Prostate cancer

Prostate cancer
Diagnosis in short
Prostate carcinoma. H&E stain.
LM	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
LM DDx	high-grade prostatic intraepithelial neoplasia, atypical small acinar proliferation (biopsy only), prostatic atrophy, seminal vesicle, basal cell hyperplasia, others
IHC	PSA +ve, PSAP +ve, AMACR +ve, p63 -ve, CK34betaE12 -ve
Site	prostate gland
Signs	firm, nodular prostate on digital rectal exam
Symptoms	often asymptomatic
Prevalence	very common
Prognosis	good-to-poor (depends on Gleason score and stage)
Clin. DDx	prostatitis

This article deals with prostate cancer.

The vast majority of prostate cancers are carcinomas and could be labelled prostatic carcinoma. Most prostatic carcinomas are gland forming; thus, they can be labelled prostatic adenocarcinoma or adenocarcinoma of the prostate.

Benign pathology of the prostate gland, and prostate histology and anatomy are 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

Dirty first approximation

• The management changes between Gleason score 6, 7 and 8.

Typically, the implications are:

• Gleason 6: observation or radioactive seeds; surgery if patient wants.
• Gleason 7: do something -- surgery or radiation therapy.
• Gleason 8+: bad cancer -- do something quickly!

Bottom line:

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

Observational strategies

• Delay of definitive treatment (surgery or radiation).
• Common in management of prostate cancer.

Classification:

• Active surveillance (AS).
  • Low risk of progression.
  • May get definitive treatment later.
• Watchful waiting (WW).
  • Higher risk of progression.

Note:

• There is no agreed upon set of criteria for active surveillance, and the large number of criteria out there vary significantly.

Active surveillance

The Klotz criteria for active surveillance - pathologic factors only:

• Gleason score 6 or less.
• All biopsies cores < 50% involvement.
• Less than 3 cores involved.

Clinical criteria:

• PSA <= 10 ng/mL.

Gross

• Prostate cancer is uncommonly apparent on gross.
• Classic location: posterior aspect of the prostate.

Prostatectomy grossing

There are several consensus papers on grossing prostatectomies by the International Society of Urological Pathology (ISUP).

• Prostate gland:
  • Embedding in toto is not required.
    • A study by Epstein suggests it is reasonable to submit all of the posterior aspect and selected sections from the mid portion.
  • The prostate should be painted -- to mark the margins.
  • Sectioning should be done after fixation.
  • The prostate should be weighted after trimming the seminal vesicles.
  • The apex of the prostate and the bladder neck should be sliced-off, sagittally sectioned, and submitted separately on edge (to assess the margin).
• Lymph nodes and seminal vesicles (SV):
  • All lymph nodes should be submitted.
    • Metastases are found in over 5% of tissue not grossly recognized as a lymph node; thus, it makes sense to submit all tissue.
  • The base of the SV/prostate junction must be submitted.
    • SV does not have to be submitted in total.

Microscopic

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.

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)
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 and there is consensus on how it is done.
• Score range: 6-10.
  • Technically 2-10... but almost no one uses 2-5.
• Reported 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).

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.

Examples

• A biopsy with 80% pattern 4, 16% pattern 3 and 4% pattern 5... would be reported as: 4+5=9.
• A biopsy with 92% pattern 4, and 8% pattern 3... would be reported as: 4+3=7.
• A biopsy with 98% pattern 4, and 2% pattern 3... would be reported as: 4+4=8.
• A prostatectomy with 80% pattern 4, 16% pattern 3 and 4% pattern 5... would be reported as: 4+3=7 with tertiary pattern 5.

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)

www:

• 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 the centre) (comedonecrosis) or (intraluminal) necrosis in a cribriform pattern.
  • Necrosis:
    • Nuclear changes:
      • Karyorrhexis (nuclear fragmentation).
      • Pynosis (nuclear shrinkage).
      • Karyolysis (nuclear dissolution).
    • Cell ghosts (cells without a nucleus).

Notes:

• Pattern 5 may be under-diagnosed.
• Single cells is the most commonly missed pattern.

Images

www:

• Gleason pattern 5 - sheeting (webpathology.com).

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.

Biopsy-prostatectomy concordance of Gleason score

• Discordance is common.
  • Upgrade on prostatectomy: 25-40%.
  • Downgrade on prostatectomy: 5-15%.

Selected studies on concordance:

Study	Upgrade	Downgrade	Notes
Sfoungaristos et al.	42.1%	13.7%	high volume of tumour predicts upgrade
Thomas et al.	38.1%	4.7%
Truesdale et al.	23%	11%

Upgrading

Gleason score upgrading on prostatectomy is considered relatively common; it is reported 
to occur in 23% to 42.1% of cases.[1][2]

1. BJU Int. 2011 107 (5): 749-54.
2. Can Urol Assoc J. 2012 Jan 24:1-5.

Downgrading

Gleason score downgrading on prostatectomy is considered uncommon; however, it is reported 
in 4.7% to 13.7% of cases.[1][2]

1. BJU Int. 2012 Jan; 109(2):214-9.
2. Can Urol Assoc J. 2012 Jan; 24;1-5.

Staging parameters and margins

Surgical margins

Main article: Surgical margins

• Positive is tumour touching ink.†
  • "Close" margins have an increased 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.
• † Epstein says not touching may be enough, as tumour close to the margin is damaged from the surgery.

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).
• France: 13-17% -- PSA and prostate size predictors of positivity.

Note:

• Stage and grade (Gleason score) seem to have less impact than surgeons volume on margin positivity rate.

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.

General

• Extraprostatic extension (EPE) is difficult to assess in prostatectomy specimens.
  • The prostate does NOT have a well defined capsule.
    • Intraobserver agreement for EPE is fair-moderate and lower than for the surgical margin.
• EPE, typically, upstages tumours from T2x to T3a.

Prostatectomy specimens

EPE is present in a prostatectomy 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 apex of the prostate gland may have some skeletal muscle. Thus, it is difficult to define extension at this site. EPE is not called at the apex by some pathologists; however, it is generally believed to exist.

Prostate biopsy

EPE is present in prostate biopsy if:

• Tumour touches adipose tissue.

Seminal vesicle invasion

Abbreviated SVI.

General:

• Typically upstages to pT3b.
• Associations:
  • Most SVI is by direct extension ~90%.
  • Approximately 20% of patients with pT3x have SVI.
  • Usually associated with a large tumour volume (22% versus 12%).

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.

Notes:

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

Lymph node metastases

Main article: Lymph node metastasis

• Essentially never happens in Gleason score 6 cancers.
  • A study of over 14,000 Gleason score <=6 cases found 22 cases with lymph node metastases -- all of the 19 cases available for review were determined to have a higher Gleason score and some Gleason pattern 4 or 5.

IHC

Benign prostate versus neoplastic prostate

• 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.

Prostate versus urothelium

• Prostate: PSA +ve, CK20 -ve, CK7 -ve.
• Urothelial: CK20 +ve, CK7 +ve, PSA -ve.

Note:

• AMACR not useful - positive in ~ 50% of UCC.

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.

Sign out

Prostatectomy specimens

See: CAP checklist.

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.

Transurethral resection of prostate

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.

Biopsy specimens

Important elements - a list:

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.
  • 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.
  • A review by Epstein on the topic of tumour volume suggests it does not have predictive value in multivariante analyses.
  • The biopsy tumour volume is a predictor of Gleason score upgrading on prostatectomy.

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

• 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

Major criteria

Required major criteria:

1. Glands 2x normal (peripheral zone) glands.
2. Basal cell present (proven by IHC).
3. "Cytologically malignant cells" = nuclear hyperchromasia, nuclear enlargement, nucleoli.
4. Fills the lumen ("expansile") but does not have to be "solid".
   • Solid = no spaces between the cells.

Additional (major) criterion:

• Comedonecrosis.

Minor criteria

Minor criteria:

1. Branching of ducts at right angles.
2. Rounded/smooth gland outlines.
3. Two cell populations:
   • Malignant population (enlarged nuclei with hyperchromasia and nucleoli) = peripheral location in gland.
   • Benign population (smaller nuclei, no nucleoli) = central location in gland.

DDx:

• High-grade prostatic intraepithelial neoplasia (HGPIN).

IHC

Features - basal cells present:

• CK34betaE12 +ve.
• p63 +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.
• Not completely uncontroversial - may represent acinar adenocarcinoma with periurethral ducts involvement.
• More aggressive than conventional (acinar) prostate carcinoma.

Microscopic

Features:

1. Pseudostratified (crowded appearing) columnar (or cigar-shaped) nuclei - key feature.
   • Vaguely resembles colonic adenocarcinoma.
2. Compatible architecture:
   • Papillary.
   • Cribriform.
   • Single gland (large glands).
   • Endometrioid - vaguely looks like endometrioid endometrial carcinoma (with back-to-back glands).
3. >= 50% of tumour.^{[citation needed]}
   • 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.

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

• AKA foamy gland adenocarcinoma.

General

• Rare.
• Usually low grade, i.e. Gleason score 6/10.

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!

DDx:

• Adenosis of the prostate.

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.
• Most often Gleason 3+4 ~ 80% in one series of 47 cases.
• The prognosis is similar or may be better than the conventional type of prostate cancer; however, this is not without controversy.

Microscopic

Features:

• Cytologically malignant cells floating in mucin.
• > 25% of tumour mucinous.
  • Two studies suggests >= 25%.

Notes:

• Mucinous carcinoma - percentage required to call varies by site.

DDx:

• Metastatic mucinous carcinoma.
• Mucinous adenocarcinoma of the prostatic urethra - analogous to the mucinous adenocarcinoma of the urinary bladder.

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:
  1. Spindle cells (sarcomatous component).
     • May include components of: osteosarcoma, chondrosarcoma and/or rhabdomyosarcoma.
  2. 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

• Very rare.
• Most common small cell carcinoma outside of the lung.
• 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.

Notes:

• Similar to small cell carcinoma of the lung.
• High-grade squamoid component favours metastatic urothelial carcinoma.
  • UCC usu. HWCK +ve.

Images:

• SmCC of the prostate - low mag. (webpathology.com).
• SmCC of the prostate - high mag. (webpathology.com).
• SmCC of the prostate - low mag. (nih.gov).
• SmCC of the prostate - high mag. (nih.gov).

IHC

Features:

• PSA weak +ve/-ve.
• Chromogranin +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

• Prostate gland.
• Genitourinary pathology