Department Of Pathology

Phase II Curriculum, 4th year (2011 intake)

Renal, Reproductive and Breast system module
Seminar

Topic: Diseases of the prostate

ID #: 3339
Monday, 22 December, 2014
11:10 - 12:00
Weekly Learning Objective(s):
Be able to explain the process of prostatic hyperplasia, its
pathological features, clinical presentation and
sequelae.(WLO6016)
Be able to describe the factors implicated in the development
of prostatic cancer and discuss the role of screening in its early
detection.(WLO6018)
Objectives:
Describe the pathological changes, clinical presentation and
complications of prostatic hyperplasia.
Describe the basic pathological changes in prostatic carcinoma.
Explain the role of clinical chemistry in the screening for

prostatic carcinoma
 Prostate
BPH and carcinoma are two major
lesions affecting the prostate.
The prostate is a complex organ
consisting of epithelial, stromal, and
muscular element.
Anatomically the prostate gland [app 20
gm] is the shape of an inverted cone
encircling neck of bladder & urethra
Retroperitoneal - FOUR zones
- Peripheral
- Central
- Transitional
- Periuretheral
Histology of
Prostate

Glands

Fibromuscular
stroma
 Enlargement of Prostate
Inflammations
infections BPH

BPH
Benign
Prostatic
Hyperplasia
Neoplasms
Carcinoma.
Clinical Significance:
Hyperplasia Periuretheral zones (Urinary obstruction)
Carcinomas Peripheral zone (Palpable by digital examination)
 Diseases of Prostate

Acute / Chronic Prostatitis

Benign Prostatic Hyperplasia (BPH)
Prostatic Carcinoma
 NIH Consensus Conference on Prostatitis

Category I:Acute Bacterial Prostatitis

Acute infection of the prostate gland
Category II:Chronic Bacterial Prostatitis
Recurrent infection of the prostate
Category III:Chronic AbacterialProstatitis
No demonstrable infection
Category IV:Asymptomatic Inflammatory
Prostatitis
 Acute Bacterial Prostatitis
Organisms associated with UTI (e.g. E coli,
Gram negative rods).
The possible routes of infection include:
-Ascent from the urethra.
-Reflux of infected urine into prost ducts
-Direct extension
Symptoms - Fever, chills, dysuria, boggy
tender prostate.
Diagnosis: Clinical features + urine culture.
 Acute Bacterial Prostatitis
Laboratory Findings Complications
Voided urine - pyuria, Acute urinary retention.

microscopic hematuria, Acute bacterial cystitis.

and bacilluria. Acute pyelonephritis.
The prostatic expressate
Unilateral or bilateral
is purulent and yields acute bacterial
growth on culture plates. epididymitis.
prostatic massage and
bactermia with possible
transurethral septic shock.
instrumentation should be
Rarely meningitis
avoided during the acute
stage of bacterial Prostate abcess

prostatitis.
Chronic Bacterial Prostatitis
Asymptomatic or associated with low back
pain, supra-pubic discomfort, and dysuria.
H/O recurrent UTIs caused by the same
organism, or insidious onset without H/O of
acute prostatitis
Diagnosis: Leukocytes in expressed prostatic
secretions, positive bacterial cultures in
prostatic secretions and urine
Chronic abacterial prostatitis
Most common form of prostatitis.
Affects sexually active men.
Clinical presentation is similar to chronic
bacterial prostatitis but without H/O
recurrent UTIs.
Diagnosis: Leukocytes in expressed
prostatic secretions with negative
cultures.
causes no known organic complications
Prostatitis: acute on chronic
 Granulomatous Prostatitis

Non-specific granulomatous
prostatitis.
Common, represents reaction
to secretions from ruptured
prostatic glands or ducts.
Specific causes:
Administering BCG for

treatment of superficial
urinary bladder cancer.
Tuberculosis
Benign Prostatic Hyperplasia (BPH)
BPH is the commonest non-neoplastic hormone
induced hyperplasia - not hypertrophy
Hormone-induced Androgens
Castration no BPH
Incidence increases with age
Prevalence
-20% in men aged 41-50
-50% in men aged 51-60
>90% in men aged 80 and older
Symptoms are also age related: at age 55 25% of
men report obstructive voiding symptoms
Only one of 9 BPH patients with symptoms seek
treatment.
 BPH-Pathophysiology:
Testosterone DHT GF

The etiology of BPH is

unclear.

Two factors necessary

for BPH to occur are:
(1) endocrine control (DHT)
(2) aging

The relative roles of

androgen and estrogen
in inducing BPH,
however , are complex
and not completely
understood.
 BPH Pathophysiology:
Nodular proliferation of prostate gland
Stromal epithelial interaction
-normal 2:1, BPH 3 or 4:1
-major change is connective tissue
The smooth muscle tone mediated via alpha adrenergic
receptors may make a significant contribution to the
symptoms
Medications
Alpha blockers
5alpha reductase inhibitors
Combination therapy
The differential representation of the histologic
components of BPH explain the potential responsiveness
to medical therapy
Benign Prostatic
Hyperplasia
Hyperplasia of :
Stromal and
Epithelial cells
Formation of nodules in
periurethral region
 Benign Prostatic
Hyperplasia

Microscopically, nodular
prostatic hyperplasia consists of
nodules of glands and
intervening stroma. (both)
Hyperplasia of :
Stromal and
Epithelial cells
Formation of nodules
Nodular hyperplasia is NOT a
precursor to carcinoma.
Obstruction secondary to BPH
Obstruction secondary to BPH occurs because
of TWO factors:
a. Dynamic component: a result of
contraction of smooth muscles of the prostate
and prostatic urethra mediated mostly by
adrenergic receptors.
b. Mechanical component: related to the
presence of a mass which compresses and
narrows the urethral lumen.
BPH-mechanism of obstruction:
Median lobe (3rd lobe)
Ball valve mechanism
Obstruction.
Urgency/hesitation..
BPH-Complications:

1. Obstructive Uropathy
2. Bladder hypertrophy
3. Trabeculation
4. Diverticula formation
5. Hydroureter bilateral
6. Hydronephrosis
7. Lithiasis / stone.
8. Secondary infection.

Not a risk factor for

Carcinoma prostate.
BPH - Bladder Gross
Hyperplasia of the median
lobe of prostate protruding
into the bladder as an
exophytic mass
Trabeculations
Hypertrophy of wall
Stone - urolithiasis
Inflammation
Median lobe- ball valve.
Enlarged prostate.
 Symptoms
Symptoms of BPH
are related to:

1- Compression of
urethra
2- Retention of urine
in bladder
 Lower Urinary Tract Symptoms
Obstructive and Irritative Symptoms
Voiding (obstructive) Storage (Irritative)
Decrease in force & caliber of
the stream: due to urethral Frequency
compression is one of the early
& constant features of BPH. Nocturia
Hesitancy: occurs because the Urgency
detrusor takes a longer time to
generate the initial increased Dysuria
pressure to overcome the
urethral resistance.
Intermittency: occurs because
the detrusor is unable to
sustain the increased pressure
until the end of voiding.
Terminal dribbling of urine &
incomplete sense of bladder
emptying
 Signs of BPH
Rectal examination may reveal an
enlarged prostate.
Distinction between right & left lobes
of the prostate is usually lost in BPH.
Median sulcus is present.
Signs of renal failure in
advanced cases include
elevated BP, rapid pulse and
respiration, uremic fetor,
pericarditis and pallor of nail
beds.
Abdominal examination may
reveal palpable kidney or
flank tenderness if there is
hydronephrosis /
pyelonephritis
A distended bladder may be
noted on palpation or
percussion.
 Investigations-BPH
Digital rectal examination (DRE) 60%
accurate in differentiating BPH from prostate
cancer.
Prostate-specific antigen (PSA) Upper limit of
normal is 4 ng/ml. 50% of BPH show increase
above 4 ng/ml. (Therefore, PSA is not an
ideal screening tool for prostate cancer.
However, elevation of this marker when
adjusted for patient age and size of BPH,
should alert the urologist to the underlying of
prostate cancer).
 Investigations-BPH
1. Urinalysis M&C: R/O infection or the presence of hematuria.
2. Renal function test: BU, electrolytes and creatinine
3. Uroflowmetry: At a volume of 125-150ml, normal individuals
have average flow rates of 12ml/sec & peak flow close to
20ml/sec.
Mild 11-15 ml/sec
Moderate 7 and 10 ml/sec
Severe 7ml/sec
4. Residual Urine: estimated by U/S or catheterizations.
Volumes >150 ml are considered significant since they
constitute approximately 1/3rd of normal bladder volume.
 Carcinoma of Prostate
Commonest form of cancer in men
Second leading cause of cancer death
Disease of men over 50.
Incidence increases with age
Risk Factors
- Black race
- Family history
- High dietary fat intake
Rare in Asians
Many carcinomas are small and clinically
insignificant.
Commonest cause of tumor-related deaths
after lung carcinoma.
 Diseases of prostate

Prostatic carcinoma precursor

lesions:

Prostate intra-epithelial neoplasia

(PIN):

Present in 80% of cases of

carcinoma

Intermediate between normal and

malignant tissue

30% of PIN progresses to invasive

cancer in 10 years
Pathogenesis: PIN & carcinoma

Prostatic intraepithelial neoplasia (PIN)

Multilayered, pleomorphic (low & High grade).
Malignancy is single layered, & well
differentiated to start with
 Low grade PIN

PIN:
Crowding,
Stratificatio
Pleomorphism
Nuclear
enlargement.

High grade PIN

Incidence & mortality of common cancers in man
 The incidence of prostate cancer in Kuwaiti Arabs is
What is the incidence currently about 13/100,000 men/year.
of prostate cancer in It is the 4th common cause of cancer in Kuwaiti men
The mortality figure is difficult to come by in Kuwait.
Kuwait?
However, it is the 6th commonest cause of cancer
mortality in Kuwait.
 Diagnosis of prostate cancer:
Clinical: Digital Rectal examination (DRE)
hard, gritty, fixed tumor.

Loss of median groove.

Imaging:
Transrectal ultrasound (TRUS), MRI, CT imaging to
detect regional LN and intra-abdominal metastases.
Radionuclide bone scan for PSA > 20ng/ml
Laboratory:
Tumor Marker PSA

Biopsy TURP, TRUS biopsy

None of these methods can reliably detect small cancers &
microscopic occult cancers
 Prostate Cancer - Essentials of Diagnosis

Prostatic induration on
digital rectal
examination (DRE) or
elevated level of serum
prostate-specific antigen
(PSA).
Most often
asymptomatic.
Rarely, systemic
symptoms (weight loss,
bone pain)
Digital examination
 Transrectal Ultrasonography (TRUS)

A small probe is placed in the

rectum and sound waves are
released from the probe.
These sound waves bounce off the
prostate tissue and an image is
created.
Since normal prostate tissue and
prostate tumors reflect the
sound waves differently, the test
is an efficient and accurate way to
detect tumors.
The procedure may be slightly
uncomfortable, is generally painless
and takes only 20 minutes.
 The PSA Blood Test
Early Detection & Screening
PSA is a protein produced by the prostate and is a marker for prostate
cell activity
PSA is used as a marker for Diagnosis and Disease Progression.

PSA test measures the level of PSA :

Levels under 4 ng/mL are usually considered normal.
Levels over 10 ng/mL are usually considered high
Levels between 4 and 10 ng/mL are usually considered intermediate.

A rising PSA is typically the first sign seen, coming well before any
clinical signs or symptoms of recurrence or metastasis.

PSA is not a perfect test. Levels can be elevated if other prostate

problems are present, such as BPH or prostatitis. Some men with prostate
cancer may even have low levels of PSA. PSA can also be diluted in men who
are overweight or obese, due to a larger blood volume, and a biopsy at a
relatively lower number (i.e. 3.5 instead of 4) should be considered.
Elevated Serum PSA
Prostate carcinoma
Glandular hyperplasia associated with
BPH
Acute bacterial prostatitis and prostate
abscess (transitory)
Prostatic infarction (transitory)
Manipulation of prostate (transitory)
TRUS Needle Biopsy
If cancer is suspected from
the results of any of the
above tests, the doctor will
remove a small piece of
prostate tissue with a hollow
needle.
Prostate cancer can also be
diagnosed based on the
examination of the tissue
removed during a
transurethral resection of the
prostate (TURP).
TUR Prostatic Resection
 A series of 6 biopsies
from the right and left
upper, middle and lower
lobes of the prostate,
which diagnostic yield,
and likelihood of
detecting prostate CA.
Adeno-Ca Prostate

Posterior Lateral lobes: Carcinoma

Rectal examination.
Solid, hard, adenocarcinoma
 Adeno-Ca Prostate
Benign:
Double layer,
Secretion (clear cytopl)
Uniform cells
Papillary folds
Malignant
Single / crowded.
Less/no secretion.
Uniform/Pleomorphic
No papillary folds. But
crowding & clustering.
 Gleason Grading & Scoring.
Grade/Pattern 1 well defined
glands with limited infiltration of
the surrounding tissue.
Grade/Pattern 2 not well
demarcated, pleopmorphic cells.
Grade/Pattern 3 Crowding of
glands, irregular glands.
Gleason Pattern 2
Grade/Pattern 4 Fusion of
glands.
Grade/Pattern 5 cell clusters,
No clear gland structure.
Gleason Score: Add to most
prominent grades in the slide.
E.g. 3+4=7
Gleason Pattern 4
Gleason Pattern 1 Gleason Pattern 2

Gleason Pattern 3 Gleason Pattern 4

 Carcinoma of prostate

Gleasons grading system of prostate carcinoma

Five grades on the basis of:
1. Glandular patterns .and
2. Degree of tumor differentiation

Grade 1 most well differentiated tumors

Grade 5 least differentiated tumors
Two commonest patterns added to give the

Gleason Score
e.g. 3+4 (Gleason score of 7)
Total score out of 10
 Pattern of Progression
Local Spread
Cancers arising in close
proximity are prone to spread
early to the urethra,
periprostatic tissues, bladder
and seminal vesicles.
Rectal invasion is rare, ? Due to
the tough Denonvilliers fascia in
between.
Ureteral invasion by direct
extension can occur but late,
usually lymph node and distant
metastasis present at this time.
Distant Metastasis
Osseous metastases is most
common form of hematogenous
metastases and occur in 85% of
patients dying from prostate
cancer
Frequent sites: lumbar spines,
pelvis, proximal femur, thoracic
spines, ribs, sternum and skull.
Extension to the axial skeleton
via the plexus of presacral veins
which communicate with the pre
& periprostatic venous complex.
Prognosis of Adenocarcinoma
Grade & Stage Prognosis.
Gleason score 2-4 well differentiated.
Gleason score 8-10 poorly
differentiated.
Urinary obstruction
Metastasize to lymph nodes and bones.
Bladder, kidney damage - Hematuria.
Spread to rectum bleeding.
Spread to Lungs or liver rare.
Ca Prostate Stage & Prognosis