prostatitis - patho.szote.u

DISORDERS OF THE PENIS AND THE
URETHRA
Congenital abnormalities of the urethra
Abnormal location of the urethral orifice
• Hypospadias: the meatus is situated on the ventral
surface of the penis or in the perineum
• Epispadias: the meatus opens on the dorsal aspect
of the penis
Posterior urethral valve
• In the prostatic portion of the urethra
• Connective tissue covered by transitional
epithelium bulges into the lumen
Consequence
• Outflow obstruction  bilateral hydronephrosis,
recurrent urinary tract infections (UTIs)
Control of pregnancy by
ultrasound examination
of the fetus.
Oligohydramnios, abdominal
cyst?,
bilateral hydronephrosis
were observed, and
the pregnancy was
interrupted.
The autopsy identified the
posterior urethral valve and
the extreme dilation of the
bladder as the consequence
of urinary tract obstruction
developed in the fetus.
Urethritis
Pathogenesis
• Gram-neg. bacteria in individuals with abnormal
urinary tract (E. coli, Enterobacter, Proteus, etc.)
• Polyresistant nosocomial strains after
catheterization, cystoscopy (e.g., Pseudomonas)
• Sexually transmitted: Neisseria gonorrhoeae;
Chlamydia trachomatis, and Ureaplasma
urealyticum
Gonorrhoea
2-7 days after exposure:
acute purulent
urethritis;
+ purulent prostatitis,
seminal vesiculitis,
epididymitis
Late consequences:
• Urethral stricture 
UTO
• Fibrosis of the prostate
• Fibrosis of the
epididymis; if bilateral:
obstructive azoospermia
Dr. Husz Sándor, Dermatology
Urethritis induced by Chlamydia or Ureaplasma
infection
• Mild mucopurulent urethral discharge
• Complications: acute cystitis; frequently turns into
chronic  chronic seminal vesiculitis, prostatitis,
epididymitis
Venereal ulceration of the glans penis
• Genital herpes: HSV2, HSV1 (increasing incidence
due to practice of oral sex); painful vesicles 
ulcer + inguinal lymphadenitis
• Firm chancre: Treponema pallidum;
Firm (luetic)
chancre:
painless ulcer
at the site of
initial
inoculation
Heals with a
subtle scar
2 months later:
secondary
syphylis: gen.
lymph node
enlargement,
mucocutaneous
lesions
Dr. Husz Sándor, SZTE Dermatology
Venereal ulceration of the glans penis
• Genital herpes: HSV2, HSV1 (increasing incidence
due to practice of oral sex); painful vesicles 
ulcer + inguinal lymphadenitis
• Firm chancre: Treponema pallidum; painless firm
ulcer + painless inguinal lymphadenitis; heals with
a subtle scar; 2 months later: secondary syphilis:
gen. lymph node enlargement, mucocutaneous
lesions
• Soft chancre (chancroid): Hemophilus ducreyi;
common in Africa and Southeast Asia; painful soft
ulcer + painful inguinal lymphadenitis with central
abscesses
Phimosis
• Abnormally small orifice in the foreskin; does not permit the
retraction of the foreskin over the glans penis
• Acquired (inflammatory scarring) or congential
Füzesi Kristóf, SZTE, Pediatrics
Consequences
• Accumulation of secretion and cell debris under the
prepuce: balanitis - inflamm. of the glans, posthitis
- inflamm. of the prepuce  balanoposthitis
• Lower urinary tract obstruction
• In adults: disturbed sexual life
Tumors of the penis
Strong association with HPV-infection
Condyloma acuminatum (venereal wart)
Condyloma acuminatum (venereal wart).
Cauliflowerlike lesions involving the coronal sulcus, the
glans, and inner prepuce
Dr. Husz Sándor, Dermatology
LM: acanthosis, papillomatosis, vacuolation of epithelial
cells (koilocytes).
Tumors of the penis
Strong association with HPV-infection
Condyloma acuminatum (venereal wart)
• Single or multiple reddish, cauliflowerlike lesions,
involving the coronal sulcus, the inner prepuce
• LM: acanthosis, papillomatosis, vacuolation of
epithelial cells (koilocytes)
• Benign; however, tends to recur after excision
Squamous cc in situ
• In men usually older than 35 years
• Bowen disease: involves the shaft of the penis and
the scrotum; erythroplasia of Queyrat: appears on
the glans and prepuce
• Gross: gray-white or red shiny plaques
• Over the span of years, both can transform into
invasive squamous cell cc
Erythroplasia of Queyrat: plaques on the glans,
prepuce and orifice.
Dr. Husz Sándor, Dermatology
Invasive carcinoma of the penis
• Infrequent; peak: around age 65
• Risk factors:
- HPV 16 and 18;
- 30 or more sexual partners
- chronic irritation
- no circumscision
- smoking
• Gross: ulcerative or a fungating lesion on the glans
or foreskin
• LM: well or moderately diff. squamous cell cc
• Slow course; lymphatic metastases in the inguinal
nodes
• 5-y-survival rate: 70%
Carcinoma of the penis
Dr. Husz Sándor, Dermatology
Invading nests of squamous cell carcinoma surrounded by
dense infiltrate of lymphocytes (host’s reaction)
PATHOLOGY OF THE PROSTATE
• Inflammation
• Hyperplasia
• Carcinoma
PROSTATITIS
• Acute
• Chronic
• Granulomatous
Acute prostatitis
Pathogenesis
• Colonization: from direct extension from the
urethra (urethritis) or the bladder (cystitis)
• Agents: E. coli, enterococci, gonococci  purulent
inflammation
Morphology
• LM: accumulation of ng-s within and around acini
• Large abscesses can develop in gonococcal
prostatitis, in diabetics
Clinical features
• Tender and swollen prostate
• Difficulty in micturition with perineal or rectal pain
(dysuria)
• Fever
Outcome
• Heals completely or with scarring (insuff. antibiotic
th)
• Can turn into chronic prostatitis
Chronic prostatitis
Pathogenesis
• Bacterial: Gram-neg. microorganisms
• Non-bacterial: Ureaplasma or Chlamydia - the
most common type of prostatic inflammation
LM: dilated glands
with
ng-s and foamy ma-s,
Idültfilled
aktív
prostatitis
stroma: ly-s, ma-s
Clinical features
• Difficulty in micturition + low back pain
• Disturbed ejaculation
• Harbours foci of infection, causing arthritis,
myositis, neuritis, iritis
Outcome
• Acinar atrophy, stromal fibrosis
Granulomatous prostatitis
Pathogenesis
• Secretions escape into the stroma and elicite
inflammation
LM
Destructed acini, surrounded by epitheloid cells, giant cells,
ly-s, plasma cells + dense fibrosis
Clinical features
• Disturbed micturition
• ”Stony hard” prostate by palpation because of
marked fibrosis  clinically simulates prostatic cc
• Dg.: biopsy of the prostate
NODULAR HYPERPLASIA
• Very common, the incidence increases with age:
up to 70% of men by age 60 years
• The nodules arise from the inner portions of the
prostate (central zone [close to the bladder]),
periurethral zone)
• Compression of the prostatic urethra 
obstruction of the urinary flow
Pathogenesis
• A relative increase in the level of estrogens that
occurs with aging may facilitate the growth
promoting effect of dihydrotestosterone (castrated
boys do not develop NH when they age)
• DHT increases the production of fibroblast growth
factor-7 by stromal cells
• FGF-7 inhibits apoptosis of glandular epithelial
cells and stimulates stromal cell proliferation 
nodular overgrowth of the glands and the
fibromuscular tissue
Gross: nodular enlargement (60-100 g; normal: 20 g),
the nodules have no capsule
LM: hyperplasia of glands and stromal fibroblasts and
smooth muscle cells
Glands are lined by an
inner secretory
columnar layer and an
outer layer of basal
cells positive for HMW
cytokeratins
Mechanic consequences of urethra
obstruction
Bladder:
• detrusor muscle hypertrophy (first concentric, then
dilative  residual urine)
• diverticula
Bilateral ureterectasis, pyelectasis, hydronephrosis
Frequent: the hyperplastic nodule elevates the trigone and compresses
the internal urethral meatus.
Note trabecular hypertrophy and acute cystitis
Obstruction of urinary flow caused by hyperplastic nodule
Infection of residual urine in the bladder: acute cystitis,
ascending pyelonephritis
Clinical features
• Difficulty in micturition: delay in starting to pass
urine; poor, intermittent stream, dribbling at the end
of micturition
• If there is cystitis: frequency, lower abdominal pain,
dysuria, hematuria
• If there is bilateral hydronephrosis: azotemia,
chronic renal insufficiency
• Emergency situation: acute complete obstruction
 painful distension of the urinary bladder  risk
of bladder rupture; acute postrenal uremia
Therapy
• Pharmacologic: inhibition of DHT and/or relaxation
of smooth muscles by blocking alpha adrenergic
receptors
• Surgical: transurethral resection
PROSTATE CARCINOMA (PCC)
• The most common non-skin malignancy in males
in the developed countries
• Peak: between the ages 65 and 75 years
Pathogenesis
Androgens,
diet,
hereditary factors, and
acquired somatic mutations have roles
• The tumor cells express androgen-receptors
(ARs); growth of the tumor is inhibited by androgen
deprivation and administration of estrogens
• Rare in Asians who live in Asia; common in
Caucasians (particularly in Scandinavia) and AfroAmericans
• Diet: increased fat and/or meat consumption
• Family history (germline mutations): 2x risk in a
man with a father or brother who developed PCC
• Acquired mutations:
creation of TPRSS2-ETS fusion gene
activation of the oncogenic pathway PI3K/AKT
signaling pathway
inactivation of the tumor suppressor gene PTEN
Gross
• PCCs arise multifocally in the peripheral posterior
zone of the prostate, facilitating palpation during
rectal digital examination
• Appear as multifocal firm, grayish-yellowish
masses
PCC appears as multifocal
firm, grayish-yellowish
Prostatarák
masses
LM
• Precursor lesion: prostatic intraepithelial neoplasia
(PIN): cytologic atypia in glands, but the outer
basal layer of cells is retained
PIN: the basal layer is retained
LM
• Precursor lesion: prostatic intraepithelial neoplasia
(PIN): cytologic atypia in glands, but the outer
basal layer of cells is retained
• The invasive cancers are adenocarcinomas: the
atypical glands are lined by a single layer of
epithelium
Focus of adenocarcinoma (marked) between normal glands
Normal glands (basal cells present) are replaced by
adenocarcinomatous glands (negative for basal cells)
Gleason score system of grading
Combination of very well; well; moderately;
poorly; very poorly diff. patterns
Example: adenocarcinoma of prostate, Gleason score: 2+3= 5
Gleason grade 2
Gleason grade 3
Spread
• Continuously: involvement of the entire prostate 
the seminal vesicles  the bladder neck
‘Early’ adenocarcinoma: extraprostatic spread is not evident
(courtesy of dr. Sükösd Farkas)
Carcinoma invading the periprostatic tissues;
the prostatic urethra is narrowed (arrow).
Urinary bladder
Spread
• Continuously: involvement of the entire prostate 
the seminal vesicles  the bladder neck
• Lymphatic metastases in nodes below the
bifurcation of the common iliac arteries
• Hematogeneous metastases: to the spine, pelvis,
and ribs; to the lungs
Continuous spread: involvement of seminal vesicles.
Lymphatic metastases (arrow) along the iliac arteries
Seminal
vesicle
Rectum
Prostatic carcinoma: hematogeneous metastases in
the spine (retrograde venous spread)
Clinical presentation
Prostate specific antigen
• Normal acini produce a protein, termed prostate
specific antigen (PSA), which liquifies the semen
• Tumor cells also elaborate PSA
• Elevation in serum PSA level is of value in the dg
of prostate carcinoma:
normal up to 4 ng/L, suspicious above 10 ng/L,
almost sure >20 ng/L
Non-metastatic, clinically localized prostate cancer
• Difficulty of micturition, urinary retention; urinary
tract infection
• Raised PSA on screening
Metastatic disease
• Back pain from vertebral metastases + pathologic
bone fracture
• Anaemia + uraemia because of urinary tract
obstruction
• High levels of serum PSA
Dg.: ultrasound-guided transrectal biopsy
Prognosis
• Non-metastatic prostate cancer: radical
prostatectomy or radiotherapy + anti-testosterone
blockade: favourable outcome
• Metastatic disease: worse outcome; antitestosterone th + radioth - response can be
achieved in a few individuals
NON-TUMOROUS DISORDERS OF THE
SPERMATIC CORD AND THE TESTIS
Twisting of the spermatic cord
• Torsion and subsequent hemorrhagic necrosis of
the testis because of venous obstruction
• Most common in 10-to-25 year-olds
• Acute dramatic testicular pain; requires immediate
surgery to save the testicle
Twisting of the spermatic cord  hemorrhagic necrosis
of the testis; orchiectomy head to be performed
Füzesi Kristóf, SZTE, Pediatrics
Varicocele
• Varicosity of the pampiniform venous plexus within
the spermatic cord
• Frequent in young men; more common on the left
side (the left internal spermatic vein empties into
the renal vein, the right internal spermatic vein
drains directly the inferior vena cava)
• Consequence: the intrascrotal temperature raises
 a reduction in the rate of spermiogenesis 
oligospermia in the semen  danger of infertility
Varicocele (marked) and small seminoma were
verified during the examination of 26-y-old man has
oligospermia
Hydrocele
Serous fluid accumulates in the tunica vaginalis
Causes
• Right sided HF
• Blockade of lymphatic drainage of scrotum
• Epididymo-orchitis
Cryptorchidism
• A failure of descent of testis; affects 1% of 1-y-old
boys
• Undescended testis may be abdominal, in the
inguinal canal or at the external inguinal ring
• Mainly unilateral; affects the right testis more
frequently
• Association with other urological abnormalities
and/or inguinal hernias
Consequences
• The malpositioned testis undergoes atrophy; the
contralateral, descended testis can also display
histological signs of atrophy
• Bilateral and some unilateral cases  infertility
• Risk of testicular cancer
Testicular inflammation (orchitis)
• Acute orchitis
• Chronic orchitis
• Granulomatous orchitis
Acute orchitis
Pathogenesis
• Result of urethritis, cystitis, or seminal vesiculitis
spread along the vas deferens and epididymis
• Under age 35: Neisseria gonorrhoeae,
Ureaplasma, Chlamydia
• Older patients: Gram-neg. bacteria
Morphology
• Acute purulent epididymo-orchitis
• Large destructive abscesses may develop
• Healing: by scar formation
Clinical features
• Painful, enlarged, firm testis
• Fever
• Orchiectomy may be necessary
Chronic orchitis
Pathogenesis
• If acute orchitis is not treated or inadequately
treated
• Mumps-virus induced orchitis after puberty
Morphology
• One or both testes may be involved in a focal or
diffuse fashion
• LM: interstitial lymphocytic infiltrates and fibrosis,
tubular hyalinization
Outcome
• Testicular atrophy; bilateral involvement 
infertility
Granulomatous orchitis
Uncommon, in middle-aged males
Pathogenesis
• autoimmune mechanism is suspected
Morphology
• Gross: the testis is enlarged, the tunica albuginea
is thickened
• LM: intratubular inflammation composed of
epitheloid cells, multinucleated giant cells, ly-s, pl-s
 fibrosis
Clinical features
• Painless to moderately tender testicular mass of
sudden onset
• Simulates tumor or tbc
Male infertility
• Infertile couple: no success during a 12-month
period of wished gestation
• Male partner disease is present in 25-40% of the
couples
• Evaluation reveals azoospermic or oligospermic (<
20 M sperms/ml) ejaculate [normospermic: more
than 40 M sperms/ml]
Cells in the seminiferous tubule: spermatogonia, spermatocytes, spermatids; Sertolicells (FSH). In interstitium: Leydig-cells (arrow; LH)
Testicular biopsy from azoospermic men
4 conditions
• Normal spermatogenesis
Bilateral posttesticular obstruction, commonly due
to previous gonorrhea
• Germ cell aplasia (Sertoli cell only sy)
Congenital or acquired;  FSH
Normal spermatogenesis
(previous history of gonorrhoea)
Germ cell aplasia (Sertoli cell only)
Maturation arrest
• The spermatogenic process abruptly fails to
progress one of the early stages of maturation
• Causes:
varicocele,
mumps orchitis,
exposure to lead or petroleum, etc.
Maturation arrest (petrol station worker)
Tubular hyalinization and peritubular fibrosis
• Causes:
trauma
alcoholism
diabetes
irradiation
Tubular hyalinization and peritubular fibrosis
Testicular biopsy from oligospermic men
4 conditions
• Spermatogenic hypoplasia
Spermatogenic cells are present in reduced
numbers.
Causes: idiopathic, malnutrition, antecedent febrile
illness, varicocele, insecticides, chemotherapy.
May respond to clomiphen citrate
• Incomplete maturation arrest
Causes: varicocele, mumps orchitis, exposure to
lead or petroleum, etc.
• Focal peritubular fibrosis and tubular hyalinization
Causes:
trauma,
alcoholism,
diabetes,
irradiation
• Sloughing of immature germ cells
Sertoli cells and spermatogonia appear normal, the
spermatocytes have sloughed into the lumen.
Causes:
varicocele,
mumps orchitis, etc.
Treatment option: in vitro fertilization
• Mature spermatids (if any) in the biopsy specimen
can be selectively isolated and injected into
oocytes;
• preembryos are transferred to the cavity of uterine
corpus where they implant
• 2010: Nobel prize for IVF: Robert Edward,
Cambridge, UK; the gynecologist Patrick Steptoe,
inventor of embryotransfer, died earlier
TESTICULAR TUMORS
• 95% of testicular tumors arise from the germinal
(seminiferus) epithelium, termed germ cell tumors
• Malignant (exception: dermoid cyst in childhood)
• Occur with increased frequencies in association
with undescended testis
General features
• Present with Insidious painless enlargement of the
testis
• Lymphatic metastases: in nodes along the aorta
and mediastinum
• Hematogeneous metastases: lungs, followed by
liver, brain, and bones
• Treatment: radical orchiectomy + postoperative
therapy (radiation, chemotherapy)
Histogenesis
• Precursor: intratubular germ cell tumor (ITGCT)
• Occurs in utero, but remains dormant untill
puberty, malignant transformation in adulthood
• ITGCT cells give rise to seminoma or transform
into a totipotential neoplastic cell ( e.g., embryonal
carcinoma) capable of further differentiation
Precursor: intratubular germ cell tumor (ITGCT)
Occurs in utero, dormant till puberty, malignant transformation
in adulthood
Histogenesis of germ cell tumors
Embryonal
cc
Germ cell
ITGCT
Seminoma
Yolk sac cc
AFP
Teratoma
Seminoma
+ syncytiotrophoblast
Choriocc
HCG
Seminomas
Most frequent germ cell tumors, mainly at about age
40
Gross:
• well-demarcated homogeneous,
• lobulated bulky mass (sometimes ten times the
size of the normal testis;
• the tunica albuginea is saved
Seminoma invading the paratesticular structures:
homogeneous, lobulated cut surface
The seminoma cells have clear, glycogen containing
cytoplasm; the nucleus has a prominent nucleolus;
the strome is rich in ly-s (not shown)
Clinical features
• Remain confined to the testis for long intervals;
produce lymphatic metastases; hematogeneous
metastases occur late
• Radiosensitive; the overall prognosis is good
Non-seminomatous germ cell tumors
Highly malignant tumors, peak: about 30 y of age
Gross:
• infiltrative tumors with necrosis + hemorrhage
LM
• Composed of a single histologic type: embryonal
cc, choriocc (serum marker: hCG), yolk sac cc
(serum marker: alfa-fetoprotein), teratoma
• Mixed: contain more than one element, most
common: embryonal cc + teratoma + yolk sac cc
Embryonal carcinoma surrounded by hemorrhage and necrosis
Non-seminomatous mixed GCT
(this case: seminoma + embryonal cc + teratoma)
S
E
T
Embryonal carcinoma + choriocarcinoma
Clinical features
• At dg.: lymph node and lung metastases
• Prognosis: chemotherapy achieves remission in
the majority of cases
• Pure choriocc: particularly agressive, extensive
hematogeneous metastases can be present even
with small primary lesion – the prognosis is dismal