Pathology of

Lower Urinary Tract

dr. Fairuz, Sp.PA

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Pathology
of Lower Urinary Tract

1. Ureter
2. Vesica Urinaria
3. Urethra

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*

PATHOLOGY OF URETER

1. Congenital
2. Obstructive lesions
3. Stricture of fibrous
4. Inflammation
5. Tumor/Neoplasia

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PATHOLOGY OF VESICA URINARIA

• Congenital
• Inflammation
• Tumor/Neoplasia

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*

PATHOLOGY OF URETHRA

• Inflammation
• Tumor/neoplasia

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Pathology of Ureter

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 PATHOLOGY OF URETER

1. Congenital
2. Obstructive lesions
3. Stricture of fibrous
4. Inflammation
5. Tumor/Neoplasia

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*
Normal Ureter

• Mesonephric Wolffian duct (diverticulum mesonephric).

• Panjang: 30 cm , dia: 5mm, retroperitoneal
• Histology : - Dilapisi sel transitional

- Longitudinal smooth muscle (inner) &

circular (outer) & serosa
• Symptoms muncul due to ureter:
obstruction → hydroureter → hydronephrosis

Acute obstruction → colic ureter (kolik pain) due to hyperactivity of ureter muscle.
Chronic obstruction does not cause nyeri yang parah
• Three stricture areas: margin of ureter & renal pyelum, gangguan of ureter to vesica
urinaria, persimpangan of ureter with iliaca a. & v.
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 1. Congenital
• Anatomic anomali
Accidentally found in 2-3 % from otopsy without
clinical relevancy

- Can be caused congenital stenosis in orificium

of ureter in vesica urinaria
- Children & young people: 10 % bilateral
- Asymptomatic
- Sometimes disertai by ureter obstruction,
hydroureter, hydronephrosis

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• Megaureter (megaloureter)

- Langka
- Ureter is dilatated very large disertai by enlargement
of muscle layer, but the lumen of ureter is tetap
- Abnormal pengaturan in distal muscle
layer

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*

• Etiologies: stones (calculi), tumor, stricture, blood cloth

{Stricture due to trauma of pembedahan, inflammation
(diverticulitis, chronic salphingitis & endometriosis}

• Etiologies : malignant tumor (rectum, vesica urinaria,

female urogenital organs in pelvis).

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 *
2. Obstructive lesion

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 3. Stricture of Ureter Fibrous
*

Non-neoplastic abnormalities that cause fibrosis and

stricture of ureter
1. Urethritis chronic non spesific
2. Tuberculosis of ureter
3. Ureter injury
4. Radiation → pengentalan of fibrous of ureter wall
5. Fibrosis, fibromatosis retroperitoneal, sclerosing peritonitis
6. Endometriosis of ureter wall

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 4. Tumor

• Primary Tumor:
Transitional cell carcinoma  paling banyak
squamous cell carcinoma & adenocarcinoma Jarang
5ysr 50%.
Related to smoker, analgetic, food coloring
Symptom : haematurie

• Metastatic Tumor
1. Via retroperitoneal lymphnode, (usually in carcinoma of vesica
urinaria or cervical carcinoma, germ cell tumor of testis &
malignant limphoma)
2. Direct Metastases in ureter wall
(continuitatum) → malignant stricture

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Pathology of Urinary Bladder

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 Pathology of Urinary Bladder

• Congenital
• Inflammation
• Tumor/Neoplasia

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 Urinary Bladder
Normal
• In pelvis, extraperitoneal.
• Dekat dengan uterus, prostate & seminalis vesicle →
easily in getting infected diseases
• Dilapisi oleh urothel (transitional cell)
• If the urinary bladder is empty lined by 6-7 cells, if full
of urine, lined by 3-4 cells

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 1. Congenital

1. Anatomical malformation
Rarely found (agenesis, complete–incomplete, hour-glass
bladder, congenital fistula) due to abnormal development
of kloaka and urogenital sinus

2. Urachus malformation
Urachus (a tube connecting vesica urinaria & alantois in fetus) → at
birth is obliterated
Sisanya → fibrous cord (median umbilicle ligament). If all urachus
persistent → fistula vesicoumbilicalis (predisposition of infection,
sinuses and fistula formation). If the hanya sebagian yang tertutup to
umbilicle → cyst.
Sisa urachus; sangat jarang become carcinoma.

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3. Diverticle
- Kemiringan arah luar ( eversi ) of vesica urinaria wall mirip dengan
saku
- Often due to persistent urethral obstruction
- → urine stasis ( tersumbat atau tertahan ) & predisposition for
vesicoureteral reflux
- Rarely menyebabkan carcinoma.

4. Exstrophy
- Abnormal development of anterior wall of vesica urinaria,
abdomen wall, pubical simphysis → can be seen from outside
(reddish (kemerahan) & granular)
- → recurrent infection → squamous metaplasia
- Usually related to other congenital diseases
- Incidence of carcinoma is higher (usually adenocarcinoma)

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 2. Inflammation

• Acute cystitis
- Symptoms: fever, lower abdominal pain (supra
simphysis), polyuria (kencing terus), dysuria (rasa sakit saat
kencing)
polyuria due to irritation of trigonum → stimulate
urination sensoric reflex
- urynalisis → proteinurie, PMN cells and sedikit
erythrocyte.
- Microorganism can be cultured from urine
- Women >> (due to short urethra and microorganism
tends to colonize in vagina & urethra)

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1. Acute Cystitis Bacterial
- Ascendence infection, caused by coliform (usually
escherchia coli), proteus species, & streptococcus
faecalis)
- Women: related to coitus, pregnancy &
instrumentation
- Older people; presdisposition of chronic urine
retension (prostate hyperplasia), related to acute
pyelonephritis

2. Acute Cystitis Radiation

- Terjadi in pelvic radiation (malignant tumor)

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3. Medication

- Chemotherapy (eg: cyclophosphamid)

→ Acute cystitis haemorrhagic with atypical severe
of urothel

- Macroscopic: mucosal edema, reddish and ulcus

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• "Encrusted cystitis"
- Cystitis due to precipitation phosphate crystal in
mucosa, disebabkan oleh urine alkalinisation
- Infection by urea (form ammonia) bakteri pemisah eg.
proteus

• Cystitis bulous
- Variant of acute cystitis marked by bullae contain
terlalu banyak edema in lamina propria
- In uremic patient, at initial radiation therapy
- Micr: mucosal hyperemi & lamina propria infiltrated by
PMNs

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• Chronic Cystitis Non-specific

- Urothel hyperplasia, mucosa is infiltrated by lymphocyte and plasma

cells, cystic dilatation of sarang urothel in lamina propria (“Brunn”
nest).
can cause multiple cysts lined by urothel → Cystitis cystica, if
metaplasia glandularis → Cystitis glandularis.

- Cystitis interstitialis ulcerative (Chronic interstitial cystitis/Hunner’s

ulcer)
Chronic cystitis non-specific persistent (menetap/ters mnrus) disertai
by ulcer in mucosa (Hunner ulcer) with inflammation and fibrosis in
all layers of vesica urinaria
Etiologies are unknown, difficult to cure
Suprapubical pain
In middle age women

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Chronic cystitis exhibiting marked hyperemia, edema, and mixed
mononuclear cell infiltrate.
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Low-power views of cystitis cystica. Most of the epithelial nests have a
central lumen.

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Cystitis glandularis. A complex glandular structure lined by
mucin-producing cells connects with the overlying transitional
epithelium. 27
• Malakoplakia
• Specific cystitis chronic, rare
• Multiple plaque in mucosa (kekuning-kuninngan)
• Clinically mimic carcinoma.

• Microscopic:
Banyak of histiocyte with granular cytoplasm terletak under
superficial epithel, several concentric oval bodies in intra
cytoplasmic (Michaelis–gutmann bodies) positive with
pewarnaan khusus for calcium & iron, histiocyte containing
bacterial

• Theory → due to the sisa of material from bacteria that

phagocytised by macrophage.
• Can be found in pelvis renalis, ureter, prostate, epididimis, colon
and lung
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High-power view of malakoplakia of bladder, showing
Michaelis–Gutmann bodies and numerous histiocytes.

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 • Chronic Specific Cystitis
Tuberculosis
- Symptoms; polakisuria (kencing sedikit-sedkit), disuria , piuria,
demam ringan, and lost of wieght
- Diagnosis → mycobacterium culture (+)
- In 70 % patient with renal tbc (ureter & epididimis). mulanya in
trigonum (small granuloma mengganggu to submucosa), causes benjolan
and ulcer
- If fibrosis → retraction of ureter orificium to the wall of vesica
urinaria (golf hole ureter) → reflux vesicoureteral.
If spread diffusely→ contraction of fibrous of vesica urinaria (thimble
bladder)

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Granulomas (Courtesy of Dr. Victor E. Reuter, Memorial Sloan-
Kettering Cancer Center)

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• Schistosomiosis

- Schistosoma haematobium.
The eggs mengganggu the wall of vesica urinaria and
excreted in urine (causes severe inflammation with absces
and granuloma contain kelebihan eosinophyl)
- Cystoscopy; small tonjolan in mucosa & fibrosis
- In chronic stage akhir; hard fibrosis
- Urothel; squamous metaplasia → high risk for squamous cell
carcinoma

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 Tumor/Neoplasma

- Epithelial
- Non-epithelial

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 Environment factors increase the risk of vesica urinary cancer
1. Carcinogen from industry or chemistry, anilin contains
benzidine & 2 alfanaphthylamine
2. Tryptophane metabolite –kynurenine
3. Smoking
4. Mechanical irritation (eg. due to stone, diverticle)
5. Parasite (schistosoma haematobium)
6. Therapy with Cyclophosphamide.
7. Analgetic abuse

- Pemanis Buatan (sacharine & siclamate)

causes cancer of vesica urinary in animal (no terbukti in
human)

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- Symptoms :
Hematuria without pain, polakisuria, disuria.
- Pathology
95%: epithelial (dominant; transitional cell tumor,
followed by squamous cell carcinoma &
adenocarcinoma)
- Predisposition → trigonum, particularly in lateral
- Men > women

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3. Epithelial Tumor
• Transitional Cell Papilloma

- Epithelial Tumor Jinak

- Rare, can be by multifocal
- papillary mimic fingers with batang longgar fibromuscular lined
by ‘normal’ transitional cells (similar to N mucosal epithel of vesica
urinaria
- Epithelial ketebalan; no more than 6 layers
- Usually recurrence (50% in a year) and become carcinoma
(17-25%) in 5 th
- Inverted papiloma → papilloma of terbalik transitional with
endophyitic pola pertumbuhan
Differentiated from brunn nest and invasive carcinoma

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Inverted papilloma of bladder. A large polypoid, but not
papillary, mass protrudes in the trigone
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Inverted papilloma of bladder.

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Inverted papilloma of bladder. B, High-power view showing the
oval to spindle shape of the cells and their total lack of atypia

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• Transitional Cell Carcinoma

- Four growth pola :

1. Papillary
2. Papillary and invasive/infiltrative
3. Non-papillary and invasive.
4. Non-papillary and non-invasive (carcinoma in situ = CIS)

- Metastases terjadi in stage akhir.

- Usually the biopsy is too superficial → diagnosis has to be dilakukan

berdasarkan on gambaran anaplastic

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• Characteristic of anaplasia :

- Hyperplastic ≥ 7 layers, group, dispolarity, kegagalan

differensiation (from the base to superficial) cells:
polymorph; irregular form, size & chromatin pattern in
nuclei, abnormal mitosis or displaced, datia cell/giant cell
(+)
- Based on the grade of anaplasia→3 grade
grade 1 : mild anaplasia/sedang
grade 2 : moderate anaplasia
grade 3 : severe anaplasia

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Grading TCC VU
Grade I
Macr :- Pedunculated / sessile
- Rare Necrosis
Micr : - papillary structure lined by regular hiperplastic transitional ≥
7 layers
- Abnormal polarisation
- R/C increases ,hyperchromatic, abnormal mitosis: rarely
found
Grade II :
Macr :- sessile ~ cauliflower/bunga kol
- increase necrosis and ulcus
Micr :- Papillary structure lined by regular hyperplastic transitional, ≥
7 layers, cells in small group
- nuclei; polymorph, hyperchromatic, abnormal mitosis are
easily found

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Grading TCC VU

Grade III :
Macr:- Sessile cauliflower/kembang kol is more solid
- Necrosis and wide ulcer
Micr :- Papillary structure and transitional
structure is jelas , hyperplastic cells, cells are in
irregular grouped
- Nuclei are polymorph,
hyperchromatic, abnormal mitosis
(abundance/melimpah) and deep
invasive

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• Staging (Berdasarkan kedalaman of invasion)
pTNM-UICC system (clinically is TNM, in pathology examination is initiated
with p)

pTis= carcinoma in situ (flat non-invasive tcc)

pTo = papillary carcinoma without invasive (non-invasive papillary tcc)
pT1 = invasion into lamina propia
pT2 = invasion into superfisial muscle
pT3 = pT3a = invasion into deeper muscle
pT3b = invasion into vesica urinaria wall and perivesicle fat
pT4 = pT4a = invasion into prostate ,vagina or uterus
pT4b = tumor is menetap in pelvic wall or
abdomen

• N1-3 = metastases in pelvis lympnodes

• N4 = metastases in lymphnodes bifurcation aorta atas
• M = jauh metastases

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depth of invasion of bladder cancer menurut to the classic
Jewett scheme

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Exophytic and papillary pattern of growth of a transitional cell
carcinoma timbul in a bladder with hypertrophy of the wall due to
prostatic nodular hyperplasia. The tumor which is located in the left
lateral wall, was diobati by total cystoprostatectomy. The prostate
shows an incidental infarct. 46
Various types of transitional cell neoplasms of
the bladder: B, papillary neoplasm of low
malignant potential.

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low-grade transitional cell carcinoma

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high-grade transitional cell carcinoma.

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• ±70% of papillary non invasive carcinoma,
25% low grade invasive with various
atypical cytology
• Prognosis depends on:
tumor type, histological grade,
clinicopathologic stage
• If invasion in superficial muscle 5ysr → 10-
30 %.a

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 Parameters for prognostic

1. Stage, the most important factor

2. Enlargement of lymphnodes → worse prognosis/buruk
3. There is correlation between morphologic grading &
stages (grade I → superficial invasive, Gr. II & III deep
invasion)
4. Ages (≤ decade II well diff and non-invasive)
5. Localisation (Bladder neck → worse prognosis)
6. Vascular invasion → increase recurrence
7. P53 Over-expression → progressive

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• Carcinoma in situ = CIS
Flat non invasive transitional cell carcinoma
– Transitional lesion is flat, non-invasive high
grade ( grade 3)
– Majority of invasive transitional cell ca is originated
from CIS

• Squamous cell carcinoma

- Rarely found, 5% from all urinary bladder tumor
- Usually related to vesicolithiasis and
schistosomiasis (Lots in Egypt)
- Worse prognosis/buruk

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Carcinoma in situ of bladder. The tumor has terpisah from the inti
stroma, only a few residual malignant cells sisa. The inti stroma is
nyata inflamed and hyperemic, resulting in the picture
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Pure squamous cell carcinoma of bladder. The tumor is berat
keratinized.
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• Adenocarcinoma
- Originated from: the sisa of urachus,
cystitis cystica, cystitis glandularis, glandular
metaplasia urothel
- The glands secret mucin

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Non-epitelial Tumor
• Paraganglioma
–Originated from paraganglionic structure in bladder wall
–Mimic pheochromocytoma of adrenal
–Majority are not functional
–The functional one secretes catecolamin when urinated causes
palpitation and hypertension

• Mesenchymal Tumor
–Rare
–Kebanyakan is leiomyoma and leiomyosarcoma
–Embryonal rhabdomyosarcoma is found in children
–Due to it’s penampilan mimics anggur (botrioid)→ sarcoma botrioid
→ keliru as polyposis

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 OTHERS

Stones in Bladders

- Generally from presipitation of urine salts (calcium oxalat,

uric acid, triple phosphate)
particularly phosphate combined with magnesium and calcium,
precipitated by microorganisms that can memisahkan the urea.
- The stone can descend from ureter and enlarge due
to phosphate deposit
- Related to diverticle, urethral obstruction and chronic cystitis
- particularly in older men
- recurrence 10 %
- Risk for carcinoma development particularly
squamous cell carcinoma

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PATHOLOGY OF URETHRA

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 PATHOLOGY OF URETHRA

• Inflammation
• Tumor/neoplasia
• Urethral caruncle

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 Inflammation
Urethritis Gonococcal

- Related to STD (sexual transmitted disease )

- Usually Neisseria gonorrhoe (diplococcus negative gram)
- Acute suppurative, incubation 2-5 days post intercourse
- 90 % men without symptom, 70% women without symptom.
- Gonococcus enter normal mucous ---> periurethral
glands, prostate, epididimis

- Micr: Swab urethral mucous  gram (-) diplococcus in PMN

leucocyte (+) for fast diagnosis
confirmed by microorganism culture

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Urethritis non-gonorheal (NGU=non-gonococcal
urethritis)
- Etiology:
Chlamidia (c. trachomatis), E. coli, other enterics, mycoplasm
(ureaplasma, urealyticum).

- Related to cystitis in women,

in men related to prostatitis.
- mucopurulent urethral discharge
- The one of “reiter syndrome” components (trias :
arthritis, conjunctivitis and uretritis)

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• Tumor/neoplasia
 Carcinoma
- Primary, very rare
- Transitional cell carcinoma,
in older women in proximal urethra,
in men in urethra pars prostatica
- In distal urethra; squamous cell carcinoma
- Prognosis: worse/buruk
- Secondary tumor originated from penis, prostate, bladder,
vulva, vagina, cervix and
uterus.

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• Urethral caruncle

- Inflammation lesion, usually found, particularly in older women

-Polypoid small benjol (diameter 1- 1,5 cm) red, easily broken,
usually ulcerated and bleeding in orificium of external urethra,
pain
-Micr: vascular and inflammation, granulation/angiomatous with
severe infiltration of PMN
-Etiology is unknown, may due to degenerative, not neoplastic
-Therapy: excision

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