) glands that are 2-3 times larger.


===High power features===
==Atrophy of the prostate==
*Nuclei.  
*[[AKA]] ''atrophy''.
**Hyperchromatic nuclei (like in HGPIN).
*[[AKA]] ''prostatic atrophy''.
**Nuclear enlargement.
*[[AKA]] ''atrophy of the prostate gland''.
***Difficult to appreciate (if cancer isn't side-by-side with normal prostate).
{{Main|Atrophy of the prostate gland}}
***Difficult to see if not on high power.
*Nucleoli visible on high power (200x or 100X)
**May be difficult to see - especially if light intensity is low.
***One should not use 400x to look for nucleoli (it is a waste of time + you risk overcalling something benign).
**If I see three good nucleoli in a gland I'm usually confident it is cancer.
*Loss of basal cells - diagnostic feature.
**Like in breast pathology (where one looks for loss of myoepithelial cells) - this may be difficult to see.


Notes:
==Mesonephric remnant of the prostate gland==
*Mitoses are not a common feature - don't waste time looking for them.
{{Main|Mesonephric remnant of the prostate gland}}


===IHC===
=Benign conditions=
*AMACR +ve, p63 -ve, HMWCK (34betaE12) -ve .
==Prostatic nodular hyperplasia==
*Usually positive: PSA, PSAP.
*[[AKA]] ''nodular hyperplasia of the prostate''.
*AKA ''benign prostatic hyperplasia'' (abbreviated BPH).
*AKA ''benign prostatic hypertrophy''.
**This is a misnomer. It is ''not'' a hypertrophy.
{{Main|Nodular hyperplasia of the prostate}}


===Mimics===
==Acute inflammation of the prostate gland==
Mimics of prostate adenocarcinoma:<ref>TPOSP. PP.100-3.</ref>
{{ Infobox external links
{| class="wikitable"
| Name          = {{PAGENAME}}
| '''Entity'''
| EHVSC          = 10176
| '''Key feature'''
| pathprotocols  =
| '''Detailed microscopic'''
| wikipedia      =
| '''Other'''
| pathoutlines  =
| '''Image'''
}}
|-
*[[AKA]] ''prostate gland with acute inflammation''.
| Adenosis
===General===
| gradual transition between normal & small gland (NOT two populations)
*A may lead to an increase in the PSA and prompt biopsy.
| many small glands, lack nuclear size variation, basal layer present
| nucleoli may be present; may need to do p63 or 34betaE12 to find basal layer
| '''Image'''
|-
| Sclerosing adenosis
| gradual transition between normal & small gland (NOT two populations), fibrosis
| many small glands, lack nuclear size variation, basal layer present
| analogous to sclerosing adenosis of breast (???)
| '''Image'''
|-
| Atropy
| scant cytoplasm
| nuclear hyperchromasia
| may appear right beside non-atrophic tissue
| '''Image'''
|-
| Basal cell hyperplasia
| two distinct cell populations (in epithelial component)
| abundant epithelial cells; nucleoli in pale ('blue') nuclei of basal cells, glandular cell nuclei darker ('purple')
| vaguely similar to epithelial hyperplasia of usual type (EHUT) in breast
| '''Image'''
|-
| Bulbourethral gland
| no nuclear atypia
| clear cytoplasm
| apex of prostate
| '''Image'''
|-
| Seminal vesicles
| lipofuscin (yellow granular material in cytoplasm)
| fern-like arrangement of epithelium, nucleoli, surrounded by muscle
| involvement by cancer changes staging
| '''Image'''
|-
| Radiation exposure
| marked nuclear size variation
| lack nucleoli ???
| history of Rx; uniform nuc. size with Hx of Rx should raise susp. of cancer
| '''Image'''
|-
| Prostatitis
| inflammatory cells (lymphocytes, plasma cells, PMNs)
| no nuclear atypia, normal gland arch.
| clinical mimic of cancer (elevated PSA); usu. not a problem for the pathologist
| '''Image'''
|}
Memory device: '''AAABBRS''' = atropy, adenosis, adenosis (sclerosing), basal cell hyperplasia, bulbourethral gland, seminal vescicles, radiation.


===Grading===
Note:
There is only one grading system that any one talks about...
*"[[Prostatitis]]" is considered a clinical diagnosis.
**Cases are signed out as "acute inflammation".
***Some pathologists do not comment on the presence (or absence) of inflammation.  


====Gleason grading system====
===Microscopic===
*Score range: 2-10.
Features:
*Reported as on biopsy as: (primary pattern) + (secondary pattern ''or'' tertiary pattern with the highest grade) = sum.
*[[Neutrophil]]s within the glands, between the epithelial cells ''or'' within the stroma - '''key feature'''.
**e.g. ''Gleason grade 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.
*+/-Chronic inflammation (lymphocytes) within the surrounding stroma.
*Reported as on prostatectomies as: (primary pattern) + (secondary pattern) = sum, (tertiary pattern)


*Tertiary Gleason pattern - definition: a pattern that is seen in than 5% of the tumour (volume), that is higher grade than the two dominant patterns.<ref>GUP P.72.</ref>
DDx:
**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).<ref>GUP P.72.</ref>
*[[Prostatic infarction]].


Examples:
====Image====
*A biopsy has 80% pattern 4, 15.1% pattern 3 and 4.9% pattern 5... it would be reported as: 4+5=9.
<gallery>
*A prostatectomy has 80% pattern 4, 15.1% pattern 3 and 4.9% pattern 5... it would be reported as: 4+3=7 with tertiary pattern 5.
Image:Acute_inflammation_of_prostate.jpg| Prostate with acute inflammation. (WC/Nephron)
</gallery>
===Sign out===
<pre>
G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE;
- FOCAL ACUTE INFLAMMATION.  
</pre>


====Gleason pattern 1 & 2====
<pre>
*Academic thing - you can forget about 'em.
G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE;
- FOCAL ACUTE AND CHRONIC INFLAMMATION.  
</pre>


====Gleason pattern 3====
==Chronic inflammation not otherwise specified==
*Glands smaller than normal prostate glands + loss of epithelial folding.
===General===
*Can draw a line around each gland.
*Common.
*Non-specific finding.
*Etiology usually not apparent on histomorphology.
 
===Microscopic===
Features:
*Lymphocytes within the glands, between the epithelial cells ''or'' within the stroma - '''key feature'''.


Notes:
Notes:
*All ''cribriform'' is now classified as Gleason pattern 4.<ref name=pmid20006878>{{cite journal |author=Epstein JI |title=An update of the Gleason grading system |journal=J. Urol. |volume=183 |issue=2 |pages=433–40 |year=2010 |month=February |pmid=20006878 |doi=10.1016/j.juro.2009.10.046 |url=}}</ref>
*Rare scattered lymphocytes are common, especially in the central portion of the gland.
*"Focal" one field with a 2.2 mm diameter involved.


====Gleason pattern 4====
====Image====
*Loss of gland lumina.
<gallery>
*Gland fusion.
Image:Inflammation_of_prostate.jpg | Prostate with chronic inflammation. (WC/Nephron)
*Benign looking cords ('hypernephroid pattern').
</gallery>
*Cribriform.
===Sign out===
*One gland is not enough to call Gleason 4.
<pre>
G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE;
- FOCAL CHRONIC INFLAMMATION.  
</pre>


====Gleason pattern 5====
<pre>
*Sheets.
F. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
**Must be differentiated from intraductal growth (which like in the breast are well circumscribed nests).
- BENIGN PROSTATE TISSUE;
*Single cells.
- CHRONIC INFLAMMATION.  
**May be confused with stromal/lymphocytic infiltration.
</pre>
***Look for nucleoli, cells should be round (prostatic stroma cells are spindle cells).
*Cords.
*Nests of cells with necrosis at centre.


Testing yourself:
Note:
*There is a nice test-yourself quiz from Johns Hopkins: [http://162.129.103.34/prostate/ http://162.129.103.34/prostate/].
*Opinion is divided on whether this finding should be reported.
**It was studied in a paper by Kronz et al..<ref name=pmid11014569>{{Cite journal  | last1 = Kronz | first1 = JD. | last2 = Silberman | first2 = MA. | last3 = Allsbrook | first3 = WC. | last4 = Bastacky | first4 = SI. | last5 = Burks | first5 = RT. | last6 = Cina | first6 = SJ. | last7 = Mills | first7 = SE. | last8 = Ross | first8 = JS. | last9 = Sakr | first9 = WA. | last10 = Tomaszewski | first10 = JE. | last11 = True | first11 = LD. | last12 = Ulbright | first12 = TM. | last13 = Weinstein | first13 = MW. | last14 = Yantiss | first14 = RK. | last15 = Young | first15 = RH. | last16 = Epstein | first16 = JI. | title = Pathology residents' use of a Web-based tutorial to improve Gleason grading of prostate carcinoma on needle biopsies. | journal = Hum Pathol | volume = 31 | issue = 9 | pages = 1044-50 | month = Sep | year = 2000 | doi = 10.1053/hupa.2000.16278 | PMID = 11014569 }}</ref>
**Advocates for reporting inflammation say "[i]t is just reporting what you see and may explain the bump in PSA."
**Naysayers opine that "[i]t may provide false assurance that no cancer is present."


===Management===
==Granulomatous prostatitis==
The management changes between Gleason 6, 7 & 8; typically, the implications are:
{{Main|Granulomatous prostatitis}}
* Gleason 6: watchful waiting or radioactive seeds, surgery if patient wants.
* Gleason 7: do something.
* Gleason 8+: bad cancer - do something quickly!


Bottom line: You want to be sure when you call something Gleason pattern 4.
==Prostatic infarct==
 
*[[AKA]] ''prostatic [[infarction]]''.
Note:
===General===
*The usual caveats apply to the above; if the patient is moribund-- nothing is done, if the patient refuses treatment... nothing is done et cetera.
*Rare < 0.1% of core biopsies.<ref name=pmid11023099>{{Cite journal  | last1 = Milord | first1 = RA. | last2 = Kahane | first2 = H. | last3 = Epstein | first3 = JI. | title = Infarct of the prostate gland: experience on needle biopsy specimens. | journal = Am J Surg Pathol | volume = 24 | issue = 10 | pages = 1378-84 | month = Oct | year = 2000 | doi = | PMID = 11023099 }}</ref>
===Margins + Extension===
*Can mimic cancer - [[urothelial carcinoma]].<ref name=pmid11023099/>
Definitions:
*Prostate usually large.
*Extraprostatic extension (EPE) is difficult to assess (in prostatectomy specimens) as there is no consensus definition.
**The prostate does NOT have a well defined capsule.
***Intraobserver agreement for EPE is fair-moderate and lower than for the surgical margin.<ref name=pmid18708939>{{Cite journal  | last1 = Evans | first1 = AJ. | last2 = Henry | first2 = PC. | last3 = Van der Kwast | first3 = TH. | last4 = Tkachuk | first4 = DC. | last5 = Watson | first5 = K. | last6 = Lockwood | first6 = GA. | last7 = Fleshner | first7 = NE. | last8 = Cheung | first8 = C. | last9 = Belanger | first9 = EC. | last10 = Amin | first10 = MB. | last11 = Boccon-Gibod | first11 = L. | last12 = Bostwick | first12 = DG. | last13 = Egevad | first13 = L. | last14 = Epstein | first14 = JI. | last15 = Grignon | first15 = DJ. | last16 = Jones | first16 = EC. | last17 = Montironi | first17 = R. | last18 = Moussa | first18 = M. | last19 = Sweet | first19 = JM. | last20 = Trpkov | first20 = K. | last21 = Wheeler | first21 = TM. | last22 = Srigley | first22 = JR. | title = Interobserver variability between expert urologic pathologists for extraprostatic extension and surgical margin status in radical prostatectomy specimens. | journal = Am J Surg Pathol | volume = 32 | issue = 10 | pages = 1503-12 | month = Oct | year = 2008 | doi = 10.1097/PAS.0b013e31817fb3a0 | PMID = 18708939 }}</ref>
*Surgical margin - where the surgeon cut.
**It is possible to have EPE without a positive margin.
**It is possible to have a positive margin without EPE.
 
Important:
*EPE cannot be called on a biopsy unless the tumour is next to adipose tissue.<ref>AE. 4 June 2010.</ref>
 
====Extraprostatic extension (EPE)====
*Prostatectomy specimens: EPE is present if there is a "significant bulge" in the contour of the prostate at low power.
*Prostate biopsy: EPE is present if tumour touches adipose tissue.<ref name=pmid17707261>{{Cite journal  | last1 = Epstein | first1 = JI. | last2 = Srigley | first2 = J. | last3 = Grignon | first3 = D. | last4 = Humphrey | first4 = P. | title = Recommendations for the reporting of prostate carcinoma. | journal = Hum Pathol | volume = 38 | issue = 9 | pages = 1305-9 | month = Sep | year = 2007 | doi = 10.1016/j.humpath.2007.05.015 | PMID = 17707261 }}
</ref>
**The prostate, at the apex, may have some skeletal muscle -- it is hard to define the extent... ergo no EPE at apex. (????)


===Reporting prostate cancer===
===Microscopic===
====Elements of a prostate biopsy report with cancer====
Features:
Important elements:<ref name=pmid17213347/>
*Classic findings of [[necrosis]]:
#Type of cancer, e.g. "prostatic adenocarcinoma, acinar type".
**Karyolysis (loss of nuclei), karyorrhexis (frag. of nuclei), pyknosis (small shrunken nuclei).
#Gleason score including primary and secondary pattern, e.g. "Gleason score 3+4=7".
*+/-Squamous metaplasia of prostate gland epithelium.
#Number of cores and number involved, e.g. "2/3 cores involved by cancer".
#Percent area involved, i.e. how much of the core is cancer, e.g. "75% of specimen is tumour".
#Percent area involved that is Gleason pattern 4 or 5, e.g. "25% of the tumour is Gleason pattern 4 or 5".
#Presence of perineural invasion.
#Presence of extension into fat (extraprostatic extension).


Notes:
Notes:
*"Percent area involved" may seem like an odd thing to request 'cause it is sampling dependent, i.e. if the radiologist sticks the biopsy needle deeper into the lesion more of the core is positive, but urologists think it is important -- more important than perineural invasion.<ref>{{cite journal |author=Rubin MA, Bismar TA, Curtis S, Montie JE |title=Prostate needle biopsy reporting: how are the surgical members of the Society of Urologic Oncology using pathology reports to guide treatment of prostate cancer patients? |journal=Am. J. Surg. Pathol. |volume=28 |issue=7 |pages=946–52 |year=2004 |month=July |pmid=15223967 |doi= |url=}}</ref>
*Corpora amylacea - help... call it benign.
*Glands maintain normal spacing.


====Prostatectomy specimens====
DDx:
See: [http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=/portlets/contentViewer/show&_windowLabel=cntvwrPtlt&cntvwrPtlt{actionForm.contentReference}=committees/cancer/cancer_protocols/protocols_index.html&_pageLabel=cntvwr CAP checklist].
*[[Urothelial carcinoma]] with squamous differentiation.  


==HGPIN (high grade prostatic intraepithelial neoplasia)==
Image:
*Diagnosed on basis of nuclear changes.
*[http://www.sciencephoto.com/media/258565/enlarge Prostatic thrombosis (sciencephoto.com)].
**Hyperchromatic nuclei.
**Nucleoli present.
**Often increased N/C ratio.
*Different architectures (e.g. papillary).
*Usually epithelial hyperplasia.


Note: Low grade PIN (LGPIN) is ''never'' diagnosed. It was found to be a useless diagnosis with no significant prognostic significance.
=Preneoplastic changes and atypical changes=
 
==High-grade prostatic intraepithelial neoplasia==
===HGPIN architecture===
*Abbreviated as ''HGPIN''.
There are several forms:<ref>WMSP P.380.</ref><ref>[http://www.nature.com/modpathol/journal/v17/n3/pdf/3800053a.pdf]</ref>
*May be referred to as ''prostatic intraepithelial neoplasia'', abbreviated ''PIN''.
*Flat.
{{Main|High-grade prostatic intraepithelial neoplasia}}
*Tufting.
*Micropapillary - common.
*Cribriform - rare.
 
Note: The architectural pattern is NOT thought to have any prognostic significance -- may, however, be useful for picking it out from benign prostate.
 
===Differentiating between diagnoses===
HGPIN vs. adenocarcinoma:
*Glands with HGPIN have two or more distinct cells layers.
 
HGPIN vs. normal:
*HPGIN has nuclear changes.
 
May need IHC (especially for cancer vs. HGPIN).
 
IHC patterns:
*Cancer: AMACR+, p63-, HMWCK-.
*HGPIN: AMACR+, p63+, HMWCK+.
*Normal: AMACR-, p63+, HMWCK+.
 
==Atrophy==
*Small glands (may mimic Gleason score 3 pattern).
*Glands often have a jagged edges/prows (in cancer the glands tend to have round edges).
**Prow = forward most part of a ship's bow that cuts through the water.<ref>[http://en.wikipedia.org/wiki/Prow http://en.wikipedia.org/wiki/Prow]</ref>
***You may have come across ''prow'' in the context of [[breast cancer]], i.e. ''tubular carcinoma''.
*Atrophic glands are often hyperchromatic.<ref>SN. June 3, 2009.</ref>
 
Negatives:
*Nuclei like normal.
*Should have two cell layers, i.e. epithelial and myoepithelial (may be difficult to see).
 
===Differentiating between diagnoses===
Atrophy vs. low grade cancer (Gleason pattern 3)
*Atrophy - has two distinct cells layers in the gland.
*Atrophy - has an acinar arrangement/look like they originate from one large duct.
*Cancer - glands are back-to-back and do not look like they originate from one large duct.
*Cancer - has nucleoli (atrophy does NOT).
 
==Basal cell hyperplasia==
*Atypical appearing glands - typically in transition zone.<ref>[http://pathologyoutlines.com/prostate.html#bch]</ref>
*May have nucleoli.
 
===Differentiating between diagnoses===
Basal cell hyperplasia vs. cancer[http://pathologyoutlines.com/prostate.html#bch]
*Low power gland architecture near normal.[http://www.nature.com/modpathol/journal/v16/n6/fig_tab/3880810f1.html][http://www.nature.com/modpathol/journal/v16/n6/fig_tab/3880810f2.html]
**Glands ''not'' as small as cancer.
**Folds in gland lumina.
**No hyperchromasia.
**Two cell layers (as in normal prostate glands).


==Atypical small acinar proliferation==
==Atypical small acinar proliferation==
===General===
*Abbreviated ''ASAP''.
*Abbreviated ''ASAP''.
*Can be considered to be a ''waffle'' diagnosis... like ''ASCUS'' is on the pap test.
*[[AKA]] ''suspicious for carcinoma''.<ref>THvdK. 19 June 2010.</ref>
*Should be used sparingly.
**''ASAP'' is preferred as it does not contain the word ''carcinoma'' and, thus, cannot be misread as ''carcinoma'', i.e. positive for malignancy.
*Never diagnosed on excision, i.e. prostatectomy specimen.
{{Main|Atypical small acinar proliferation}}
*Some experts consider this diagnosis bogus, i.e. some don't believe it exists.<ref>{{cite journal |author=Flury SC, Galgano MT, Mills SE, Smolkin ME, Theodorescu D |title=Atypical small acinar proliferation: biopsy artefact or distinct pathological entity |journal=BJU International |volume=99 |issue=4 |pages=780-5 |year=2007 |month=January |pmid= |doi= |url=http://www3.interscience.wiley.com/journal/118508438/abstract}}</ref>
 
===Histologic characteristics===
*Atypical appearing acini.
*Limited extent, e.g. 2-3 glands.
*IHC not contributory.
*Deeper cuts didn't yield anything.
 
===Association with adenocarcinoma===
*On subsequent [[biopsy]] - chance of finding [[adenocarcinoma]] is approximately 40%; this is higher than if there is [[high-grade prostatic intraepithelial neoplasia]] (HGPIN).<ref>{{cite journal |author=Leite KR, Camara-Lopes LH, Cury J, Dall'oglio MF, Sañudo A, Srougi M |title=Prostate cancer detection at rebiopsy after an initial benign diagnosis: results using sextant extended prostate biopsy |journal=Clinics |volume=63 |issue=3 |pages=339–42 |year=2008 |month=June |pmid=18568243 |doi= |url=http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300009&lng=en&nrm=iso&tlng=en}}</ref>
 
===Management===
*ASAP is considered an [[indication]] for re-biopsy;<ref>{{cite journal |author=Bostwick DG, Meiers I |title=Atypical small acinar proliferation in the prostate: clinical significance in 2006 |journal=Arch. Pathol. Lab. Med. |volume=130 |issue=7 |pages=952–7 |year=2006 |month=July |pmid=16831049 |doi= |url=http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=130&page=952}}</ref> in one survey of [[urologist]]s<ref>{{cite journal |author=Rubin MA, Bismar TA, Curtis S, Montie JE |title=Prostate needle biopsy reporting: how are the surgical members of the Society of Urologic Oncology using pathology reports to guide treatment of prostate cancer patients? |journal=Am. J. Surg. Pathol. |volume=28 |issue=7 |pages=946–52 |year=2004 |month=July |pmid=15223967 |doi= |url=}}</ref> 41/42 (~98%) of respondents considered it a sufficient reason to re-biopsy.


Ref.:[http://en.wikipedia.org/wiki/Atypical_small_acinar_proliferation ASAP (en.wikipedia.org)].
=Prostate cancer=
{{Main|Prostate cancer}}
This is a big topic that is dealt with in its own article.


==See also==
=See also=
*[[Urothelium]].
*[[Urothelium]].
*[[Genitourinary pathology]].
*[[Genitourinary pathology]].


==References==
=References=
{{reflist|2}}
{{reflist|2}}


==External links==
*[http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2006/prostate06_ckw.pdf CAP prostate check list] - cap.org.
*[http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2006/prostate06_ckw.pdf CAP prostate protocol] - cap.org.
*[http://162.129.103.34/prostate/ Gleason score quiz] - Johns Hopkins Prostate Center.


[[Category: Genitourinary pathology]]
[[Category: Genitourinary pathology]]

Latest revision as of 19:21, 10 February 2019

The prostate gland and its surrounding structures. (WC/NCI)

The prostate gland adds juice to the sperm. In old men it creates a lot of problems... nodular hyperplasia (commonly called BPH or benign prostatic hyperplasia) and cancer (usually adenocarcinoma).

Prostate cancer is such a big topic it is dealt with in its own article.

The female homologue of the prostate gland is considered to be Skene's gland.[1]

Normal prostate gland

Anatomy

Divided into three zones:[2]

  1. Peripheral zone - posterior aspect, palpable with digit.
  2. Central zone - considered resistant to disease.
  3. Transition zone - usual location for nodular hyperplasia.

Histology

  • Glands have two cell layers (similar to glands in breast).
    • Second cell layer may be difficult to see (like in breast).
  • Epithelium in glands is "folded" or "tufted".
    • Very important - helps to differentiate from Gleason pattern 3.
  • Luminal epithelium often clear cytoplasm.
  • Single nucleus.

Benign normal:

  • Corpora amylacea.
    • Round/ovoid-eosinophilic bodies -- with laminations (layered appearance).
    • In gland lumina.
    • Usually in benign glands - but cannot be used to exclude cancer.[3]
    • Very common.
    • These should be differentiated from eosinophilic proteinaceous debris - which is associated with cancer.

Negatives:

  • No nucleoli present (if you see nuclei think: cancer, HGPIN, reactive changes, basal cell hyperplasia).
  • No mitoses - these are uncommon... even in high grade prostate cancer.

Notes:

Images

  • Benign prostate with corpora amylacea - low mag. (WC/Nephron)

  • Benign prostate with corpora amylacea - high mag. (WC/Nephron)

IHC of normal prostate

Normal prostate:

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Staining slightly abnormal - morphology not definitely abnormal

COMMENT:
Very focal AMACR staining is seen; this is interpreted as negative, in the
context of no definite cytologic changes.  The basal cells appear to be 
preserved in all of the tissue sampled.

Compatible with previous biopsy

COMMENT:
Siderophages are seen in several cores; this is compatible with the history 
of a previous biopsy.

Other accessory glands

Bulbourethral gland

  • AKA Cowper's gland.
Main article: Bulbourethral gland

Seminal vesicles

Main article: Seminal vesicles

Specimens

Approach

  • Know the common diagnoses well.
  • Core biopsies - scan the slides with the 10x objective.

Common diagnoses

  • Benign.
    • Atrophy - may resemble adenocarcinoma - typically not reported.
    • Adenosis - may resemble adenocarcinoma - typically not reported.
  • Prostate adenocarcinoma.
  • HGPIN (high-grade prostatic intraepithelial neoplasia) - prostate adenocarcinoma precursor lesion.
  • ASAP (atypical small acinar proliferation) - used if you have a few abnormal appearing glands... but can't decide between prostate adenocarcinoma & benign.
  • Chronic inflammation.
  • Acute inflammation - can result in an elevated PSA and may have prompted the biopsy you're looking at.
  • Nodular hyperplasia of the prostate; AKA benign prostatic hypertrophy (BPH).
    • Not diagnosed on needle biopsies.
    • BPH is technically incorrect -- the process is a hyperplasia.
      • Hyperplasia = proliferation of cells, hypertrophy = enlargement of cells.
        • How to remember? A. Prostate... hyperPlasia.

Clinical history

Main article: Prostate specific antigen
  • PSA (serum).
    • >10 ng/mL worrisome for prostate cancer.
    • Normal is age dependent - increases with age, usu. cut-off ~ 4 ng/mL.
  • HIFU = High Intensity Focused Ultrasound - an ablation procedure for prostate cancer.[6]

Benign changes and remnants

Adenosis of the prostate gland

  • AKA atypical adenomatous hyperplasia of the prostate gland (or atypical adenomatous hyperplasia).
Main article: Adenosis of the prostate gland

Basal cell hyperplasia of the prostate

Main article: Basal cell hyperplasia of the prostate

Atrophy of the prostate

  • AKA atrophy.
  • AKA prostatic atrophy.
  • AKA atrophy of the prostate gland.
Main article: Atrophy of the prostate gland

Mesonephric remnant of the prostate gland

Main article: Mesonephric remnant of the prostate gland

Benign conditions

Prostatic nodular hyperplasia

  • AKA nodular hyperplasia of the prostate.
  • AKA benign prostatic hyperplasia (abbreviated BPH).
  • AKA benign prostatic hypertrophy.
    • This is a misnomer. It is not a hypertrophy.
Main article: Nodular hyperplasia of the prostate

Acute inflammation of the prostate gland

Prostate gland
External resources
EHVSC 10176
  • AKA prostate gland with acute inflammation.

General

  • A may lead to an increase in the PSA and prompt biopsy.

Note:

  • "Prostatitis" is considered a clinical diagnosis.
    • Cases are signed out as "acute inflammation".
      • Some pathologists do not comment on the presence (or absence) of inflammation.

Microscopic

Features:

  • Neutrophils within the glands, between the epithelial cells or within the stroma - key feature.
  • +/-Chronic inflammation (lymphocytes) within the surrounding stroma.

DDx:

Image

  • Prostate with acute inflammation. (WC/Nephron)

Sign out

G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE;
- FOCAL ACUTE INFLAMMATION. 

G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE;
- FOCAL ACUTE AND CHRONIC INFLAMMATION.

Chronic inflammation not otherwise specified

General

  • Common.
  • Non-specific finding.
  • Etiology usually not apparent on histomorphology.

Microscopic

Features:

  • Lymphocytes within the glands, between the epithelial cells or within the stroma - key feature.

Notes:

  • Rare scattered lymphocytes are common, especially in the central portion of the gland.
  • "Focal" one field with a 2.2 mm diameter involved.

Image

  • Prostate with chronic inflammation. (WC/Nephron)

Sign out

G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE;
- FOCAL CHRONIC INFLAMMATION. 

F. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE;
- CHRONIC INFLAMMATION.

Note:

  • Opinion is divided on whether this finding should be reported.
    • Advocates for reporting inflammation say "[i]t is just reporting what you see and may explain the bump in PSA."
    • Naysayers opine that "[i]t may provide false assurance that no cancer is present."

Granulomatous prostatitis

Main article: Granulomatous prostatitis

Prostatic infarct

General

Microscopic

Features:

  • Classic findings of necrosis:
    • Karyolysis (loss of nuclei), karyorrhexis (frag. of nuclei), pyknosis (small shrunken nuclei).
  • +/-Squamous metaplasia of prostate gland epithelium.

Notes:

  • Corpora amylacea - help... call it benign.
  • Glands maintain normal spacing.

DDx:

Image:

Preneoplastic changes and atypical changes

High-grade prostatic intraepithelial neoplasia

  • Abbreviated as HGPIN.
  • May be referred to as prostatic intraepithelial neoplasia, abbreviated PIN.
Main article: High-grade prostatic intraepithelial neoplasia

Atypical small acinar proliferation

  • Abbreviated ASAP.
  • AKA suspicious for carcinoma.[8]
    • ASAP is preferred as it does not contain the word carcinoma and, thus, cannot be misread as carcinoma, i.e. positive for malignancy.
Main article: Atypical small acinar proliferation

Prostate cancer

Main article: Prostate cancer

This is a big topic that is dealt with in its own article.

See also

References

  1. ↑ Dodson, MK.; Cliby, WA.; Pettavel, PP.; Keeney, GL.; Podratz, KC. (Dec 1995). "Female urethral adenocarcinoma: evidence for more than one tissue of origin?". Gynecol Oncol 59 (3): 352-7. doi:10.1006/gyno.1995.9963. PMID 8522254.
  2. ↑ McNeal, JE. (Aug 1988). "Normal histology of the prostate.". Am J Surg Pathol 12 (8): 619-33. PMID 2456702.
  3. ↑ Christian JD, Lamm TC, Morrow JF, Bostwick DG (January 2005). "Corpora amylacea in adenocarcinoma of the prostate: incidence and histology within needle core biopsies". Mod. Pathol. 18 (1): 36–9. doi:10.1038/modpathol.3800250.
  4. ↑ Trpkov, K.; Bartczak-McKay, J.; Yilmaz, A. (Aug 2009). "Usefulness of cytokeratin 5/6 and AMACR applied as double sequential immunostains for diagnostic assessment of problematic prostate specimens.". Am J Clin Pathol 132 (2): 211-20; quiz 307. doi:10.1309/AJCPGFJP83IXZEUR. PMID 19605815.
  5. ↑ URL: http://www.cancer.gov/dictionary?cdrid=446218. Accessed on: 23 February 2012.
  6. ↑ URL: http://www.internationalhifu.com/what-is-hifu-mainmenu-132.html. Accessed on: 15 June 2010.
  7. ↑ 7.0 7.1 Milord, RA.; Kahane, H.; Epstein, JI. (Oct 2000). "Infarct of the prostate gland: experience on needle biopsy specimens.". Am J Surg Pathol 24 (10): 1378-84. PMID 11023099.
  8. ↑ THvdK. 19 June 2010.
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