Prostate cancer

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This article deals with prostate cancer. The vast majority of prostate cancers are carcinomas, i.e. prostatic adenocarcinoma (AKA adenocarcinoma of the prostate, prostatic carcinoma). Benign pathology of the prostate gland is dealt with in the prostate gland article.

Conventional prostate cancer

General

  • Very common.
  • Increasing incidence with age - the age in years is an approximation of the percentage of men with prostate cancer.
  • Usually an indolent course - most old men die with prostate cancer not from prostate cancer.

Management

The management changes between Gleason 6, 7 & 8; typically, the implications are:

  • Gleason 6: watchful waiting or radioactive seeds; surgery if patient wants.
  • Gleason 7: do something - often surgery.
  • Gleason 8+: bad cancer - do something quickly!

Bottom line:

  • You want to be sure when you call something Gleason pattern 4.

Microscopic

Criteria as a list

Major criteria (the ABCs of prostate pathology):[1]

  1. Architecture.
    • Increased gland density.
    • Small circular glands.
      • In rare subtypes - large branching glands.
    • "Infiltrative growth" pattern - malignant glands between benign ones.
  2. Basal cells lacking.
  3. Cytological abnormalities:
    • Nuclear enlargement.
    • Nucleoli.

Minor criteria:[1]

  1. Nuclear hyperchromasia.
  2. Wispy blue mucin.
  3. Pink amorphous secretions.
  4. Intraluminal crystalloid.
  5. Amphophilic cytoplasm.
  6. Adjacent HGPIN.
  7. Mitoses - quite rare.

Extent/quantity criteria:

  • There is no agreed upon minimum number of glands; however, one paper suggests that agreement among experts is low with 5 or less glands.[4]
    • Thus, it has been suggested that six or more glands should be present to diagnose cancer.[4]

Low power features

  • Architecture is the key to diagnosing low grade cancer.
    • 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

  • Nuclei.
    • Hyperchromatic nuclei (like in HGPIN).
    • Nuclear enlargement.
      • Difficult to appreciate (if cancer isn't side-by-side with normal prostate).
      • 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:

  • Mitoses are not a common feature - don't waste time looking for them.

Mimics

Mimics of prostate adenocarcinoma:[5]

Entity Key feature Detailed microscopic Other Image
Adenosis (AKA atypical adenomatous hyperplasia) gradual transition between normal & small gland (NOT two populations) 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 AAH (webpathology.com)
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 (???) Sclerosing adenosis (webpathology.com)
Atrophy sharp angulation of gland nuclear hyperchromasia, scant cytoplasm may appear right beside non-atrophic tissue Atrophy (webpathology.com), Partial atrophy (webpathology.com) Sclerotic atrophy (webpathology.com)
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 BCH (webpathology.com)
Bulbourethral gland no nuclear atypia clear cytoplasm apex of prostate Cowper gland (webpathology.com)
Seminal vesicles / ejaculatory ducts lipofuscin (yellow granular material in cytoplasm), smudge cells (smeared appearance + hyperchromatic) 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 SV - high mag. (WC), SV - low mag. (WC)
Radiation effect marked nuclear size variation increased stroma (fibrosis), lack nucleoli ??? history of Rx; uniform nuc. size with Hx of Rx should raise susp. of cancer Radiation changes (webpathology.com), Radiation changes (webpathology.com)
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 Prostatic inflammation (WC)
Vasitis nodosa sperm within ducts, clinical history (usu. post-vasectomy) small tubules, nucleoli common, mild atypia, may "invade" vessels, track along nerves mimics metastatic prostate carcinoma, IHC stains: PSA-, PSAP- VN (webpathology.com)

Memory device: AAABBRS = atrophy, adenosis, adenosis (sclerosing), basal cell hyperplasia, bulbourethral gland, radiation, seminal vesicles.

Gleason grading system

Overview:

  • This system is only one any one talks about.
  • Score range: 6-10.
    • Technically 2-10... but almost no one uses 2-5.
  • Reported as on biopsy as: (primary pattern) + (secondary pattern or tertiary pattern with the highest grade) = sum.
    • 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.
  • 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.[6]
    • 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).[6]

Examples:

  • A biopsy has 80% pattern 4, 16% pattern 3 and 4% pattern 5... it would be reported as: 4+5=9.
  • 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.

Testing yourself:

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.[8]

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.[8]

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:

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.
  • Nests of cells with necrosis at centre.

Image: Gleason pattern 4 - small glands & Gleason pattern 5 - single cells (WC).

Special types

Special types of prostate cancer have set Gleason scores:[9]

Special type Gleason pattern Comment
Ductal carcinoma 4 may be graded 3 or 5[10]
Mucinous carcinoma 4
Sarcomatoid carcinoma 5 glands graded separately
Signet ring cell carcinoma 5
Small cell carcinoma not graded may be graded 5[10]
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 Lung carcinomas (Urothelial carcinoma, Lymphoepithelioma-like carcinoma):

  • Small cell carcinoma.
  • Squamous cell carcinoma.
  • Adenosquamous carcinoma.
  • Adenoid cystic carcinoma.

Staging parameters and margins

Surgical margins

Main article: Surgical margins
  • Positive is tumour touching ink.[11]
    • "Close" margins have an increase recurrence risk.

Notes:

  • 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.
Rates and implication

Positivity rate varies substantially (13-44%):

  • Norway: 26% -- strong dependence on surgeon volume (18% high case load vs. 44% low case load).[12]
  • France: 13-17%.[13]

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.

The impact of positive margins:

  • Significant modest negative affect on long-term outcome in node negative cancers (pT2-4 pN0).[14]
  • Weaker impact than stage and Gleason score.[15]

Extraprostatic extension

Abbreviated EPE.

General:

  • 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.[16]
  • EPE, typically, upstages tumours from T2x to T3a.

Prostatectomy specimens - EPE is present if there is either:

  1. A "significant bulge" in the contour of the prostate at low power and no fibromuscular tissue surrounding the malignant cells.
  2. Malignant cells directly adjacent to peri-prostatic adipose tissue.

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.

Prostate biopsy - EPE is present if:

Seminal vesicle invasion

General:

  • Typically upstages to T3b.

Microscopic:

  • 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.[19][20]

Notes:

  • Invasion of the adventitia (only) would quality as EPE; this is, usually, T3a.

IHC

  • AMACR +ve.
  • AR +ve -- in prostate confined cancer.
    • Usu. -ve in LN +ve disease.[21]
  • PSA +ve.
  • PSAP +ve.
  • p63 -ve.
  • HMWCK (34betaE12) -ve.

Combination immunostains:

  • PIN-4 -- consists of: CK5 + CK14 + p63 + P504S (AMACR).[23][24][25]
    • AKA PIN.
    • AKA CAP.
      • Why CAP?
        • A. CAncer of the Prostate.

Molecular changes in prostate cancer

A fusion gene between TMPRSS2 and ERG is described.[26][27]

  • Both genes are on chromosome 21.
  • Currently not used diagnostically.
  • Fusion gene seen in approximately 50% of prostate cancer.[27]
  • A subset of TMPRSS2-ERG known as 2+Edel (seen in ~7% of all prostate cancer cases) predicts poor survival.[28]

Sign out

Prostatectomy specimens

See: CAP checklist.

Biopsy specimens

Important elements - a list:[1]

  1. Type of cancer, e.g. "prostatic adenocarcinoma, acinar type".
  2. Gleason score including primary and secondary pattern, e.g. "Gleason score 3+4=7".
  3. Number of cores and number involved, e.g. "2/3 cores involved by cancer".
  4. Percent area involved, i.e. how much of the core is cancer, e.g. "75% of specimen is tumour".
  5. Percent area involved that is Gleason pattern 4 or 5, e.g. "25% of the tumour is Gleason pattern 4 or 5".
  6. Presence of perineural invasion.
  7. Presence of extension into fat (extraprostatic extension).

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.[29]

Completely negative

A. PROSTATE, RIGHT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

B. PROSTATE, RIGHT MEDIAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

C. PROSTATE, RIGHT LATERAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

D. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

E. PROSTATE, RIGHT LATERAL INTERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

F. PROSTATE, RIGHT MEDIAL INFERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

H. PROSTATE, LEFT MEDIAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

I. PROSTATE, LEFT LATERAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

J. PROSTATE, LEFT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

K. PROSTATE, LEFT LATERAL INTERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

L. PROSTATE, LEFT MEDIAL INFERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

No glands

F. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN FIBROMUSCULAR TISSUE;
- NO PROSTATIC GLANDULAR TISSUE PRESENT.

Inflammation

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

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

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

Positive

F. PROSTATE, RIGHT MEDIAL INFERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 6/10 (3+3);
- 1/1 CORE INVOLVED; APPROXIMATELY 5% OF TISSUE INVOLVED.

F. PROSTATE, RIGHT MEDIAL INFERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 6/10 (3+3);
- 1/1 CORE INVOLVED; APPROXIMATELY 25% OF TISSUE INVOLVED;
- PERINEURAL INVASION PRESENT.

G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 7/10 (4+3);
- 1/1 CORE INVOLVED; APPROXIMATELY 5% OF TISSUE INVOLVED;
- PERINEURAL INVASION PRESENT.

H. PROSTATE, LEFT MEDIAL SUPERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 8/10 (4+4);
- 1/1 CORE INVOLVED; APPROXIMATELY 15% OF TISSUE INVOLVED.

H. PROSTATE, LEFT MEDIAL SUPERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 8/10 (4+4);
- 1/1 CORE INVOLVED; APPROXIMATELY 15% OF TISSUE INVOLVED;
- PERINEURAL INVASION PRESENT.

TUMOUR SUMMARY - PROSTATE CORE BIOPSIES:
- HISTOLOGIC TYPE: ADENOCARCINOMA (ACINAR, NOT OTHERWISE SPECIFIED).
- TOTAL GLEASON SCORE: 7.
- PRIMARY PATTERN: 4.
- SECONDARY PATTERN: 3.
- PERCENT OF TUMOUR WITH PATTERN HIGHER THAN GRADE 3: 75%.

- NUMBER OF CORES POSITIVE: 10.
- TOTAL NUMBER OF CORES: 12.
- TOTAL LINEAR MILLIMETERS OF NEEDLE CORE TISSUE: 152 MM.
- PERCENT OF NEEDLE CORE TISSUE THAT IS TUMOUR: 44%.

- PERIPROSTATIC FAT INVASION: NOT IDENTIFIED.
- SEMINAL VESICLE INVASION: SEMINAL VESICLE NOT IDENTIFIED.
- LYMPHOVASCULAR INVASION: NOT IDENTIFIED.
- PERINEURAL INVASION: PRESENT.

- ADDITIONAL FINDINGS: HIGH-GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA, CHRONIC INFLAMMATION (FOCAL).

Intraductal spread of prostate cancer

Intraductal carcinoma of the prostate

General

  • Associated with a poor prognosis.[30]
  • Strong association with aggressive invasive carcinomas on prostatectomy when identified in isolation on biopsy.[31]

Microscopic

Features:

  • Malignant cells in glands with basal cells - key feature.
    • Two cell populations:
      1. Obviously malignant cells with enlarged nuclei, granular chromatin, hyperchromasia and nucleoli.
      2. Cells with pale cytoplasm and smaller nuclei.

DDx:

IHC

Features - basal cells present:

  • HMWK +ve.

Unusual forms of prostate cancer

Prostatic ductal adenocarcinoma

  • AKA ductal adenocarcinoma of the prostate.
  • AKA prostatic adenocarcinoma, large duct type.

General

  • Sometimes it is referred to as endometrioid or endometrial adenocarcinoma; both terms are discouraged.[32]
  • Not completely uncontroversial - may represent acinar adenocarcinoma with periurethral ducts involvement.[33]
  • More aggressive than conventional (acinar) prostate carcinoma.

Microscopic

Features:[34]

  • Pseudostratified (crowded appearing) columnar (or cigar-shaped) nuclei - key feature.
  • Variable architecture:
    • Papillary.
    • Cribriform.
    • Single gland (large glands).
    • Endometrioid - vaguely looks like endometrial carcinoma (with back-to-back glands).

Notes:

  • Usually seen in association with conventional (acinar) prostate adenocarcinoma.
    • Proportion of ductal component should be quantified:
      • <10% ductal component of no prognostic significance.[35]

Images:

IHC

Features:[36]

  • p53 +ve in ~ 75% of cases.
  • Ki-67 high in ~ 70% of cases.
  • Chromogranin A +ve (cytoplasm) in ~ 70% of cases.

Others:[37]

  • PSA +ve.

PIN-like prostatic ductal adenocarcinoma

General

Microscopic

Features:[38]

  • Stratified malignant epithelium.

Note:

  • Vaguely similar to a tubular adenoma of the colon.

DDx:

Image:

Foamy gland carcinoma

General

  • Rare.

Microscopic

Features:

  • Tufted glandular border.
  • Abundant eosinophilic (or hyperchromatic) cytoplasm - key feature.
  • Gland size larger than "typical" prostate cancer.

Image: Foamy gland carcinoma (nature.com).

Atrophic prostate carcinoma

  • AKA atrophic carcinoma.

General

  • Uncommon.

Note:

  • An atrophic component in prostate cancer is common; one study identified it in ~15% of cases.[40]

Microscopic

Features:

  • Scant cytoplasm.
  • Nuclear features of conventional prostate cancer (nucleoli, nuclear enlargement).
  • Increased gland density.

DDx:

Image: Atrophic carcinoma (nature.com).

Mucinous prostate carcinoma

General

  • Rare.

Microscopic

Features:

  • Cytologically malignant cells floating in mucin.
  • > 25% of tumour mucinous.[9]
    • One study suggests >= 25%.[41]

DDx:

Notes:

Pseudohyperplastic prostatic adenocarcinoma

General

  • Rare.

Microscopic

Features:[42][43]

  • 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: 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

Main article: Signet ring cell carcinoma

General

  • Very rare - 9 cases in a series of 29,783 prostate cancer cases.[44]
  • Criteria vary - percentage of SRCs required for Dx varies from 20% to 50%.[44]

Microscopic

Features:

  • Signet ring cells - see basics article.

Image:

Sarcomatoid prostate carcinoma

  • AKA carcinosarcoma.

General

  • Rare.

Microscopic

Features:[45]

IHC

Features - typical:[45]

  • PSA +ve.
  • Keratin +ve.

Small cell carcinoma of the prostate gland

Main article: Small cell carcinoma

General

  • Rare.

Microscopic

Features:

  • Nuclear moulding.
  • Stippled chromatin.
  • High NC ratio.
  • Small cells.

Notes:

Adenoid cystic/basal cell carcinoma of the prostate

  • Abbreviated ACBCC.

General

  • Rare.
  • Typically indolent - may be aggressive.[46]

Microscopic

Features:

Images:

IHC

  • HER2/neu +ve (strong).[47]

See also

References

  1. ↑ 1.0 1.1 1.2 Humphrey PA (January 2007). "Diagnosis of adenocarcinoma in prostate needle biopsy tissue". J. Clin. Pathol. 60 (1): 35–42. doi:10.1136/jcp.2005.036442. PMC 1860598. PMID 17213347. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860598/?tool=pubmed.
  2. ↑ 2.0 2.1 2.2 Epstein JI (March 2004). "Diagnosis and reporting of limited adenocarcinoma of the prostate on needle biopsy". Mod. Pathol. 17 (3): 307–15. doi:10.1038/modpathol.3800050. PMID 14739905. http://www.nature.com/modpathol/journal/v17/n3/full/3800050a.html.
  3. ↑ URL: http://pancreaticcancer2000.com/page1.htm. Accessed on: 3 June 2010.
  4. ↑ 4.0 4.1 Van der Kwast, TH.; Evans, A.; Lockwood, G.; Tkachuk, D.; Bostwick, DG.; Epstein, JI.; Humphrey, PA.; Montironi, R. et al. (Feb 2010). "Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies.". Am J Surg Pathol 34 (2): 169-77. doi:10.1097/PAS.0b013e3181c7997b. PMID 20061936.
  5. ↑ Weedman Molavi, Diana (2008). The Practice of Surgical Pathology: A Beginner's Guide to the Diagnostic Process (1st ed.). Springer. pp. 100-3. ISBN 978-0387744858.
  6. ↑ 6.0 6.1 Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 72. ISBN 978-0443066771.
  7. ↑ Kronz, JD.; Silberman, MA.; Allsbrook, WC.; Bastacky, SI.; Burks, RT.; Cina, SJ.; Mills, SE.; Ross, JS. et al. (Sep 2000). "Pathology residents' use of a Web-based tutorial to improve Gleason grading of prostate carcinoma on needle biopsies.". Hum Pathol 31 (9): 1044-50. doi:10.1053/hupa.2000.16278. PMID 11014569.
  8. ↑ 8.0 8.1 Epstein, JI. (Feb 2010). "An update of the Gleason grading system.". J Urol 183 (2): 433-40. doi:10.1016/j.juro.2009.10.046. PMID 20006878. Cite error: Invalid <ref> tag; name "pmid20006878" defined multiple times with different content
  9. ↑ 9.0 9.1 Grignon DJ (March 2004). "Unusual subtypes of prostate cancer". Mod. Pathol. 17 (3): 316–27. doi:10.1038/modpathol.3800052. PMID 14976541.
  10. ↑ 10.0 10.1 URL: https://www.bostwicklaboratories.com/global/physicians/medical-library/articles/gleason-grading.aspx. Accessed on: 26 November 2011.
  11. ↑ Lu, J.; Wirth, GJ.; Wu, S.; Chen, J.; Dahl, DM.; Olumi, AF.; Young, RH.; McDougal, WS. et al. (Jul 2012). "A close surgical margin after radical prostatectomy is an independent predictor of recurrence.". J Urol 188 (1): 91-7. doi:10.1016/j.juro.2012.02.2565. PMID 22578729.
  12. ↑ Steinsvik, EA.; Axcrona, K.; Angelsen, A.; Beisland, C.; Dahl, A.; Eri, LM.; Haug, ES.; Svindland, A. et al. (Aug 2012). "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.". Scand J Urol Nephrol. doi:10.3109/00365599.2012.707684. PMID 22860630.
  13. ↑ Koutlidis, N.; Mourey, E.; Champigneulle, J.; Mangin, P.; Cormier, L. (Jul 2012). "Robot-assisted or pure laparoscopic nerve-sparing radical prostatectomy: What is the optimal procedure for the surgical margins? A single center experience.". Int J Urol. doi:10.1111/j.1442-2042.2012.03102.x. PMID 22860572.
  14. ↑ Mauermann, J.; Fradet, V.; Lacombe, L.; Dujardin, T.; Tiguert, R.; Tetu, B.; Fradet, Y. (Aug 2012). "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.". Eur Urol. doi:10.1016/j.eururo.2012.08.002. PMID 22901983.
  15. ↑ Chalfin, HJ.; Dinizo, M.; Trock, BJ.; Feng, Z.; Partin, AW.; Walsh, PC.; Humphreys, E.; Han, M. (Jul 2012). "Impact of surgical margin status on prostate-cancer-specific mortality.". BJU Int. doi:10.1111/j.1464-410X.2012.11371.x. PMID 22788795.
  16. ↑ Evans, AJ.; Henry, PC.; Van der Kwast, TH.; Tkachuk, DC.; Watson, K.; Lockwood, GA.; Fleshner, NE.; Cheung, C. et al. (Oct 2008). "Interobserver variability between expert urologic pathologists for extraprostatic extension and surgical margin status in radical prostatectomy specimens.". Am J Surg Pathol 32 (10): 1503-12. doi:10.1097/PAS.0b013e31817fb3a0. PMID 18708939.
  17. ↑ Epstein, JI.; Srigley, J.; Grignon, D.; Humphrey, P. (Sep 2007). "Recommendations for the reporting of prostate carcinoma.". Hum Pathol 38 (9): 1305-9. doi:10.1016/j.humpath.2007.05.015. PMID 17707261.
  18. ↑ Evans, A. 4 June 2010.
  19. ↑ Lester, Susan Carole (2010). Manual of Surgical Pathology (3rd ed.). Saunders. pp. 409. ISBN 978-0-323-06516-0.
  20. ↑ Berney, DM.; Wheeler, TM.; Grignon, DJ.; Epstein, JI.; Griffiths, DF.; Humphrey, PA.; van der Kwast, T.; Montironi, R. et al. (Jan 2011). "International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 4: seminal vesicles and lymph nodes.". Mod Pathol 24 (1): 39-47. doi:10.1038/modpathol.2010.160. PMID 20818343.
  21. ↑ Fleischmann, A.; Rocha, C.; Schobinger, S.; Seiler, R.; Wiese, B.; Thalmann, GN. (Apr 2011). "Androgen receptors are differentially expressed in Gleason patterns of prostate cancer and down-regulated in matched lymph node metastases.". Prostate 71 (5): 453-60. doi:10.1002/pros.21259. PMID 20878946.
  22. ↑ Azumi, N.; Traweek, ST.; Battifora, H. (Aug 1991). "Prostatic acid phosphatase in carcinoid tumors. Immunohistochemical and immunoblot studies.". Am J Surg Pathol 15 (8): 785-90. PMID 1712549.
  23. ↑ URL: http://biocare.net/wp-content/uploads/225DS.pdf. Accessed on: 18 October 2011.
  24. ↑ URL: http://www.antibodies-online.com/antibody/308235/anti-PIN-4+p63+Cytokeratin+HMW+p504S++AMACR/. Accessed on: 18 October 2011.
  25. ↑ URL: http://www.webpathology.com/image.asp?case=96&n=5. Accessed on: 18 October 2011.
  26. ↑ Yu J, Yu J, Mani RS, Cao Q, Brenner CJ, Cao X, Wang X, Wu L, Li J, Hu M, Gong Y, Cheng H, Laxman B, Vellaichamy A, Shankar S, Li Y, Dhanasekaran SM, Morey R, Barrette T, Lonigro RJ, Tomlins SA, Varambally S, Qin ZS, Chinnaiyan AM (May 2010). "An Integrated Network of Androgen Receptor, Polycomb, and TMPRSS2-ERG Gene Fusions in Prostate Cancer Progression". Cancer Cell 17 (5): 443–54. doi:10.1016/j.ccr.2010.03.018. PMC 2874722. PMID 20478527. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874722/.
  27. ↑ 27.0 27.1 Online 'Mendelian Inheritance in Man' (OMIM) 602060
  28. ↑ Attard, G.; Clark, J.; Ambroisine, L.; Fisher, G.; Kovacs, G.; Flohr, P.; Berney, D.; Foster, CS. et al. (Jan 2008). "Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer.". Oncogene 27 (3): 253-63. doi:10.1038/sj.onc.1210640. PMID 17637754.
  29. ↑ Rubin MA, Bismar TA, Curtis S, Montie JE (July 2004). "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?". Am. J. Surg. Pathol. 28 (7): 946–52. PMID 15223967.
  30. ↑ Henry, PC.; Evans, AJ. (Jul 2009). "Intraductal carcinoma of the prostate: a distinct histopathological entity with important prognostic implications.". J Clin Pathol 62 (7): 579-83. doi:10.1136/jcp.2009.065003. PMID 19246509.
  31. ↑ Robinson, BD.; Epstein, JI. (Oct 2010). "Intraductal carcinoma of the prostate without invasive carcinoma on needle biopsy: emphasis on radical prostatectomy findings.". J Urol 184 (4): 1328-33. doi:10.1016/j.juro.2010.06.017. PMID 20723921.
  32. ↑ Samaratunga, H.; Delahunt, B. (Aug 2008). "Ductal adenocarcinoma of the prostate: current opinion and controversies.". Anal Quant Cytol Histol 30 (4): 237-46. PMID 18773743.
  33. ↑ Bock, BJ.; Bostwick, DG. (Jul 1999). "Does prostatic ductal adenocarcinoma exist?". Am J Surg Pathol 23 (7): 781-5. PMID 10403300.
  34. ↑ Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 88. ISBN 978-0443066771.
  35. ↑ Amin, A.; Epstein, JI. (Apr 2011). "Pathologic stage of prostatic ductal adenocarcinoma at radical prostatectomy: effect of percentage of the ductal component and associated grade of acinar adenocarcinoma.". Am J Surg Pathol 35 (4): 615-9. doi:10.1097/PAS.0b013e31820eb25b. PMID 21383610.
  36. ↑ Tarján, M.; Lenngren, A.; Hellberg, D.; Tot, T. (Jun 2012). "Immunohistochemical verification of ductal differentiation in prostate cancer.". APMIS 120 (6): 510-8. doi:10.1111/j.1600-0463.2011.02862.x. PMID 22583364.
  37. ↑ Kumar, A.; Mukherjee, SD. (Apr 2010). "Metastatic ductal carcinoma of the prostate: a rare variant responding to a common treatment.". Can Urol Assoc J 4 (2): E50-4. PMID 20368883.
  38. ↑ 38.0 38.1 Hameed, O.; Humphrey, PA. (Jul 2006). "Stratified epithelium in prostatic adenocarcinoma: a mimic of high-grade prostatic intraepithelial neoplasia.". Mod Pathol 19 (7): 899-906. doi:10.1038/modpathol.3800601. PMID 16607376.
  39. ↑ Lee, TK.; Miller, JS.; Epstein, JI. (Jun 2010). "Rare histological patterns of prostatic ductal adenocarcinoma.". Pathology 42 (4): 319-24. doi:10.3109/00313021003767314. PMID 20438402.
  40. ↑ Kaleem, Z.; Swanson, PE.; Vollmer, RT.; Humphrey, PA. (Jun 1998). "Prostatic adenocarcinoma with atrophic features: a study of 202 consecutive completely embedded radical prostatectomy specimens.". Am J Clin Pathol 109 (6): 695-703. PMID 9620026.
  41. ↑ Osunkoya AO, Nielsen ME, Epstein JI (March 2008). "Prognosis of mucinous adenocarcinoma of the prostate treated by radical prostatectomy: a study of 47 cases". Am. J. Surg. Pathol. 32 (3): 468–72. doi:10.1097/PAS.0b013e3181589f72. PMID 18300802.
  42. ↑ Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 77. ISBN 978-0443066771.
  43. ↑ Arista-Nasr J, Martinez-Benitez B, Valdes S, Hernández M, Bornstein-Quevedo L (2003). "Pseudohyperplastic prostatic adenocarcinoma in transurethral resections of the prostate". Pathol. Oncol. Res. 9 (4): 232–5. doi:PAOR.2003.9.4.0232. PMID 14688829.
  44. ↑ 44.0 44.1 Warner, JN.; Nakamura, LY.; Pacelli, A.; Humphreys, MR.; Castle, EP. (Dec 2010). "Primary signet ring cell carcinoma of the prostate.". Mayo Clin Proc 85 (12): 1130-6. doi:10.4065/mcp.2010.0463. PMID 21123640.
  45. ↑ 45.0 45.1 Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 77 & 80. ISBN 978-0443066771.
  46. ↑ Iczkowski, KA.; Ferguson, KL.; Grier, DD.; Hossain, D.; Banerjee, SS.; McNeal, JE.; Bostwick, DG. (Dec 2003). "Adenoid cystic/basal cell carcinoma of the prostate: clinicopathologic findings in 19 cases.". Am J Surg Pathol 27 (12): 1523-9. PMID 14657711.
  47. ↑ Iczkowski, KA.; Montironi, R. (Dec 2006). "Adenoid cystic/basal cell carcinoma of the prostate strongly expresses HER-2/neu.". J Clin Pathol 59 (12): 1327-30. doi:10.1136/jcp.2005.035147. PMID 17142577.
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