Pathology 5.1 Dr.

Mesina
LOWER URINARY TRACT December 17, 2013

OUTLINE o Underlying urothelium composed of several layers of cells with

I. Introduction smaller oval nuclei often with linear nuclear groove and less
a. Components of the LUT cytoplasm
b. General Scheme of the LUT  Smooth muscle
II. Ureters o Lamina propria in the urinary bladder contains wisps of smooth
a. Congenital Anomalies muscle that form a discontinuous muscularis mucosae
b. Inflammatory/Obstructive o Important to differentiate it from muscularis propria: deeper, well-
c. Neoplasms defined larger muscle bundles of the detrussor muscle
III. Bladder o Bladder cancers are staged on the basis of invasion of muscularis
a. Congenital Anomalies propria and not just muscularis mucosae
b. Inflammatory
c. Metaplasia
d. Tumors/Neoplasms
e. Obstructive
IV. Urethra
a. Inflammatory
b. Neoplasms

OBJECTIVES
 Introduction – review the normal anatomy, histology, & physiology
 To be able to discuss the important pathologic lesions – epidemiology,
pathogenesis, morphology, clinical outcome

INTRODUCTION Figure 2. Transitional epithelium or Urothelium. Normally transitional

COMPONENTS OF THE LOWER URINARY TRACT urothelium has 6-7 layers. If the bladder is contracting, the layers should not
 It is lined by transitional epithelium or urothelium exceed 7. If it is stretched or distended, urothelium can comprise of 2-3
 Components: layers. Classically the textbooks say urothelium ranges from 4-8 layers thick
o Renal pelvis normally from calices to urethra, but this is highly variable.
o Ureters
o Bladder
o Urethra (except its terminal portion which is lined by stratified
squamous epithelium)
 Two principles:
o The entire lower urinary tract reacts to inflammatory and
neoplastic influences similarly because it is all of the same type of
mucosa (transitional epithelium or urothelial); histologically and
embryologically, too.
o The lower urinary tract shows that neoplastic influence acting on
one part of the urothelium is also acting on others.
*Cut out a cancer in one place, the etiologic agents are still acting
on other transitional mucosal places

GENERAL SCHEME OF THE LOWER URINARY TRACT Figure 3. Cross section of ureter. Unlike appendix (which is histologically
inner longitudinal and outer circular), here the muscularis mucosa of ureter
is not continuous. There are interruptions in between and its lumen is
stellate in shape. Observe lamina propria, muscularis layer and adventia.

Figure 1. General scheme of the lower urinay tract

 Transitional epithelium (“Urothelium”)
o Surface layer consists of large, flattened umbrella cells with
abundant cytoplasm that horizontally cover underlying cells
Group 29 | Steph, Adrian, Reena, Karen, Gab
Figure 4. Identify, mucosa, wall, detrusor muscle, prostate, prostatic urethra,
seminal vesicles, perivesicle fat. Classically, the bladder submucosa is often
called, interchangeably, the lamina propria because there is no clear cut
differentiation between the two. Serosa layer is only present at dome of
bladder.
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 Where would the membranous urethra be?
o Passes through the external urethral sphincter (narrowest
part)
 Where would the “spongy” urethra (known as the penile urethra)
be?
o Runs along the length of the penis on its ventral
(underneath) surface
Figure 5. Bladder Histology
URETERS
 Lined by transitional epithelium or urothelium
 Histologically: Stellate-shaped lumen
 Lamina propria: submucosa, muscularis, & adventitia
What are the three most likely places to have ureteral constriction
and points of potential obstruction just from the gross anatomy
alone?
1) Uretero-pelvic junction (UPJ): in the renal hilum
2) Pelvic brim: near the bifurcation of iliac arteries
3) Bladder
Note from lecture: Diameter of ureter will not allow stones greater
than 5 mm to pass through the ureter. A common site stones get
stuck in is the renal pelvis.
A. Congenital Anomalies
a. Double & Bifid Ureters
b. Uretero-Pelvic Junction (UPJ) Obstruction/ Congenital
Hydronephrosis
c. Diverticula
d. Hydroureter
B. Inflammatory/Obstructive (Acute VS Chronic)
a. Ureteritis
b. Ureteral Obstruction
c. Sclerosing Retroperitoneal Fibrosis
C. Neoplasms (Benign VS Malignant, Epithelial VS Stromal)
a. Fibroepithelial polyp
b. Leiomyoma
c. Transitional Cell Carcinoma (TCC)/ Urothelial CA
CONGENITAL ANOMALIES OF THE URETER
DOUBLE & BIFID URETERS
 Almost invariable associated either with totally distinct double
renal pelvis or with the anomalous development of a large kidney
having partially bifid pelvis terminating in separate ureters.
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 Double ureters may pursue separate courses to the bladder but
commonly are joined within the bladder wall and drain through a single
ureteral orifice.
 Majority are unilateral and of no clinical significance
 Incidental finding through radiographic examination and asymptomatic
unless there’s an underlying problem
Figure 6. Double Ureters
URETERO-PELVIC JUNCTION (UPJ) OBSTRUCTION
 Usually presents in infants or children; more common in boys
 It is bilateral in 20% of the cases; may be associated with other
congenital anomalies
 In adults, more common in women and is often unilateral.
 Due to disorganized proliferation of smooth muscles at the UPJ
 Excess stromal deposition of collagen between smooth muscle
bundles, or rarely due to congenitally extrinsic compression by polar
renal vessels causing narrowing of the ureteral lumen with
consequence of congenital nephrosis
 Unusual fibrous proliferation causing narrowing of the ureteral
lumen, resulting in hydronephrosis
 Results in agenesis of kidney on opposite side
Figure 7. Obstructed UPJ. Due to the dilation and distortion of renal pelvis
and calices which is usually due to obstruction of urine output from the
kidney, may result in hydronephrosis.
DIVERTICULA OF THE URETER
 Saccular outpouching of the ureteral wall that become pockets of
stasis and secondary infection
 Appear as congenital or acquired
 Uncommon; usually asymptomatic
 Found incidentally through imaging studies
HYDROURETER
 Dilation (hydroureter), elongation, tortuosity of ureters may occur
as congenital anomalies or as acquired defects
 Megaloureter: enlargement of ureter due to functional defect in the
ureteral muscle
 Significance: prone to kidney infection or pyelonephritis and can lead to
renal scaring
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Figure 10 (right). Ureteritis cystica is the ureteral counterpart of Cystitis

cystica, i.e., little mucosal cysts lined by COLUMNAR epithelium, NOT
Figure 8. Hydroureter Gross. There is marked dilatation of the ureter with transitional (Cystic structures filled with fluid form due to the inflammatory
accompanying hydronephrosis process).

INFLAMMATION/OBSTRUCTION OF THE URETER URETERAL OBSTRUCTION

URETERITIS  Usually results to obstruction to urinary outflow and hydronephrosis
 Typically not associated with infection and is of little clinical  Either Intrinsic or Extrinsic
consequence
 Of little significance Table 1. Major Causes of Ureteral Obstruction (From 2015B trans)
 Morphologic patterns: TYPE OF
o Ureteritis Follicularis CAUSE
OBSTRUCTION
 Collections of lymphoid follicles are seen underneath the
INTRINSIC
mucosa of the ureter
 Accumulation of lymphocytes forming germinal centers in Of renal origin, rarely more than 5 mm in diameter
the subepithelial region may cause slight elevations of the Larger renal stones cannot enter ureters
mucosa and produce a fine granular mucosal surface Impact at loci of ureteral narrowing—ureteropelvic
Calculi
o Ureteritis Cystica junction, where ureters cross iliac vessels, and where
 There is formation of small cystic-like structures that are filled they enter bladder—and cause excruciating “renal
with fluid colic”
 Mucosa may become sprinkled with fine cysts varying in Strictures Congenital or acquired (inflammations)
diameter (1-5 mm) line by flattened urothelium Transitional cell carcinomas arising in ureters
Tumors
 Linked to OBSTRUCTION, not due to an abnormality in the ureter per se, Rarely, benign tumors or fibroepithelial polyps
but an extension usually from below and ascending upwards Massive hematuria from renal calculi, tumors, or
Blood clots
papillary necrosis
Neurogenic Interruption of the neural pathways to the bladder
EXTRINSIC
Physiologic relaxation of smooth muscle or pressure on
Pregnancy
ureters at pelvic brim from enlarging fundus
Periureteral Salpingitis, diverticulitis, peritonitis, sclerosing
inflammation retroperitoneal fibrosis
Endometriosis With pelvic lesions, followed by scarring
Cancers of the rectum, bladder, prostate, ovaries,
Tumors
uterus, cervix; lymphomas, sarcomas

SCLEROSING RETROPERITONEAL FIBROSIS

Figure 9 (left). Ureteritis Follicularis: Acute urothelial-itis: neutrophils
(POLYmorphonuclears), and Chronic urothelial–itis: lymphs and
macrophages (i.e., MONOnucleated cells)
 Fibrous proliferative inflammatory process affecting retroperitoneal
structures and causes hydronephrosis.
 Occurs in middle to late age
 70% idiopathic (Ormond’s disease: Retroperitoneal fibrosis in general,
fibrous exuberant proliferation of any hollow organ, cause is unknown)

Note: When sclerosis is found anywhere in the retroperitoneum, it is

called Ormond’s disease, but when ureters are affected, it is called
Sclerosing peritoneal fibrosis.

 30% drugs (ergot derivatives, beta blockers) or known retroperitoneal

inflammatory conditions, e.g., vasculitis, diverticulitis, Crohn’s disease

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NEOPLASMS OF THE URETER

FIBROEPITHELIAL POLYP
 The polyp is composed of a loose, vascularized connective tissue mass
lying beneath the mucosa.
 Grossly presents as a small mass projecting into the lumen
 Polypoid, exophytic lesion projecting ot the ureteral lumen
 Often seen in children
 Commonly occurs in ureters but may also appear in the bladder, renal
pelvis, and urethra

Figure 14. Transitional cell carcinoma, ureter, microscopic. Up until now all
of the “Papillary” tumors we talked about were ADENOCARCINOMAS. In the
lower urinary tract however, all of the papillary tumors are TRANSITIONAL
(UROTHELIAL) carcinomas, NOT adenocarcinomas.

BLADDER
 Temporary depository of urine
 If contracted: mucosal surface appears corrugated

A. Congenital Anomalies
Figure 11. Fibroepithelial Polyp. Partly covered by normal urothelial a. Diverticula
epithelium with some fibrous proliferation interspersed with some blood b. Exstrophy
vessels c. Vesico-Ureteral Reflux
d. Persistent Urachus
LEIOMYOMA B. Inflammatory
 Round, white well-circumscribed ovoid lesions that are merely a. Cystitis
composed of proliferations of interlacing bundles of spindle-shaped b. Interstitial Cystitis
cells that look similar to smooth muscle fibers c. Malacoplakia
C. Metaplasia
a. Cystitis Glandularis & Cystitis Cystica
b. Squamous Metaplasia
D. Tumors/Neoplasms
a. Urothelial Tumors
b. Urothelial Papilloma
c. Papillary Urothelial Neoplasm of Low Malignant Potential
d. Low Grade Papillary Urothelial Carcinoma
e. High Grade Papillary Urothelial Carcinoma
f. Flat Urothelial Carcinoma/Carcinoma In Situ (CIS)
g. Invasive Urothelial Carcinoma
E. Obstructive
a. Urinary Bladder Obstruction

Figure 12. Leiomyoma. Histologically, it is composed of spindle-shaped
lesions.
TRANSITIONAL CELL CARCINOMA (TCC)
 Also known as Urothelial Carcinoma
Figure 13. Transitional Cell Carcinoma of the Ureter (gross)
CONGENITAL ANOMALIES OF THE BLADDER
DIVERTICULA OF THE BLADDER
 A pouch-like evagination of the bladder wall
 Either congenital or acquired
 Can pose as pockets with urinary stasis. Hence, if urine stays there it
can be prone to inflammation followed by infection.
 Sites for stone formation.
 Frequently multiple, have narrow necks located between the
interweaving hypertrophied muscle bundles
 Mostly small and asymptomatic but may be clinically significant since
they constitute sites of urinary stasis and predispose to infection and
the formation of bladder calculi
 Predispose to vesico-ureteral reflux as a result of impingement on the
ureter.
 Congenital
o Pathogenesis: failure of the development of the musculature of
the bladder wall which is replaced by fibrous connective tissue,
hence it is a weak point.

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 PATHOLOGY 5.1
 Acquired (more common)
o Usually due to an obstruction distally, most commonly due to
benign prostatic hyperplasia in elderly males producing
obstruction to urine outflow and marked muscle thickening of the
bladder wall.
Figure 15. Diverticula of the Bladder. The diverticulum usually consists of a
round to ovoid, saclike pouch that varies from less than 1cm to 5-10cm in
diameter.
Figure 16. X-ray cystogram, Bladder Diverticulum. At the Upper right, there
is a pouch-like evagination near the ureteral orifice
Figure 17. Real Acquired Bladder Diverticulum. These do not have to
communicate with the main lumen.
EXSTROPHY
 Developmental failure of the anterior abdominal wall and bladder to
develop
 The bladder either communicates directly through a large defect with
the surface of the body or lies as an opened sac
 Exposure of the bladder  may undergo colonic glandular metaplasia
and pose a risk to infection that often spread to upper levels of urinary
system
 Increase risk of adenocarcinoma
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Figure 17. Gross picture of Exstrophy
VESICO-URETERAL REFLUX
 Most common and serious anomaly (especially in children)
 Major contributor to renal infection and scarring
 Very serious in its role in chronic pyelonephritis and hydronephrosis
 Reflux has the same consequences as obstruction; associated with
chronic infection and proximal dilatation. Remember BACTERIA are
normally in the bladder urine, the HIGHER this refluxes, the more likely
it is to cause infection
Figure 18. Three ways in which the ureter can pierce into the bladder wall
and the likelihood that it will develop into a vesico-ureteral reflux is indicated.
The ureter is shown tunneling through the bladder wall. 1-if the tunneling of
the ureter ends here, reflux is likely. 2-if the tunneling of the ureter ends
here, reflux is possible. 3- if the tunneling of ureter ends here, reflux is
unlikely.
Figure 19. A consequence of the Vesico-Ureteral Reflux: Hydronephrosis. You
can see the dilatation of the ureter and calyces.
PERSISTENT URACHUS
 Urachus is the canal that connects the fetal bladder with the allantois.
It may remain patent in part or in whole.
 When totally patent, a fistulous urinary tract is created that connects
the bladder with the umbilicus.
 At times, only the central region of the urachus persists, giving rise to
urachal cysts, lined by either urothelium or metaplastic glandular
epithelium.
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 PATHOLOGY 5.1

o Carcinomas, mostly glandular tumors, may arise from such cysts.  Polypoid
These account for only a minority of all bladder cancers (0.1% to o Resulting from irritation to the bladder mucosa
0.3%) but 20% to 40% of bladder adenocarcinomas. o Due to long term catherization (indwelling catheters)

Figure 21. Gross and histologic picture of Nonspecific Cystitis

Figure 20. Anomalies formed when different parts of the urachus remain
patent. Total: Patent Urachus (fistulous urinary tract). Proximal to the
umbilicus: Urachal sinus. Proximal to the bladder: Urachal diverticulum.
Central Region: Urachal cyst. Because of the connection of the umbilicus to
the bladder, it is usually wet or moist.

INFLAMMATION OF THE BLADDER Figure 22. Gross picture of Hemorrhagic Cystitis

CYSTITIS Etiologic agents: infectious and noninfectious
 Acute (neutrophils) vs Chronic (macrophages) depending on the Clinical features: urinary frequency, lower abdominal pain, dysuria
leukocyte that you see: acute if neutrophils are present and chronic if
mononuclear infiltrates are present Special Types of Cystitis
 Gm (-) confirms : E.coli followed by Proteus Klebsiella and Enterobacter  Interstitial Cystitis
 Bacterial pyelonephritis is frequently preceded by infection of the  Malacoplakia
urinary bladder, with retrograde (ascending) spread of
microorganisms into the kidneys and their collecting systems. INTERSTITIAL CYSTITIS
 Women are more likely to develop cystitis as a result of 
their shorter  Chronic Pelvic Pain Syndrome or Hunner’s Cystitis
urethras.  (-) bacterial infection
 Others: Tuberculous cystitis, Candida, Cryptococcus, Schistosoma and  Women (elderly) > men
viruses  Clinical manifestations: intermittent, often severe suprapubic pain,
urinary frequency, urgency, hematuria and dysuria without evidence of
Predisposing Factors: bacterial infection (unresponsive to antimicrobial therapy)
 Bladder calculi  Cystoscopic findings: fissures and punctate hemorrhages
 Urinary obstruction (glomerulations) in the bladder mucosa after luminal distention
 Diabetes mellitus  Interstitial cystitis is still a mysterious disease with all kinds of
 Instrumentation “theories”. But remember, it is largely “interstitial” which means
 Immune deficiency fibrosis of the muscular bladder wall itself, if common. – Dr. Mesina

Forms of Cystitis (Morphology)

 Nonspecific
o In most cases of cystitis such that whatever the etiologic agent is,
the morphology would just be the same. Gross appearance :
hyperemi of the mucosa and edema of the stroma, sometimes
associated with exudates
 Hemorrhagic
o Cytotoxic antitumor drugs (e.g. cyclophosphamide)
o Adenovirus infection
 Follicular
o Aggregation of lymphocytes into lymphoid follicles within the
bladder mucosa and underlying wall
o Not necessarily associated with infection Figures 23 & 24. (Left) Presence of punctate hemorrhages in Interstitial
 Eosinophilic Cystitis. (Right) Presence of mucosal ulcerations (just denudation in the lining
o Infiltration with submucosal eosinophils of the mucosa), mononuclear inflammation and sometimes edema of the
o Typically represents nonspecific subacute inflammation underlying stroma.
o Rarely a manifestation of a systemic allergic disorder
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MALACOPLAKIA
 A peculiar pattern of vesical inflammatory reaction
 Yellow raised mucosal plaques
 Pathology: defect in the phagocytic and degradative function of
macrophages.
 Histology: infiltration of foamy macrophages mixed with
multinucleated giant cells and lymphocytes; Michaelis-Gutmann
bodies
o The macrophages have an abundant granular cytoplasm due to
phagosomes stuffed with particulate and membranous debris of
bacterial origin.
o Michaelis-Gutmann bodies: Laminated mineralized concretions
resulting from deposition of calcium in enlarged lysosomes
 Chronic bacterial infection - E. coli, occasional Proteus Figure 27. Cystitis Glandularis. Take note of the invagination of the
 Seen in immunosuppressed transplant recipients transitional epithelium down into the underlying stroma forming glandular-
 Malacoplakia is associated with: like structures. Sometimes, there is transformation of the lining/epithelium
o Prolonged therapy with systemic corticosteroids into columnar cells. Note: Brunn nests are clusters of urothelium which
o Organ transplantation usually lie UNDER the surface mucosa. They can undergo glandular (i.e.,
o Diabetes mellitus columnar) metaplasia.
o Lymphoma
o Rheumatoid arthritis SQUAMOUS METAPLASIA OF THE BLADDER
 As a response to injury, the urothelium is often replaced by squamous
epithelium (more durable lining).

Figure 25. Cystitis with malacoplakia of bladder showing inflammatory

exudates and broad, flat plaques. Note: Not just seen in the bladder, can be
seen in other locations such as the colon.

Figure 28. Squamous Metaplasia (with edematous infiltrates). Note:

Whereas squamous metaplasia of transitional mucosa can be nonspecific, it
is almost universally found with schistosome infections of the bladder, i.e.,
bilharziasis. Squamous cell carcinoma of the bladder arises from squamous
metaplasia and is very common in Egypt, where bilharziasis is rampant.

TUMORS/NEOPLASMS OF THE BLADDER

Table 2. Tumors of the Urinary Bladder

Figure 26. Michaelis-Gutmann bodies (arrow). Note the presence of a lot of

histiocytes. Note: The pathognomonic sign of Malacoplakia is the presence
of Michaelis-Gutmann Bodies (round calcific laminated concretions seen in
macrophages). In PAS stain, it is intensely red.

METAPLASIA OF THE BLADDER

CYSTITIS GLANDULARIS & CYSTITIS CYSTICA
 Common lesions of the urinary bladder in which nests of urothelium
(Brunn nests) grow downward into the lamina propia and undergo
 Cystitis Glandularis: Transformation of their central epithelial cells into UROTHELIAL TUMORS OF THE BLADDER
cuboidal columnar epithelium lining  Also known as TCC, or Transitional Cell Carcinomas
 Cystitis Cystica: Transformation into cystic spaces filled with clear fluid  MOST common in the bladder (90%)
lined by flattened urothelium

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 PATHOLOGY 5.1
 May be seen at any site where there is urothelium, from the renal
pelvis to the distal urethra
 Multifocal
 Two precursor lesion:
o Non-invasive Papillary Tumors (more common): usually comes
from the subsequent hyperplasia of papillary urothelial cells.
Lesions of this nature show a high degree of atypia, and are
graded according to their biological behavior. Better prognosis.
o Flat Urothelial Carcinoma or Carcinoma in situ: with cytologic
changes of malignancy but confined to the epithelium and without
basement membrane invasion. These lesions are already
considered to be high-grade. More aggressive.
 Grading: I, II, III, or wellpoor
o If Grade I: Well-differentiated
o If Grade II: Moderately-differentiated
o If Grade III: poorly-differentiated
 Staging: TNM, based on biologic behavior, really based on normal
anatomy
Note: The general rule is: ALL papillary tumors of the bladder are
regarded as cancer or potentially cancer. You will ALMOST NEVER see
a path report of a SQUAMOUS PAPILLOMA, especially in the USA.
Figures 29 & 30. Grading of Urothelial (Transitional Cell) Tumors.
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Figure 31. Four Morphogical Patterns of Bladder Tumors.
Note: Urothelial tumors can be, most of the time, papilloma-papillary
carcinoma. In papilloma, there is no invasion of the underlying stroma
as the proliferation is upward. Flat non-invasive carcinomas (carcinoma
in-situ) are the precursor lesions that are monitored since they usually
develop into flat invasive carcinomas (aggressive type) *these are
scarier according to Dra. Mesina.
UROTHELIAL PAPILLOMA
 A benign lesion usually seen in younger patients
 Typically seen as singular nodules that are attached superficially to the
mucosal surface by a stalk (exophytic papillomas)
o The finger-like papillae have a core of loose fibrovascular tissue
that is covered with epithelial cells similar to transitional
epithelium (normal urothelium).
 Can be a lesion that consists of inter-anastomosing cords of
cytologically bland urothelium that extend down into the lamina
propria (inverted papillomas)
 Histology: Uniform nuclei, maintained polarity, normal mitotic figures,
papilloma does not exceed 7 cell layers, rapidly proliferating
Note: WHO Qualification
(+) Fibrovascular cord in the middle
(+) Covered in normal urothelial cells not exceeding 7 layers
(+) In patients less than 50 years old
(+) Located commonly near the areas of the ureteral orifices
(+) Superficial layer of urothelium may show cytoplasmic vacuolations
Figure 32. Urothelial Papilloma
INVERTED PAPILLOMA
 Unlike urothelial papilloma, these tend to arise from older age group
60-70.
 Microscopic: inverted (downward) growth pattern of anastomosing
islands and trabeculae of histologically normal urothelial cells
invaginating from the surface urothelium into the lamina propia
 male predominance (7:1)
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 PATHOLOGY 5.1
 similarly hematuria is the presenting complaint
 the region of the Trigone and bladder neck are the areas of which they
are commonly seen
Figure 33. Inverted Papilloma
PAPILLARY UROTHELIAL NEOPLASM OF LOW MALIGNANT POTENTIAL
 Same as urothelial papilloma but has thicker urothelium or diffuse
nuclear enlargement
 Exceeds 7 cell layers (usually 10)
 Rare mitotic figures
 Low rate of recurrence
Figure 34. Papillary Urothelial Neoplasm of Low Malignant Potential
LOW GRADE PAPILLARY UROTHELIAL CARCINOMA
 Has an orderly appearance both architecturally and cytologically
 Cohesiveness of cell structures and the cells are evenly spaced (i.e.
maintain polarity)
 Minimal but definite signs of nuclear atypia that displays scattered
hyperchromatic nuclei, infrequent mitotic figures that are found at the
base, mild nuclear size and shape variations
 Infrequent recurrence
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Figure 35. Low Grade Papillary Urothelial Carcinoma
HIGH GRADE PAPILLARY UROTHELIAL CARCINOMA
 Presence of large hyperchromatic nuclei in cells that are disorganized in
nature (dyscohesive)
 Frequent mitotic figures, including atypical ones
 They are more solid, bulky, and ulcerative
 There is disarray and loss of polarity
 Usually invades the muscular layer
 A higher risk of progression than low-grade lesions, and, when
associated with invasion, a significant metastatic potential
Figure 36. High Grade Papillary Urothelial Carcinoma
FLAT UROTHELIAL CARCINOMA/CARCINOMA IN SITU (CIS)
 Presence of cytologically malignant flat urothelium which range from
atypia of the entire thickness of the urothelium to scattered malignant
cells among normal ones
 Similar to high grade papillary carcinomas due to lack of cohesiveness
 Grossly seen as reddening and thickening of the mucosa without
evidence of intraluminal masses
 Multifocal, may involve the ureters and urethra
 50-75% of untreated cases progress to invasive carcinoma
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Figure 38. Opened bladder showing a high-grade invasive transitional cell

carcinoma at an advanced stage. The aggressive multinodular neoplasm has
fungated into the bladder lumen and spread over a wide area. The yellow
areas represent areas of ulceration and necrosis.
Figure 37. (A) Normal urothelium with uniform nuclei and well-developed
umbrella cell layer (arrow). (B) Flat carcinoma in situ with numerous cells
having enlarged and pleomorphic nuclei.

INVASIVE UROTHELIAL CARCINOMA

 May be associated with CIS or high-grade papillary urothelial carcinoma
 Muscularis mucosae and propria are already invaded
o Extent of invasion is of prognostic significance
o The extent of spread (staging) becomes a key factor in
determining the clinical outcome of the patient.

th th Figure 39. Cross-section of bladder with upper section showing a large

Note: Transitional Cell Carcinomas are usually found in the 5 -6
decade upwards of life. There is slight male predominance. Causes are papillary tumor. The lower section demonstrates multifocal smaller papillary
both of genetic and environmental factors. neoplasms.
Papillary tumors: deletions in Chromosome 9
Invasive (high-grade) tumors: deletions in Chromosome 17

Causes/Risk Factors:
 Cigarette smoking
 Exposure to Arylamines
 Schistosoma infection
o The ova are deposited in the bladder wall and incite a brisk chronic
inflammatory response that induces progressive mucosal
squamous metaplasia and dysplasia and, in some instances,
neoplasia.
o Can be of mixed histology: urothelial carcinomas with areas of Figure 40. Cytology of urothelial cells that are normal (left) and malignant
squamous carcinoma (right).
o Pure squamous cell carcinoma in the bladder is an indication that
it is due to Schistosoma haematobium infection. Biologic Behavior:
o Note that squamous cell carcinoma is due to longstanding Sequence of spread:
conditions of bladder irritation and inflammation. Normal mucosa  Dysplasia, severe dysplasia, carcinoma in situ, infiltration
 Chronic usage of analgesics, same as those drugs that can lead to  Basement membrane  Lamina propria  Muscularis mucosa 
analgesic nephropathy Muscularis propria  Serosa/adventia  Lymph nodes  Metastasis
 Chemotherapy agents (Cyclophosphamide)
 Radiation therapy Staging of a Tumor:
Ta: non-invasive, papillary tumor
Tis: carcinoma in situ
T1: Lamina propria invaded
T2: Muscularis propria invaded
T3a: Microscopically beyond luminal wall
T3b: Gross protuberance beyond the luminal wall
T4: invasion of adjacent structures

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 PATHOLOGY 5.1

URINARY BLADDER OBSTRUCTION

 Cystocele of the bladder, MOST common cause in women (i.e., elderly
and multigravid)
 Prostate gland enlargement, MOST common cause in MEN
 Congenital urethral strictures
 Inflammation urethral structures
 Bladder tumors, either benign or malignant
 Invasion of the bladder neck by tumors arising in contiguous organs
(foreign bodies, calculi)
 Injury to the innervations of the bladder causing neurogenic bladder

Figure 43. Urethral Caruncle in women

NEOPLASMS OF THE URETHRA

 Benign: Squamous and urothelial papillomas, inverted urothelial
papillomas, condyloma
 Malignant: Urothelial carcinoma
o Uncommon lesion
o If within the proximal urethra: show urothelial differentiation and
are analogous to those occurring within the bladder
o If within the distal urethra: more typically squamous carcinomas

REFERENCES
th
Figure 41 (Left). Bladder obstruction due prostate gland enlargement.  Robbins and Coltran Pathologic Basis of Diseases, 8 Edition
Figure 42 (Right). Bladder obstruction due to cystocele formation in elderly,  Dra. Mesina’s lecture & ppt
multigravid women. There’s weakening of the pelvic floor causing the  2015A & 2015B trans
descent of the uterus. And because the bladder is located anterior to the
uterus, it is pushed and herniates the vaginal wall. “Forget the former things; do not dwell on the past.
See, I am doing a new thing! Now it springs up; do you not perceive it?
URETHRA I am making a way in the wilderness and streams in the wasteland.”
A. Inflammatory (Isaiah 43:18-19)
B. Tumor & Tumor-like lesions
a. Urethral Caruncle
b. Neoplasms Edited by: Gab Tan

INFLAMMATION OF THE URETHRA

URETHRITIS
 Classically divided into gonococcal and nongonococcal.
o Gonococcal Urethritis: one of the earliest manifestations of this
venereal infection
o Nongonococcal Urethritis: common and can be caused by a
variety of bacteria
 E. coli and other enteric organisms predominate
 Chlamydia (C. trachomatis) – cause of % to 60% of
nongonococcal urethritis in men and about 20% in women
 Mycoplasma (Ureaplasma urealyticum)
 Reiter Syndrome: comprises the clinical triad of arthritis, conjunctivitis,
and urethritis
 Urethritis is often accompanied by cystitis in women and by prostatitis
in men
 Caused by distal urethral prolapse and related to estrogen withdrawal

TUMORS & TUMOR-LIKE LESIONS

URETHRAL CARUNCLE
 Inflammatory lesion presenting as a small, red, painful mass about the
external urethral meatus, typically in older females
 It may be covered by an intact mucosa but is extremely friable, and the
slightest trauma may cause ulceration of the surface and bleeding.
 Histology: composed of an inflamed granulation tissue polyp
 Urethral caruncles, which often originate from the posterior lip of the
urethra, may be described as fleshy outgrowths of distal urethral
mucosa.
 They are usually small but can grow to 1-2 cm in diameter.

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