Pathology of Male Genital

System
HARI ATMOKO
Disorders of the male genital system include:

A variety of malformations,
Inflammatory conditions, and
Neoplasms involving the penis and
scrotum, prostate, and testes.
Trauma
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. Occurs 1 in
250 male alive births.
There is often associated cryptorchidism,
ureterovesical reflux, inguinal hernia, and/or other
developmental problems.
Right now there is a pop claim that hypospadias
has doubled in frequency in the past twenty
years, and the cause is chemical pollutants
acting as "endocrine disruptors".
 The urethral meatus may open on the ventral surface
of the penis, at the base of the penis or the
perineum.
This infant with ambiguous genitalia was a genetic
male. The arrow points to the urethral orifice that
opens unto the perineum.
 PHIMOSIS
Present when the preapuce can not be retracted over the corona.
Phimosis may be congenital, the orifice of the prepuce being too
small.
More often, phimosis is due to poor hygiene, resulting in
chronic inflammation and scarring, which sets up a vicious
cycle requiring circumcision.
Such an ongoing infection of the glans and prepuce is called
balanoposthitis.
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.
 EPISPADIAS

Abnormal opening of the urethra on the dorsal

surface of the penis.
Epispadias is a form of extrophy of the urinary
bladder.
There is usually an associated separation of the
pubic bones and inadequacy of the urinary
sphincters.
Incontinence and bladder infections are usual.
Epispadias is fortunately less common than
hypospadias and more difficult to correct surgically.
 PRIAPISM

A persistent, non-pleasurable erection.

"Priapus" was the classical-era Greek god of
erections.
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
papaverine treatment of impotence (rare)
trauma.
INFLAMMATION of Male
Urogenital Tract
-Balanoposthitis
-Urethritis
-Cystitis
-Prostatitis
-Epididymitis
-Orchitis
 Necrotizing fasciitis
of genitalia and
perineum
Usually due to Staph
or Strep in children;
gram negative rods
or anaerobic
bacteria in adults
Affects Bucks fascia
and foreskin, sparing
glans
Risk factors:
trauma, burns,
Fourniers gangrene anorectal disease,
diabetes, leukemia,
alcoholic cirrhosis
URETHRITIS
 Gonorrhea and non-gonococcal urethritis (urethral syndrome)

Due to chlamydia, mycoplasma, trichomonas, perhaps others,

Important sexually-transmitted diseases.
Gonorrhea tends to come on fast after the contact, while chlamydia comes
on insidiously.
Gonorrhea tends to have a more purulent discharge.
 Reiter's syndrome
The triad of
(1) arthritis involving many joints,
(2) conjunctivitis, and
(3) urethritis.
It is a males disease and lasts for several months.
The urethritis is usually (if not always) chlamydia, and one
new study finds chlamydial RNA in the synovium; if the initial
episode of urethritis is treated appropriately,
As with other "reactive arthropathies", there's an impressive
proliferation of T-cells specific for chlamydia within the
affected joints.
Patients with Reiter's syndrome are likely to have circinate
balanitis, keratoderma blennorrhagica of soles, ulcers of the
mouth, iritis, or even ankylosing spondylitis.
Reiter's syndrome
 Peyronies Disease
Proliferation of dense fibrous tissue involving a portion of the fascia.
This leads to curvature of erection.
Other names:
"painful erection in the wrong direction",
"squint of the cock".
This is one of several abnormal hyperplasias of fibrous tissue which are
sometimes called "fibromatoses.
Another common one is 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.
Peyronies Disease
 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.
Ectopic testis is less common; it may stray into
the superficial inguinal region, penis, or
femoral sheath.
 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.
It may be accompanied by
other developmental abnormalities,
poorly-understood anatomic and hormonal problems.
 EPIDIDYMITIS and ORCHITIS

Non-specific 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 usually follows the onset of parotitis by a
week or so, and may cause atrophy of the germinal
epithelium and infertility. The Leydig cells are
spared.
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")

Twistingof the spermatic cord is likely to result

in venous infarction and gangrene in a few hours.
Thisis quite common, especially in children and
adolescents.
The involved testis is painful and elevated; the
cord is typically twisted.
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 SPERMATIC
CORD
 Hydrocele
Hematocele
Spermatocele
 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.
 Hematocele
Blood in the tunica vaginalis.
May follow trauma, or a sing 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.
A new varicocele in an old man often indicates
occlusion of the vein by renal cell carcinoma.
VARICOCELE
PROSTATE
 PROSTATITIS

Acute and chronic prostatitis are uncomfortable problems,

and are common in
sexually-transmitted urethritis
lower urinary tract infections.
E. coli is the most common etiologic agent of both acute and
chronic prostatitis.
The diagnosis depends on physical and lab exams.
In acute prostatitis the gland is exquisitely tender.
Gonorrhea is an important cause of acute prostatitis
(secondary to urethritis; it can also cause epididymitis).
In chronic prostatitis the gland is somewhat tender and the
prostatic fluid contains WBC's and bacteria.
 Granulomatous prostatitis may be due to
Tbc (hematogenous spread from the lungs),
"idiopathic"(no Tbc, no caseation, no clues as to
the etiology).
The histiocytes may resemble cancer cells.

In "non-bacterial prostatitis", the findings are as in

chronic prostatitis, but no organisms grow, probably;
Chlamydia

Trichomonas

Autoimmunity

Heroic abstinence.
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.
PROSTATIC HYPERPLASIA
Benign prostatic hypertrophy or hyperplasia, BPH.
Most men over about age 50; 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.
The hyperplasia most often involves the lateral and
median lobes.
Median lobe hyperplasia by itself produces a "median
bar", obstruction without an enlarged gland.
 The etiology of prostatic hyperplasia is obscure.
Hormonal imbalance with ageing.
Estrogen sensitive peri-urethral glands.
Accumulation of dihydrotestosterone in the
prostate and its growth-promoting androgenic
effect.
Heroin abuse is also rumored to be a risk factor.
The most interesting work right now focuses in a
nerve-growth factor-like protein produced by the
stromal cells which causes hyperplasia of both glands
and stroma
 Microscopy
Nodular prostatic hyperplasia consists of nodules of glands and intervening
stroma (mostly glands)
The glands variably sized, with larger glands have more prominent papillary
infoldings.
Prostatism (This is a clinical term)
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),
bladderhypertrophy and trabeculation (accentuation of the
normal muscles),
bladder diverticula, bladder stones,
hydronephrosis,
renal failure
Penis Tumors
 The TUMORS of the
MALE REPRODUCTIVE
SYSTEM
 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.
Pearly penile papules
Little bumps, sometimes hairy, which pop up in young adults,
especially on the corona.
Each is a single big dermal papilla. No need to treat.
Condyloma acuminatum
Condyloma latum
Pearly penile papules
 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.
 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.
Giant condyloma of Busck-Lowenstein
verrucous carcinoma
HPV-related, cauliflower-like lesion.
 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.
CARCINOMA of PENIS
 Risk factors :
phimosis,
smegma,
balanoposthitis,
infection with HPV (notably HPV-16).
Males circumcised as infants almost never get cancer of
the penis. The incidence is much lower in those
circumcised at a later age than among the
uncircumcised.
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.
Many older men get a few angiokeratomas
(hemangiomas with each dermal papilla stretched wide
by a single ectatic blood vessel), especially on their
scrotums.
Testicular tumors
 Over 95% of tumors of the
testis are malignant germ
cell tumors.
Testicular neoplasms are
the most important cause
of firm, painless
enlargement of the testis.
Such neoplasms occur in
roughly 5 per 100,000
males, with a peak
incidence between the
ages of 20 and 34 years.
Current thinking about the
histogenesis of cancers of
the testis emphasizes
their common origin from
germ cells:
 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 carcinoma
Choriocarcinoma
Yolk sac tumor (endodermal sinus 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.
Variant: spermatocytic seminoma of older men has
somewhat different histology, no in situ phase, even
better prognosis (it almost never metastasizes).
Seminoma
 Chorionic gonadotropin (hCG) is a tumor marker for the
50% or so of seminomas that contain syncytiotrophoblast
(i.e., 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 and response to therapy like
testicular seminomas (or other germ cell tumors) also
arise in other midline structures including the
retroperitoneum, thymus, and pineal ("germinomas"), as
well as in the ovary ("dysgerminoma").
 Embryonal 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.
The cured metastases may turn into scar tissue, or just plain
necrotic debris.
Microscopically, the tumor cells grow in sheets, knobs, etc.
Distinguish from a seminoma by absent glycogen and
positive staining for cytokeratin (seminomas are usually
weak or negative).
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,
orchioblastoma, infantile embryonal cell
carcinoma):

Rare
The most common testicular tumor of children.
It is composed of papillary structures (Schiller-Duval
bodies) with extracellular globs of alfa-fetoprotein
and alfa-1-protease inhibitor.
Those PAS positive extracellular hyaline globoid
material is found typically in yolc sac tumor.
This carcinoma is also unusual because it
metastasizes hematogenously.
 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.
Even if an adult's teratoma appears altogether benign,
there is likely to be nearby intratubular carcinoma in
situ.
WARNING: Any tumor of germ cell origin may be mixed with any other tumor
of germ cell origin.

Further, any tumor of germ cell origin may metastasize as another histologic type of
germ cell tumor.
We now know both in-situ and microinvasive testicular cancer.
Germ-cell tumors (seminomas, embryonal cell tumors, teratocarcinomas,
choriocarcinomas, teratomas) can and do arise in the retroperitoneum, and
mediastinum.
Stromal tumors (sex-cord 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%)

The gross and microscopic appearances are typical for

endocrine tumors.
Criteria for malignancy are necrosis, mitotic figures, local
invasion, and nuclear pleomorphism.
May elaborate androgens/androgens & estrogens
Hormonally active (50%) Macrogenitosomia, Precocious puberty, Gynecomastia
 SUMMARY OF TESTICULAR GERM CELL TUMORS

Peak
Age
Tumor (yr) Morphology Tumor Markers
Seminoma 40-50 Sheets of uniform polygonal cells with cleared cytoplasm; 10% have
lymphocytes in the stroma elevated hCG

Embryonal 20-30 Poorly differentiated, pleomorphic cells in cords, sheets, or 90% have
carcinoma papillary formation; most contain some yolk sac and elevated hCG or
choriocarcinoma cells AFP or both

Yolk sac 3 Poorly differentiated endothelium-like, cuboidal, or columnar 90% have

tumor cells elevated AFP

Chorio 20-30 Cytotrophoblast and syncytiotrophoblast without villus 100% have

carcinoma formation elevated hCG
(pure)

Teratoma All Tissues from all three germ-cell layers with varying degrees of 50% have
ages differentiation elevated hCG or
AFP or both

Mixed 15-30 Variable, depending on mixture; commonly teratoma and 90% have
tumor embryonal carcinoma elevated hCG
and AFP
 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 CANCER

Prostate cancer is the most common cancer in

men (age:50-80)
Second cancer after lung carcinoma as a cause
for tumor-related deaths among males.
Latent prostate cancer: found only at autopsy
(incidental prostate cancer)
Occult prostate cancer might pop up in bone
marrow or lymph node prior to becoming
symptomatic.
The tremendous increase in the incidence of
prostate cancer during the 1990's (about 30%)
reflects the improved screening.
The total number of people dying of the disease is
actually decreasing slightly.
 General Features of Prostate Cancer

Over age 50
Prostate cancer is rare in Oriental folks in Asia,
more common in Asian-Americans,
common in U.S. whites,
most common in U.S. Blacks.
The majority, but not all, prostate cancers arise in the posterior
lobe.
Microcarcinoma : Some more recent studies suggest that, after a
man turns thirty, his percentage chance of having a little
histological cancer is about the same as his age (30%).
This is the reason : Occult prostate cancers are common
"incidental" findings in prostate chips obtained at turp.
 Etiology of prostate cancer:
Essentially unknown.
Androgens
earlycastration 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).
 Clinic:
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 or fine-needle aspiration

(first).
Prostatectomy.
PSA (prostate-specific antigen)
urologists are likely to do sextant biopsies on prostates of men with elevated PSA's
and no palpable lump.
Prostatic Intra-epithelial Neoplasia PIN

The in-situ lesion (prostatic intra-epithelial

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
loss of secretion, piling up of cells ("tufting"), blue cytoplasm,

High grade
with high Nuclear/Cytoplasmic ratio
prominent nucleoli and a papillary or cribriform pattern
 Histology of prostatic adenocarcinoma:
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
(on fine needle biopsy, pathologists pay special attention to the presence or absence of the
basal layer)

As in breast, several benign lesions exist that are

easily mistaken for cancer.
 TNM Staging (affects prognosis):

T1: CLINICALLY INAPPARENT LESION (BY PALPATION/IMAGING

STUDIES)
T2: PALPABLE OR VISIBLE CANCER CONFINED TO PROSTATE
T3: LOCAL EXTRAPROSTATIC EXTENSION
T4: INVASION OF CONTIGUOUS ORGANS AND/OR SUPPORTING
STRUCTURES INCLUDING BLADDER NECK, RECTUM, EXTERNAL
SPHINCTER, LEVATOR MUSCLES, OR PELVIC FLOOR
Uncommon prostate cancers include squamous and endometrioid,
plus adenoidcystic, 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
axialskeleton (causing miserable
bone pain often with osteoblastic
lesions)
leptomeninges (not the brain tissue).
THANK YOU