Prostate gland

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

Normal

Prostate

Anatomy

Divided into three zones:

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

Histology

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

Benign normal:

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

Negatives:

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

Notes:

• Tufted epithelium is a strong indicator of benignancy; however two uncommon prostate cancer typically have tufted epithelium:
  • Pseudohyperplastic adenocarcinoma.
  • Foamy gland carcinoma.

Images:

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

IHC of normal prostate

Normal prostate:

• AMACR -ve (mark epithelial cells).
• CK5/6 +ve, p63 +ve, HMWCK +ve (mark basal cells).
• PSA (prostate-specific antigen) +ve, PSAP (prostatic-specific acid phosphatase) +ve.

Other accessory glands

Bulbourethral gland

• AKA Cowper's gland.
• Mucinous glands at the apex of the prostate.
  • Resemble (mucinous) salivary glands.

Image: Mucinous/serous salivary gland (duke.edu).

Seminal vesicles

• Fern-like architecture - epithelial component clustered closely, looks like it connects.
  • Epithelium surrounded by a thick layer of muscle (>10 cells across ~80 microns).
• Lipofuscin (coarse cytoplasmic yellow granules approximately 1-2 micrometers) - key feature.
• Nucleoli - common.
• Nuclear inclusions - common.

Notes:

• The ejaculatory ducts have the same epithelium as the seminal vesicles.

Images:

• SV - showing fern-like architecture (WC).
• SV - looking vaguely like to prostate adenocarcinoma (WC).
• SV - looks a bit like prostate but lumina too big (WC).
• SV (udel.edu).

Specimens

• Prostate core biopsy - done transrectal.
• Prostate chips (from a transurethral resection of the prostate, abbreviated TURP) - usu. done for nodular hyperplasia of the prostate gland; may be done in the context of obstructing cancer.
• Radical prostatectomy - includes the seminal vesicles.
• Radical cystoprostatectomy - includes the urinary bladder and seminal vesicles.

Common diagnoses

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

Clinical history

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

Specific conditions

Prostatic nodular hyperplasia

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

General

• Very common.
• Incidence increases with age.

Clinical - mnemonic I WISH 2p:

• Intermittency.
• Weak stream.
• Incomplete emptying.
• Straining.
• Hesitancy.
• Post-void dribbling.
• Prolonged voiding.

Treatment:

• Medications.
• Transurethral resection of the prostate (TURP).

Microscopic

Features:

• Stromal and/or glandular hyperplasia.

Note:

• Should not be diagnosed on core biopsy!

Image:

• Prostatic nodular hyperplasia (WC).

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PROSTATE GLAND, TRANSURETHRAL RESECTION OF THE PROSTATE (TURP):
- BENIGN PROSTATIC TISSUE WITH GLANDULAR AND STROMAL PROLIFERATION.

Acute inflammation

General

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

Microscopic

Features:

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

Note:

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

Image:

• Prostate with acute inflammation (WC).

Chronic inflammation not otherwise specified

General

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

Microscopic

Features:

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

Image:

• Prostate with chronic inflammation (WC).

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

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

Note:

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

Granulomatous prostatitis

• AKA prostatic granuloma.
• AKA prostate gland granuloma.

General

• Common.
• Usually secondary to BCG treatment of bladder cancer.
• Several classifications exist - the most commonly used is by Epstein & Hutchins.

Epstein & Hutchins classification

The groupings:

1. Non-specific.
   • No cause identified, usu. incidentally discovered.
   • Most common.
2. Post-TURP.
   • Palisading granuloma with necrotic core (histology similar to a rheumatoid nodule) +/- eosinophils.
3. Specific.
   • Identifiable infectious agent, usu. BCG (in the context of treating bladder cancer), rarely tuberculosis and even more rarely various fungi and syphilis.
4. Allergic granulomatous prostatitis.
   • Usually associated with eosinophils.
   • Examples:
     1. Wegener granulomatosis.
     2. Churg-Strauss syndrome.

Microscopic

Features:

• Granulomas in the prostate - key feature.
  • Palisading granulomas with a necrotic core (similar to a rheumatoid nodule) consistent a prior TURP.
• +/-Eosinophils.

Images:

• Granulomatous inflammation of the prostate/bladder neck - low mag. (WC).
• Granulomatous inflammation of the prostate/bladder neck - high mag. (WC).

Stains

• GMS stain.
• Ziehl-Neelsen stain.

Note:

• Stains are indicated when there is a suspicion of an infective etiology based on histomorphology or clinical information (e.g. immunosuppression).

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PROSTATE GLAND, TRANSURETHRAL RESECTION OF THE PROSTATE (TURP):
- BENIGN PROSTATIC TISSUE WITH GLANDULAR AND STROMAL PROLIFERATION.
- PALISADING GRANULOMA WITH NECROTIC CORE, SEE COMMENT.

COMMENT:
This is morphologically consistent with a post-TURP granuloma.

Atrophy of the prostate

• AKA atrophy.
• AKA prostatic atrophy.

General

• Small glands (may mimic Gleason score 3 pattern).

Microscopic

Features:

• Glands often have a jagged edges/prows (in cancer the glands tend to have round edges) - key feature.
  • Prow = forward most part of a ship's bow that cuts through the water.
    • You may have come across prow in the context of breast cancer, i.e. tubular carcinoma.
• Gland density is usually lower than in prostate carcinoma, i.e. glands are not back-to-back - key feature.
• Atrophic glands are often hyperchromatic.
• Scant cytoplasm - usually.

Negatives:

• Nuclei like normal, i.e. nucleoli uncommon.
• Should have two cell layers, i.e. epithelial and myoepithelial (may be difficult to see).

Notes:

• Atrophic glands may be scattered with non-atrophic ones.
• IHC may be misleading - basal cell loss.

DDx:

• Atrophic prostate carcinoma.

Atrophy versus cancer

Histologic feature	Atrophy	Cancer
Glandular architecture/ arrangement	angulated glands, may look like they originate from one large duct	round glands, often back-to-back
Nuclear hyperchromasia	marked	moderate
Cytoplasm	scant/minimal	moderate, may be amphophilic
Basal cells	may be visible	absent
Nucleoli	absent	present
Secretions in glands	no	yes - eosinophilic or blue

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Generally, this finding is not reported; it is considered a normal finding.

Prostatic infarct

• AKA prostatic infarction.

General

• Rare < 0.1% of core biopsies.
• Can mimic cancer - urothelial carcinoma.
• Prostate usually large.

Microscopic

Features:

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

Notes:

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

DDx:

• Urothelial carcinoma with squamous differentiation.

Image:

• Prostatic thrombosis (sciencephoto.com).

Basal cell hyperplasia of the prostate

• AKA basal cell hyperplasia.

General

• Benign lesion that can be misdiagnosed as cancer.

Microscopic

Features:

• Low power gland architecture near normal.
  • Glands not as small as cancer.
  • Folds in gland lumina.
• No hyperchromasia.
• Two cell populations (as in normal prostate glands).
• May have nucleoli.

DDx:

• HGPIN.
• Prostatic adenocarcinoma.

Image:

• Basal cell hyperplasia of the prostate (webpathology.com).

High-grade prostatic intraepithelial neoplasia

• Abbreviated as HGPIN.
• May be referred to as prostatic intraepithelial neoplasia, abbreviated PIN.

General

• Thought to be a precursor lesion for prostate adenocarcinoma.
  • Multifocal HGPIN considered a risk for prostate cancer on re-biopsy.
  • Small a small focus of HGPIN does not appear to be associated with increased risk for prostate cancer on re-biopsy at one year if the initial biopsy had 8 or more cores.

Low-grade prostatic intraepithelial neoplasia:

• Not reported and generally believed to be irrelevant biologically/clinically.
  • PIN not otherwise specified refers to HGPIN.
  • Low-grade PIN has the architecture of HGPIN but lacks the nuclear atypia.

Microscopic

Features:

• Diagnosed on basis of nuclear changes.
  • Hyperchromatic nuclei - key (low power) feature.
  • Nucleoli present - key (high power) feature.
  • Often increased N/C ratio.
  • Nuclear enlargement.
• Different architectures (e.g. micropapillary).
• Usually epithelial hyperplasia.

Notes:

• Nucleoli should be visible with the 20x objective.
  • If one uses the 40x objective... one over calls.
• May need IHC for cancer versus HGPIN.

DDx:

• Basal cell hyperplasia of the prostate.
• Intraductal carcinoma of the prostate.
• Prostatic adenocarcinoma - glands with HGPIN have two or more distinct cells layers.
  • PIN-like prostatic ductal adenocarcinoma.
• Benign prostate - HPGIN has nuclear changes.

HGPIN architecture

There are several forms:

• Flat - uncommon.
• Tufting - common.
• Micropapillary - common.
• Cribriform - rare.

Note:

• The architectural pattern is NOT thought to have any prognostic significance; however, it may be useful for differentiating it from benign prostate.

Images:

• HGPIN - low mag. (WC).
• HGPIN - intermed. mag. (WC).
• HGPIN - high mag. (WC).

IHC

• HGPIN: AMACR +ve, p63 +ve, HMWCK +ve.
• Cancer: AMACR +ve, p63 -ve, HMWCK -ve.
• Normal: AMACR -ve, p63 +ve, HMWCK +ve.

Atypical small acinar proliferation

• Abbreviated ASAP.
• AKA suspicious for carcinoma.
  • ASAP is preferred as it does not contain the word carcinoma and, thus, cannot be misread as carcinoma, i.e. positive for malignancy.

General

• It is a waffle diagnosis, i.e. it is not considered an entity with a distinct pathobiology.
  • Analogous to ASCUS on a pap test.
• ASAP should be used sparingly.
  • One benchmark is < 3-5% of biopsies.
• Never diagnosed on excision, i.e. prostatectomy specimen.

Association with adenocarcinoma

• On subsequent biopsy - chance of finding adenocarcinoma is approximately 40%; this is higher than if there is high-grade prostatic intraepithelial neoplasia (HGPIN).

Management

• ASAP is considered an indication for re-biopsy; in one survey of urologists 41/42 (~98%) of respondents considered it a sufficient reason to re-biopsy.

Microscopic

Features:

• Atypical appearing acini.
• Limited extent, e.g. 2-3 glands.

Notes:

• IHC not contributory.
• Deeper cuts didn't yield anything - important.

DDx:

• Prostatic adenocarcinoma.

Intraductal carcinoma of the prostate

• AKA intraductal carcinoma.
• AKA intraductal prostate carcinoma.

General

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

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:

• HGPIN.

IHC

Features - basal cells present:

• HMWK +ve.

Prostatic adenocarcinoma

• AKA adenocarcinoma of the prostate.
• AKA prostatic carcinoma.

Criteria as a list

Major criteria (the ABCs of prostate pathology):

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

Minor criteria:

1. Nuclear hyperchromasia.
2. Wispy blue mucin.
   • Image: Wispy blue mucin (nature.com) - from Epstein.
3. Pink amorphous secretions.
   • Image: Pink amorphous secretions (nature.com) - from Epstein.
4. Intraluminal crystalloid.
   • Image: Intraluminal crystalloid (nature.com) - from Epstein.
5. Amphophilic cytoplasm.
   • Amphopilic is said to be bluish-red -- though might also be described as blue-grey.
     • Image: Amphophilic cytoplasm is prostate carcinoma.
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.
  • Thus, it has been suggested that six or more glands should be present to diagnose cancer.

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.

IHC

• AMACR +ve.
• AR +ve -- in prostate confined cancer.
  • Usu. -ve in LN +ve disease.
• PSA +ve.
• PSAP +ve.
  • May be positive in hindgut neuroendocrine tumours.
• p63 -ve.
• HMWCK (34betaE12) -ve.

Combination immunostains:

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

Mimics

Mimics of prostate adenocarcinoma:

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.

Grading

There is only one grading system that any one talks about - the Gleason system.

Gleason grading system

• Score range: 2-10.
• 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.
  • 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).

Examples:

• A biopsy has 80% pattern 4, 15.1% pattern 3 and 4.9% pattern 5... it would be reported as: 4+5=9.
• A prostatectomy has 80% pattern 4, 15.1% pattern 3 and 4.9% pattern 5... it would be reported as: 4+3=7 with tertiary pattern 5.

Testing yourself:

• There is a nice test-yourself quiz from Johns Hopkins: http://162.129.103.34/prostate/.
  • It was studied in a paper by Kronz et al.

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.

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.

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

Special type	Gleason pattern	Comment
Ductal carcinoma	4	may be graded 3 or 5
Mucinous carcinoma	4
Sarcomatoid carcinoma	5	glands graded separately
Signet ring cell carcinoma	5
Small cell carcinoma	not graded	may be graded 5
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.

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.
• Gleason 8+: bad cancer - do something quickly!

Bottom line: You want to be sure when you call something Gleason pattern 4.

Note:

• The usual caveats apply to the above; if the patient is moribund-- nothing is done, if the patient refuses treatment... nothing is done et cetera.

Surgical margins and extraprostatic extension

Definitions:

• 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.
• Surgical margin - where the surgeon cut.
  • It is possible to have EPE without a positive margin.
  • It is possible to have a positive margin without EPE.

Important:

• EPE cannot be called on a biopsy unless the tumour is next to adipose tissue.

Surgical margins

Main article: Surgical margins

• Positive is tumour touching ink.
  • "Close" margins have an increase recurrence risk.

Positivity rate varies substantially (13-44%):

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

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).
• Weaker impact than stage and Gleason score.

Extraprostatic extension

Abbreviated EPE.

• 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.
• Prostate biopsy: EPE is present if tumour touches adipose tissue.
  • The prostate, at the apex, may have some skeletal muscle. Thus, it is difficult to define extention... ergo EPE not called at the apex.

Reporting prostate cancer

Elements of a prostate biopsy report with cancer

Important elements:

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.

Prostatectomy specimens

See: CAP checklist.

Molecular changes in prostate cancer

A fusion gene between TMPRSS2 and ERG is described.

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

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Biopsy

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; TUMOUR MEASURES 1 MM IN LENGTH.

G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY: - ADENOCARCINOMA, GLEASON SCORE 8/10 (4+4); - 1/1 CORE INVOLVED; APPROXIMATELY 15% OF TISSUE INVOLVED; TUMOUR MEASURES 3 MM IN LENGTH.

H. PROSTATE, LEFT MEDIAL SUPERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 7/10 (4+3);
- 1/1 CORE INVOLVED; APPROXIMATELY 5% OF TISSUE INVOLVED; TUMOUR MEASURES 1 MM IN LENGTH;
- FOCAL PERINEURAL INVASION PRESENT.

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.
*Controversial - may represent acinar adenocarcinoma with periurethral ducts involvement.

Microscopic
Features:
*Pseudostratified (crowded appearing) columnar (or cigar-shaped) nuclei - key feature.
**Vaguely resembles colonic adenocarcinoma.
*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.

Images:
*Prostatic ductal adenocarcinoma - several images (upmc.edu).
*Prostatic ductal adenocarcinoma - another case - several images (upmc.edu).
*Prostatic ductal adenocarcinoma - F1 (nih.gov).
*Prostatic ductal adenocarcinoma - F2 (nih.gov).
*Prostatic ductal adenocarcinoma (webpathology.com).

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

Others:
*PSA +ve.

PIN-like prostatic ductal adenocarcinoma
General
*Recently described.
*May be confused with prostatic intraepithelial neoplasia (PIN).

Microscopic
Features:
*Stratified malignant epithelium.

Note:
*Vaguely similar to a tubular adenoma of the colon.

DDx:
*HGPIN.

Image: 
*PIN-like adenocarcinoma (nature.com).

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.

Microscopic
Features:
*Scant cytoplasm.
*Nuclear features of conventional prostate cancer (nucleoli, nuclear enlargement).
*Increased gland density.

DDx:
*Atrophy of the prostate.

Image: Atrophic carcinoma (nature.com).

Mucinous prostate carcinoma
General
*Rare.

Microscopic
Features:
*Cytologically malignant cells floating in mucin.
*> 25% of tumour mucinous. 
**One study suggests >= 25%.

DDx:
*Metastatic mucinous carcinoma.

Notes:
*Mucinous carcinoma - percentage required to call varies by site.

Pseudohyperplastic prostatic adenocarcinoma
General
*Rare.

Microscopic
Features:
*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.
*Criteria vary - percentage of SRCs required for Dx varies from 20% to 50%.

Microscopic
Features:
*Signet ring cells - see basics article.

Image:
*Prostatic SRC (nih.gov).

Sarcomatoid prostate carcinoma
*AKA carcinosarcoma.
General
*Rare.

Microscopic
Features:
*Biphasic tumour:
*#Spindle cells (sarcomatous component).
*#*May include components of: osteosarcoma, chondrosarcoma and/or rhabdomyosarcoma.
*#Glandular component (like conventional prostate carcinoma).

IHC
Features - typical:
*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:
*Similar to small cell carcinoma of the lung.
*High-grade squamoid component favours metastatic urothelial carcinoma.
**UCC usu. HWCK +ve.

Adenoid cystic/basal cell carcinoma of the prostate
*Abbreviated ACBCC.
General
*Rare.
*Typically indolent - may be aggressive.

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:
*Adenoid basal cell tumour (webpathology.com).
*Adenoid basal cell tumour (webpathology.com).

IHC
*HER2/neu +ve (strong).

See also
*Urothelium.
*Genitourinary pathology.

References



External links
*CAP prostate check list - cap.org.
*CAP prostate protocol - cap.org.
*Gleason score quiz - Johns Hopkins Prostate Center.