Prostate Dr.CSBR.Prasad, M.D.

Normal Prostate • Retroperitoneal organ

• Encircles the neck of the bladder and urethra

• No definitive capsule

• Weighs approx 20gms

• Measures 3-4cms in greatest dimension

• Divided into 4 anatomically and biologically distinct zones

1-Peripheral

2-Central

3-Transitional zones

4-Region of anterior fibromuscular stroma

Note: Most hyperplasias arise in the transitional zone, where

as most carcinomas originate in the peripheral zone.

CSBRP-July-2012

This is a transverse (axial) section through a normal prostate. There is a central urethra (White

arrow) at the depth of the cut made to open this prostate anteriorly at autopsy, with the left lateral

lobe (Red arrow) and the right lateral lobe (Yellow arrow) and the posterior lobe (Green arrow).

The consistency is uniform, without nodularity. The normal prostate is 3 to 4 cm in diameter.

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This is a diagram of the classic 4 prostatic lobes. The x marks the

site through which the urethra traverses. It is easy to see that most

pathology related to the prostate will present with obstructive

uropathy symptoms.

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Histology:

• Compound tubuloalveolar organ

• Glandular lining epithelium has two layers of cells and has distinct BM

1-Basal layer of cuboidal epithelium &

2-Tall columnar secretory cells towards the lumen

• There are small papillary inbuddings of the epithelium

• Glands are separated by abundant fibromuscular stroma

Normal Prostate

CSBRP-July-2012

The normal male prostate gland below the bladder is composed of a

mixture of glands and intervening fibromuscular stroma, in about equal

proportions, as seen here at low power.

Normal prostate is composed of a mixture of glands lined by tall

columnar cells with infoldings and the intervening fibromuscular stroma,

in about equal proportions, as seen here at medium power.

The normal appearance of prostate is shown at high magnification. Note the small pink

laminated concretion (these are corpora amylacea) in the gland lumen to the left of

center. Note the infoldings of the columnar epithelium.

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Pathological processes

involving prostate

• Inflammations

• Nodular hyperplasia

• Tumors

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Prostatitis

1. Acute bacterial prostatitis

2. Chronic bacterial prostatitis

3. Granulomatous prostatitis

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Acute bacterial prostatitis

• Usually due to extension of infection from the urethra or bladder

• It can follow manipulation of the urethra or prostate secondary to catherization or cystoscopy

• The bacterial "culprits" are:

• -- Urinary pathogens (Enterobacteriaceae)

• -- Enterococcus and Staphylococcus

• CF: dysuria, chills and fever

• The prostate is very tender to palpation

• Neutrophilic infiltrate

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Acute bacterial prostatitis

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Chronic Prostatitis

• Chronic Bacterial Prostatitis Antibiotics do not penetrate the prostate well

The common presentation is recurrent UTI

• Chronic Prostatitis

Lymphocytic infiltrate and fibrosis

Chronic non-bacterial prostatitis:

-- the most common type

-- WBCs may been seen in prostatic secretions, but

-- no bacteria can be identified

-- suspects – ‘chlamydia and mycoplasma’ infection

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Chronic Prostatitis

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Granulomatous Prostatitis

• Tuberculosis

• Fungal (immunocompromised patients)

• Secondary to secretions from

obstructed ducts

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Prostatic hyperplasia

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BPH (Nodular hyperplasia)

• Common disorder, aging process. >40yrs=20%, >60yrs=70%, >70yrs=90%.

• >50yrs

• Periurethral portion is involved

• Present with urinary obstruction

• Hyperplasia of stroma and epithelial

cells

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BPH / NPH

(Nodular hyperplasia)

Pathogenesis:

• Androgen related

• Dihydrotestosterone mediates growth and

proliferation in stromal and epithelial cells

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Clinical Features

• Retention of urine

• UTI

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The most commonly used and effective medical therapy:

• α-blockers, which decrease prostate smooth muscle

tone via inhibition of α1-adrenergic receptors

• Shrinking the prostate with inhibitor of DHT synthesis

(5-α-reductase Inhibitors)

BPH / NPH

• Prostate is enlarged, 60-100gms

• Nodular in the inner aspect of the

gland

• Compressed urethra

• c/s milky white fluid may ooze

• Bladder wall thickening / Trabaculation

• Microscopically – fibromyoglandular

hyperplasia

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This anatomical midline

sagital section reveals a

markedly enlarged prostate

with a nodular appearance

from hyperplasia. The

prostatic urethra (Yellow)

that traverses the enlarged

gland is compressed. The

bladder wall is

hypertrophic. Other

structures seen here include

the pubic symphysis

(White), the rectum (Blue),

and the penile urethra

(Red).

Bladder

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Multinodularity

Solid areas

Microcystic areas

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This is the gross appearance of nodular prostatic hyperplasia (benign

prostatic hyperplasia, or BPH). The normal prostate is 3 to 4 cm in cross

section, by comparison.

BPH

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This is the microscopic appearance of nodular prostatic hyperplasia at medium power.

Note that the columnar arrangement of cells near the gland lumina is preserved. Note

several pink corpora amylacea in gland lumens.

This is the microscopic appearance of nodular prostatic hyperplasia at low

magnification. Note the nodule filled with enlarged glands. Though crowded, there is

still stroma between the glands. CSBRP-July-2012

The enlarged prostate gland seen

here not only has enlarged

lateral lobes, but also a greatly

enlarged median lobe that

obstructs the prostatic urethra.

This led to obstruction with

bladder hypertrophy, as

evidenced by the prominent

trabeculation of the bladder wall

seen here from the mucosal

surface. Obstruction with stasis

also led to the formation of the

yellow-brown calculus (stone).

Lateral

lobes

Median

lobe

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Trabaculation and thickening of the wall [Fighting Urinary bladder]

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Do you know what is fighting

Gall bladder?

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The prostate "chips" seen here are the firm, rubbery fragments obtained

from transurethral resection of prostate (TUR-P) performed for

symptomatic nodular hyperplasia.

Areas of infarction Areas of nodular hyperplasia

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BPH and malignancy

Nodular hyperplasia is NOT

considered to be a

premalignant lesion

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Carcinoma of Prostate

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Prostatic carcinoma

• One of the most common cancers in

men

• >50yrs (men from the age of 40yrs should be screened for prostatic

cancer)

• The incidence increases with age

50s 20%; 70s 70%

• More common in whites (50-60/lakh)

and rare in Asians (1-4/lakh)

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• Risk factors: age, race, family history, hormone levels, environmental factors

• Familiy history: One 1 relative – 2x

Two 1 relatives – 5x

• Androgens (AR mutations in CAG repeats)

• Prostatic cancer susceptibility gene – 1q24-25

• Loss of cancer supressor genes: 8p, 10q, 13q, 16q.

• Mutations in p53, PTEN and KAI 1

• Over expression of : Hepsin, alfa-methyl-acyl COA racemase, and EZH2.

• Hypermethylation of GSTP1

Prostatic carcinoma – Etiology

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• 70% of cancers arise in the periphery

• Firm to gritty

• Local extensions involve seminal vesicles, base of the bladder and may result in urinary obstruction

• Blood spread: Bone (axial skeleton, femur, pelvis, ribs)

• Bone mets: Osteoblastic

• Lymphatic spread: perivesical, hypogastric, iliac, parasacral, para-aortic

Prostatic carcinoma – GROSS

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This is a diagram of the classic 4 prostatic lobes. The x marks the

site through which the urethra traverses. It is easy to see that most

pathology related to the prostate will present with obstructive

uropathy symptoms.

CSBRP-July-2012

This anatomical midline

sagital section reveals a

markedly enlarged prostate

with a nodular appearance

from hyperplasia. The

prostatic urethra (Yellow)

that traverses the enlarged

gland is compressed. The

bladder wall is

hypertrophic. Other

structures seen here include

the pubic symphysis

(White), the rectum (Blue),

and the penile urethra

(Red).

Bladder

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Secondary deposits in bone

• Breast

• Kidney

• Prostate

• Adrenals

• Testis

• Intestines

• Lung

B.K.PATIL

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Pathology Pearls

“Bone seeking Kidney tumor”

• Clear cell sarcoma of the kidney

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Pathology Pearls

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The gross appearance of

adenocarcinoma of the prostate

is shown here in cross section.

The entire prostate is involved.

The yellowish nodules

represent larger foci of

carcinoma.

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• Gland formations:

1-Single cell layer, no basal layer

2-Small, crowded glands

3-Nuclei are large, contain 1-2 nucleoli

4-Mitotic figures are uncommon

• Perineural invasion

• One feature that distinguishes benign from

malignant gland is – basal layer (HMWCK)

Prostatic carcinoma – micro

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Whole mount of large duct adenocarcinoma. The tumor is

centrally located and has a distinctly papillary configuration.

Lack of basal cells around the malignant acini.

Some benign glands show basal layer (arrow)

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Adenocarcinoma of the prostate is shown here at medium power. Some

of the neoplastic glands have lumens, but there is no stroma between.

This is a high grade, poorly differentiated adenocarcinoma of prostate.

There is no gland formation, only single cells infiltrating through the

stroma. CSBRP-July-2012

This is a moderately well-differentiated adenocarcinoma of the prostate

at high magnification.

Prostate

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A hallmark of prostatic adenocarcinoma is the presence of prominent

large nucleoli, as seen here. CSBRP-July-2012

Many large nucleoi are seen here in the nuclei of cells in this prostatic

adenocarcinoma. CSBRP-July-2012

Adenocarcinoma of the prostate is shown here at low power on the left, compared to

benign prostate (in which glands contain corpora amylacea) at the right. Note how small

and close-packed the neoplastic glands are.

This is a high grade adenocarcinoma of prostate. There are ill-defined

glands, and at the top just single infiltrating cells.

Grading of prostatic carcinoma

Gleason’s grading:

grade 1-5

grade-1: WD tumor

grade-5: PD tumor

Reported score which is a total of

predominant grade and other grade

eg: Score 3+5=8

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Prostatic intraepithelial neoplasia -

PIN

• Benign glands with intraacinar

proliferations of cells which exhibit

nuclear anaplasia

• glands surrounded by patchy layer of

basal cells and have intact BM

• Larger branching glands with papillary

infoldings (in cancers – small glands

with straight luminal border)

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• Evidence that link high grade PIN to invasive Ca:

1-high grade predominate at the periphery

2-high grade PIN is also seen in association with invasive Ca.

3-molecular abnormalities seen in invasive cancers are also present in PINs

Prostatic intraepithelial neoplasia -

PIN

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Prostatic intraepithelial neoplasia (PIN) can be low or high grade (as seen here). The

finding of PIN suggests that prostatic adenocarcinoma may also be present (about half

the time with high grade PIN). CSBRP-July-2012

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Diagnosis of prostatic carcinoma

• DRE

• PSA

• TRUS (transrectal US)

• Biopsy

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PSA:

1. Serien protease-liquifies semen

2. 4ng/ml

3. PSA value

4. PSA density

5. PSA velocity

6. Age specific reference range

7. Ratio of free and bound forms

PSA is of great value in assessing the response to Tx

Diagnosis of prostatic carcinoma

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E N D

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E N D