SUBJECT

LECTURE : LOWER URINARY TRACT PATHOLOGY

Teacher| 2nd TERM | A.Y. 2022-2023

OUTLINE
I. Lower Urinary Tract
II. Ureters
a. Congenital Ureter
Anomalies
b. Inflammation
c. Tumors
III. Bladder
a. Exstrophy
b. Vesico-ureteral Reflux
c. Cystitis
d. Metaplasia
e. Tumors ● Transitional epithelium composed of several layers of
IV. Urethra urothelium (picture below)
● umbrella cells (on top) covering the upper part of
transitional epithelium
LOWER URINARY TRACT ● Normally, the urothelium has 4-6 cell thickness, more
● Lower urinary tract = transitional epithelium = “uro”thelium than 10 can be considered hyperplasia or neoplasia
○ Minor calyces
○ Major calyces
○ Renal pelvis
■ made of transitional epithelium (a.k.a.
urothelium) which is unique as it can be flat or
layered depending on the content of the
structure
■ when urine volume is increased in the pelvis,
there is flattening of the epithelium
■ when there is less urine volume, there is layered
epithelium of about 6 layers
■ it can transition from flat to layered
○ Ureters
○ Bladder ● Ureter (figure on the left below) epithelium cross section
○ Urethra ○ smooth muscle around the ureter
○ *Papilla is NOT included since it is part of the renal ○ 3 constrictions of the ureter happen because of
parenchyma anatomic location (normal)
● 2 principles of the lower urinary tract: ■ ureteropelvic junction
○ the entire lower urinary tract reacts to inflammatory ■ pelvic brim
cells and neoplastic influences, similarly, if not ■ bladder inlet
identically, since they are all transitional epithelia ■ *ureter is a channel for urine so it spans from the
■ if ureter is affected then the bladder may also be pelvis to the bladder
affected since they have the same mucosa ● transitional epithelium (figure on the right below)
■ they have the same embryonic origin so they
share the same dynamic system; they are all
connected
■ neoplasm or cancer in one area may cause a
cancer in another part as well
● General scheme:
○ composed of transitional epithelium and smooth
muscle (and adventitia)

● urinary bladder (figure below)

● Embryology
○ Mullerian tissue of females and Wolffian tissue of
males behave similarly
■ they are connected via the mesonephric duct to
the mesonephros so they can be interrelated as
well
● Lower UT is mostly composed of metanephric tissue
● In males, there is a considerable overlap between the
metanephric and Wolffian system, unlike with females
● ductus deferens
○ medially located
○ is tied up (or cut) in vasectomy
● seminal vesicle
● prostate is inferior to bladder

● Parts seen in figure below:

○ renal adrenal gland (suprarenal gland)
○ renal parenchyma (medulla and cortex)
○ calyxes
○ pelvis
○ hip veins out of ureter

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● detrusor (smooth) muscle of urinary bladder (below)
○ purple border is the transitional epithelium of the
lamina propria

URETERS
● Anomalies (congenital)
● Inflammation/Obstruction (i.e., ureteritis)
○ Acute, Chronic
○ ureteritis - inflammation of the ureter
○ obstruction causes kidney stones
■ usually dislodged at the constrictions or sites of
narrowing
● Neoplasms
● figure below is the urothelium is 4-6 layers thick and spans ○ Benign vs malignant
from calyces to the urethra ○ Epithelial vs “stromal” (i.e., mesoderm derived)
● layers can look overlapping because of the tangential cut ■ epithelial - transitional cell carcinoma
● layer thickness and nuclear features can indicate the ■ stromal - rhabdomyocycoma
difference of hyperplasia and neoplasia
CONGENITAL URETER ANOMALIES
● Double ureters
○ two ureters per side
○ Usually asymptomatic; does not cause any damage

● bladder wall, transitional epithelium, lamina propria with

blood vessels and smooth muscles

● UPJ (Uretero-Pelvic Junction) obstruction

○ happens due to the severe narrowing of the UPJ
○ Consequences:
■ Hydronephrosis
● Dilatation or distention proximal to the
obstruction due to accumulation of fluid
● Consequently damages kidney because it
becomes mechanically compressed
● Leads to renal failure
● Needs to be corrected right away
(recognition is important)
● empty bladder = NOT flattened cells ■ Can lead to ascending infection →
pyelonephritis

LOWER URINARY TRACT

● Ureter (anomalies, inflammation, neoplasm)
● Bladder (anomalies, inflammation, neoplasm)
● Urethra (anomalies, inflammation, neoplasm)
● Constrictions: (red dots)
○ ureteropelvic junction (first constriction from the top)
○ pelvic brim (second constriction)
○ bladder inlet

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● Diverticula OBSTRUCTION FACTORS
○ Outpouching of the walls of the ureter ● Intrinsic: (within or endogenous production)
● Hydroureter ○ Calculi
○ collection of water or urine that backflows to the ■ stones
kidney ○ Strictures
○ Dilated ureter because of backflow or obstruction ■ narrowing
■ Most likely due to pelvic rim or bladder inlet ○ TCC, tumors
■ Can also result in hydronephrosis ■ Transitional cell carcinoma
○ Hydronephrosis vs hydroureter ○ Clots
■ Hydroureter = whole ureter is filled up with urine ○ Neurogenic paralysis
■ Hydronephrosis = affects the kidney/located ■ Loss of innervations in the ureter
within the kidney ■ Ureter can’t transition from being flat or relaxed
■ Smooth muscles are not working due to paralysis
■ Accidents in lumbar spine or sacrum
● Extrinsic: (from external influences)
○ Pregnancy
■ Due to the enlargement of the uterus
■ Compresses the ureter
■ Physically obstructed
○ Inflammation
○ Endometriosis
■ Related to menstrual cycle
■ Backflow of endometrial contents
● Instead of excreting through the vagina,
there would be backflow of endometrial
tissue
○ Fallopian tubes, ovary, lower urinary
tract or abdomen
INFLAMMATION ○ Poses internal (abdominal)
● The usual reasons hemorrhages
● The usual patterns, i.e.? ○ Tumors
○ Usual types of bacteria ○ Surgery
■ Provides inflammation ■ Ex: Surgery of prostate and ureter is accidentally
● Linked to obstruction cut
○ If urine is kept long in body/room temperature, there
would be accumulation of contaminants SCLEROSING RETROPERITONEAL FIBROSIS
■ There is urinary stasis ● 70% Idiopathic*
■ Can cause ureteritis ● 30% Drugs (ergot derivatives, beta blockers) or known
○ If there is obstruction, there is no flow of urine → retroperitoneal inflammatory conditions, e.g., Vasculitis,
urinary stasis Diverticulitis, Crohn’s disease
● Glandularis/cystica ● Can affect the ureters due to obstructive properties
● Follicularis
● Cystitis cystica (picture below)
○ Inflammation of walls that provide outgrowth of small TUMORS
cysts in the epithelium ● Benign
○ Little mucosal cysts lined by columnar epithelium ○ Fibroepithelial Polyp
■ Columnar epithelium in the cysts indicate ○ Leiomyoma
metaplastic change due to inflammation ■ Neoplasm of smooth muscle
■ Happens due to ureteritis cystica ● Malignant
○ Benign; nothing to worry about ○ Transitional cell carcinoma, aka, TCC
○ Enlargement of these cysts can cause obstruction ○ Also called Urothelial carcinoma
● Left ureter and UPJ is affected (picture below)
○ Ureteral urothelial carcinoma
○ Need to rule out between a stone, narrowing or tumor
first

● Chronic Ureteritis (picture below) ● Fibro-epithelial polyp (picture below)

○ Inflammatory cells found ○ Composed of fibrous tissue with edema
■ Acute = neutrophils ○ Lighter areas = accumulation of water
■ Chronic = lymphocytic/macrophages

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 ● Leiomyoma (picture below)
○ Cigar shaped nucleus
○ Mostly smooth muscle

● Transitional cell carcinoma in the ureter (pictures

below)
○ Appearance is papillary or finger-like projections
○ Also called PUCA = papillary urothelial
carcinoma
○ Have distinct fibrovascular tissues in the middle
■ Provides nutritive/lucrative (?) capabilities for
neoplasm to grow
○ Lumen is obstructed due to neoplasia
○ Can pose retrograde urinary flow or
hydronephrosis

○ Exstrophy
○ Vesico-ureteral reflux
○ Persistent urachus
■ Persistent embryological tissue called urachus
■ Posing as site for inflammation
■ Connection between external environment to the
bladder
○ Fistulas: vagina, rectum, uterus
■ Abnormal connection between bladder and
vagina, bladder and rectum, and bladder and
uterus

EXSTROPHY
● Eversion of an organ in reference to the bladder
● M>F; 1 in 50,000
● Developmental anomaly
● Bladder is growing out
● Consequence:
○ Predisposition to be infected
○ Needs to be brought back into the pelvis
● Very good surgical correction rate

BLADDER
● Anomalies
○ Diverticula (plural of -um) [pictures below]
■ Outpouching of tissue
■ Due to weakness of the bladder wall
■ Increased pressure inside the bladder
■ Pose as a site of infection or inflammation due to
urinary stasis
● Can be complicated to diverticulitis when
inflammation happens
■ Outpouching has communication with the bladder
lumen (Pseudo diverticulum)
■ Outpouching can be separated from the bladder
wall (true diverticulum)
● Leakage of fluid accumulation can cause
ruptures or can leak into the abdomen VESICO-URETERAL REFLUX
● Can be contaminated with urine or merely a ● Most common anomaly
fluid accumulation ● Very serious in its role in chronic pyelonephritis and
hydronephrosis
○ Reflux has the same consequences as obstruction
that is associated with chronic infection and proximal
dilatation
● Picture below shows full bladder
○ Hydroureter + hydronephrosis
○ Left side is worse (but both sides are affected)

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 SYMPTOMS FOR CYSTITIS
● Frequency*
○ Frequency of urination
● Urgency
○ Urgency to urinate
● Hematuria
● Abdominal pain
○ Particularly in hypogastric region
● Dysuria
○ Difficulty in urination
● Systemic sepsis, i.e., fever, leukocytosis
ADJECTIVES FOR CYSTITIS ○ non -correction of cystitis can lead to systemic sepsis
● Acute = neutrophils
● Chronic = lymphocytes SPECIAL TYPES OF CYSTITIS
● Hemorrhagic = tendency to bleed ● “Interstitial” cystitis, aka, Hunner ulcer
○ Women>>Men
○ Bladder wall fibrosis
○ Aka, “Hunner” ulcer
○ Erosions are seen due to fibrosis of the muscular
bladder

○ Comparison between empty bladder vs irritated

■ We can see pinpoint hemorrhagic spots and
glomerulations
● Glomerulations = aggregates of capillaries
that are engorged

● Suppurative = producing pus

● Follicular = forming lymphoid aggregates due to severe
chronic cystitis
○ Severe enough to be a chronic cystitis

● Malacoplakia
○ Yellow mucosal “plaques”
○ Chronic bacterial infection
○ Michaelis-Gutmann bodies contain Fe and Ca in
macrophages
● Eosinophilic = eosinophils; parasitic infections or allergies ■ Causes yellow-brown discolorations
○ pink/orange cells are the eosinophils

● Interstitial = affecting interstitium

CAUSES FOR CYSTITIS METAPLASIA

● Escherichia coli* ● Glandular(is) (cystica), from Von Brunn nests
● Proteus, Klebsiella, Enterobacter ○ Von Brunn nests = normal clusters of urothelium that
● Schistosomes (egypt) lie under transitional epithelium
○ Can be seen in Visayas regions ■ Undergo glandular or columnar metaplasia
○ Blood flukes ○ Not malignant and not pre-malignant
○ Schistosoma haematobium reside in the blood
vessels
● Chlamydia
● Mycoplasma
● Viruses, e.g., adenoviruses
● ChemoRX
● RadiationRX

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 ● Low grade transitional cell carcinoma (pictures below)
○ Layers thick is more than 8
○ Nuclear features are benign
○ Counting mitoses is important
○ Low grade = malignant but not aggressive

● Squamous metaplasia
○ Smoking, irritation of bladder, parasites
○ Transitional to squamous metaplastic change
○ Skin-like
■ There is a stratum corneum
○ Happens due to Schistosoma haematobium
■ Irritates the transitional mucosa
○ Consequence:
■ Predisposition to develop squamous cell
carcinoma
○ Mitosis is seen (arrows)
■ More than 10 layers thick
■ Signifies neoplasm

TUMORS
● 95% Epithelial (urothelial), 5% mesenchymal, i.e.,
mesodermally derived (mostly smooth muscle)
● Benign or malignant
● Primarily urothelial or transitional, but a few squamous, ● High grade transitional cell carcinoma (pictures below)
from antecedent squamous metaplasia, and a few ○ Enlargement of nucleus
adenocarcinomas, from antecedent glandular metaplasia ○ Presence of mitosis
○ Pleomorphism
○ Hyperchromasia
TCC TUMORS
○ Irregularly shaped nucleus
● Multiple, multiple, multiple, i.e., “soil” theory
○ Soil theory
■ Genetic mutations that provide development of
TCC
■ From being normal histology to hyperplastic then
dysplasia, and finally TCC
● Papillomas vs carcinomas
○ Squamous cell papilloma
■ Benign counterpart of papillary carcinomas of the
bladder
● Grading, I, II, III, or well → poor
○ Well differentiated = closely resembles normal
histology ○ Papillary projections seen below
○ Poorly differentiated = does not resemble normal ■ Cystoscopy procedure
● Staging, TNM, based on biologic behavior, really based on
normal anatomy
● Causes/risk factors
○ Arylamines (aniline dyes)*
○ Cigarettes*
○ Schistosomiasis*
○ Longstanding analgesics, same as analgesic
nephropathy drugs, most common NSAIDS
○ ChemoRX, esp. Cyclophosphamides
○ Radiation RX

PAPILLOMAS VS CARCINOMAS
● Very few pathologists will have enough guts to diagnose a ○ Necrosis, hemorrhage, and invasion to the detrusor
transitional papilloma. Why? muscle (seen below)
● PUNLMP, Papillary Urothelial Neoplasm of Low Malignant ■ Criteria:
Potential → (borderline between a papilloma to become ● Aggression of the TCC
carcinoma)
○ Low grade PUC (TCC) →
○ High grade PUC (TCC)
● Papillary tumors of the urothelium (picture below)
○ Forms fingerlike projections
○ Has a papillary architecture

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 ○ Urine cytology of the bladder (seen below)
■ Normal (left); abnormal (right)
■ Overlapping and presence of nucleolus
■ Pleomorphism
■ Nuclear cytoplasmic ratio increased

BIOLOGICAL BEHAVIOR
● Normal mucosa → dysplasia, severe dysplasia, carcinoma
in situ, infiltration → basement membrane → lamina
propria → muscularis mucosa → muscularis propria***
(i.e., wall) → serosa or adventitia → lymph nodes →
distant metastases
● TNM
● TNM example
○ Ta — noninvasive, papillary
○ Tis — Carcinoma in situ, flat
○ T1 — Lamina Propria
○ T2 — Muscularis propria
○ T3a — Microscopic beyond the wall
○ T3b — Grossly beyond the bladder wall
○ T4 — Invades adjacent structures
■ Prostate, ureter, abdominal organs

BLADDER NECK OBSTRUCTION

● Cystocele, most common cause in women
○ Medical condition that occurs when the tough fibrous
wall between the bladder and vagina is torn by
childbirth
○ Allows the bladder to herniate in the vagina
○ Abnormal connection between the bladder and vagina
● Prostate, most common cause in men
● Congenital
● Inflammation
● Tumors
● Foreign bodies, calculi
● Neurogenic

URETHRA
● Inflammations:
○ Gonococcus
○ Chlamydia
○ Mycoplasma
○ Reiter’s syndrome (men)
○ “Caruncle” (women)
■ Originating from the posterior lip of urethra
■ Fleshy outgrowths of distal urethral mucosa
■ Caused by distal urethral prolapse relating to
estrogen withdrawal
● Neoplasms:
○ Transitional
○ Squamous
○ Glandular