21 Lower Urinary Tract and Male Genital System

Question 1

What are the four zones of the prostate?

Answer 1

1) peripheral zone
2) central zone
3) transitional zone
4) region of the anterior fibromuscular stroma

Question 2

From which zone do the most hyperplasias arise?

Answer 2

Transitional zone

Question 3

From which zone do the most carcinomas arise?

Answer 3

Peripheral zone

Question 4

What are the two histological layers of the prostate gland?

Answer 4

1) Basal layer

2) Columnar secretory cells

Question 5

What hormone controls growth and survival of prostatic cells and what occurs in its withdrawal?

Answer 5

Testicular androgens; castration results in atrophy caused by widespread apoptosis

Question 6

Classify types of prostatitis

Answer 6

Acute
Chronic bacterial
Chronic abacterial
Granulomatous

Question 7

What are the typical sources for acute prostatitis?

Answer 7

1) ascending - intraprostatic reflux of urine
2) lymphohematogenous routes from distant foci
3) surgical manipulation of urethra or prostate - catheterisation, cystoscopy, urethal dilation or resection

Question 8

What are the typical organisms of acute prostatitis?

Answer 8

E. coli, Gram negative rods, enterococci and staphylococci; typically similar to UTI

Question 9

What is the pathogenesis of chronic bacterial prostatitis?

Answer 9

• recurrent urinary tract infections by organisms identical to those that cause acute prostatitis
• poor antibiotic penetration of prostate
• bacterial organisms colonise and then seed recurrent infections

Question 10

What is the most common form of prostatitis?

Answer 10

Chronic abacterial prostatitis

Question 11

What are causes of granulmoatous prostatitis?

Answer 11

1) BCG (most common)
2) Fungal (immunocompromised pt)
3) reaction to ruptured prostatic ducts and acini

Question 12

What is the main androgen active in the prostate?

Answer 12

Dihydrotestosterone

Question 13

What is the mechanism for benign prostatic hyperplasia?

Answer 13

• Impaired cell death of epithelial cells
• there is no clear evidence of increased epithelial cellular proliferation
• increased stromal proliferation leading to increased DHT conversion
• DHT binds to nuclear androgen receptors to increase transcription of growth factors and their receptors leading ultimately to stromal growth and impaired epithelial cell death

Question 14

How are stromal cells of the prostate responsible for androgen-dependent prostatic growth?

Answer 14

• only stromal cells contain type 2 5-alpha-reductase which converts testosterone to the more potent dihydrotestosterone (higher receptor affinity, greater ligand-receptor complex stability). (Type 1 5-alpha-reductase is found in the skin and liver.)
• DHT binds nuclear androgen receptor in stromal and epithelial prostate cells
• increased transcription of genes for small growth factors and receptors (DHT is not a direct mitogen)
• these growth factors include: FGF-7, FGF1, FGF2 and TGFbeta
• FGF7 most important

Question 15

What is median lobe hypertrophy

Answer 15

Nodular enlargement projecting into the floor of the urethra as a hemispheric mass beneath the mucosa

Question 16

What is the pathophysiology of benign prostatic hyperplasia to symptoms of prostatism?

Answer 16

• increased size of gland due to increased DHT levels causing impaired epithelial death and stromal proliferation
• smooth muscle-mediated contraction of prostate leads to urethral obstruction
• increased resistance to urinary outflow –> bladder hypertrophy, distention and urinary retention
• increased risk of infection

Question 17

What are the main therapies used for BPH?

Answer 17

Conservative: decreasing evening fluid intake, moderating alcohol and caffeine, timed voiding schedules
Medical: alpha-blockers, 5-alpha reductase inhibitors
Surgical: TURP

Question 18

What are the approximate incidences of prostate cancer in their 50s and then between 70-80?

Answer 18

50s - 20%

70-80 - 70%

Question 19

What are risk factors for prostate cancer?

Answer 19

Non-modifiable: age, race, family history, hormone levels
Environmental: consumption of fats
Protective (putative): lycopenes, selenium, soy products, vitamin D

Question 20

What are the heritable risk factors that play a role in prostate cancer?

Answer 20

• AR gene polymorphism (CAG repeats, short sensitive, long resistant)
• resistance to androgen blockade: AR gene amplification, mutations in AR giving rise to non-androgen ligand binding, activating P13 kinase /AKT signalling
• BRCA2: 20X risk
• locus at 8q24: only increased risk in men of African origin
• tumour-specific:ETS family transcription factor (ERG, ETV1) rearrangements with TMPRSS2 promoter (androgen-sensitive); hypermethylation of GSTP1
• epigenetic changes in tmour suppressor genes: PTEN, RB, p16/INK4a, MLH1, MSH2, APC

Question 21

What are some of the characteristic features of ETS family transcription factor gene rearranged tumours?

Answer 21

• increased invasiveness, possible through matrix metalloproteinases
• morphologic features

Question 22

What are some of the molecular characteristics of prostate carcinoma?

Answer 22

• ETS family transcription factor (ERG, ETV1) rearrangements with TMPRSS2 promoter (androgen-sensitive)
• hypermethylation of GSTP1
• epigenetic changes in tmour suppressor genes: PTEN, RB, p16/INK4a, MLH1, MSH2, APC
• loss of E-cadherin (associated with high EXH2)
• increased AMACR
• increased PCA3

Question 23

What is the actual variant which comprises the most common prostate carcinoma?

Answer 23

Prostate adenocarcinoma, acinar variant

Question 24

Where does prostate carcinoma usually spread?

Answer 24

Local extension: Periprostatic tissue, seminal vesicles, base of urinary bladder
LN: obturatory nodes, then paraaortic nodes
Hematogenous: bones of axial skeleton > femur>ribs

Question 25

Name benign mimics of prostatic carcinoma.

Answer 25

``` Adenosis (atypical adenomatous hyperplasia) Atrophy and variants (partial, PAH) Basal cell hyperplasia Seminal vesicle / ejaculatory duct epithelium Mucinous metaplasia Nephrogenic metaplasia (adenoma) Cowper’s glands Paraganglion Xanthoma ```

Question 26

Name prostatic carcinomas which mimic benign lesions.

Answer 26

Atrophic cancer Foamy cancer Pseudohyperplastic cancer

Question 27

What lines of evidence show the relation between PIN and prostate carcinoma?

Answer 27

- PIN and PCA both predominant in the peripheral zone - prostates with cancer have higher PIN frequency and extent - PIN is seen in proximity to PCA - molecular changes seen in invasive cancers are present in PIN

Question 28

What are the most common subtypes of acinar adenocarcinoma?

Answer 28

``` Atrophic Pseudohypertrophic PIN-like Stratified/double cell layer Foamy gland (xantomatous) With Paneth cell-like differentiation Oncocytic ```