LOWER URINARY TRACT
Ureters
Congenital anomalies
Uretopelvic junction (UPJ) obstruction
- MC cause of hydronephrosis in infants & children
- boys > girls but in adults women>men
- 20% bilateral
Diverticula
- saccular outpouchings of the uretal wall
- may cause stasis and 2 inf.
- may be acquired or congenital
Inflammation
Ureteritis follicularis
- accum. or aggregation of lymphocytes forming
germinal centers in subepithelial region
- may cause slight  of the mucosa & produce a
fine granular mucosal surface
Ureteritis cystica
- mucosa sprinkled with fine cysts
- lined by flattened urothelium
Urinary bladder
Congenital anomalies
Diverticula
- congenital = focal failure of development of
normal musculature
- acquired
o more common
o caused by persistent urethral obstruction
o most often seen w/ prostatic enlargement
- may predispose to inf., calculi formation, VUR
Exstrophy
- developmental failure in anterior wall of
abdomen & bladder
- bladder communicates directly thru large defect
on surface of the body or lies as open sac
- exposed bladder mucosa subject to infection
-  risk of adenocarcinoma
VUR
- MC and serious anomaly
-  risk of renal inf.
Patent urachus
- urachal cysts in partial patency
- carcinomas may rise from cysts
Tumors
Fibroepithelial polyp
- tumor like lesion
- small mass projecting into lumen
- often in children
Urothelial carcinomas
- MC in 6-7th decades of life
- may cause obstruction of ureteral lumen
Obstructive lesions
- may give rise to hydroureter, hydronephrosis, or
pyelonephritis
- intrinsic obstruction: calculi, strictures, tumors,
blood clots, neurogenic
- extrinsic: pregnancy, periuretal inflammation,
endometriosis, tumors
Sclerosing retroperitoneal fibrosis
- uncommon cause of ureter narrowing or
obstruction
- fibrous proliferative inflammatory process
encasing the retroperitoneal structures and
causing hydronephrosis
- assoc. w/ other fibrotic conditions (Reidel
thyroiditis)
- may be autoimmune response
- 70% have no identifiable cause (Ormond dz)
- drugs (ergot derivatives, β-blockers)
- adjacent inflammatory conditions (Crohn)
- malignancy (lymphoma, UT carcinoma)
Inflammation
Acute & chronic cystitis
- etiologic accents:
o bacterial (E. coli, Proteus, Klebsiella,
Enterobacter)
o TB
o Candida, Cryptococcal
o Chlamydia, Mycoplasma
o Schistosomiasis
o Adenovirus
- predisposing factors: female, calculi, urinary
obstruction, DM, instrumentation, immune
deficiency, irradiation of bladder
- triad: frequency, lower abdominal pain, dysuria
Special forms of cystitis
- interstitial
o chronic pelvic pain syndrome
o persistent, painful, chronic cystitis w/out
evidence of bacterial inf.
o MC in women
o punctate hemorrhages
o Hunner ulcers in the late (classic, ulcerative)
phase
o mast cells characteristic
- malacoplakia
o peculiar pattern of vesical inflammatory rxn
o soft, yellow, slightly raised mucosal plaques
o large-foamy macrophages mixed w/
multinucleate giant cells & lymphocytes
o Michaelis-Gutman bodies (Ca deposition in
enlarged lysosomes)
o chronic bacterial inf. w/ E. coli or Proteus
- polyploidy
o irritation to bladder mucosa
o MC culprit = indwelling catheters
o broad bulbous polyploidy projection
- hemorrhagic
o cyclophosphaminde (anti-CA drug)
o adenovirus inf.
- follicular
o aggregates of lymphocytes
- eosinophilic
o nonspecific subacute inf.
Metaplastic lesions
Cystitis cystica & glandularis
- Brunn nests (nests of urothelium) grown
downward into lamina propria
- cystitis glandularis = undergo transformation of
their central epithelial cells into cuboidal or
columnar epithelium lining
- cystitis cystica = cystic spaces filled w/ clear fluid
lined by flattened urothelium
- two commonly coexist (cystitis cystica et
glandularis)
Squamous metaplasia
- in response to injury, urothelium often replaced
by squamous epithelium (more durable)
Nephrogenic adenoma
- shed renal tubular cells that implant in the
urothelium in response to injury
- overlying urothelium may be replaced by
cuboidal epithelium  papillary growth pattern
- can mimic malignant process
Neoplasms
Urothelial (transitional) tumors
- 90% of all bladder tumors
- 2 precursor lesions:
o non-invasive papillary (MC)
o flat non-invasive urothelial carcinoma
- major  in survival assoc. w/ invasion of
muscularis propria (detrusor m.)
- Papilloma type
o seen in younger pts
o exophytic papillomas = attached to mucosa
by stalk; finger-like papillae covered by
normal urothelium
o inverted papillomas = benign lesions; interanastomosing cords of cytologically bland
urothelium that extend down into lamina
propria
- PUNLMPs
o papillary urothelial neoplasm of low
malignant potential
o thicker urothelium or diffuse nuclear
enlargement
o larger than papillomas
- Low & high-grade papillary urothelial CAs
o low grade = orderly appearance
architecturally & cytologically
o high grade = dyscohesive cells w/ large
hyperchromatic nuclei; invasion into
muscular layer
- Carcinoma in situ, CIS (flat urothelial carcinoma)
o cytologically malignant cells w/ flat
urothelium
o may have full-thickness cytologic atypia or
pagetoid spread (scattered malignant cells)
o lack of cohesiveness  shed of malignant
cells into urine
o mucosal reddening, granularity, or
thickening w/out evident intraluminal mass
- invasive urothelial CA
o assoc. w/ papillary urothelial CA (high grade
or CIS)
Other epithelial tumors
- squamous cell carcinoma
o freq. where schistosomiasis is endemic
o chronic bladder irritation & inf.
- mixed urothelial carcinomas w/ areas of
squamous carcinoma
o more common
o invasive & fungating or infiltrative &
ulcerative
- adenocarcinoma
- small-cell carcinoma
Epidemiology & pathogenesis
- males > females
- developed nations, urban dwellers
- 50-80 years old
- non-familial
- cigarette smoking = most important influence
- industrial exposure to arylamines
- schistosomiasis
o endemic in Egypt and Sudan
o mucosal squamous metaplasia, dysplasia,
and neoplasia
o 70% of CA are squamous
- long term use of analgesics
- long-term use of cyclophosphamide
- prior exposure to irradiation
- chromosome 9 deletions (esp. in superficial
papillary tumors)
Clinical
- painless hematuria
- frequency, urgency, dysuria
- squamous cell carcinoma & adenocarcinoma =
worse prognosis than urothelial carcinoma
- urothelial tumors have tendency to recur
- pts at high risk for recurrence or progression of
non-high-grade tumors can receive
immunotherapy
o attenuated strain of TB (BCG)
o elicits local inflammatory rxn that destroy
tumor
Mesenchymal tumors
- benign tumors:
o MC = leiomyoma (MC tumors in women)
- sarcoma
o MC in infancy/childhood = embryonal
rhabdomyosarcoma
o MC in adults = leiomyosarcoma
o produce large masses that protrude into
vesicle lumen
Obstruction
- in males, most important lesion = enlargement of
the prostate due to nodular hyperplasia
- in females, most often caused by cystocele of
bladder
- early stages = thickening + smooth m.
hypertrophy
- progressive hypertrophy  trabeculation of
bladder wall  crypt formation  diverticula
- bladder may become extremely dilated & thinned
Urethra
Inflammation
Gonococcal urethritis
- earliest manifestation of gonorrhea
Nongonococcal urethritis
- E coli and other enteric organisms
- C. trachomatis
- Mycoplasma (Ureaplasma urealyticum)
- often accompanied by cystitis in women and
prostatitis in men
- Reiter syndrome = triad of arthritis,
conjunctivitis, urethritis
Tumors & tumor-like lesions
Urethral caruncle
- inflammatory lesion
- presents as small, red, painful mass about
external urethral meatus
- older females
- friable (easily ulcerates and bleeds)
Peyronie disease
- fibrous bands involving corpus cavernosum of
penis
- penile curvature and pain on intercourse
Carcinoma of urethra
- uncommon
- proximal urethra show urothelial differentiation
- distal urethra show squamous carcinomas
MALE GENITAL TRACT
Penis
Congenital anomalies
Hypospadias and epispadias
- hypospadias = abnormal opening on ventral
penis; more common
- epispadias = abnormal opening on dorsal penis;
defect of genital tubercle
- assoc. w/ abnormal descent of testes and
malformation of urinary tract
Phimosis
- orifice of prepuce is too small to permit normal
retraction
- frequently from repeated attacks of inf. that
cause scarring of preputial ring
- permits accumulations of secretions and detritus
under the prepuce, favoring inf. and carcinoma
Inflammation
Balanoposthitis
- infection of glans and prepuce
- C. albicans, anaerobic bact, Gardnerella, pyogenic
bact.
- poor local hygiene in uncircumcised males
Tumors
Benign tumors: Condyloma acuminatum
- HPV 6 and 11
- sexually transmitted
- most often about coronal sulcus and inner
surface of prepuce
- red papillary excrescences
- branching, villous, papillary CT stroma
- hyperkeratosis & acanthosis of overlying
epithelium
- koilocytosis (cytoplasmic vacuolization of
squamous cells)
Carcinoma in Situ (CIS)
- strong association with HPV 16
- Bowen disease
o single erythematous plaque
o > 35 years old
o skin of shaft of penis and scrotum
o single thickened gray-white opaque plaque
or shiny red velvety plaques
o dermal-epidermal border sharply
delineated by intact BM
o may transform into infiltrating squamous
cell carcinoma
- Bowenoid papulosis
o histologically identical to Bowen dz
o sexually active younger adults
o non-cancerous
o can spontaneously regress
Invasive squamous cell carcinoma
- HPV 16 is MC; HPV 18 also present
- smoking  risk
- 40-70 years old
- circumcision is protective
- 2 types of lesions: papillary & flat
- papillary lesions
o stimulate condylomata acuminata
o cauliflower-like fungating mass
- flat lesions
o epithelial thickening
o graying & fissuring of mucosal surface
o ulcerated papule develops
- verrucous carcinoma = exophytic welldifferentiated variant; low malignancy
- lesions are nonpainful until 2 ulceration & inf.
- metastases to inguinal nodes
Testis and epididymis
Congenital anomalies
Cryptorchidism
- incomplete descent of testes into scrotal sack
- can be arrested in transabdominal descent or in
descent down inguinal canal (MC)
- rarely assoc. w/ well-defined hormonal disorder
- asymptomatic
- most cases are unilateral
- arrest in development of germ cells
- marked hyalinization & thickening of BM of
spermatic tubules
- testis is small and firm
- assoc w/ sterility, inguinal hernia, risk of
testicular CA
- tx: orchiopexy (placement in scrotal sac)
- orchiopexy doesn’t guarantee fertility or prevent
CA completely
Regressive changes
Atrophy and decreased fertility
- causes:
o progressive atherosclerotic narrowing of
blood supply in old age
o end stage of inflammatory orchitis
o cryptorchidism
o hypopituitarism
o generalized malnutrition or cachexia
o irradiation
o antiandrogen therapy (prostate CA)
o exhaustion atrophy
- can occur from Klinefelter syndrome
Vascular disorders
Torsion
- twisting of spermatic cord
- cuts off venous drainage of testis
- thick-walled arteries remain patent 
hemorrhagic infarction
- neonatal & adult types
- adult type
o presents w/ sudden testicular pain without
inciting injury
o urologic emergency
o results from B/L anatomic defect where
testis has  mobility (bell-clapper
abnormality
Inflammation
- more common in epididymis than testis
- gonorrhea and TB arise in epididymis
- syphilis affects testis first
Nonspecific epididymitis and orchitis
- assoc. w/ inf. in urinary tract
- cause varies w/ age of pt.
- children = gram neg. rods
- <35 = C. trachomatis and N. gonorrhoeae
- >35 = E. coli and Pseudomonas
- may cause fibrous scarring and lead to sterility
Granulomatous (autoimmune) orchitis
- presents in middle age as moderately tender
testicular mass of sudden onset
- assoc. w/ fever
- granulomas restricted to spermatic tubules
- diffusely throughout testis
Gonorrhea
- extension of inf. from posterior urethra 
prostate seminal vesicles  epididymis
- development of frank abscess in epididymis 
extensive destruction of organ
Mumps
- systemic viral dz in school aged children
- orchitis may develop in postpubertal males
TB
- begins in epididymis and may spread to testis
- caseating granulomatous inflammation
Syphilis
- testis is involved 1st
- production of gummas
- diffuse interstitial inflammation characterized by
edema & lymphocytic + plasma cell infiltration
- obliterative endarteritis w/ perivascular cuffing
of lymphocytes and plasma cells
Spermatic cord & paratesticular tumors
- lipomas = common lesions involving proximal
spermatic cord
- adenomatoid tumor
o MC benign paratesticular tumor
o mesothelial
o small nodules near upper pole of epididymis
- MC malignant paratesticular tumor at distal end
of spermatic cord
o rhabdomyosarcoma in children
o liposarcoma in adults
Testicular germ cell tumors
- 95% of testicular tumors arise from germ cells
- MC tumors of men in 15-34; MC in whites
- Testicular dysgenesis syndrome (TDS)
o cryptorchidism
o hypospadias
o poor sperm quality
o may be influenced by in utero exposure to
nonsteroidal estrogens & pesticides
- cryptorchidism is assoc w/ 10% of testicular
germ cell tumors (most important risk factor)
- Klinefleter syndrome assoc w/  risk for
mediastinal germ cell tumors
- strong family disposition
- intratubular germ cell neoplasia (ITGCN)
o precursor lesion for germ cell tumors
o not for yolk sac, teratomas, or adult
spermatocytic seminoma
o occur in utero; stay dormant until puberty
- grouped into seminomas & non-seminomas
o seminomas = made of cells that resemble
primordial germ cells or early gonocytes
o NSGCTs = made of undifferentiated cells that
resemble embryonic stem cells
o 60% of cases = mix of seminomatous & nonseminomatous components
- Clinical:
o unilateral painless enlargement of testis
o lymphatic spread via para-aortic nodes to
mediastinal & supraclavicular nodes
o hematogenous spread to lungs (also liver,
brain, bones)
o seminomas remain localized for long time;
metastases involve lymph nodes;
radiosensitive
o NSGCTs more aggressive; poor prognosis;
prefer hematogenous spread; radio-resistant
o pure choriocarcinoma is the most aggressive
NSGCT
o HCG = choriocarcinoma
o AFP = yolk sac tumors
o LDH = mass of tumor cells
Staging:
o I = confined to testis, epididymis, or
spermatic cord
o II = distant spread confined to
retroperitoneal nodes below the diaphragm
o III = metastases outside retriperitoneal
nodes or above diaphragm
Seminoma
- MC germ cell tumor (50% of germ cell tumors)
- peak incidence in 3rd decade
- analogous to dysgerminoma in females
- morphology:
o large & round to polyhedral
o distinct cell membrane
o clear or watery cytoplasm
o large central nucleus w/ 1-2 prominent
nucleoli
o diffusely positive for c-KIT, OCT4, placental
alkaline phosphatase (PLAP)
o some have  HCG
Spermatocytic seminoma
- uncommon tumor in elderly (>65 years old)
- slow-growing; doesn’t metastasize
Embryonal carcinoma
- occur in 20-30 years old
- more aggressive than seminomas
- smaller than seminoma
- cells grow in alveolar or tubular patterns
(sometimes papillary convolutions)
- positive for OCT3/4, PLAP, cytokeratin, CD30
- negative for C-KIT
Yolk sac tumor
- aka endodermal sinus tumor
- MC testicular tumor in kids up to 3
- morphology:
o nonencapsulated
o homogenous mucinous appearance
o lacelike (reticular) network of cells
o Schiller-Duval bodies (endodermal sinus
structures)
o hyaline-like globules contain AFP and α1antitrypsin
o AFP in tumor cells = highly characteristic
Choriocarcinoma
- highly malignant
- no testicular enlargement
- small palpable nodule
- hemorrhage & necrosis are common
- 2 types of cells:
o syncytiotrophoblastic cells (HCG +)
o cytotrophoblastic cells
Teratoma
- from more than 1 germ layer
- occur at any age
- pure teratomas fairly common in infants and
children
- mixed teratomas in 45%
- large, heterogenous, helter-skelter collection of
differentiated cells or organoid structures
(neural, muscle, cartilage, squamous epithelium,
thyroid tissue, bronchial epithelium, intestinal, or
brain substance)
- benign in children, but in postpubertal males
malignant
Mixed tumor
- 60% of tumors are composed of more than 1 of
the pure patterns
Testicular sex cord-stromal tumors
Leydig cell tumor
- most are benign
- may elaborate androgens, estrogens,
corticosteroids
- most occur from 20-60 years of age
- MC presenting symptom = testicular swelling
- gynecomastia may be first symptom
- sexual precocity may be dominating feature in
children
- morphology:
o circumscribed nodueles
o distinctive golden brown, homogenous cut
surface
o rod-shaped crystalloids of Reinke
Sertoli cell tumor
- hormonally silent
- present as testicular mass
- firm, small nodules
- most are benign
Other testicular tumors
Gonadoblastoma
- mix of germ cells and gonadal stromal elements
- arise in gonads with some form of testicular
dysgenesis
- germ cell component may become malignant
Testicular lymphoma
- presents only with testicular mass
- aggressive non-Hodgkin lymphoma = MC
testicular neoplasm in men >60
- MC testicular lymphoma = diffuse large B cell
lymphoma
- higher incidence of CNS involvement than tumors
located elsewhere
Miscellaneous lesions of tunica vaginalis
- tunica vaginalis is a mesothelial-lined surface
exterior to the testis
- hydrocele = accumulation of serious fluid; causes
enlargement of scrotal sac
- hematocele = blood in tunica vaginalis; from
trauma or torsion
- chylocele = accumulation of lymph in the tunica;
elephantiasis from filiariasis
- spermatocele = accumulation of semen in dilated
efferent ducts or ducts of rete testis
- varicocele = dilated vein in spermatic cord; may
cause infertility
Prostate
- prostate is a retroperitoneal organ
- 4 biologically and anatomically distinct zones:
o peripheral – most carcinomas
o central
o transitional – most hyperplasia
o anterior fibromuscular stroma
Inflammation
Acute bacterial
- same organisms as UTI (E. coli, gram neg rods,
enterococci, staphylococci)
- fever, chills, dysuria, tender, boggy prostate
- dx from urine culture + clinical features
Chronic bacterial
- difficult to dx and tx
- hx of recurrent UTIs (antibiotics penetrate
prostate poorly)
- leukocytosis in prostatic secretions
- positive bacterial cultures
- low back pain, abd discomfort, dysuria
Chronic abacterial
- MC form
- clinically identical to chronic bacterial but with
no hx of recurrent UTIs
- leukocytosis in prostatic secretions
- negative bacterial cultures
Granulomatous
- MC cause related to instillation of BCG in the
bladder for tx of superficial bladder CA
- requires no tx
- fungal granulomatous prostatitis seen only in
ummunocomrpomised hosts
BPH or nodular hyperplasia
- extremely common in men > 50
- hyperplasia of prostatic stromal & epithelial cells
- large, discrete nodules in periurethral region
- can cause partial or complete obstruction of
urethra
- accumulation of senescent cells in prostate due to
impaired cell death
- main androgen of prostate is DHT
o testosterone  DHT by type 2 5αreductase
o this enzyme located in stromal cells
o stromal cells responsible for androgendependent prostatic growth
- morphology:
o nodular hyperplasia in transition zone
o encroach on lateral walls of urethra to
compress it to a slitlike orifice
o median lobe hypertrophy
o nodularity = hallmark of BPH
- clinical:
o urethral obstruction
o bladder hypertrophy & distension
o urine retention
o risk of infection
o  frequency, nocturia, difficulty starting &
stopping stream, overflow dribbling,
dysuria
o Tx: α-blockers decrease prostate smooth
muscle tone; TURP (transurethral resection
of prostate)
Tumors
Adenocarcinoma
- MC form of cancer in men
- men >50
- uncommon in Asian; MC in blacks
- androgens play an important role
o tx with anti-androgens induce dz
regression
o most tumors eventually become resistant
to androgen blockade
- family hx =  risk at earlier age
- BRCA2 mutation = 20-fold  risk
- inflammation may set stage for CA development
- mutation in ETS family txn factor gene (ERG or
ETV1) next to androgen-regulated TMPRSS2
promoter is common
o may cause androgen-dependent overexpression of ETS  prostate epithelial
cells more invasive
- MC epigenetic alteration in prostate CA =
hypermethylation of glutathione S-transferase
(GSTP1)  down-regulates GSTP1 expression
o GSTP1 prevents damage from carcinogens
- biomarkers for prostate CA:
o EZH-2 (due to loss of E-cadherin
expression in prostate CA)
o α-methylacyl-CoA racemase (AMACR)
o PCA3
- PSA
o most important test in dx & management of
prostate CA
o product of prostatic epithelium
o normally secreted in semen
o  blood PSA in local & advanced CA
o 4 ng/mL = cutoff for normal
o organ specific but not CA specific
o PSA velocity = men w/ CA have  rate of
rise in PSA
o free PSA is lower in prostate CA than BPH
- prostatic intraepithelial neoplasia (PIN)
o precursor lesion
- morphology:
o peripheral zone in posterior location
o gritty and firm
o metastases 1st spread via lymphatics 
obturator nodes  para-aortic nodes
o hematogenous spread to bones (axial
skeleton)
o bony metastases typically osteoblastic
o prostate CA glands more crowded; lack
branching & papillary infolding
o outer basal cell layer typical of benign
glands is absent
o α-methylacyl-CoA-racemase (AMACR)
positive
- Gleason system
o 1 = most well-differentiated
o 5 = no glandular differentiation; tumor cells
infiltrate stroma
o grade assigned to dominant pattern and 2nd
most frequent pattern and added
- Clinical:
o localized prostate CA is asymptomatic
o urinary symptoms occur late
o osteoblastic metastases is diagnostic of
prostate CA and have universally fatal
outcome
o transrectal needle biopsy is required to
confirm dx
- Tx:
o surgery
 MC tx for localized CA = radical
prostatectomy
o radiation therapy
 external beam radiation = CA that is
too locally advanced to tx w/ surgery
 interstitial radiation therapy
o hormonal manipulation
 orchiectomy or LHRH agonist =
advanced metastatic CA
 induces remissions but eventually
tumors develop testosteroneresistance followed by rapid
progression + death
Ductal adenocarcinoma
- poor prognosis
- prostate adenocarcinoma arising from prostatic
ducts
Colloid carcinoma of the prostate
- prostate CA that reveal abundant mucinous
secretions
Small-cell cancer
- most aggressive variant of prostate CA
- almost all cases are rapidly fatal
Secondary involvement
- MC tumor to secondarily involve prostate =
urothelial CA