Lower Urinary tract and Male

Genital System
Eric M. Mirandilla MD, DPSP
 Prostate Specific Antigen
most important test used in the diagnosis and
management of prostate cancer.
PSA is a product of prostatic epithelium and is
normally secreted in the semen
serum levels are elevated to a lesser extent in
BPH than prostate cancer, although there is
considerable overlap between the two entities
 PSA
PSA is organ-specific, yet not cancer-specific.
Other factors such as BPH, prostatitis, infarct, and
instrumentation of the prostate can increase serum
PSA levels.
As men age, their prostates tend to enlarge with
BPH, with corresponding higher serum PSA levels.
Furthermore, 20% to 40% of patients with organ-
confined prostate cancer have PSA below the
thresholds usually set for screening for
malignancy.
 PSA
PSA velocity (rate of change of PSA)
may be a more useful measurement than just a
single PSA value.
This reflects the finding
that PSA levels rise faster in prostate cancer
than for age-related hyperplasia.
Multiple measurements need to be made over
a period of 1 to 2 years.
 PSA
In the setting of known prostatic carcinoma,
PSA monitoring is useful in assessing response
to therapy or progression of disease.
NV: less than 4 ng/ml
 The LOWER URINARY TRACT
Ureters
Congenital anomalies
Inflammations
Tumors and tumor-like lesions
Obstructive lesions
Urinary Bladder
Congenital anomalies
Inflammations
Metaplastic lesions
Neoplasms
Obstruction
Urethra
Inflammations
Tumor and tumor-like lesions
 Congenital Anomalies
Double Ureters
Almost in every case associated either with totally
distinct double renal pelves or
with the anomalous development of a large kidney
having a partially bifid pelvis terminating in
separate ureters
Double ureters may pursue separate courses to the
bladder but commonly joined within the bladder
wall and drain through a single ureteral orifice
Majority are unilateral and no clinical significance
Double Ureters
 Congenital Anomalies

Ureteropelvic junction obstruction

Most common cause of hydronephrosis in infants and
children
More commonly in boys, usually in left ureter
Bilateral in 20 % of cases and associated with other
congenital anomalies
In adults, it is more common in women and most often
unilateral
There is a agenesis of the kidney on the opposite side in a
significant number of cases, probably resulting from
obstructive lesion in utero
Utero pelvic junction obstruction
 Congenital Anomalies

Diverticula (Saccular outpouchings of the ureteral wall)

Uncommon lesions, usually asymptomatic and found incidentally on
imaging studies
They are appear as congenital or acquired defects and are of importance
as pockets of stasis and secondary infections
Dilation, elongation and tortousity of the ureters may occur as congenital
or acquired defects.
Congenital hydroureter is thought to reflect some neurogenic defect in the
innervation of the ureteral musculature.
Megaloureter is probably due to a functional defect of ureteral muscle
Hydronephrosis and decresed renal function results if the lesion goes
untreated
These anomalies are sometimes associated with some congenital defect of
the kidney
Hydroureter
 Inflammations

Ureteritis
Develop as component of urinary tract infections
Morphologic changes are entirely unspecific
Persistence of infection or repeated acute exacerbation may
give rise to chronic inflammatory changes within the ureters
Morphology:
Accumulation or aggregation of lymphocytes in the subepithelial
region may cause slight elevations of the mucosa and produce a fine
granular mucosal surface (ureteritis follicularis)
Mucosa may become sprinkled with fine cysts varying in diameter from
1 to 5 mm (ureteritis cystica).
Cysts may aggregate to form small, grapelike clusters.
Histologic section of cysts demonstrate a lining of modified transitional
epithelium with some flattening of the superficial layer of cell.
 Tumors and Tumor-like Lesions

Primary neoplasia is rare

Small benign tumors are generally mesenchymal origin
Most common are fibroepithelial polyps and leiomyomas
Fibroepithelial polyp:
tumor-like lesion that grossly presents as a small mass projecting into the lumen.
Occurs more commonly in the ureters (left more often than right)
Polyp presents as a loose, vascularized connective tissue mass lying beneath the
mucosa
Primary malignant tumors majority are transitional cell carcinomas
They cause obstruction of the ureteral lumen and found frequently on
the 6th and 7th decades of life.
They are sometimes multiple and occasionally occur concurrently with
similar neoplasms in the bladder and renal pelvis
 Obstructive Lesions

Pathologic lesions may obstruct the ureters and give rise to

hydroureter, hydronephrosis and sometimes pyelonephrosis.
Important causes, divided into intrinsic and extrinsic origin
Unilateral obstruction, typically results from proximal cause
Bilateral obstruction rises from distal cause, such as nodular
hyperplasia of the prostate.
 Obstructive Lesions

Major Causes of Ureteral Obstruction

Calculi Of renal origin, rarely more than 5 mm in diameter

I Larger renal stones cannot enter ureters
Impact at loci of ureteral narrowing- ureteropelvic juntions, where ureters cross iliac vessels, and where they
N
enter bladder and cause excruciating renal colic
T
R Strictures Congenital or acquired (inflammations)
I
Tumors Transitional cell carcinomas arising in ureters
N Rarely, benign tumors of fibroepithelial polyps
S
I Blood clots Massive hematuria from renal calculi, tumors, or papillary necrosis
C Neurogenic Interruption of the neural pathways to the bladder

E Pregnancy Physiologic relaxation of smooth muscle or pressure on ureters at pelvic brim from enlarging fundus
X
T Periureteral inflammation Salpingitis, diverticulitis, peritonitis, sclerosing retroperitoneal fibrosis
R
I Endometriosis With pelvic lesions, followed by scarring
N
S Tumors Cancers of the rectum, bladder, prostate, ovaries, uterus, cervix, lymphomas, sarcomas
I
C
 Obstructive Lesions

Sclerosing Retroperitoneal Fibrosis

Fibrous proliferative inflammatory process encasing the
retroperitoneal structures and causing hydronephrosis
Occurs in middle and late age
Some cases may have specific cause, such as drugs, adjacent
inflammatory conditions, or malignant disease
However 70% of cases have no obvious cause and considered
idiopathic
Microscopic examination: inflammatory fibrosis is marked by
a prominent inflammatory infiltrate of lymphocytes, often
with germinal centers, plasma cells, and eosinophils.
Sometimes, foci of fat necrosis and granulomatous
inflammation are seen in and about the fibrosis.
 Urinary bladder
(normal transitional epithelium)
 Urinary bladder

Diverticula
Bladder or vesical diverticulum consists of a puchlike eversion
or evagination of the bladder wall.
May arise as congenital defects or acquired lesions
Congenital diverticula
Due to a focal failure of development of the normal musculature or to
some urinary tract obstruction during fetal development.
Acquired diverticula
Most often seen with prostatic enlargement, producing obstruction to
urine outflow and marked muscle thickening of the bladder wall
Increased intravesicular pressure causes outpouching of the
bladder wall and the formation of diverticula
Diveticulum usually consists of a round to ovoid, saclike pouch
that varies from less than 1 cm to 5 to 10 cm in diameter.
 Urinary bladder

Diverticula
Most diverticula are small and asymptomatic
Clinically significant, as they constitutes sites of urinary
stasis and predispose to infection and the formation of
bladder calculi
Also predispose to vesicoureteral reflux as a result of
impingement on the ureter
Rarely, carcinomas may arise in bladder diverticuli
When invasive cancers arise in diverticula, they tend to
be more advanced in stage as a result of diverticulas thin
or absent muscle wall
Urinary bladder divverticulum
 Urinary bladder

Exstrophy
Presence of a developmental failure in the anterior wall
of the abdomen and in the bladder, so that the bladder
either communicates directly through a large defect with
the surface of the body or lies as an opened sac.
Exposed bladder mucosa may undergo colonic glandular
metaplasia and is subject to the development of
infections that often spread to upper levels of the urinary
system
Increased tendency toward the development of
carcinoma later in life, mostly adenocarcinoma of the
colon.
 Congenital Anomalies

Exstrophy of the
bladder in a newborn
boy. The tied
umbilical cord seen
above the hyperemic
mucosa of the
everted bladder.
Below is an
incompletely formed
penis with marked
epispadias
 Inflammations

Acute and Chronic Inflammations

Common etiologic agents of cystitis are coliforms: E. coli, followed by
Proteus, Klebsiella, and Enterobacter.
Tuberculous cystitis: almost always sequel to renal tuberculosis
Predisposing factors include bladder calculi, urinary obstruction, DM,
instrumentation, and immune deficiency
Hemorrhagic cystitis: patients receiving cytotoxic antitumor drugs, such as
cyclophosphamide
Triad of symptoms:
Frequency, urination every 15 to 20 minutes
Lower abdominal pain localized over the bladder region or in the suprapubic region
dysuria
Associated with these localized changes, there may be systematic signs of
inflammation such as elevation of temperature, chills, and general malaise.
 Urinary bladder

Acute and Chronic Inflammations

Morphology
Gross appearance, there is hyperemia of the mucosa,
sometimes associated with exudate.
Hemorrhagic cystitis:
when there is hemorrhagic component
Form of cystitis sometimes follows radiation injury or antitumor
chemotherapy and often accompanied by epithelial atypia
Suppurative cystitis:
Accumulation of large amounts of suppurative exudate
Ulcerative cystitis:
when there is large ulceration of large areas of the mucosa, or
sometimes the entire bladder mucosa
 Urinary bladder
Inflammations
Acute and Chronic Inflammations
Chronic cystitis:
Differs from acute form only in the character of inflammatory infiltrate.
More extreme heaping up of the epithelium with the formation of a
red, friable, granular sometimes ulcerated surface.
Chronicity of the infection gives rise to fibrous thickening in the
muscularis propia and consequent thickening and inelasticity of the
bladder wall.
Histologic variants:
Follicular cystitis
Aggregation of lymphocytes into lymphoid follicle within the bladder
mucosa and underlying wall
Eosinophilic cystitis
Manifested by infiltration with submucosal eosinophils together with
fibrosis and occasionally giant cells
Most cases represent nonspecific subacute inflammation and these
lesions are manifestations of systemic allergic disorder
Cystitis, gross Cystitis, microscopic
 Urinary bladder
Inflammations

Special Forms of Cystitis

Interstitial Cystitis (Hunner Ulcer)
Most frequently in women and associated with
inflammation and fibrosis of all layers of the bladder wall
Characterized clinically by intermittent, often severe,
suprapubic pain, urinary frequency, urgency, hematuria
and dysuria without evidence of bacterial infection, and
cystoscopic findings of fissures and punctuate hemorrhages
in the bladder mucosa after luminal distention
Early form, submucosal hemorrhages are noted
Late phase, localized ulceration (Hunner ulcer) with
inflammation and fibrosis of all bladder wall layers.
 Inflammations
Urinary bladder
Special Forms of Cystitis
Malakoplakia
Refers to a peculiar pattern of vesicular inflammatory reaction
characterized
macroscopically by soft, yellow, slightly raised mucosal plaques 3 to 4
cm in diameter
Histologically by infiltration with large, foamy macrophages with
occasional multinucleate giant cells and interspersed lymphocytes
Foamy histiocytes contains periodic-acid Shiff-positive granules and
targetoid intracellular structures called Michaelis-Gutmann bodies.
Related to chronic bacterial infection, mostly E. coli and
occasionally Proteus
 Inflammations
Urinary bladder
Special Forms of Cystitis
Malacoplakia

Note the large macrophages with granular PAS-positive cytoplasm

and several dense, round Michaelis-Gutmann bodies surrounded by
Showing inflammatory exudate and
artifactual cleard holes in the middle upper fieled
broad, flat plaques
 Inflammations
Urinary bladder
Special Forms of Cystitis
Polypoid Cystitis
Inflammatory condition resulting from irritation to the
bladder mucosa
Most common cause: indwelling catheters
Urothelium is thrown into broad, bulbous, polypoid
projections as a result of marked submucosal edema.
Can be confused with papillary urothelial carcinoma both
clinically and histologically.
 Metaplastic Lesions
Urinary bladder
Cystitis Glandularis and Cystitis Cystica
Refers to common lesions of the urinary bladder in which
nests of transitional epithelium (Brunn nests) grow
downward into the lamina propia and undergo
transformation of their central epithelial cells into
cuboidal or columnar epithelium lining (cystitis
glandularis) or cystic spaces lined by urothelium (cystitis
cystica)
Both variants are common incidental findings in relatively
normal bladder
Cystitis cystica: usually 0.1 to 1.0 cm in diameter, filled
with clear fluid, and lined by cuboidal or urothelial cells.
Cystitis glandularis and Cysytica
 Urinary bladder
Metaplastic Lesions

Squamous Metaplasia
As a response to injury, the urothelium often converts to
squamous epithelium, which is a more durable lining
Nephrogenic Metaplasia (Nephrogenic Adenoma)
Represents a reaction of the urothelium to injury
Overlying urothelium focally replaced by cuboidal epithelium,
which can assume a papillary growth pattern
A tubular proliferation in the underlying lamina propia and
superficial detrusor muscle may produce lesions that
histologically mimic a carcinoma
Typically it is less than a centimeter in diameter, they may be
sizable, and thus they may also clinically resemble cancer.
 Urinary bladder
Neoplasms

95% of bladder tumors are epithelial origin, the remainder being mesenchymal tumors
Tumors of the Urinary Bladder

Urothelial (transitional cell) tumors

Inverted papilloma
Papilloma
Urothelial tumors of the low malignant potential
Papillary urothelial carcinoma
Mixed carcinoma
Carcinoma in situ

Squamous cell carcinoma

Mixed carcinoma

Adenocarcinoma

Small cell carcinoma

Sarcomas
 Urinary bladder
Neoplasms
Urothelial (Transitional Cell) Tumors
These represent about 90% of all bladder tumors and run the
gamut from small, benign lesions that might never recur to
aggressive cancers associated with high risk of death.
There are two distinct precursor lesions to invasive urothelial
carcinoma
Noninvasive papillary tumors:
More common
Arises from papillary urothelial hyperplasia
Flat urothelial carcinoma
Referred to as carcinoma in situ (CIS)
In about half of the patients with invasive bladder cancer, at
the time of presentation the tumor has already invaded the
bladder wall, and there is no associated precursor lesion.
 Urinary bladder
Neoplasms

Urothelial (Transitional Cell) Tumors

Invasion in the lamina propria worsens the prognosis
The major decrease in survival is associated with
tumor invading the muscularis propria (detrusor
muscle)
There is a 50% 5-year mortality rate once muscularis
propria invasion occurs
 Urinary bladder
Neoplasms

Urothelial (Transitional Cell) Tumors

Gross patterns of urothelial cell tumors
vary from purely papillary to nodular or flat
Tumors may also be invasive or noninvasive
Papillary lesions appear as red, elevated
excrescences varying in size from less than
1 cm in diameter to large masses up to 5
cm in diameter
Histologic changes encompass a spectrum
from benign papilloma to highly aggressive
anaplastic cancer
Majority of papillary tumors are low grade
Most arise from lateral or posterior walls at
the bladder base
 Urinary bladder
Neoplasms
Urothelial (Transitional Cell) Tumors

Cross-section of bladder
showing large papillary tumor

Multifocal smaller papillary

neoplasms
 Urinary bladder
Neoplasms

Urothelial (Transitional Cell)

Tumors
Papillomas
Represent 1% or fewer of bladder
tumors most commonly seen in
younger patients.
Tumors usually arise singly as
small (0.5 to 2.0 cm), delicate,
structures, superficially attached
to the mucosa by a stalk.
Individual finger-like papillae Papilloma consisting of a small
have a central core of loose papillary fronds lined by normal-
fibrovascular tissue covered by appearing urothelium
transitional epithelial cells that
are histologically identical to
normal urothelium.
 Urinary bladder
Neoplasms

Urothelial (Transitional Cell) Tumors

Papillary urothelial neoplasms of low malignant
potential (PUNLMP)
Hare many histologic features with papilloma
The only differences being either thicker urothelium or
diffuse nuclear enlargement in PUNLMP
At cystoscopy, PUNLMP tend to be larger than papillomas
and may be distinguishable form low- and high-grade
papillary cancers.
May recur with the same morphology, are not associated
with invasion, and only rarely recur as higher-grade tumors
associated with invasion and progression.
 Urinary bladder
Neoplasms
Urothelial (Transitional Cell)
Tumors
Low-grade papillary urothelial
carcinomas
Characterized by an orderly
appearance both architecturally
and cytologically.
Cells are evenly spaced and
cohesive
There is minimal but definite
evidence of nuclear atypia
consisting of scattered
Low-grade papillary urothelial carcinoma with
hyperchromatic nuclei, infrequent and overall orderly appearance, a thicker lining
mitotic figures predominantly than papilloma, and scattered hyperchromatic
towards the base and mild nuclei and mitotic figures (arrows)
variation in nuclear size and shape
 Urinary bladder
Neoplasms
Urothelial (Transitional Cell) Tumors
High-grade papillary urothelial
cancers
Contain cell that may be dyscohesive
and have large hyperchromatic nuclei
Some of the tumor cells have frank
anaplasia
Mitotic figures, including atypical ones,
are frequent
Architecturally, there is a disarray with
loss of polarity
Have a much higher incidence of
invsions into the muscular layer, a
higher risk of progression than low- High-grade papillary urothelial carcinoma with
grade lesions, and significant metastatic marked cytologic atypia
potential.
 Urinary bladder
Neoplasms

Urothelial (Transitional Cell) Tumors

Epidemiology of carcinoma of the bladder resembles that of bronchogenic
carcinoma
More common in men than in women
Male to female ratio for transitional cell tumors is approximately 3:1
About 80% of patients are between ages of 50 to 80 years.
Bladder cancer in not familial
Factors that implicated in the causation of transitional cell carcinoma
Cigarette smoking
Industrial exposure to arylamines
Schistosoma haematobium
Long-term use of analgesics, implicated also in analgesic nepthropathy
Heavy long-term exposure to cyclosphamide, an immunosuppresive agent, induces,
as noted in hemorrhagic cystitis and increases the risk of bladder cancer
 Urinary bladder
Neoplasms

Urothelial (Transitional Cell) Tumors

Factors that implicated in the causation of transitional cell
carcinoma
Cigarette smoking
Industrial exposure to arylamines
Schistosoma haematobium
Long-term use of analgesics, implicated also in analgesic nepthropathy
Heavy long-term exposure to cyclosphamide, an immunosuppresive
agent, induces, as noted in hemorrhagic cystitis and increases the risk
of bladder cancer
Prior exposure of the bladder to radiation, often performed for other
pelvic malignancies, increase the risk of urothelial carcinoma. In this
setting, bladder cancer occurs many years after the radiation.
 Urinary bladder
Neoplasms
Urothelial (Transitional Cell) Tumors
A number of genetic alterations have been observed in
urothelial cell carcinoma
Particularly common (occurring in 30% to 60% of tumors
studied) are chromosome 9 monosomy or deletions of 9p
and 9q as well as deletions of 17p, 13q, 11p, and 14q.
Chromosome 9 deletions are the only genetic changes
that are present frequently in superficial papillary tumors
and occasionally in noninvasive flat tumors.
The 9p deletions involve the tumor-suppressor gene
p16(MTS1), which encodes an inhibitor of a cyclin-
dependent kinase INK4a.
 Urinary bladder
Neoplasms

Urothelial (Transitional Cell) Tumors

Clinical course
Bladder tumors classically produce painless hematuria
Frequency, urgency and dysuria occasionally accompanies the
hematuria
When the ureteral orifice is involved, pyelonephritis or hydronephrosis
may follow
About 60% of neoplasms, when first discovered, are single, and 70%
are localized to the bladder.
Patients with urothelial tumors, whatever their gradde, have a
tendency to develop new tumors after excision, and recurrences may
exhibit a higher grade.
Most important factors for progression-free survival are: (1) grade, (2)
presence of lamina propria invasion, and (3) associated carcinoma in
situ
 Urinary bladder
Neoplasms

Urothelial (Transitional Cell) Tumors

Clinical course
Papillomas, papillary urothelial neoplasms of low malignant
potential, and low-grade papillary urothelial cancer yield a
98% 10-year survival rate regardless of the number of
recurrences
Only a few patients (<10%) experience progression of their
disease to higher-grade lesions
In contrast, only about 40% of individuals with a high-grade
cancer survive 10 years; the tumor is progressive in 65%.
Approximately 70% of patients with squamous cell
carcinomas are dead within the year.
 Urinary bladder
Neoplasms

Urothelial (Transitional Cell) Tumors

Clinical course
Bladder cancer therapy depends on the grade and stage, and whether the
lesion is flat or papillary.
Small localized papillary tumors that are not high grade, the initial diagnostic
transurethral resection is all that is done.
Patients are closely followed with periodic cystoscopic and urine cytologic
examinations for the rest of their lives for recurrent tumor.
After the biopsy site has healed, patients who are at high risk of recurrence of
progression received topical immunotherapy consisting of intravesicle
installation of an attenuated strain of tubercullous bacillus called bacillus
Calmette-Guerin (BCG).
 Urinary bladder
Neoplasms

Urothelial (Transitional Cell) Tumors

Clinical course
Radical cystectomy is typically performed for:
Tumor invading the muscularis propria
CIS or high-grade paillary cancer refractory to BCG
CIS extending into the prostatic urethra and extending down the
prostatic ducts, where BCG will not come into contact with the
neoplastic cells
Advanced bladder cancer is treated by chemotherapy
 urethra
Inflammations
Urethritis
Two variants:
Gonococcal urethritis
One of the earliest manifestation of this venereal infections.
Nongonococcal urethritis
Cause by a variety of bacteria, among which E. coli and other enteric
organisms predominate.
Accompanied by cystitis in women and by prostatitis in men.
Various strains of Chlamydia causes 25 % to 60% of
nongonococcal urethritis in men and about 20 % in women
Morphologic changes are entirely typical of inflammation in
other sites within the urinary tract
 urethra
Tumors and Tumor-like Lesions

Urethral Caruncle
Inflammatory lesion presenting as a small, red, painful mass about
the external urethral meatus in the female patient
Can be found at any age but more common in later life
Lesion consists of a hemispheric, friable, 1- to 2- cm nodule that
occurs singly, either outside or within the external urethral meatus
Histologic exam: composed of highly vascularized, young
fibroblastic, connective tissue, usually heavily infiltrated with
leukocytes.
Surgical excision affords prompt relief and cure
Benign epithelial tumors of the urethra include squamous and
transitional cell papillomas, inverted papillomas and
condylomas
Urethral Caruncle
 urethra
Tumors and Tumor-like Lesions

Primary carcinoma of the urethra is uncommon

Occurs in advanced age in women
Lesions found within the distal urethra are more
typically squamous carcinomas
Glandular carcinomas less frequently occur in the
urethra as primary tumors, and are also frequent
in women