DEVELOPMENTAL DISORDERS

***HYPOSPADIAS
• Abnormal opening of the urethra onto the ventral
surface of the penis or scrotum.
• This results from failure of fusion of the urethral
folds, i.e., it is a form of feminization.
EPISPADIAS

• Abnormal opening of the urethra on the dorsal surface

of the penis.
• Incontinence and bladder infections are usual.
• Epispadias is fortunately less common than
hypospadias and more difficult to correct surgically.
PHIMOSIS
• Phimosis is a condition in which
the prepuce cannot be retracted
easily over the glans penis.
• Phimosis may be congenital
• More often, phimosis is due to
poor hygiene, resulting in chronic
inflammation and scarring,

• Paraphimosis results when a tight foreskin

is forcibly retracted, and edema of the
glans prevents its replacement.
• This can quickly lead to acute urinary
retention and even gangrene of the glans.
Balanoposthitis: Infection of the glans and prepuce
PRIAPISM
• A persistent, non-pleasurable erection.
• Most cases of priapism are probably due to
obstruction of the deep dorsal vein of the penis.
• Causes:
– idiopathic,sickle cell disease,leukemia
– metastatic cancer, trauma.
– papaverine treatment of impotence (rare)
INFLAMMATION of Male Urogenital Tract

Balanoposthitis, Urethritis, Cystitis, Prostatitis,

Epididymitis, Orchitis,
**Reiter's syndrome
• The triad of
– (1) arthritis involving many joints,
– (2) conjunctivitis, and
– (3) urethritis.
• It's a man's disease and lasts for
several months.
• The urethritis is usually chlamydia,
and one new study finds chlamydial
RNA in the synovium.
• Patients with Reiter's syndrome are
likely to have circinate balanitis,
ulcers of the mouth, iritis, or even
ankylosing spondylitis.
 **PEYRONIE'S DISEASE
• Proliferation of fibrous tissue involving a
portion of the fascia.
• This leads to curvature of erection.
• Other names:"painful erection in the wrong
direction",
• This is one of several abnormal
hyperplasias of fibrous tissue which are
sometimes called "fibromatoses“.
– Palmar fibromatosis (Dupuytren's
contracture of the hand) which often
occurs with Peyronie's disease.

• Metaplastic ossification and calcification are common.

• Treatment for Peyronie's disease is not very satisfactory, and
many patients eventually require a penile prosthesis.
 SCROTUM, TESTIS, AND EPIDIDYMIS
Several inflammatory processes may affect the skin
of the scrotum, including local fungal infections
and systemic dermatoses (psoriasis).

Squamous cell carcinoma,

 ***CRYPTORCHIDISM (cryptorchism)

– Incomplete descent of the testis into the scrotal

sac.
– Unilateral or bilateral cryptorchidism occurs in
around 4% of prepubertal boys.
– Cryptorchid testes may be found anywhere along
the normal route of descent (abdomen, inguinal
canal, prepubic).
– The epididymis is likely to be malformed or at
least elongated.
– Failure of the testes to descend into the scrotum
causes problems:
□ The tubules will undergo atrophy and fibrosis,
beginning in infancy and advanced around
puberty.
□ There is an increased risk of torsion of the
spermatic cord and gangrene of the testis.
□ The risk of germ cell cancer (usually seminoma)
in undescended testes is around 30x greater
than normal.
– Most cryptorchidism is idiopathic.
Infertility:
Female causes 50% Male causes 50%

Male Infertility
• Pretesticular, Testicular, Post testicular

Spermatogenesis can be temporarily diminished or

even stopped by a host of factors ranging from heavy
drinking to anabolic steroid abuse to alcoholism to
bicycling.
 EPIDIDYMITIS and ORCHITIS
• Nonspecific infections of the contents of the scrotum
are usually complications of urinary tract infection,
instrumentation or prostate surgery.
• Gonorrhea: the infection often spreads to the
epididymis, less often the testis.
• Mumps: orchitis is common in adolescents and adults.
It follows the onset of parotitis by a week, and may
cause atrophy of the germinal epithelium and infertility.
• Tuberculosis: granulomas involving the epididymis;
may spread to the testis.
• Syphilis: gummas involving the testis; may spread to
the epididymis.
TORSION OF SPERMATIC CORD
("torsion of the testis")

– Twisting of the spermatic cord is likely to result in

venous infarction and gangrene in a few hours.
– This is quite common, especially in children and
adolescents.
– The involved testis is painful and elevated
– There may or may not be a history of trauma
(often minor, as in baseball or break dancing).
– The underlying problem may be abnormal
fixation of the testis or cryptorchidism.
– Torsion of the appendices of the testis and
epididymis are painful but not so serious.
 ***HYDROCELE

• Fluid in the tunica vaginalis.

• Usually idiopathic

• A hydrocele may contain 100 cc or more of serous

fluid
• If ascites is present and the patient has a patent
processus vaginalis, a hydrocele will appear and
disappear as the patient changes position.
• One can distinguish a hydrocele from a tumor mass
by trans-illuminating it with a bright flashlight in a
dark room.
The clear fluid of a hydrocele allows light to pass through
(transluminescence), distinguishing it from collections of
blood, pus, or lymph, all of which are cloudy or opaque.
**Hematocele
– Blood in the tunica vaginalis.
– May follow trauma, or warn of an underlying
testicular cancer.
**Chylocele: Accumulation of lymphatic fluid in the
tunica.
**Spermatocele: A cystic lesion up to 1 cm or so in the
area of the rete testis, filled with fluid and dead
sperms.
VARICOCELE
**Varicosities of the pampiniform plexus,
– Usually on the left side.
– This is common in young men, may cause fertility
problems by warming the testes.
 The TUMORS of the
MALE REPRODUCTIVE SYSTEM
Penis Tumors; WARTS
Condyloma acuminatum
• A papillary, keratinizing lesion caused by the
sexually-transmitted "human papilloma virus"
(usually strain 6).
• In males, it commonly occurs in the urethral
meatus, which is a mess.
Condyloma latum
• Groups of flat-topped lesions which may ooze
serous fluid
• Caused by secondary syphilis.
• Typically occur in skin folds.
 PREMALIGNANT LESIONS OF THE PENIS
• Erythroplasia of Queyrat
– A raised, velvety plaque on the uncircumcised
glans or prepuce.
– Histologic study shows dysplasia of the squamous
epithelium.

– A minority of cases
(5-10%) develop into
squamous cell
carcinoma if not
removed.
• Bowen's disease
– Carcinoma in situ of the skin, most often on the
penis or scrotum in men.
– Some cases (maybe 10%) develop into invasive
squamous cell carcinoma.
– In many cases, the appearance of Bowen's disease
on the skin heralds the growth of another
malignancy internally.

Bowen's disease
tends to spare the
sweat glands and
involve the hairs.
• Bowenoid papulosis
– Multifocal intraepithelial neoplasia, caused by HPV-
16.
– The atypia is mild.
– Bowenoid papulosis tends to spare the hairs and
involve the sweat glands.
– Bowen's disease tends to spare the sweat glands
and involve the hairs.
CARCINOMA of PENIS

• Almost all are variations on squamous cell

carcinoma
• This is a disease of older men (~60 years)
• It originates on glans and prepuce.
– Only 1% of cancers among American men begin
on the penis; the figure is as high as 18% in the
Orient.
• Risk factors :
– phimosis, smegma, balanoposthitis,
– infection with HPV (notably HPV-16).
• Males circumcised as infants almost never get cancer
• Carcinoma of the penis spreads to the inguinal lymph
nodes.
• Five year survival is around 50% overall.
• Scrotal squamous cell carcinoma is the subject of the
famous chimney sweep story.
 Testicular tumors
• Over 95% of tumors of the testis are malignant
germ cell tumors.
• All present as painless, non-tender masses in the
testis.
• The primary may be occult, especially pure
choriocarcinomas.
• Many cause gynecomastia (after puberty) or
precocious puberty (children)
• Risk factors
– Cryptorchidism, some intersex
malformations,familial.
Germ-Cell tumors

• Seminoma
• Embryonal cell carcinoma
• Choriocarcinoma
• Yolk sac tumor
• Teratoma &Teratocarcinoma
Seminoma
• Cancer that closely resembles young spermatocytes.
• Grossly these tumors are homogeneously soft and
yellowish.
• Tumor cells have "fried egg" appearance (glycogen-
rich cytoplasm); arranged in masses separated by
fibrous septa with a lymphocytic infiltrate, may have
syncytiotrophoblast and/or granuloma formation.
Seminoma
• Cancer that closely resembles young spermatocytes.
• Grossly these tumors are homogeneously soft and
yellowish.
– Variant: spermatocytic seminoma of older men
has somewhat different histology, no in situ
phase, even better prognosis (it almost never
metastasizes).
• Chorionic gonadotropin (hCG) is a tumor marker for the
50% or so of seminomas that contain syncytiotrophoblast
(the man has a positive pregnancy test).
• Seminomas typically metastasize to the retroperitoneal
lymph nodes and then to the lungs.
• Seminomas are remarkable for their good response to
radiation or chemotherapy as appropriate, and even
widespread disease can usually be treated with five-year
survivals of 95% or better.
• Tumors with histology like testicular seminomas also arise
in other midline structures including the retroperitoneum,
thymus, and pineal ("germinomas"), as well as in the
ovary ("dysgerminoma").
Embryonal cell carcinoma
• A very primitive cancer that arises in the testis.
• Grossly these are grayish-white masses with hemorrhage
and necrosis.
• Tumors with an embryonal cell carcinoma component
metastasize to the retroperitoneum and everywhere else.
• Microscopically, the tumor cells grow in sheets, knobs.
– Distinguish from a seminoma by absent glycogen and
positive staining for cytokeratin
– Many embryonal cell carcinomas also contain
differentiated structures of a teratoma.
– Teratoma + embryonal cell carcinoma =
teratocarcinoma.
Choriocarcinoma
• The bloodiest tumor in pathology; solid areas may be
hard to find.
• The malignant cells resemble placenta, and the
pathologist must identify cytotrophoblast and
syncytiotrophoblast.
• There are no villi.
• ***HCG levels are always very elevated (serum,
urine.)
• Choriocarcinoma most often is a component in a
teratocarcinoma, but may be pure or mixed with any
other germ cell tumor components.
• Until recently, choriocarcinoma arising in the testis
was always lethal.
– Today the prognosis is not much worse than for
embryonal cell carcinoma, even if the tumor is
"pure choriocarcinoma".
Yolk sac tumor (endodermal sinus tumor, infantile
embryonal cell carcinoma)
• Rare
• The commonest testicular tumor of children.
• It is composed of papillary structures (***Schiller-
Duval bodies) with extracellular globs of **alfa-
fetoprotein.
Teratoma & Teratocarcinoma
• Cystic teratoma of testis is rare (but common in ovary)
and seldom contains hair.
– Teratomas are the only testicular tumors that are
often cystic.
• Solid teratomas are of two types:
– Mature solid teratoma is benign, usually occurs in
children.

– Immature solid teratoma is

malignant, usually contains
embryonal cell carcinoma
(teratocarcinoma) or sometimes
squamous cell carcinoma.
**Stromal tumors (sexcord tumors)
– Leydig cell Tumor
– Sertoli cell tumor (androblastoma).
• Leydig cell tumors >Sertoli cell tumors
• Less than 5% of all testicular tumors
• Benign (90%), malignant (10%)
– Criteria for malignancy are necrosis, mitotic
figures, local invasion, and nuclear
pleomorphism.
• May elaborate androgens/androgens&estrogens
• Hormonally active (50%)
• Macrogenitosomia, precocious puberty,
gynecomastia
 OTHER TUMORS of TESTIS

• Lymphoma arises in the testes of older

men with some frequency.
• Adenomatoid tumor is a benign, hard
spherical nubbin, usually in the head of the
epididymis, derived from mesothelium.
 PROSTATE
• The prostate divided into several distinct regions
• **Hyperplastic lesions arise in the inner transition
zone, while most carcinomas (70% to 80%) arise in
the peripheral zones.

• It is involved by infectious,
inflammatory, hyperplastic,
and neoplastic disorders.
• The normal prostate
contains glands with two
cell layers, a flat basal cell
layer and an overlying
columnar secretory cell
layer.

• Surrounding prostatic
stroma contains a
mixture of smooth
muscle and fibrous tissue.
Prostatism
• Prostatic hyperplasia causes many problems (collectively called
"prostatism"), though most patients are asymptomatic.
• frequency (i.e., only small amounts are voided at a time),
• nocturia (urinating at night, same reason),
• difficulty starting and stopping urination,
• incontinence (dribbling),
• dysuria (painful urination),
• hernias (from straining),
• acute urinary retention (emergency)
• hematuria (due to stretching of veins),
• bladder hypertrophy and trabeculation,
• bladder diverticula,
• bladder stones,
• hydronephrosis,
• renal failure
• Residual urine accumulates in an enlarged bladder behind the
prostate gland.
• This gets infected.
**Prostatodynia is a stress-related pain syndrome
in which there are no WBC's in the prostatic
fluid.

• Other exacerbating factors include

– constipation, smoking, coffee, spices.
 Prostatitis
Prostatitis is divided into four categories:
• (1) acute bacterial prostatitis (2% to 5% of cases),
• (2) chronic bacterial prostatitis (2% to 5% of cases),
• (3) chronic nonbacterial prostatitis, or chronic pelvic
pain syndrome (90% to 95% of cases), in which no
uropathogen is identified despite the presence of
local symptoms;
• (4) asymptomatic inflammatory prostatitis,
associated with incidental identification of leukocytes
in prostatic secretions without uropathogens.
• In "non-bacterial prostatitis", the findings are as in
chronic prostatitis, but no organisms grow, probably;
– Chlamydia, Trichomonas
– Autoimmunity , Heroic abstinence.
• Granulomatous prostatitis may be due to
– TB (hematogenous spread from the lungs),
 Clinical Features
• Acute bacterial prostatitis is associated with fever,
chills, and dysuria.
• On rectal examination, the prostate is tender.
• Chronic bacterial prostatitis usually is associated with
recurrent urinary tract infections.
• Presenting manifestations may include with low back
pain, dysuria, and perineal and suprapubic
discomfort.
• Acute and chronic bacterial prostatitis are treated
with antibiotics.
• The diagnosis of chronic nonbacterial prostatitis
(chronic pelvic pain syndrome) is difficult.
• There are no proven therapies for chronic pelvic pain
syndrome
 Benign Prostatic Hyperplasia
(Nodular Hyperplasia)
• BPH is an extremely common abnormality.
• 10% of men living to age 80 will need prostate
surgery.
– The normal prostate weighs around 20 gm.
– Old men's prostates enlarge to 60-200+ gm.
• The increased tissue is nodular overgrowth of
periurethral glands and stroma.
• Press upon the prostatic urethra.
• BPH does not occur in males castrated before the
onset of puberty or in men with genetic diseases
that block androgen activity.
• The etiology of prostatic hyperplasia is obscure.

– Hormonal imbalance with ageing.

– Estrogen sensitive periurethral glands.
– Accumulation of dihydrotestosterone in the
prostate and its growth-promoting androgenic
effect.

**it is clear that excessive androgen-dependent growth

of stromal and glandular elements has a central role.
• Heroic abstinence is also rumored to be a risk factor.
 Clinical Features
• Clinical manifestations of prostatic hyperplasia
occur in only about 10% of BPH.
• Because BPH preferentially involves the inner
portions of the prostate, the most common
manifestations are related to lower urinary tract
obstruction.
• -Difficulty in starting the stream of urine (hesitancy)
and
• interruption of the urinary stream while voiding
• These symptoms frequently are accompanied by
urinary urgency, frequency, and nocturia, all
indicative of bladder irritation.
❖ The presence of residual urine in the bladder increases
the risk of urinary tract infections.
❖ In some affected men, BPH leads to complete urinary
obstruction, with resultant painful distention of the
bladder and, hydronephrosis.
❖ Initial treatment is pharmacologic, using agents that
inhibit DHT formation (Finestride) or that relax smooth
muscle by blocking alpha adrenergic blockers (Flomax).

Various surgical techniques are

reserved for severely symptomatic
cases resistance to medical therapy.
Microscopy
– Nodular prostatic hyperplasia
consists of nodules of glands and
intervening stroma
– The glands variably sized, with
larger glands have more
prominent papillary infoldings.
*Nodular hyperplasia is NOT a precursor to carcinoma.
 Carcinoma of the Prostate
Adenocarcinoma of the prostate is the most common form
of cancer in men, accounting for 25% of cancer in men.
However, prostate cancer causes only 9% of cancer deaths

Prostatic intra-epithelial neoplasia“; PIN

• The in-situ lesion (prostatic intraepithelial neoplasia“; PIN) is
now well-characterized as well.
– There's always nuclear enlargement and crowding, there
are usually nucleoli
– Low-grade "PIN" is common in young men, and it probably
takes decades to transform
– Usually these lesions will involve part of a single gland
– Nowadays, the feeling is that PIN requires biopsy.
Grading of PIN
– Low grade
• PIN1: loss of secretion, piling up of cells
("tufting"), blue cytoplasm,
– High grade
• PIN2: As PIN1, but with high Nucleus/Cell ratio
• PIN3: As PIN2, but with prominent nucleoli and a
papillary or cribriform pattern
– Any: The basal layer is at least somewhat intact.
– Animal fat / meat
• ***Etiology of prostate cancer:

– Essentially unknown.
– Androgens
• early castration prevents the development of
adenocarcinoma (lack of sexual activity)
– Exposure to cadmium (i.e., battery factories)
– Animal fat / meat
– Prostate-cancer-family gene(HPC2 / ELAC2).
• Clinical:
– Cancer of the prostate presents as a painless lump
in the gland.
– These tumors are easier to feel than to see;
• they are firmer than hyperplastic nodules,
• poorly circumscribed, and yellowish.
– Diagnosis is by biopsy, prostatectomy.
– PSA (prostate-specific antigen)
• urologists are likely to do 12 biopsies on
prostates of men with elevated PSA's and no
palpable lump.
• Histology:
– prominent nucleoli in nuclei with marginated
chromatin
– invasion (especially perineural invasion; at least
loss of the normal gland-stroma interaction)
– obvious distortion of the architecture
– loss of the outer layer ("basal layer") of the
glands

Pathologists pay special attention to the presence

or absence of the basal layer
 Clinical Features
Some 70% to 80% of prostate cancers arise in the **outer
(peripheral) glands and hence may be palpable as
irregular hard nodules on digital rectal examination.

However, most prostate cancers are small, nonpalpable,

asymptomatic lesions discovered on needle biopsy
performed to investigate an elevated serum prostate-
specific antigen (PSA) level.

**Prostate cancer is less likely than BPH to cause urethral

obstruction in its initial stages.
Locally advanced cancers often infiltrate the
seminal vesicles and periurethral zones of the
prostate and may invade the adjacent soft
tissues, the wall of the urinary bladder, or the
rectum.

Bone metastases, particularly to the axial

skeleton, are frequent and typically cause
***osteoblastic (bone-producing) lesions that
can be detected on radionuclide bone scans.
**The PSA assay is the most important test used in the diagnosis
and management of prostate cancer

In most laboratories, a serum PSA level of 4 ng/mL is the cutoff

between normal and abnormal, although some guidelines
designate values above 2.5 ng/mL as abnormal

One limitation of PSA is that while it is organ-specific, it is not

cancer-specific.

BPH, prostatitis, prostatic infarcts, instrumentation of the

prostate, and ejaculation also increase serum PSA levels.

Conversely, 20 to 40% of patients with organ-confined prostate

cancer have a PSA value of 4.0 ng/mL or less.
The percentage of free PSA (the ratio of free PSA to
total PSA) is lower in cancer than benign prostatic
diseases.

Once cancer is diagnosed, serial measurements of

PSA are of great value in assessing the response to
therapy.

For example, a rising PSA level after radical

prostatectomy or radiotherapy for localized disease
is indicative of recurrent or disseminated disease
The most common treatments for clinically localized prostate
cancer are ***radical prostatectomy and radiotherapy.

***The prognosis after radical prostatectomy is based on

the pathologic stage, margin status, and Gleason grade.

Advanced metastatic carcinoma is treated by androgen

deprivation, either by orchiectomy or by administration of
synthetic agonists of luteinizing hormone–releasing
hormone (LHRH).

Although antiandrogen therapy induces remissions,

androgen-independent clones eventually emerge, leading
to rapid disease progression and death.
• Uncommon prostate cancers include squamous and
endometrioid, adenoid cystic, colloid, carcinosarcoma,
signet-ring, oat-cell, carcinoid, and lymphoepithelioma.

• Prostate cancer is often indolent even when it has

metastasized, but some prostate cancers are very
aggressive.
– Mucin-producing prostate cancer is an aggressive lesion.

• Metastases:
– regional lymph nodes
– axial skeleton (causing miserable bone pain often
with osteoblastic lesions)
– leptomeninges (not the brain tissue).
 URETER, BLADDER, AND URETHRA
The renal pelvis, ureters, bladder, and urethra are
lined by urothelium.
Beneath the mucosa: the lamina propria and, the
muscularis propria (detrusor muscle)
 Ureter
Ureteropelvic junction (UPJ) obstruction, results in
hydronephrosis

It is the most frequent cause of hydronephrosis in

children

Primary malignant tumors are urothelial carcinomas.

Retroperitoneal fibrosis is an
uncommon cause of ureteral
obstruction and causing hydronephrosis.
 Urinary Bladder
Non neoplastic conditions
❖ Diverticulum consists of a pouchlike
evagination of the bladder wall.
❖ Diverticula may be congenital but more
commonly are acquired lesions that arise as a
consequence of persistent urethral
obstruction caused by benign prostatic
hyperplasia.
❖ Although most diverticula are small and
asymptomatic, they sometimes lead to
urinary stasis and predispose to infection
❖ Cystitis takes many forms.
❖ Patients receiving cytotoxic antitumor drugs,
such as cyclophosphamide, sometimes
develop **hemorrhagic cystitis.
❖ **Polypoid cystitis is an inflammatory
condition resulting from irritation to the
bladder mucosa
❖ Polypoid cystitis may be confused with
papillary urothelial carcinoma both clinically
and histologically.
❖ The common etiologic agents of bacterial
cystitis are coliform bacteria.
Interstitial cystitis

• **Interstitial cystitis (chronic pelvic pain

syndrome) is a persistent, painful form of chronic
cystitis occurring most frequently in women.
• It is characterized by intermittent, often severe
suprapubic pain, urinary frequency, urgency,
hematuria and dysuria without evidence of
bacterial infection.
• The histologic findings are nonspecific.
• Late in the course, transmural fibrosis may ensue,
leading to a contracted bladder.
Malakoplakia

•Malakoplakia most commonly occurs in the bladder and

results from defects in phagocytic function of
macrophages.
The macrophages have abundant granular cytoplasm filled
with phagosomes stuffed with undigested bacterial
products.
In addition, laminated mineralized
concretions resulting from deposition
of calcium in enlarged lysosomes,
known as ***Michaelis-Gutmann
bodies, typically are present within the
macrophages.
Various metaplastic lesions may occur in the bladder.
Nests of urothelium (Brunn nests) may grow
downward into the lamina propria, and their central
epithelial cells may variously differentiate into a
cuboidal or columnar epithelium lining (cystitis
glandularis); cystic spaces filled with clear fluid lined
by flattened urothelium (cystitis cystica); or goblet
cells resembling intestinal mucosa (intestinal
metaplasia).
As a response to injury, the urothelium often
undergoes squamous metaplasia, which must be
differentiated from normal glycogenated squamous
epithelium, commonly found at the trigone in
women.
 Neoplasms

• Bladder cancer accounts for approximately 7% of cancers

and 3% of cancer deaths
• The vast majority of bladder cancers (90%) are
***urothelial carcinomas.
• Carcinoma of the bladder is more common in men than
in women.
• Squamous cell carcinomas represent about 3% to 7% of
bladder cancers but are much more common in countries
where urinary schistosomiasis is endemic
 Clinical Features
• Bladder tumors most commonly present with painless
hematuria.
• Patients with urothelial tumors, whatever their grade,
have a tendency to develop new tumors after excision.
• The risk of recurrence is related to several factors,
including tumor size, stage, grade, multifocality, mitotic
index, and associated dysplasia and/or CIS in the
surrounding mucosa.
• Most recurrent tumors arise at sites different than that of
the original lesion, (share the same clonal abnormalities)
that stem from shedding and implantation of the original
tumor cells at new sites.
• The treatment for bladder cancer depends on tumor grade
and stage and on whether the lesion is flat or papillary.
• For small localized low grade papillary tumors, the
transurethral resection is both diagnostic and
therapeutically sufficient.
• Patients with high-risk tumor typically receive topical
immunotherapy consisting of intravesical instillation of an
attenuated strain of the tuberculosis bacillus called bacilli
Calmette-Guérin (BCG).
• BCG elicits a typical granulomatous reaction (local
antitumor immune response)
• Patients are closely monitored for tumor recurrence with
periodic cystoscopy and urine cytologic studies for the rest
of their lives.
Radical cystectomy typically is reserved for

(1) Tumor invading the muscularis propria;

(2) CIS or high-grade papillary cancer refractory to BCG; and
(3) CIS extending into the prostatic urethra and down the prostatic
ducts, where BCG cannot contact the neoplastic cells.
Advanced bladder cancer is treated using chemotherapy, which
can palliate but is not curative
SEXUALLY TRANSMITTED DISEASES
• Women are far more likely to become infected
by an STD and to be asymptomatic.
• Of the 10 leading infectious diseases that require
notification of the Centers for Disease Control
and Prevention (CDC) in the United States, five—
chlamydial infection, gonorrhea, acquired
immunodeficiency syndrome (AIDS), syphilis,
and hepatitis B—are STDs (Table 18.3).
 Syphilis
❖ Syphilis is a chronic venereal infection caused by
the spirochete Treponema pallidum.
❖ Syphilis is endemic in all parts of the world.
❖ Once introduced into the body, the organisms
rapidly disseminate to distant sites through
lymphatics and the blood.
❖ This widespread dissemination in adults can be
divided into primary, secondary, and tertiary
stages
• Primary syphilis.
❖ Several weeks after infection (mean, 21 days), a
primary lesion, termed a chancre, appears at the
point of spirochete entry.
❖ Systemic dissemination of organisms occurs during
this period.
❖ Two types of antibodies are formed: antibodies
that cross-react with host constituents
(nontreponemal antibodies) and antibodies to
specific treponemal antigens.
❖ This humoral response, however, fails to eradicate
the organisms.
• Secondary syphilis.
❖ The chancre of primary syphilis resolves spontaneously
over a period of 4 to 6 weeks and is followed in
approximately 25% of untreated patients by the
development of secondary syphilis.
❖ The manifestations of secondary syphilis, include
generalized lymphadenopathy and mucocutaneous
lesions.
❖ The mucocutaneous lesions of both primary and
secondary syphilis are teeming with spirochetes and are
highly infectious.
❖ Like the chancre, the lesions of secondary syphilis resolve
even without antimicrobial therapy.
❖ At that point patients are said to be in early latent-phase
syphilis.
• Tertiary syphilis.
❖ Patients with untreated syphilis next enter an
asymptomatic, late latent phase of the illness
❖ In about one third of cases, new symptoms develop
over the next 5 to 20 years.
❖ This late symptomatic phase, or tertiary syphilis, is
marked by the development of lesions in the
cardiovascular system, central nervous system, or,
less frequently, other organs.
❖ Spirochetes are much more difficult to demonstrate
during the later stages of disease, and patients are
accordingly much less likely to be infectious than are
those in the primary or secondary stages of disease
Diagnosis
● Since T. pallidum has never been successfully
cultured on artificial media,
● Diagnosis depends on
● (a) Direct visualization of the organism in tissue with
immunohistochemistry, immunofluorescence or
Warthin-Starry stain,
● (b) Dark field examination demonstrating
spirochetes from an active lesion,
● (c) PCR testing or
● (d) Serologic testing
○ ***Chancres are a
superficial, nontender
ulceration, associated with
regional nonpainful
lymphadenopathy
○ Have a smooth base and
raised edges
○ They may be single or
multiple, and up to 2 cm
Neisseria gonorrhoeae
➔ Gonorrhea is a purulent infection of the mucous membrane
caused by Neisseria gonorrhoeae.
➔ It is most prevalent in the developing world
➔ These bacteria frequently colonize in the genital mucosa, but
also (the anal, ocular, and nasopharyngeal mucosa)
➔ If left untreated in the female genital tract, Neisseria
gonorrhoeae can give rise to complications including pelvic
inflammatory disease, infertility, ectopic pregnancy, and
even disseminated gonococcal infection (%3), which may
lead to infectious arthritis and endocarditis.
➔ Neisseria gonorrhoeae can also transmit from mother to
child, potentially leading to neonatal blindness
• It is a bacterial infection that affects skin and mucous membranes of
the anal and genital areas
• Granulation tissue formed during wound healing
• They are found in the macrophages cytoplasm as Donovan bodies
• Diagnosis is made by microscopic examination and identification of
“donovan bodies” in the cytoplasm of phagocytes/macrophages
taken from a lesion and dyed with wright or Giemsa stain or by
histological examination of a biopsy specimen.