Difference between revisions of "Prostate cancer"

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Prostate cancer (view source)

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{{ Infobox diagnosis
| Name      = Prostate carcinoma
| Image      = Prostate cancer with Gleason pattern 4 low mag.jpg
| Width      =
| Caption    = Prostate carcinoma. [[H&E stain]].
| Micro      = major criteria: abnormal architecture (increased gland density, usu. small circular glands, "infiltrative growth" pattern), basal cells lost, cytological abnormalities (nuclear enlargement, nucleoli); minor criteria: nuclear hyperchromasia, wispy blue mucin, pink amorphous secretions, intraluminal crystalloid, amphophilic cytoplasm, adjacent [[HGPIN]], mitoses
| Subtypes  =
| LMDDx      = [[high-grade prostatic intraepithelial neoplasia]], [[atypical small acinar proliferation]] (biopsy only), [[prostatic atrophy]], [[seminal vesicle]], [[basal cell hyperplasia of the prostate|basal cell hyperplasia]], others
| Stains    = 
| IHC        = PSA +ve, PSAP +ve, AMACR +ve, p63 -ve, CK34betaE12 -ve
| EM        =
| Molecular  = +/-[[BRCA1]] mutation (genetic predisposition), +/-[[BRCA2]] mutation (genetic predisposition)
| IF        =
| Gross      = usu. posterior aspect of the prostate - often not apparent at gross
| Grossing  = [[prostate biopsy]], [[prostate chips]], [[radical prostatectomy]]
| Staging    = [[prostate cancer staging]]
| Site      = [[prostate gland]]
| Assdx      =
| Syndromes  =
| Clinicalhx =
| Signs      = firm, nodular prostate on digital rectal exam
| Symptoms  = often asymptomatic
| Prevalence = very common
| Bloodwork  = PSA elevated (common)
| Rads      = hypoechoic areas, no apparent abnormality
| Endoscopy  =
| Prognosis  = good-to-poor (depends on [[prostate cancer grading|grade (Gleason score)]] and [[stage]])
| Other      =
| ClinDDx    = [[prostatitis]], [[nodular hyperplasia of the prostate]]
| Tx        = observation (common for low-grade, low tumour burden), radiation or radical prostatectomy
}}
This article deals with '''prostate [[cancer]]'''.   
This article deals with '''prostate [[cancer]]'''.   


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==General==
==General==
*Very common.
*Very common.
*Increasing incidence with age - the age in years is an approximation of the percentage of men with prostate cancer.
*Increasing incidence with age - the age in years is an approximation of the percentage of men with prostate cancer.<ref>{{cite journal |author=Sakr WA, Haas GP, Cassin BF, Pontes JE, Crissman JD |title=The frequency of carcinoma and intraepithelial neoplasia of the prostate in young male patients |journal=J. Urol. |volume=150 |issue=2 Pt 1 |pages=379–85 |year=1993 |month=August |pmid=8326560 |doi= |url=}}</ref>{{fact}}
*Usually an indolent course - most old men die with prostate cancer ''not'' from prostate cancer.
*Usually an indolent course - most old men die with prostate cancer ''not'' from prostate cancer.
*Risk increased with a [[BRCA1]] or [[BRCA2]] mutation<ref name=pmid23747895>{{Cite journal  | last1 = Li | first1 = D. | last2 = Kumaraswamy | first2 = E. | last3 = Harlan-Williams | first3 = LM. | last4 = Jensen | first4 = RA. | title = The role of BRCA1 and BRCA2 in prostate cancer. | journal = Front Biosci (Landmark Ed) | volume = 18 | issue =  | pages = 1445-59 | month =  | year = 2013 | doi =  | PMID = 23747895 }}</ref> - families have a mix of [[breast cancer]] and prostate cancer.
**BRCA2 mutation risk >8x for men over 65 years old.<ref name=pmid22522501>{{Cite journal  | last1 = Castro | first1 = E. | last2 = Eeles | first2 = R. | title = The role of BRCA1 and BRCA2 in prostate cancer. | journal = Asian J Androl | volume = 14 | issue = 3 | pages = 409-14 | month = May | year = 2012 | doi = 10.1038/aja.2011.150 | PMID = 22522501 }}</ref>
**A BRCA2 founder mutation is described in French Canadians.<Ref name=pmid23318356>{{Cite journal  | last1 = Taherian | first1 = N. | last2 = Hamel | first2 = N. | last3 = Bégin | first3 = LR. | last4 = Bismar | first4 = TA. | last5 = Goldgar | first5 = DE. | last6 = Feng | first6 = BJ. | last7 = Foulkes | first7 = WD. | title = Familial prostate cancer: the damage done and lessons learnt. | journal = Nat Rev Urol | volume = 10 | issue = 2 | pages = 116-22 | month = Feb | year = 2013 | doi = 10.1038/nrurol.2012.257 | PMID = 23318356 }}</ref>


===Management===
===Management===
====Dirty first approximation====
====Dirty first approximation====
*The management changes between [[Gleason score]] 6, 7 and 8.
*The management changes between [[Gleason score]] 6, 7 (3+4), 7 (4+3) and 8.


Typically, the implications are:
Typically, the implications are:
* Gleason 6: observation ''or'' radioactive seeds; surgery if patient wants.
* Gleason 6: observation ''or'' radioactive seeds; surgery if patient wants.
* Gleason 7: do something -- surgery ''or'' radiation therapy.
* Gleason 7 with a bit of Gleason pattern 4 and a low tumour volume: it is reasonable to watch ''or'' do something. ‡
* Gleason 7 with a lot of Gleason pattern 4 ''or'' a high tumour volume: do something -- surgery ''or'' radiation therapy.
* Gleason 8+: bad cancer -- do something quickly!
* Gleason 8+: bad cancer -- do something quickly!
Note:
* ‡ It has been said that ''Gleason score 7 with a bit of Gleason pattern 4 is the new Gleason score 6''.


Bottom line:  
Bottom line:  
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====Observational strategies====
====Observational strategies====
*Delay of definitive treatment (surgery ''or'' radiation).
*Delay of definitive treatment (surgery ''or'' radiation).
*Common in management of prostate cancer.
*Common in the management of prostate cancer.


Classification:<ref name=pmid23126653>{{Cite journal  | last1 = Ip | first1 = S. | last2 = Dahabreh | first2 = IJ. | last3 = Chung | first3 = M. | last4 = Yu | first4 = WW. | last5 = Balk | first5 = EM. | last6 = Iovin | first6 = RC. | last7 = Mathew | first7 = P. | last8 = Luongo | first8 = T. | last9 = Dvorak | first9 = T. | title = An evidence review of active surveillance in men with localized prostate cancer. | journal = Evid Rep Technol Assess (Full Rep) | volume =  | issue = 204 | pages = 1-341 | month = Dec | year = 2011 | doi =  | PMID = 23126653 | url = http://www.ncbi.nlm.nih.gov/books/NBK83054/ }}</ref>
Classification:<ref name=pmid23126653>{{Cite journal  | last1 = Ip | first1 = S. | last2 = Dahabreh | first2 = IJ. | last3 = Chung | first3 = M. | last4 = Yu | first4 = WW. | last5 = Balk | first5 = EM. | last6 = Iovin | first6 = RC. | last7 = Mathew | first7 = P. | last8 = Luongo | first8 = T. | last9 = Dvorak | first9 = T. | title = An evidence review of active surveillance in men with localized prostate cancer. | journal = Evid Rep Technol Assess (Full Rep) | volume =  | issue = 204 | pages = 1-341 | month = Dec | year = 2011 | doi =  | PMID = 23126653 | url = http://www.ncbi.nlm.nih.gov/books/NBK83054/ }}</ref>
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*Gleason score 6 or less.
*Gleason score 6 or less.
*All biopsies cores < 50% involvement.
*All biopsies cores < 50% involvement.
*Less than 3 cores involved.
*One or two cores involved.<ref>URL: [http://www.active-surveillance.com/laurence-klotz-md/ http://www.active-surveillance.com/laurence-klotz-md/]. Accessed on: 12 July 2013.</ref><ref name=pmid23548978>{{Cite journal  | last1 = Klotz | first1 = L. | title = Active surveillance: patient selection. | journal = Curr Opin Urol | volume = 23 | issue = 3 | pages = 239-44 | month = May | year = 2013 | doi = 10.1097/MOU.0b013e32835f8f6b | PMID = 23548978 }}</ref><ref name=pmid22891078>{{Cite journal  | last1 = Klotz | first1 = L. | title = Active surveillance for low-risk prostate cancer. | journal = F1000 Med Rep | volume = 4 | issue =  | pages = 16 | month =  | year = 2012 | doi = 10.3410/M4-16 | PMID = 22891078 | PMC = 3412317 }}</ref>
Clinical criteria:
*PSA <= 10 ng/mL.<ref name=pmid22314081/>
*Negative DRE.
 
==Gross==
*Prostate cancer is uncommonly apparent on gross.
*Classic location: posterior aspect of the prostate.
 
===Radiology===
*Hypoechoic areas = suspicious for cancer.
**It seems that size of the area matters.
***Small hypoechoic areas (<0.2 cm<sup>3</sup>) have cancer less than 4% of the time.<ref name=pmid9933054>{{Cite journal  | last1 = Fleshner | first1 = NE. | last2 = O'Sullivan | first2 = M. | last3 = Premdass | first3 = C. | last4 = Fair | first4 = WR. | title = Clinical significance of small (less than 0.2 cm3) hypoechoic lesions in men with normal digital rectal examinations and prostate-specific antigen levels less than 10 ng/mL. | journal = Urology | volume = 53 | issue = 2 | pages = 356-8 | month = Feb | year = 1999 | doi =  | PMID = 9933054 }}</ref>
***One study suggests hypoechoic lesions tend to have a worse outcome;<ref name=pmid22920545>{{Cite journal  | last1 = Nakano Junqueira | first1 = VC. | last2 = Zogbi | first2 = O. | last3 = Cologna | first3 = A. | last4 = Dos Reis | first4 = RB. | last5 = Tucci | first5 = S. | last6 = Reis | first6 = LO. | last7 = Westphalen | first7 = AC. | last8 = Muglia | first8 = VF. | title = Is a visible (hypoechoic) lesion at biopsy an independent predictor of prostate cancer outcome? | journal = Ultrasound Med Biol | volume = 38 | issue = 10 | pages = 1689-94 | month = Oct | year = 2012 | doi = 10.1016/j.ultrasmedbio.2012.06.006 | PMID = 22920545 }}</ref> however, this is not supported by an older study.<ref name=pmid1688955>{{Cite journal  | last1 = Devonec | first1 = M. | last2 = Fendler | first2 = JP. | last3 = Monsallier | first3 = M. | last4 = Mouriquand | first4 = P. | last5 = Maquet | first5 = JH. | last6 = Mestas | first6 = JL. | last7 = Dutrieux-Berger | first7 = N. | last8 = Perrin | first8 = P. | title = The significance of the prostatic hypoechoic area: results in 226 ultrasonically guided prostatic biopsies. | journal = J Urol | volume = 143 | issue = 2 | pages = 316-9 | month = Feb | year = 1990 | doi =  | PMID = 1688955 }}</ref>
 
===Prostatectomy grossing===
{{Main|Radical prostatectomy}}
 
===Cytoprostatectomy grossing===
{{Main|Cystoprostatectomy grossing}}
*Limited sampling of the prostate may lead to undersampling error.<ref name=pmid11182038>{{Cite journal  | last1 = Cindolo | first1 = L. | last2 = Benincasa | first2 = G. | last3 = Autorino | first3 = R. | last4 = Domizio | first4 = S. | last5 = De Rosa | first5 = G. | last6 = Testa | first6 = G. | last7 = D'Armiento | first7 = M. | last8 = Altieri | first8 = V. | title = Prevalence of silent prostatic adenocarcinoma in 165 patients undergone cystoprostatectomy: a retrospective study. | journal = Oncol Rep | volume = 8 | issue = 2 | pages = 269-71 | month =  | year =  | doi =  | PMID = 11182038 }}</ref>


==Microscopic==
==Microscopic==
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#Basal cells lacking.
#Basal cells lacking.
#Cytological abnormalities:
#Cytological abnormalities:
#*Nuclear enlargement.
#*Nuclear enlargement (subtle).
#*Nucleoli.
#*[[Nucleoli]] (prominent).


Minor criteria:<ref name=pmid17213347/>
Minor criteria:<ref name=pmid17213347/>
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**Thus, it has been suggested that six or more glands should be present to diagnose cancer.<ref name=pmid20061936/>
**Thus, it has been suggested that six or more glands should be present to diagnose cancer.<ref name=pmid20061936/>


===Low power features===
Features considered pathognomonic for prostate carcinoma by some authorities:<ref name=pmid16613324>{{Cite journal  | last1 = Egevad | first1 = L. | last2 = Allsbrook | first2 = WC. | last3 = Epstein | first3 = JI. | title = Current practice of diagnosis and reporting of prostate cancer on needle biopsy among genitourinary pathologists. | journal = Hum Pathol | volume = 37 | issue = 3 | pages = 292-7 | month = Mar | year = 2006 | doi =  | PMID = 16613324 }}</ref><ref name=pmid10435561>{{Cite journal  | last1 = Baisden | first1 = BL. | last2 = Kahane | first2 = H. | last3 = Epstein | first3 = JI. | title = Perineural invasion, mucinous fibroplasia, and glomerulations: diagnostic features of limited cancer on prostate needle biopsy. | journal = Am J Surg Pathol | volume = 23 | issue = 8 | pages = 918-24 | month = Aug | year = 1999 | doi =  | PMID = 10435561 }}</ref>
#Perineural invasion.
#*Must be circumferential (>95% of circumference{{fact}}).
#Glomeruloid bodies.
#[[Collagenous micronodules]] also known as ''mucinous fibroplasia''.
 
<gallery>
Image: Intraluminal eosinophilic crystalloid of prostate gland - high mag.jpg| Intraluminal eosinophilic crystalloid - high mag. (WC)
Image: Prostate carcinoma with blue mucin -- very high mag.jpg | Whispy blue mucin - very high mag. (WC)
Image: Prostate carcinoma with blue mucin - a1 -- intermed mag.jpg | Whispy blue mucin - intermed. mag. (WC)
</gallery>
 
===Divided into high and low power===
====Low power features====
*Architecture is the '''key''' to diagnosing low grade cancer.
*Architecture is the '''key''' to diagnosing low grade cancer.
**Back-to-back glands or crowding of glands -- think low grade cancer (Gleason pattern 3).
**Back-to-back glands or crowding of glands -- think low grade cancer (Gleason pattern 3).
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**"Infiltrative": small round/oval (malignant) glands (approx. 5 cells across) interspersed with larger (benign) glands that are 2-3 times larger.
**"Infiltrative": small round/oval (malignant) glands (approx. 5 cells across) interspersed with larger (benign) glands that are 2-3 times larger.


===High power features===
====High power features====
*Nuclei.  
*Nuclear changes.  
**Hyperchromatic nuclei (like in HGPIN).
**Hyperchromatic nuclei (like in HGPIN).
**Nuclear enlargement.
**Nuclear enlargement, mild (10%?).
***Difficult to appreciate (if cancer isn't side-by-side with normal prostate).
***Difficult to appreciate (if cancer isn't side-by-side with normal prostate).
***Difficult to see if not on high power.
***Difficult/impossible to see at low power.
*Nucleoli visible on high power (200x or 100X)  
*"Large" nucleoli.
**May be difficult to see - especially if light intensity is low.
**Visible on intermediate and high power (100x / 200x magnification).
***One should not use 400x to look for nucleoli (it is a waste of time + you risk overcalling something benign).
***May be difficult to see - especially if light intensity is low or the staining is of poor quality.
**If I see three good nucleoli in a gland I'm usually confident it is cancer.
***One should not use 400x to look for nucleoli (it is a waste of time + you risk over-calling something benign).
**"Large" is rarely precisely quantified; 3 micrometres has been suggested as "large" based on one study.<ref name=pmid1688728>{{Cite journal  | last1 = Kelemen | first1 = PR. | last2 = Buschmann | first2 = RJ. | last3 = Weisz-Carrington | first3 = P. | title = Nucleolar prominence as a diagnostic variable in prostatic carcinoma. | journal = Cancer | volume = 65 | issue = 4 | pages = 1017-20 | month = Feb | year = 1990 | doi =  | PMID = 1688728 }}</ref>
***Three micrometres is a little more than 1/3 of [[RBC]] diameter.
*Loss of basal cells - diagnostic feature.
*Loss of basal cells - diagnostic feature.
**Like in breast pathology (where one looks for loss of myoepithelial cells) - this may be difficult to see.
**Like in [[breast pathology]] (where one looks for loss of myoepithelial cells) - this may be difficult to see.


Notes:
Notes:
*Mitoses are not a common feature - don't waste time looking for them.
*Mitoses are not a common feature.
**If you find them the lesion is probably high-grade.
**Generally, it isn't worth looking for them.


===Mimics===
===Mimics===
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| many small glands, lack nuclear size variation, basal layer present
| 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
| nucleoli may be present; may need to do p63 or 34betaE12 to find basal layer
| [http://webpathology.com/image.asp?case=21&n=3 AAH (webpathology.com)]
| [[Image:Adenosis of prostate_--_intermed_mag.jpg|thumb|150px|center| Adenosis of prostate. (WC)]]
|-
|-
| Sclerosing adenosis
| Sclerosing adenosis
| gradual transition between normal & small gland (NOT two populations), fibrosis
| gradual transition between normal & small gland (NOT two populations), fibrosis
| many small glands, lack nuclear size variation, basal layer present
| many small glands, lack nuclear size variation, basal layer present
| analogous to sclerosing adenosis of breast (???)
| analogous to [[sclerosing adenosis of the breast]]{{fact}}
| [http://webpathology.com/image.asp?case=21&n=8 Sclerosing adenosis (webpathology.com)]
| [http://webpathology.com/image.asp?case=21&n=40 Sclerosing adenosis (webpathology.com)]
|-
|-
| [[atrophy of the prostate|Atrophy]]
| [[atrophy of the prostate|Atrophy]]
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| nuclear hyperchromasia, scant cytoplasm
| nuclear hyperchromasia, scant cytoplasm
| may appear right beside non-atrophic tissue
| may appear right beside non-atrophic tissue
| [http://webpathology.com/image.asp?case=16&n=7 Atrophy (webpathology.com)], [http://webpathology.com/image.asp?case=16&n=5 Partial atrophy (webpathology.com)] [http://webpathology.com/image.asp?case=16&n=6 Sclerotic atrophy (webpathology.com)]
| [[Image:Atrophic_prostatic_glands_--_high_mag.jpg|thumb|150px|center| Prostatic atrophy. (WC)]]
|-
|-
| [[Basal cell hyperplasia of the prostate|Basal cell hyperplasia]]
| [[Basal cell hyperplasia of the prostate|Basal cell hyperplasia]]
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| abundant epithelial cells; nucleoli in pale ('blue') nuclei of basal cells, glandular cell nuclei darker ('purple')
| 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
| vaguely similar to epithelial hyperplasia of usual type (EHUT) in breast
| [http://webpathology.com/image.asp?case=18&n=1 BCH (webpathology.com)]
| [[Image:Basal_cell_hyperplasia_of_prostate_-_high_mag.jpg|thumb|150px|center| Prostatic BCH. (WC)]]
|-
|-
| [[Bulbourethral gland]]
| [[Bulbourethral gland]]
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| clear cytoplasm
| clear cytoplasm
| apex of prostate
| apex of prostate
| [http://webpathology.com/image.asp?case=21&n=4 Cowper gland (webpathology.com)]
| [[Image:Bulbourethral gland -- very high mag.jpg |thumb|150px|center| Bulbourethral gland. (WC)]]
|-
|-
| [[Seminal vesicles]] / ejaculatory ducts
| [[Seminal vesicles]] / ejaculatory ducts
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| fern-like arrangement of epithelium (low power), nucleoli, surrounded by muscle, +/- nuclear inclusions
| fern-like arrangement of epithelium (low power), nucleoli, surrounded by muscle, +/- nuclear inclusions
| involvement by cancer changes staging, lipofuscin may be present in prostate, often has marked nuc. size var.; location: usu. base of prostate
| involvement by cancer changes staging, lipofuscin may be present in prostate, often has marked nuc. size var.; location: usu. base of prostate
| [http://commons.wikimedia.org/wiki/File:Seminal_vesicle_high_mag.jpg SV - high mag. (WC)], [http://commons.wikimedia.org/wiki/File:Seminal_vesicle_low_mag.jpg SV - low mag. (WC)]
| [[Image:Seminal_vesicle_high_mag.jpg |thumb|150px|center|Seminal vesicles. (WC)]]
|-
|-
| Radiation effect
| [[Radiation effect]]
| marked nuclear size variation
| marked nuclear size variation
| increased stroma (fibrosis), lack nucleoli ???
| increased stroma (fibrosis), lack nucleoli ???
| history of Rx; uniform nuc. size with Hx of Rx should raise susp. of cancer
| history of Rx; uniform nuc. size with Hx of Rx should raise susp. of [[postradiation prostatic carcinoma|postradiation cancer]]
| [http://webpathology.com/image.asp?case=97&n=6 Radiation changes (webpathology.com)], [http://webpathology.com/image.asp?case=97&n=7 Radiation changes (webpathology.com)]
| [[Image:Prostate_with_radiation_changes_--_high_mag.jpg|thumb|150px|center|Radiation change. (WC)]]
|-
|-
| Prostatitis
| Prostatitis
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| no nuclear atypia, normal gland arch.
| no nuclear atypia, normal gland arch.
| clinical mimic of cancer (elevated PSA); usu. not a problem for the pathologist
| clinical mimic of cancer (elevated PSA); usu. not a problem for the pathologist
| [http://commons.wikimedia.org/wiki/File:Inflammation_of_prostate.jpg Prostatic inflammation (WC)]
| [[Image:Inflammation_of_prostate.jpg|thumb|150px|center| Prostatic inflammation. (WC)]]
|-
|-
| [[Vasitis nodosa]]
| [[Vasitis nodosa]]
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| small tubules, nucleoli common, mild atypia, may "invade" vessels, track along nerves
| small tubules, nucleoli common, mild atypia, may "invade" vessels, track along nerves
| mimics metastatic prostate carcinoma, IHC stains: PSA-, PSAP-
| mimics metastatic prostate carcinoma, IHC stains: PSA-, PSAP-
| [http://www.webpathology.com/image.asp?n=11&Case=40 VN (webpathology.com)]
| [[Image:Vasitis nodosa -11- intermed mag.jpg|thumb|150px|center| VN. (WC)]]
|}
|}
Memory device: '''AAABBRS''' = atrophy, adenosis, adenosis (sclerosing), basal cell hyperplasia, bulbourethral gland, radiation, seminal vesicles.
Memory device: '''AAABBRS''' = atrophy, adenosis, adenosis (sclerosing), basal cell hyperplasia, bulbourethral gland, radiation, seminal vesicles.


===Gleason grading system===
===Situations where prostate adenocarcinoma may be missed===
Overview:
Key reasons for false negative prostate samples<ref>{{cite journal |authors=Yang C, Humphrey PA |title=False-Negative Histopathologic Diagnosis of Prostatic Adenocarcinoma |journal=Arch. Pathol. Lab. Med. |volume=144 |issue=3 |pages=326–334 |date=March 2020 |pmid=31729886 |doi=10.5858/arpa.2019-0456-RA |url=}}</ref>:
*This system is only one any one talks about and there is consensus on how it is done.<ref name=pmid16096414>{{Cite journal | last1 = Epstein | first1 = JI. | last2 = Allsbrook | first2 = WC. | last3 = Amin | first3 = MB. | last4 = Egevad | first4 = LL. | title = The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. | journal = Am J Surg Pathol | volume = 29 | issue = 9 | pages = 1228-42 | month = Sep | year = 2005 | doi = | PMID = 16096414 }}</ref>
*Tissue artefacts (try levels and/or IHC):
*Score range: 6-10.
**Crush artefact
**Technically 2-10... but almost no one uses 2-5.
**Thick sections
*Reported as on biopsy as: (primary pattern) + (secondary pattern ''or'' tertiary pattern with the highest grade) = sum.
**Aberrant H&E staining
**e.g. ''Gleason score 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.
**Freezing artefact
*Reported as on prostatectomies as: (primary pattern) + (secondary pattern) = sum, (tertiary pattern)
**Cautery
 
*Minimal adenocarcinoma (less than 1mm long or involving less than 5% of a core biopsy):
*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 name=Ref_GUP72>{{Ref GUP|72}}</ref>
*Prostatic adenocarcinoma variants that mimic benign:
**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 name=Ref_GUP72>{{Ref GUP|72}}</ref>
**[[Atrophic prostate carcinoma]]
**[[Pseudohyperplastic adenocarcinoma]]
**[[Foamy gland adenocarcinoma]]
**[[PIN-like adenocarcinoma]]
**Microcystic adenocarcinoma
*Single cells of Gleason 5 adenocarcinoma (missed or mistaken for lymphocytes; try IHC for cytokeratins, prostatic and/or hematologic markers)
*Treatment effect (check clinical information and look for treatment effect in benign glands)


Examples:
===Prostate cancer grading===
*A biopsy has 80% pattern 4, 16% pattern 3 and 4% pattern 5... it would be reported as: 4+5=9.
{{Main|Prostate cancer grading}}
*A prostatectomy has 80% pattern 4, 16% pattern 3 and 4% pattern 5... it would be reported as: 4+3=7 with tertiary pattern 5.
It covers the ''Gleason grading system'' and the (new) ''prognostic grade groupings''.


Testing yourself:
===Staging parameters, margins and more===
*There is a nice test-yourself quiz from Johns Hopkins: [http://162.129.103.34/prostate/ http://162.129.103.34/prostate/].
**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>
 
====Gleason pattern 1 & 2====
*Use strongly discouraged by a number of GU pathology experts.
 
Notes:
*Gleason pattern 1 - probably represents what today would be called ''adenosis''.
**Should never be used.
*Gleason pattern 2 - used by few GU pathology experts occasionally.
**Generally, should '''not''' be diagnosed on core biopsies.<ref name=pmid20006878>{{Cite journal  | last1 = Epstein | first1 = JI. | title = An update of the Gleason grading system. | journal = J Urol | volume = 183 | issue = 2 | pages = 433-40 | month = Feb | year = 2010 | doi = 10.1016/j.juro.2009.10.046 | PMID = 20006878 }}</ref>
 
====Gleason pattern 3====
*Glands smaller than normal prostate glands + loss of epithelial folding.
*Can draw a line around each gland.
*May have ''gland branching''.
**Glands have a X, U, V or Y shape.
 
Notes:
*Gland lumina should be seen.
*All ''cribriform'' is now, generally, 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>
 
====Gleason pattern 4====
*Loss of gland lumina.
*Gland fusion.
*Benign looking cords ('hypernephroid pattern').
*Cribriform.
*Glomeruloid pattern - resembles a glomerulus.
 
Notes:
*One gland is not enough to call Gleason 4.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Prostate_cancer_with_Gleason_pattern_4_low_mag.jpg Gleason pattern 4 - cribriform (WC)].
*[http://commons.wikimedia.org/wiki/File:Gleason_4_and_5_intermed_mag.jpg Gleason pattern 4 - small glands & Gleason pattern 5 - single cells (WC)].
*[http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f9.html#figure-title Glomeruloid pattern (nature.com)].
 
====Gleason pattern 5====
*Sheets.
**Must be differentiated from intraductal growth (which like in the breast are well circumscribed nests).
*Single cells.
**May be confused with stromal/lymphocytic infiltration.
***Look for nucleoli, cells should be round (prostatic stroma cells are spindle cells).
*Cords (strands).
**Line of cells.
**Should not be intermixed with clumps of cells (pattern 4).
*Nests of cells with [[necrosis]] at centre (comedonecrosis).
 
Notes:
*Pattern 5 may be under-diagnosed.
*Single cells is the most commonly missed pattern.<ref name=pmid21997691>{{Cite journal  | last1 = Fajardo | first1 = DA. | last2 = Miyamoto | first2 = H. | last3 = Miller | first3 = JS. | last4 = Lee | first4 = TK. | last5 = Epstein | first5 = JI. | title = Identification of Gleason pattern 5 on prostatic needle core biopsy: frequency of underdiagnosis and relation to morphology. | journal = Am J Surg Pathol | volume = 35 | issue = 11 | pages = 1706-11 | month = Nov | year = 2011 | doi = 10.1097/PAS.0b013e318228571d | PMID = 21997691 }}
</ref>
 
Images:
*[http://commons.wikimedia.org/wiki/File:Gleason_4_and_5_intermed_mag.jpg Gleason pattern 4 - small glands & Gleason pattern 5 - single cells (WC)].
*[http://www.webpathology.com/image.asp?n=17&Case=20 Gleason pattern 5 - sheeting (webpathology.com)].
 
====Special types====
Special types of prostate cancer have set Gleason scores:<ref name=pmid14976541>{{cite journal |author=Grignon DJ |title=Unusual subtypes of prostate cancer |journal=Mod. Pathol. |volume=17 |issue=3 |pages=316–27 |year=2004 |month=March |pmid=14976541 |doi=10.1038/modpathol.3800052 |url=}}</ref>
{| class="wikitable sortable"  style="margin-left:auto;margin-right:auto"
! Special type
! Gleason pattern
! Comment
|-
|Ductal carcinoma
| 4
| may be graded 3 or 5<ref name=bostwicklabs>URL: [https://www.bostwicklaboratories.com/global/physicians/medical-library/articles/gleason-grading.aspx https://www.bostwicklaboratories.com/global/physicians/medical-library/articles/gleason-grading.aspx]. Accessed on: 26 November 2011.</ref>
|-
|Mucinous carcinoma
| 4
|
|-
|Sarcomatoid carcinoma
| 5
| glands graded separately
|-
|Signet ring cell carcinoma
| 5
|
|-
|Small cell carcinoma
| not graded
| may be graded 5<ref name=bostwicklabs/>
|-
|Adenosquamous and [[squamous carcinoma]]
| not graded
|
|-
|[[Lymphoepithelioma-like carcinoma]]
| not graded
|
|-
|[[Adenoid cystic carcinoma]]
| not graded
|
|-
|[[Urothelial carcinoma]]
| not graded
|
|-
|Undifferentiated carcinoma, NOS
| not graded
|
|}
 
How to remember the ones that aren't graded - think of '''Ur''' '''L'''ung carcinomas ('''Ur'''othelial carcinoma, '''L'''ymphoepithelioma-like carcinoma):
*Small cell carcinoma.
*Squamous cell carcinoma.
*Adenosquamous carcinoma.
*Adenoid cystic carcinoma.
 
====Biopsy-prostatectomy concordance of Gleason score====
*Discordance is common.
**Upgrade on prostatectomy: 25-40%.
**Downgrade on prostatectomy: 5-15%.
 
Selected studies on concordance:
{| class="wikitable sortable"  style="margin-left:auto;margin-right:auto"
! Study
! Upgrade
! Downgrade
! Notes
|-
| Sfoungaristos et al.<ref name=pmid22277633>{{Cite journal  | last1 = Sfoungaristos | first1 = S. | last2 = Perimenis | first2 = P. | title = Clinical and pathological variables that predict changes in tumour grade after radical prostatectomy in patients with prostate cancer. | journal = Can Urol Assoc J | volume =  | issue =  | pages = 1-5 | month = Jan | year = 2012 | doi = 10.5489/cuaj.11067 | PMID = 22277633 }}</ref>
| 42.1%
| 13.7%
| high volume of tumour predicts upgrade
|-
| Thomas et al.<ref name=pmid21592293>{{Cite journal  | last1 = Thomas | first1 = C. | last2 = Pfirrmann | first2 = K. | last3 = Pieles | first3 = F. | last4 = Bogumil | first4 = A. | last5 = Gillitzer | first5 = R. | last6 = Wiesner | first6 = C. | last7 = Thüroff | first7 = JW. | last8 = Melchior | first8 = SW. | title = Predictors for clinically relevant Gleason score upgrade in patients undergoing radical prostatectomy. | journal = BJU Int | volume = 109 | issue = 2 | pages = 214-9 | month = Jan | year = 2012 | doi = 10.1111/j.1464-410X.2011.10187.x | PMID = 21592293 }}</ref>
| 38.1%
| 4.7%
|
|-
| Truesdale et al.<ref name=pmid20840549>{{Cite journal  | last1 = Truesdale | first1 = MD. | last2 = Cheetham | first2 = PJ. | last3 = Turk | first3 = AT. | last4 = Sartori | first4 = S. | last5 = Hruby | first5 = GW. | last6 = Dinneen | first6 = EP. | last7 = Benson | first7 = MC. | last8 = Badani | first8 = KK. | title = Gleason score concordance on biopsy-confirmed prostate cancer: is pathological re-evaluation necessary prior to radical prostatectomy? | journal = BJU Int | volume = 107 | issue = 5 | pages = 749-54 | month = Mar | year = 2011 | doi = 10.1111/j.1464-410X.2010.09570.x | PMID = 20840549 }}</ref>
| 23%
| 11%
|
|}
 
===Staging parameters and margins===
====Surgical margins====
====Surgical margins====
{{Main|Surgical margins}}
{{Main|Surgical margins}}
*Positive is ''tumour touching ink''.<ref name=pmid22578729>{{Cite journal  | last1 = Lu | first1 = J. | last2 = Wirth | first2 = GJ. | last3 = Wu | first3 = S. | last4 = Chen | first4 = J. | last5 = Dahl | first5 = DM. | last6 = Olumi | first6 = AF. | last7 = Young | first7 = RH. | last8 = McDougal | first8 = WS. | last9 = Wu | first9 = CL. | title = A close surgical margin after radical prostatectomy is an independent predictor of recurrence. | journal = J Urol | volume = 188 | issue = 1 | pages = 91-7 | month = Jul | year = 2012 | doi = 10.1016/j.juro.2012.02.2565 | PMID = 22578729 }}</ref>
*Positive is ''tumour touching [[ink]]''.† <ref name=pmid22578729>{{Cite journal  | last1 = Lu | first1 = J. | last2 = Wirth | first2 = GJ. | last3 = Wu | first3 = S. | last4 = Chen | first4 = J. | last5 = Dahl | first5 = DM. | last6 = Olumi | first6 = AF. | last7 = Young | first7 = RH. | last8 = McDougal | first8 = WS. | last9 = Wu | first9 = CL. | title = A close surgical margin after radical prostatectomy is an independent predictor of recurrence. | journal = J Urol | volume = 188 | issue = 1 | pages = 91-7 | month = Jul | year = 2012 | doi = 10.1016/j.juro.2012.02.2565 | PMID = 22578729 }}</ref>
**"Close" margins have an increase recurrence risk.
**"Close" margins (<0.1 mm) have an increased recurrence risk.<ref name=pmid22578729/>


Notes:
Notes:
Line 331: Line 273:
**It is possible to have EPE without a positive margin.
**It is possible to have EPE without a positive margin.
**It is possible to have a positive margin without EPE.
**It is possible to have a positive margin without EPE.
* † Epstein says not touching may be enough, as tumour close to the margin is damaged from the surgery.<ref>URL: [http://urology.jhu.edu/newsletter/prostate_cancer410.php http://urology.jhu.edu/newsletter/prostate_cancer410.php]. Accessed on: 26 March 2013.</ref>


=====Rates and implication=====
=====Rates and implication=====
Positivity rate varies substantially (13-44%):  
Positivity rate varies substantially (13-44%):  
*Norway: 26% -- strong dependence on surgeon volume (18% high case load vs. 44% low case load).<ref name=pmid22860630>{{Cite journal  | last1 = Steinsvik | first1 = EA. | last2 = Axcrona | first2 = K. | last3 = Angelsen | first3 = A. | last4 = Beisland | first4 = C. | last5 = Dahl | first5 = A. | last6 = Eri | first6 = LM. | last7 = Haug | first7 = ES. | last8 = Svindland | first8 = A. | last9 = Fosså | first9 = S. | title = Does a surgeon's annual radical prostatectomy volume predict the risk of positive surgical margins and urinary incontinence at one-year follow-up? - Findings from a prospective national study. | journal = Scand J Urol Nephrol | volume =  | issue =  | pages =  | month = Aug | year = 2012 | doi = 10.3109/00365599.2012.707684 | PMID = 22860630 }}</ref>
*Norway: 26% -- strong dependence on surgeon volume (18% high case load vs. 44% low case load).<ref name=pmid22860630>{{Cite journal  | last1 = Steinsvik | first1 = EA. | last2 = Axcrona | first2 = K. | last3 = Angelsen | first3 = A. | last4 = Beisland | first4 = C. | last5 = Dahl | first5 = A. | last6 = Eri | first6 = LM. | last7 = Haug | first7 = ES. | last8 = Svindland | first8 = A. | last9 = Fosså | first9 = S. | title = Does a surgeon's annual radical prostatectomy volume predict the risk of positive surgical margins and urinary incontinence at one-year follow-up? - Findings from a prospective national study. | journal = Scand J Urol Nephrol | volume =  | issue =  | pages =  | month = Aug | year = 2012 | doi = 10.3109/00365599.2012.707684 | PMID = 22860630 }}</ref>
*France: 13-17%.<ref name=pmid22860572>{{Cite journal  | last1 = Koutlidis | first1 = N. | last2 = Mourey | first2 = E. | last3 = Champigneulle | first3 = J. | last4 = Mangin | first4 = P. | last5 = Cormier | first5 = L. | title = Robot-assisted or pure laparoscopic nerve-sparing radical prostatectomy: What is the optimal procedure for the surgical margins? A single center experience. | journal = Int J Urol | volume =  | issue =  | pages =  | month = Jul | year = 2012 | doi = 10.1111/j.1442-2042.2012.03102.x | PMID = 22860572 }}</ref>
*France: 13-17% -- PSA and prostate size predictors of positivity.<ref name=pmid22860572>{{Cite journal  | last1 = Koutlidis | first1 = N. | last2 = Mourey | first2 = E. | last3 = Champigneulle | first3 = J. | last4 = Mangin | first4 = P. | last5 = Cormier | first5 = L. | title = Robot-assisted or pure laparoscopic nerve-sparing radical prostatectomy: What is the optimal procedure for the surgical margins? A single center experience. | journal = Int J Urol | volume =  | issue =  | pages =  | month = Jul | year = 2012 | doi = 10.1111/j.1442-2042.2012.03102.x | PMID = 22860572 }}</ref>


Note:
Note:
*There is likely a strong dependence on stage and grade of cancer, i.e. surgeons that operate more on high grade cancers will probably have a higher margin positive rates.
*Stage and grade (Gleason score) seem to have less impact than surgeons volume on margin positivity rate.<ref name=pmid22860630/>


The impact of positive margins:
The impact of positive margins:
*Significant modest negative affect on long-term outcome in node negative cancers (pT2-4 pN0).<ref name=pmid22901983>{{Cite journal  | last1 = Mauermann | first1 = J. | last2 = Fradet | first2 = V. | last3 = Lacombe | first3 = L. | last4 = Dujardin | first4 = T. | last5 = Tiguert | first5 = R. | last6 = Tetu | first6 = B. | last7 = Fradet | first7 = Y. | title = The Impact of Solitary and Multiple Positive Surgical Margins on Hard Clinical End Points in 1712 Adjuvant Treatment-Naive pT2-4 N0 Radical Prostatectomy Patients. | journal = Eur Urol | volume =  | issue =  | pages =  | month = Aug | year = 2012 | doi = 10.1016/j.eururo.2012.08.002 | PMID = 22901983 }}</ref>
*Significant modest negative affect on long-term outcome in node negative cancers (pT2-4 pN0).<ref name=pmid22901983>{{Cite journal  | last1 = Mauermann | first1 = J. | last2 = Fradet | first2 = V. | last3 = Lacombe | first3 = L. | last4 = Dujardin | first4 = T. | last5 = Tiguert | first5 = R. | last6 = Tetu | first6 = B. | last7 = Fradet | first7 = Y. | title = The Impact of Solitary and Multiple Positive Surgical Margins on Hard Clinical End Points in 1712 Adjuvant Treatment-Naive pT2-4 N0 Radical Prostatectomy Patients. | journal = Eur Urol | volume =  | issue =  | pages =  | month = Aug | year = 2012 | doi = 10.1016/j.eururo.2012.08.002 | PMID = 22901983 }}</ref>
*Weaker impact than stage and Gleason score.<ref>{{Cite journal  | last1 = Chalfin | first1 = HJ. | last2 = Dinizo | first2 = M. | last3 = Trock | first3 = BJ. | last4 = Feng | first4 = Z. | last5 = Partin | first5 = AW. | last6 = Walsh | first6 = PC. | last7 = Humphreys | first7 = E. | last8 = Han | first8 = M. | title = Impact of surgical margin status on prostate-cancer-specific mortality. | journal = BJU Int | volume =  | issue =  | pages =  | month = Jul | year = 2012 | doi = 10.1111/j.1464-410X.2012.11371.x | PMID = 22788795 }}</ref>
*Weaker impact than stage and Gleason score.<ref>{{Cite journal  | last1 = Chalfin | first1 = HJ. | last2 = Dinizo | first2 = M. | last3 = Trock | first3 = BJ. | last4 = Feng | first4 = Z. | last5 = Partin | first5 = AW. | last6 = Walsh | first6 = PC. | last7 = Humphreys | first7 = E. | last8 = Han | first8 = M. | title = Impact of surgical margin status on prostate-cancer-specific mortality. | journal = BJU Int | volume =  | issue =  | pages =  | month = Jul | year = 2012 | doi = 10.1111/j.1464-410X.2012.11371.x | PMID = 22788795 }}</ref>
*Bladder neck margin positivity may change the T-stage - see below.
=====Bladder neck margin=====
{{Main|Bladder neck invasion}}
:[[AKA]] ''invasion of the bladder neck''.<ref name=pmid19914651/>
*Bladder neck margin positivity typically is '''pT3a'''.<ref name=pmid23225909>{{Cite journal  | last1 = Chung | first1 = MS. | last2 = Lee | first2 = SH. | last3 = Lee | first3 = DH. | last4 = Chung | first4 = BH. | title = Evaluation of the 7th American Joint Committee on cancer TNM staging system for prostate cancer in point of classification of bladder neck invasion. | journal = Jpn J Clin Oncol | volume = 43 | issue = 2 | pages = 184-8 | month = Feb | year = 2013 | doi = 10.1093/jjco/hys196 | PMID = 23225909 }}</ref>
*Seen in approximately 1% of prostatectomies.<ref name=pmid19914651>{{Cite journal  | last1 = Pierorazio | first1 = PM. | last2 = Epstein | first2 = JI. | last3 = Humphreys | first3 = E. | last4 = Han | first4 = M. | last5 = Walsh | first5 = PC. | last6 = Partin | first6 = AW. | title = The significance of a positive bladder neck margin after radical prostatectomy: the American Joint Committee on Cancer Pathological Stage T4 designation is not warranted. | journal = J Urol | volume = 183 | issue = 1 | pages = 151-7 | month = Jan | year = 2010 | doi = 10.1016/j.juro.2009.08.138 | PMID = 19914651 }}</ref>


====Extraprostatic extension====
====Extraprostatic extension====
:Abbreviated ''EPE''.
:Abbreviated ''EPE''.
{{Main|Prostate cancer staging#Extraprostatic extension}}


=====General=====
====Seminal vesicle invasion====
*Extraprostatic extension (EPE) is difficult to assess (in prostatectomy specimens) as there is no consensus definition.
:Abbreviated ''SVI''.
**The prostate does NOT have a well defined capsule.
{{Main|Prostate cancer staging#Seminal vesicle invasion}}
***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>
*EPE, typically, upstages tumours from T2x to T3a.


=====Prostatectomy specimens=====  
====Perineural invasion====
EPE is present in a prostatectomy if there is either:
{{Main|Perineural invasion}}
#A "significant bulge" in the contour of the prostate at low power ''and'' no fibromuscular tissue surrounding the malignant cells.
*''Not'' a staging parameter.
#Malignant cells directly adjacent to peri-prostatic adipose tissue.
*Seen in approximately 20% of core biopsies.<ref name=pmid16096404>{{Cite journal  | last1 = Ali | first1 = TZ. | last2 = Epstein | first2 = JI. | title = Perineural involvement by benign prostatic glands on needle biopsy. | journal = Am J Surg Pathol | volume = 29 | issue = 9 | pages = 1159-63 | month = Sep | year = 2005 | doi = | PMID = 16096404 }}</ref>
*Complete wrapping of a nerve by epithelium is considered pathognomonic for cancer.<ref name=pmid10435561>{{Cite journal  | last1 = Baisden | first1 = BL. | last2 = Kahane | first2 = H. | last3 = Epstein | first3 = JI. | title = Perineural invasion, mucinous fibroplasia, and glomerulations: diagnostic features of limited cancer on prostate needle biopsy. | journal = Am J Surg Pathol | volume = 23 | issue = 8 | pages = 918-24 | month = Aug | year = 1999 | doi =  | PMID = 10435561 }}</ref><ref name=pmid16096404/>


Note:
Note:
*The prostate, at the apex, may have some skeletal muscle. Thus, it is difficult to define extention... ergo EPE not called at the apex.
*Occasionally, benign glands are found perineural.<ref name=pmid16096404/>
**These should ''not'' completely wrap around the nerve and should be cytologically benign.


=====Prostate biopsy=====  
==IHC==
EPE is present in prostate biopsy if:
===General recommendations===
*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><ref>Evans, A. 4 June 2010.</ref>
ISUP consensus statement:<ref name=pmid25025364>{{cite journal |author=Amin MB, Epstein JI, Ulbright TM, ''et al.'' |title=Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference |journal=Am. J. Surg. Pathol. |volume=38 |issue=8 |pages=1017–22 |year=2014 |month=August |pmid=25025364 |doi=10.1097/PAS.0000000000000254 |url=}}</ref>
 
*Should ''not'' be used if cancer is obvious.
====Seminal vesicle invasion====
*Should ''not'' be used if it isn't going change the clinical management.
General:
*Typically upstages to T3b.


Microscopic:
===Prostate markers===
*Tumour '''must''' be in the muscle surrounding the epithelial component; tumour in the adventitia (the loose connective tissue surrounding the seminal vesicles) does not count.<ref name=Ref_Lester3_409>{{Ref Lester3|409}}</ref><ref name=pmid20818343>{{Cite journal  | last1 = Berney | first1 = DM. | last2 = Wheeler | first2 = TM. | last3 = Grignon | first3 = DJ. | last4 = Epstein | first4 = JI. | last5 = Griffiths | first5 = DF. | last6 = Humphrey | first6 = PA. | last7 = van der Kwast | first7 = T. | last8 = Montironi | first8 = R. | last9 = Delahunt | first9 = B. | title = International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 4: seminal vesicles and lymph nodes. | journal = Mod Pathol | volume = 24 | issue = 1 | pages = 39-47 | month = Jan | year = 2011 | doi = 10.1038/modpathol.2010.160 | PMID = 20818343 }}</ref>
*[[PSA]] (prostate specific antigen) +ve.  
*[[PSAP]] (prostatic specific acid phosphatase) +ve. †
*P501S +ve. ‡
*[[NKX3.1]] +ve. ‡


Notes:
Notes:
*Invasion of the adventitia (only) would quality as EPE; this is, usually, T3a.
*† PSAP may be positive in hindgut [[neuroendocrine tumour]]s.<ref name=pmid>{{Cite journal  | last1 = Azumi | first1 = N. | last2 = Traweek | first2 = ST. | last3 = Battifora | first3 = H. | title = Prostatic acid phosphatase in carcinoid tumors. Immunohistochemical and immunoblot studies. | journal = Am J Surg Pathol | volume = 15 | issue = 8 | pages = 785-90 | month = Aug | year = 1991 | doi =  | PMID = 1712549 }}</ref>
*‡ P501S and NKX3.1 are considered second line markers.<ref name=pmid25025364/>
*Prostate carcinoma is typically CK7 -ve and CK20 -ve; however, in high [[Gleason score]] cancers focal positivity of these markers can be seen.<ref name=pmid11888088>{{Cite journal  | last1 = Goldstein | first1 = NS. | title = Immunophenotypic characterization of 225 prostate adenocarcinomas with intermediate or high Gleason scores. | journal = Am J Clin Pathol | volume = 117 | issue = 3 | pages = 471-7 | month = Mar | year = 2002 | doi = 10.1309/G6PR-Y774-X738-FG2K | PMID = 11888088 }}</ref>
**CK7: >25-50% staining seen in ~5% of cases.
***>50% staining with CK7 is not report.
**CK20: >25-50% staining seen in ~10% of cases.
***>50% staining with CK20 is not reported.


==IHC==
===Benign prostate versus neoplastic prostate===
===Benign prostate versus neoplastic prostate===
*AMACR +ve.
*AMACR +ve.
*AR +ve -- in prostate confined cancer.
**Usu. -ve in LN +ve disease.<ref name=pmid20878946>{{Cite journal  | last1 = Fleischmann | first1 = A. | last2 = Rocha | first2 = C. | last3 = Schobinger | first3 = S. | last4 = Seiler | first4 = R. | last5 = Wiese | first5 = B. | last6 = Thalmann | first6 = GN. | title = Androgen receptors are differentially expressed in Gleason patterns of prostate cancer and down-regulated in matched lymph node metastases. | journal = Prostate | volume = 71 | issue = 5 | pages = 453-60 | month = Apr | year = 2011 | doi = 10.1002/pros.21259 | PMID = 20878946 }}</ref>
*PSA +ve.
*PSAP +ve.
**May be positive in hindgut [[neuroendocrine tumour]]s.<ref name=pmid>{{Cite journal  | last1 = Azumi | first1 = N. | last2 = Traweek | first2 = ST. | last3 = Battifora | first3 = H. | title = Prostatic acid phosphatase in carcinoid tumors. Immunohistochemical and immunoblot studies. | journal = Am J Surg Pathol | volume = 15 | issue = 8 | pages = 785-90 | month = Aug | year = 1991 | doi =  | PMID = 1712549 }}</ref>
*p63 -ve.
*p63 -ve.
*HMWCK (34betaE12) -ve.
*HMWCK (34betaE12) -ve.
Line 393: Line 345:
****A. '''CA'''ncer of the '''P'''rostate.
****A. '''CA'''ncer of the '''P'''rostate.


====Prostate versus urothelium====
Other IHC stains:
*Prostate: PSA +ve, CK20 -ve, CK7 -ve.
*AR +ve -- in prostate confined cancer.
*Urothelial: CK20 +ve, CK7 +ve, PSA -ve.
**Usually -ve in lymph node +ve disease.<ref name=pmid20878946>{{Cite journal  | last1 = Fleischmann | first1 = A. | last2 = Rocha | first2 = C. | last3 = Schobinger | first3 = S. | last4 = Seiler | first4 = R. | last5 = Wiese | first5 = B. | last6 = Thalmann | first6 = GN. | title = Androgen receptors are differentially expressed in Gleason patterns of prostate cancer and down-regulated in matched lymph node metastases. | journal = Prostate | volume = 71 | issue = 5 | pages = 453-60 | month = Apr | year = 2011 | doi = 10.1002/pros.21259 | PMID = 20878946 }}</ref>


Note:
Note:
*AMACR not useful - positive in ~ 50% of [[UCC]].<ref name=pmid16315020>{{Cite journal  | last1 = Langner | first1 = C. | last2 = Rupar | first2 = G. | last3 = Leibl | first3 = S. | last4 = Hutterer | first4 = G. | last5 = Chromecki | first5 = T. | last6 = Hoefler | first6 = G. | last7 = Rehak | first7 = P. | last8 = Zigeuner | first8 = R. | title = Alpha-methylacyl-CoA racemase (AMACR/P504S) protein expression in urothelial carcinoma of the upper urinary tract correlates with tumour progression. | journal = Virchows Arch | volume = 448 | issue = 3 | pages = 325-30 | month = Mar | year = 2006 | doi = 10.1007/s00428-005-0129-6 | PMID = 16315020 }}</ref>
*Bcl-2 marks basal cells in prostate cancer.<ref name=pmid20189848>{{Cite journal  | last1 = Boran | first1 = C. | last2 = Kandirali | first2 = E. | last3 = Yilmaz | first3 = F. | last4 = Serin | first4 = E. | last5 = Akyol | first5 = M. | title = Reliability of the 34βE12, keratin 5/6, p63, bcl-2, and AMACR in the diagnosis of prostate carcinoma. | journal = Urol Oncol | volume = 29 | issue = 6 | pages = 614-23 | month =  | year =  | doi = 10.1016/j.urolonc.2009.11.013 | PMID = 20189848 }}</ref>
 
====Prostate carcinoma versus urothelial carcinoma====
The ISUP panel recommends:<ref name=pmid25025364>{{cite journal |author=Amin MB, Epstein JI, Ulbright TM, ''et al.'' |title=Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference |journal=Am. J. Surg. Pathol. |volume=38 |issue=8 |pages=1017–22 |year=2014 |month=August |pmid=25025364 |doi=10.1097/PAS.0000000000000254 |url=}}</ref>
*PSA +ve (-ve in UCC).
*GATA3 -ve (+ve in UCC).
 
Another panel - if GATA3 isn't available:
*Prostate: PSA +ve, p63 -ve, HWMCK -ve.
*Urothelial: p63 +ve, HWMCK +ve, PSA -ve.
 
Notes:
*AMACR not useful; it is positive in ~50% of [[UCC]].<ref name=pmid16315020>{{Cite journal  | last1 = Langner | first1 = C. | last2 = Rupar | first2 = G. | last3 = Leibl | first3 = S. | last4 = Hutterer | first4 = G. | last5 = Chromecki | first5 = T. | last6 = Hoefler | first6 = G. | last7 = Rehak | first7 = P. | last8 = Zigeuner | first8 = R. | title = Alpha-methylacyl-CoA racemase (AMACR/P504S) protein expression in urothelial carcinoma of the upper urinary tract correlates with tumour progression. | journal = Virchows Arch | volume = 448 | issue = 3 | pages = 325-30 | month = Mar | year = 2006 | doi = 10.1007/s00428-005-0129-6 | PMID = 16315020 }}</ref>
*CK7 and CK20 are typically negative in prostate carcinoma, and classically positive in urothelial carcinoma.
*CK34betaE12 may be positive in prostate cancer; 43% of cases in one small series of cases with lymph node metastases.<ref name=pmid9024071>{{Cite journal  | last1 = Googe | first1 = PB. | last2 = McGinley | first2 = KM. | last3 = Fitzgibbon | first3 = JF. | title = Anticytokeratin antibody 34 beta E12 staining in prostate carcinoma. | journal = Am J Clin Pathol | volume = 107 | issue = 2 | pages = 219-23 | month = Feb | year = 1997 | doi =  | PMID = 9024071 }}</ref>
 
===Rate of utilization===
*Dependent on practise setting.
**One tertiary academic institution uses it on ~ 40% of cases.<ref>{{Cite journal  | last1 = Watson | first1 = K. | last2 = Wang | first2 = C. | last3 = Yilmaz | first3 = A. | last4 = Bismar | first4 = TA. | last5 = Trpkov | first5 = K. | title = Use of immunohistochemistry in routine workup of prostate needle biopsies: a tertiary academic institution experience. | journal = Arch Pathol Lab Med | volume = 137 | issue = 4 | pages = 541-5 | month = Apr | year = 2013 | doi = 10.5858/arpa.2012-0145-OA | PMID = 23273390 }}</ref>


==Molecular changes in prostate cancer==
==Molecular changes in prostate cancer==
Line 409: Line 379:
==Sign out==
==Sign out==
===Prostatectomy specimens===
===Prostatectomy specimens===
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].
*A prostatectomy that appears to be negative should be worked-up. This is discuss in the ''[[negative prostatectomy]]'' article.
*[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].
 
<pre>
A. LYMPH NODES, RIGHT PELVIC, EXCISION:
- ONE LYMPH NODE NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 1 ).
 
B. LYMPH NODES, LEFT PELVIC, EXCISION:
- ONE LYMPH NODE NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 1 ).
 
C. PROSTATE GLAND AND SEMINAL VESICLES, RADICAL PROSTATECTOMY:
- ADENOCARCINOMA, GLEASON SCORE 7/10 (3+4), pT2c pN0.
-- SURGICAL MARGINS NEGATIVE.
-- PLEASE SEE TUMOUR SUMMARY.
</pre>
 
===Transurethral resection of prostate===
<pre>
Prostate Tissue, Transurethral Resection of Prostate (TURP):
- ADENOCARCINOMA, Gleason score 6/10 (3+3);
-- Approximately 2% of tissue involved;
-- Please see tumour summary.
 
Comment:
The World Health Organization (WHO) grade is: 1 out of 5.
</pre>
 
<pre>
Prostate Tissue, Transurethral Resection of Prostate (TURP):
- ADENOCARCINOMA, Gleason score 7/10 (3+4);
-- Approximately 4% of tissue involved;
-- Please see tumour summary.
- Benign inflamed urothelium.
 
Comment:
The World Health Organization (WHO) grade is: 2 out of 5. Gleason pattern 3 represents 90% of the tumour, and Gleason pattern 4 represents 10% of the tumour.
</pre>
 
====Block letters====
<pre>
PROSTATE TISSUE, TRANSURETHRAL RESECTION OF PROSTATE (TURP):
- ADENOCARCINOMA, GLEASON SCORE 7/10 (3+4);
- APPROXIMATELY 5% OF TISSUE INVOLVED;
- PLEASE SEE TUMOUR SUMMARY.
 
 
TUMOUR SUMMARY - TRANSURETHRAL RESECTION OF PROSTATE (TURP).
 
PROCEDURE: TRANSURETHRAL PROSTATIC RESECTION.
SPECIMEN SIZE: WEIGHT: 10 GRAMS.
HISTOLOGIC TYPE:  ADENOCARCINOMA (ACINAR, NOT OTHERWISE SPECIFIED).
 
HISTOLOGIC GRADING:
PRIMARY PATTERN: 3.
SECONDARY PATTERN: 4 (40% OF TUMOUR).
TOTAL GLEASON SCORE: 7 (3+4).
 
TUMOUR QUANTITATION - PERCENTAGE OF PROSTATIC TISSUE INVOLVED BY TUMOUR: 80 %.
 
PERIPROSTATIC FAT INVASION: NOT IDENTIFIED.
SEMINAL VESICLE INVASION: NOT IDENTIFIED.
LYMPH-VASCULAR INVASION: NOT IDENTIFIED.
PERINEURAL INVASION: NOT IDENTIFIED.
 
ADDITIONAL PATHOLOGIC FINDINGS:
HIGH-GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA (HGPIN).
NODULAR PROSTATIC HYPERPLASIA.
CHRONIC INFLAMMATION.
</pre>
 
<pre>
PROSTATE TISSUE, TRANSURETHRAL RESECTION OF THE PROSTATE (TURP):
- ADENOCARCINOMA, GLEASON SCORE 6/10 (3+3);
- APPROXIMATELY 5% OF TISSUE INVOLVED;
- PLEASE SEE TUMOUR SUMMARY.
</pre>
 
<pre>
Prostate Tissue, Transurethral Resection of Prostate (TURP):
- Adenocarcinoma, Gleason score 7 (3+4)
- Approximately 3% of sampled tissue involved
- Please see tumour summary
 
Tumour summary:
Procedure: Transurethral resection of prostate
Specimen weight: 11.7 g
Histologic type: Adenocarcinoma, acinar type
 
Histologic grade:
Primary pattern: 3
Secondary pattern: 4 (<15% of tumor)
Total Gleason score: 7/10 (3+4)
 
Tumor volume: 3% of tissue
 
Periprostate fat invasion: Periprostatic fat not identified
Seminal vesicle invasion: Seminal vesicle not identified
Lymphovascular inasion: Not identified
Perineural invasion: Not identified
 
Additional findings:
Glandular and stromal hyperplasia
Mild chronic inflammation
</pre>


===Biopsy specimens===
===Biopsy specimens===
Line 423: Line 496:
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 name=pmid15223967>{{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>
*‡ "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 name=pmid15223967>{{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>
**There is disagreement on how one should measure patchy cancer (cancer when there is interspersed normal). Epstein believes one should include the interspersed benign if the cancer is patchy, as the the groupings of tumour likely join out of the plane of section.<ref name=pmid21788055>{{Cite journal  | last1 = Epstein | first1 = JI. | title = Prognostic significance of tumor volume in radical prostatectomy and needle biopsy specimens. | journal = J Urol | volume = 186 | issue = 3 | pages = 790-7 | month = Sep | year = 2011 | doi = 10.1016/j.juro.2011.02.2695 | PMID = 21788055 }}</ref>
**There is disagreement on how one should measure patchy cancer (cancer when there is interspersed normal). Epstein believes one should include the interspersed benign if the cancer is patchy, as the groupings of tumour likely join out of the plane of section.<ref name=pmid21788055>{{Cite journal  | last1 = Epstein | first1 = JI. | title = Prognostic significance of tumor volume in radical prostatectomy and needle biopsy specimens. | journal = J Urol | volume = 186 | issue = 3 | pages = 790-7 | month = Sep | year = 2011 | doi = 10.1016/j.juro.2011.02.2695 | PMID = 21788055 }}</ref>
**A review by Epstein on the topic of tumour volume suggests it does not have predictive value in multivariante analyses.<ref name=pmid21788055/>
**A review by Epstein on the topic of tumour volume suggests it does not have predictive value in multivariante analyses.<ref name=pmid21788055/>
**The biopsy tumour volume is a predictor of Gleason score upgrading on prostatectomy.<ref name=pmid22688447>{{Cite journal  | last1 = Fu | first1 = Q. | last2 = Moul | first2 = JW. | last3 = Bañez | first3 = LL. | last4 = Sun | first4 = L. | last5 = Mouraviev | first5 = V. | last6 = Xie | first6 = D. | last7 = Polascik | first7 = TJ. | title = Association between percentage of tumor involvement and Gleason score upgrading in low-risk prostate cancer. | journal = Med Oncol | volume = 29 | issue = 5 | pages = 3339-44 | month = Dec | year = 2012 | doi = 10.1007/s12032-012-0270-4 | PMID = 22688447 }}</ref>


====Completely negative====
====Completely negative====
Line 463: Line 537:
L. PROSTATE, LEFT MEDIAL INFERIOR, BIOPSY:
L. PROSTATE, LEFT MEDIAL INFERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.
- BENIGN PROSTATE TISSUE.
</pre>
====Negative biopsy in surveillance====
<pre>
COMMENT:
The previous results are noted. The absence of cancer in this biopsy may
be due to sampling.
</pre>
</pre>


Line 524: Line 605:
- PERINEURAL INVASION PRESENT.
- PERINEURAL INVASION PRESENT.
</pre>
</pre>
=====Tumour summaries=====
*These are not completely without controversy.
*It should be noted that treatment is driven by the highest Gleason score.{{fact}}


<pre>
<pre>
Line 546: Line 631:
</pre>
</pre>


=Intraductal spread of prostate cancer=
<pre>
==Intraductal carcinoma of the prostate==
TUMOUR SUMMARY - PROSTATE CORE BIOPSIES:
*[[AKA]] ''[[intraductal carcinoma]]''.
- HISTOLOGIC TYPE: ADENOCARCINOMA (ACINAR, NOT OTHERWISE SPECIFIED).
*[[AKA]] ''intraductal prostate carcinoma''.
- HIGHEST GLEASON SCORE: 8 (4+4).
===General===
- SUMMARY GLEASON SCORE: 7 (4+3).
*Associated with a poor prognosis.<ref name=pmid19246509>{{Cite journal  | last1 = Henry | first1 = PC. | last2 = Evans | first2 = AJ. | title = Intraductal carcinoma of the prostate: a distinct histopathological entity with important prognostic implications. | journal = J Clin Pathol | volume = 62 | issue = 7 | pages = 579-83 | month = Jul | year = 2009 | doi = 10.1136/jcp.2009.065003 | PMID = 19246509 }}</ref>
- PERCENT OF TUMOUR WITH PATTERN 4: 55%.
*Strong association with aggressive invasive carcinomas on prostatectomy when identified in isolation on biopsy.<ref name=pmid20723921>{{Cite journal  | last1 = Robinson | first1 = BD. | last2 = Epstein | first2 = JI. | title = Intraductal carcinoma of the prostate without invasive carcinoma on needle biopsy: emphasis on radical prostatectomy findings. | journal = J Urol | volume = 184 | issue = 4 | pages = 1328-33 | month = Oct | year = 2010 | doi = 10.1016/j.juro.2010.06.017 | PMID = 20723921 }}</ref>
- PERCENT OF TUMOUR WITH PATTERN 5: 0%.


===Microscopic===
- NUMBER OF CORES POSITIVE: 12.
====Major criteria====
- TOTAL NUMBER OF CORES: 12.
Required major criteria:<ref name=pmid22692290>{{Cite journal  | last1 = Shah | first1 = RB. | last2 = Zhou | first2 = M. | title = Atypical cribriform lesions of the prostate: clinical significance, differential diagnosis and current concept of intraductal carcinoma of the prostate. | journal = Adv Anat Pathol | volume = 19 | issue = 4 | pages = 270-8 | month = Jul | year = 2012 | doi = 10.1097/PAP.0b013e31825c6c0e | PMID = 22692290 }}</ref><ref name=pmid17616999>{{Cite journal  | last1 = Cohen | first1 = RJ. | last2 = Wheeler | first2 = TM. | last3 = Bonkhoff | first3 = H. | last4 = Rubin | first4 = MA. | title = A proposal on the identification, histologic reporting, and implications of intraductal prostatic carcinoma. | journal = Arch Pathol Lab Med | volume = 131 | issue = 7 | pages = 1103-9 | month = Jul | year = 2007 | doi = 10.1043/1543-2165(2007)131[1103:APOTIH]2.0.CO;2 | PMID = 17616999 }}</ref>
- TOTAL LINEAR MILLIMETERS OF NEEDLE CORE TISSUE: 178 MM.
#Glands 2x normal (peripheral zone) glands.
- PERCENT OF NEEDLE CORE TISSUE THAT IS TUMOUR: 80%.
#Basal cell present (proven by IHC).
#"Cytologically malignant cells" = nuclear hyperchromasia, nuclear enlargement, nucleoli.
#Fills the lumen ("expansile") but does not have to be "solid".
#*Solid = no spaces between the cells.


Additional (major) criterion:<ref name=pmid22692290/>
- PERINEURAL INVASION: PRESENT.
*Comedo[[necrosis]].
- PERIPROSTATIC FAT INVASION: PRESENT.
- LYMPHOVASCULAR INVASION: NOT IDENTIFIED.
- SEMINAL VESICLE INVASION: NOT IDENTIFIED.
</pre>


====Minor criteria====
===Seminal vesicle/ejaculatory duct invasion on biopsy===
Minor criteria:<ref name=pmid22692290/>
<pre>
#Branching of ducts at right angles.
COMMENT:
#Rounded/smooth gland outlines.
The seminal vesicles and ejaculatory ducts have the same histology; thus, it is not
#Two cell populations:
usually possible to confidently differentiate them in a needle biopsy.
#*Malignant population (enlarged nuclei with hyperchromasia and nucleoli) = peripheral location in gland.
#*Benign population (smaller nuclei, no nucleoli) = central location in gland.


DDx:
SV/ED invasion was demonstrated with CK7, CK34betaE12/AMACR, PSA and p63 immunostaining.
*[[High-grade prostatic intraepithelial neoplasia]] (HGPIN).
The tumour is PSA and AMACR positive.
</pre>


===IHC===
=Intraductal spread of prostate cancer=
Features - basal cells present:
==Intraductal carcinoma of the prostate==
*CK34betaE12 +ve.
*[[AKA]] ''[[intraductal carcinoma]]''.
*p63 +ve.
*[[AKA]] ''intraductal prostate carcinoma''.
{{Main|Intraductal carcinoma of the prostate}}


=Unusual forms of prostate cancer=
=Unusual forms of prostate cancer=
Line 586: Line 670:
*[[AKA]] ''ductal adenocarcinoma of the prostate''.
*[[AKA]] ''ductal adenocarcinoma of the prostate''.
*[[AKA]] ''prostatic adenocarcinoma, large duct type''.
*[[AKA]] ''prostatic adenocarcinoma, large duct type''.
===General===
{{Main|Ductal adenocarcinoma of the prostate gland}}
*Sometimes it is referred to as ''endometrioid'' or ''endometrial'' adenocarcinoma; both terms are discouraged.<ref name=pmid18773743>{{Cite journal  | last1 = Samaratunga | first1 = H. | last2 = Delahunt | first2 = B. | title = Ductal adenocarcinoma of the prostate: current opinion and controversies. | journal = Anal Quant Cytol Histol | volume = 30 | issue = 4 | pages = 237-46 | month = Aug | year = 2008 | doi =  | PMID = 18773743 }}</ref>
*Not completely uncontroversial - may represent ''acinar adenocarcinoma'' with periurethral ducts involvement.<ref name=pmid10403300>{{Cite journal  | last1 = Bock | first1 = BJ. | last2 = Bostwick | first2 = DG. | title = Does prostatic ductal adenocarcinoma exist? | journal = Am J Surg Pathol | volume = 23 | issue = 7 | pages = 781-5 | month = Jul | year = 1999 | doi =  | PMID = 10403300 }}</ref>
*More aggressive than conventional (acinar) prostate carcinoma.
 
===Microscopic===
Features:<ref name=Ref_GUP88>{{Ref GUP|88}}</ref>
#Pseudostratified (crowded appearing) columnar (or cigar-shaped) nuclei - '''key feature'''.
#*Vaguely resembles [[colonic adenocarcinoma]].
#Compatible architecture:
#*Papillary.
#*Cribriform.
#*Single gland (large glands).
#*Endometrioid - vaguely looks like [[endometrioid endometrial carcinoma]] (with back-to-back glands).
#>= 50% of tumour.<ref name=pmid21383610/>{{fact}}
#*If ductal component <50%, it is a conventional (acinar) adenocarcinoma with a ductal component.
 
Notes:
*Proportion of ductal component should be quantified:
**<10% ductal component of no prognostic significance.<ref name=pmid21383610>{{Cite journal  | last1 = Amin | first1 = A. | last2 = Epstein | first2 = JI. | title = Pathologic stage of prostatic ductal adenocarcinoma at radical prostatectomy: effect of percentage of the ductal component and associated grade of acinar adenocarcinoma. | journal = Am J Surg Pathol | volume = 35 | issue = 4 | pages = 615-9 | month = Apr | year = 2011 | doi = 10.1097/PAS.0b013e31820eb25b | PMID = 21383610 }}</ref>
 
Images:
*[http://path.upmc.edu/cases/case203.html Prostatic ductal adenocarcinoma - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case711.html Prostatic ductal adenocarcinoma - another case - several images (upmc.edu)].
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024288/figure/F1/ Prostatic ductal adenocarcinoma - F1 (nih.gov)].
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024288/figure/F2/ Prostatic ductal adenocarcinoma - F2 (nih.gov)].
*[http://www.webpathology.com/image.asp?n=13&Case=23 Prostatic ductal adenocarcinoma (webpathology.com)].
 
===IHC===
Features:<ref name=pmid22583364>{{Cite journal  | last1 = Tarján | first1 = M. | last2 = Lenngren | first2 = A. | last3 = Hellberg | first3 = D. | last4 = Tot | first4 = T. | title = Immunohistochemical verification of ductal differentiation in prostate cancer. | journal = APMIS | volume = 120 | issue = 6 | pages = 510-8 | month = Jun | year = 2012 | doi = 10.1111/j.1600-0463.2011.02862.x | PMID = 22583364 }}</ref>
*p53 +ve in ~ 75% of cases.
*Ki-67 high in ~ 70% of cases.
*Chromogranin A +ve (cytoplasm) in ~ 70% of cases.
 
Others:<ref name=pmid20368883>{{Cite journal  | last1 = Kumar | first1 = A. | last2 = Mukherjee | first2 = SD. | title = Metastatic ductal carcinoma of the prostate: a rare variant responding to a common treatment. | journal = Can Urol Assoc J | volume = 4 | issue = 2 | pages = E50-4 | month = Apr | year = 2010 | doi =  | PMID = 20368883 }}</ref>
*PSA +ve.


==PIN-like prostatic ductal adenocarcinoma==
==PIN-like prostatic ductal adenocarcinoma==
===General===
{{Main|High-grade prostatic intraepithelial neoplasia-like ductal adenocarcinoma of the prostate}}
*Recently described.<ref name=pmid16607376>{{Cite journal  | last1 = Hameed | first1 = O. | last2 = Humphrey | first2 = PA. | title = Stratified epithelium in prostatic adenocarcinoma: a mimic of high-grade prostatic intraepithelial neoplasia. | journal = Mod Pathol | volume = 19 | issue = 7 | pages = 899-906 | month = Jul | year = 2006 | doi = 10.1038/modpathol.3800601 | PMID = 16607376 }}</ref><ref name=pmid20438402>{{Cite journal  | last1 = Lee | first1 = TK. | last2 = Miller | first2 = JS. | last3 = Epstein | first3 = JI. | title = Rare histological patterns of prostatic ductal adenocarcinoma. | journal = Pathology | volume = 42 | issue = 4 | pages = 319-24 | month = Jun | year = 2010 | doi = 10.3109/00313021003767314 | PMID = 20438402 }}</ref>
*May be confused with [[prostatic intraepithelial neoplasia]] (PIN).
 
===Microscopic===
Features:<ref name=pmid16607376>{{Cite journal  | last1 = Hameed | first1 = O. | last2 = Humphrey | first2 = PA. | title = Stratified epithelium in prostatic adenocarcinoma: a mimic of high-grade prostatic intraepithelial neoplasia. | journal = Mod Pathol | volume = 19 | issue = 7 | pages = 899-906 | month = Jul | year = 2006 | doi = 10.1038/modpathol.3800601 | PMID = 16607376 }}</ref>
*Stratified malignant epithelium.
 
Note:
*Vaguely similar to a tubular adenoma of the colon.
 
DDx:
*[[HGPIN]].
 
Image:
*[http://www.nature.com/modpathol/journal/v19/n7/fig_tab/3800601f1.html#figure-title PIN-like adenocarcinoma (nature.com)].


==Foamy gland carcinoma==
==Foamy gland carcinoma==
*[[AKA]] ''foamy gland adenocarcinoma''.<ref name=pmid19033862/>
*[[AKA]] ''foamy gland adenocarcinoma''.<ref name=pmid19033862>{{Cite journal  | last1 = Zhao | first1 = J. | last2 = Epstein | first2 = JI. | title = High-grade foamy gland prostatic adenocarcinoma on biopsy or transurethral resection: a morphologic study of 55 cases. | journal = Am J Surg Pathol | volume = 33 | issue = 4 | pages = 583-90 | month = Apr | year = 2009 | doi = 10.1097/PAS.0b013e31818a5c6c | PMID = 19033862 }}</ref>
===General===
{{Main|Foamy gland carcinoma}}
*Rare.
*Usually low grade, i.e. Gleason score 6/10.<ref name=pmid19033862>{{Cite journal  | last1 = Zhao | first1 = J. | last2 = Epstein | first2 = JI. | title = High-grade foamy gland prostatic adenocarcinoma on biopsy or transurethral resection: a morphologic study of 55 cases. | journal = Am J Surg Pathol | volume = 33 | issue = 4 | pages = 583-90 | month = Apr | year = 2009 | doi = 10.1097/PAS.0b013e31818a5c6c | PMID = 19033862 }}</ref>
 
===Microscopic===
Features:
*Increased glandular density  - '''key feature'''.
*Eosinophilic intraluminal amorphous secretions - '''key feature'''.
*Abundant foamy cytoplasm.
*Tufted glandular border.
*Gland size larger than "typical" prostate cancer.
 
Note:
*Prominent [[nucleoli]] usually infrequent ''or'' absent!<ref name=pmid19033862/>
 
DDx:
*[[Adenosis of the prostate]].
 
Image:
*[http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f11.html#figure-title Foamy gland carcinoma (nature.com)].


==Atrophic prostate carcinoma==
==Atrophic prostate carcinoma==
*[[AKA]] ''atrophic carcinoma''.
*[[AKA]] ''atrophic carcinoma''.
 
{{Main|Atrophic prostate carcinoma}}
===General===
*Uncommon.
 
Note:
*An atrophic component in prostate cancer is common; one study identified it in ~15% of cases.<ref name=pmid9620026>{{Cite journal  | last1 = Kaleem | first1 = Z. | last2 = Swanson | first2 = PE. | last3 = Vollmer | first3 = RT. | last4 = Humphrey | first4 = PA. | title = Prostatic adenocarcinoma with atrophic features: a study of 202 consecutive completely embedded radical prostatectomy specimens. | journal = Am J Clin Pathol | volume = 109 | issue = 6 | pages = 695-703 | month = Jun | year = 1998 | doi =  | PMID = 9620026 }}</ref>
 
===Microscopic===
Features:
*Scant cytoplasm.
*Nuclear features of conventional prostate cancer (nucleoli, nuclear enlargement).
*Increased gland density.
 
DDx:
*[[Atrophy of the prostate]].
 
Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f12.html#figure-title Atrophic carcinoma (nature.com)].


==Mucinous prostate carcinoma==
==Mucinous prostate carcinoma==
===General===
{{Main|Mucinous adenocarcinoma of the prostate}}
*Rare.
 
===Microscopic===
Features:
*Cytologically malignant cells floating in mucin.
*> 25% of tumour mucinous.<ref name=pmid14976541>{{cite journal |author=Grignon DJ |title=Unusual subtypes of prostate cancer |journal=Mod. Pathol. |volume=17 |issue=3 |pages=316–27 |year=2004 |month=March |pmid=14976541 |doi=10.1038/modpathol.3800052 |url=}}</ref>
**One study suggests '''>=''' 25%.<ref>{{cite journal |author=Osunkoya AO, Nielsen ME, Epstein JI |title=Prognosis of mucinous adenocarcinoma of the prostate treated by radical prostatectomy: a study of 47 cases |journal=Am. J. Surg. Pathol. |volume=32 |issue=3 |pages=468–72 |year=2008 |month=March |pmid=18300802 |doi=10.1097/PAS.0b013e3181589f72 |url=}}</ref>
 
DDx:
*Metastatic [[mucinous carcinoma]].
 
Notes:
*[[Mucinous carcinoma]] - percentage required to call varies by site.


==Pseudohyperplastic prostatic adenocarcinoma==
==Pseudohyperplastic prostatic adenocarcinoma==
===General===
*[[AKA]] ''pseudohyperplastic adenocarcinoma''.
*Rare.
{{Main|Pseudohyperplastic prostatic adenocarcinoma}}
 
===Microscopic===
Features:<ref name=Ref_GUP77>{{Ref GUP|77}}</ref><ref name=pmid14688829>{{cite journal |author=Arista-Nasr J, Martinez-Benitez B, Valdes S, Hernández M, Bornstein-Quevedo L |title=Pseudohyperplastic prostatic adenocarcinoma in transurethral resections of the prostate |journal=Pathol. Oncol. Res. |volume=9 |issue=4 |pages=232–5 |year=2003 |pmid=14688829 |doi=PAOR.2003.9.4.0232 |url=}}</ref>
*Medium to large glands with an atypical morphology - '''key low power feature''':
**Papillary or pseudopapillary infoldings, luminal undulations, branching or cystic dilatation.
*Nuclear features of conventional prostate cancer (nucleoli, nuclear enlargement).
 
Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f13.html Pseudohyperplastic prostatic adenocarcinoma (nature.com)].
 
Notes:
*Usually associated with conventional (acinar) prostate adenocarcinoma.
*Pale abundant cytoplasm - similar to normal prostate.


==Prostatic signet ring cell carcinoma==
==Prostatic signet ring cell carcinoma==
Line 726: Line 700:
*Signet ring cells - see ''[[basics]]'' article.
*Signet ring cells - see ''[[basics]]'' article.


Image:
DDx:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2996149/figure/F1/ Prostatic SRC (nih.gov)].
*Acinar adenocarcinoma - Gleason pattern 4 with very small glands.


==Sarcomatoid prostate carcinoma==
====Images====
*[[AKA]] ''carcinosarcoma''.
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2996149/figure/F1/ Prostatic SRCC (nih.gov)].
===General===
*[http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800052f7.html#figure-title Prostatic SRCC (nature.com)].
*Rare.
*[http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800052f8.html Prostatic SRCC (nature.com)].
*[http://www.webpathology.com/image.asp?case=23&n=34 Prostatic SRCC (webpathology.com)] - looks like ''acinar adenocarcinoma''.


===Microscopic===
===Stains===
Features:<ref name=Ref_GUP80>{{Ref GUP|77 & 80}}</ref>
*Alcian blue-PAS stain +ve.
*Biphasic tumour:
*[[PAS stain|PAS]] -- 50% of cases +ve.<ref name=pmid21123640/>
*#Spindle cells (sarcomatous component).
*[[Alcian blue stain|Alcian blue]] -- 44% of cases +ve.<ref name=pmid21123640/>
*#*May include components of: [[osteosarcoma]], [[chondrosarcoma]] and/or [[rhabdomyosarcoma]].
*#Glandular component (like conventional prostate carcinoma).


===IHC===
==Sarcomatoid carcinoma of the prostate==
Features - typical:<ref name=Ref_GUP80>{{Ref GUP|77 & 80}}</ref>
{{Main|Sarcomatoid carcinoma of the prostate}}
*PSA +ve.
*Keratin +ve.


==Small cell carcinoma of the prostate gland==
==Small cell carcinoma of the prostate gland==
{{Main|Small cell carcinoma}}
{{Main|Small cell carcinoma of the prostate gland}}
===General===
*Very rare.<ref name=pmid22110988>{{Cite journal  | last1 = Furtado | first1 = P. | last2 = Lima | first2 = MV. | last3 = Nogueira | first3 = C. | last4 = Franco | first4 = M. | last5 = Tavora | first5 = F. | title = Review of small cell carcinomas of the prostate. | journal = Prostate Cancer | volume = 2011 | issue =  | pages = 543272 | month =  | year = 2011 | doi = 10.1155/2011/543272 | PMID = 22110988 }}</ref>
*Most common small cell carcinoma outside of the lung.<ref name=pmid22110988/>
*Poor prognosis.
 
===Microscopic===
Features:
*Small cells with:
**Nuclear moulding.
**Stippled chromatin.
**High [[NC ratio]].
*+/-High-grade acinar adenocarcinoma, i.e. conventional prostate carcinoma, seen in ~50% of cases.<ref name=pmid22110988/>
 
Notes:
*Similar to [[small cell carcinoma of the lung]].
*High-grade squamoid component favours metastatic [[urothelial carcinoma]].
**UCC usu. HWCK +ve.
 
Images:
*[http://www.webpathology.com/image.asp?case=23&n=6 SmCC of the prostate - low mag. (webpathology.com)].
*[http://www.webpathology.com/image.asp?n=7&Case=23 SmCC of the prostate - high mag. (webpathology.com)].
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3200299/figure/fig1/ SmCC of the prostate - low mag. (nih.gov)].
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3200299/figure/fig3/ SmCC of the prostate - high mag. (nih.gov)].
 
===IHC===
Features:<ref name=pmid22110988/>
*PSA weak +ve/-ve.
*Chromogranin +ve.


==Adenoid cystic/basal cell carcinoma of the prostate==
==Adenoid cystic/basal cell carcinoma of the prostate==
*Abbreviated ''ACBCC''.
*Abbreviated ''ACBCC''.
===General===
{{Main|Adenoid cystic/basal cell carcinoma of the prostate}}
*Rare.
*Typically indolent - may be aggressive.<ref name=pmid14657711>{{Cite journal  | last1 = Iczkowski | first1 = KA. | last2 = Ferguson | first2 = KL. | last3 = Grier | first3 = DD. | last4 = Hossain | first4 = D. | last5 = Banerjee | first5 = SS. | last6 = McNeal | first6 = JE. | last7 = Bostwick | first7 = DG. | title = Adenoid cystic/basal cell carcinoma of the prostate: clinicopathologic findings in 19 cases. | journal = Am J Surg Pathol | volume = 27 | issue = 12 | pages = 1523-9 | month = Dec | year = 2003 | doi =  | PMID = 14657711 }}</ref>
 
===Microscopic===
Features:
*[[Adenoid cystic carcinoma]]-like and [[basal cell adenoma]]-like:
**Nests of cells that have round spaces filled by whispy blue mucin.
**Dense collagenous stroma.


Images:
==Postradiation prostate cancer==
*[http://www.webpathology.com/image.asp?case=23&n=15 Adenoid basal cell tumour (webpathology.com)].
{{Main|Postradiation prostate cancer}}
*[http://www.webpathology.com/image.asp?case=23&n=16 Adenoid basal cell tumour (webpathology.com)].


===IHC===
=Metastatic disease and other cancers of the prostate=
*HER2/neu +ve (strong).<ref name=pmid17142577>{{Cite journal  | last1 = Iczkowski | first1 = KA. | last2 = Montironi | first2 = R. | title = Adenoid cystic/basal cell carcinoma of the prostate strongly expresses HER-2/neu. | journal = J Clin Pathol | volume = 59 | issue = 12 | pages = 1327-30 | month = Dec | year = 2006 | doi = 10.1136/jcp.2005.035147 | PMID = 17142577 }}</ref>
==Urothelial carcinoma==
{{Main|Urothelial carcinoma of the urethra}}


=See also=
=See also=
Line 804: Line 739:


[[Category:Genitourinary pathology]]
[[Category:Genitourinary pathology]]
[[Category:Prostate carcinoma]]
Michael
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