Far Eastern University – Nicanor Reyes Medical Foundation INFLAMMATION

Pathology B – Lower Urinary Tract and Male Genitalia
Cherry Mae Tan M.D.
LOWER URINARY TRACT
 Lined by urothelium, composed of 5-6 layers of cells with oval
nuclei, often with linear nuclear grooves and surface layer consists
of flattened umbrella cells with abundant cytoplasm.
 The epithelium rests on a well-developed basement membrane.
 The lamina propria beneath contains wisps of smooth muscle that
form discontinuous muscularis mucosa.
 There is a deeper well-defined muscle bundles of the detrusor
muscle (muscularis propria).
 Obstruction of urine outflow results to increase in intravesical
pressure and musculature undergoes hypertrophy.
 Ureters lie in a retroperitoneal position, as it enters the pelvis;
pass anterior to either the common iliac or external iliac artery.
 In females, they lie close to uterine arteries.
 Narrowings of the ureter:
 Ureteropelvic junction
 Pelvic brim
 Ureterovesical junction
 The narrowing are sites
where stones can lodge.
 Ureteritis is typically NOT associated with infection.
Morphology
 Accumulation of lymphocytes forming germinal centers in the
subepithelial region may cause slight elevations of the mucosa
and produce a fine granular mucosal surface (ureteritis follicularis)
 Mucosa may become sprinkled with fine cysts (ureteritis cystica).
TUMORS & TUMOR-LIKE LESIONS
 Primary tumors are rare.
 Small benign tumors are of mesenchymal origin.
 Fibroepithelial Polyp – tumor-like lesion presents as small mass
projecting into the lumen, often in children, composed of loose,
vascularized connective tissue overlaid by urothelium.
 Primary malignant tumors resemble those arising in the renal
pelvis, calyces, and bladder.
 Majority are urothelial carcinomas may cause obstruction.
OBSTRUCTIVE LESIONS
 Obstruction may give rice to hydroureter, hydronephrosis, and
sometimes pyelonephritis.
 Involvement of the kidney is of clinical significance.
 Can be divided into intrinsic or extrinsic cause.
 Unilateral obstruction results to proximal causes, while bilateral
obstruction arises from distal causes.

Ureters
CONGENITAL ANOMALIES
 Little clinical significance may obstruct outflow.

Double and Bifid Ureters

 Double ureters are associated with double renal pelvises or with
anomalous large kidney terminating in separate ureters.
 May pursue separate course in the bladder but commonly joined
in the bladder and drain in a single orifice.
 Most are unilateral, no clinical significance.

Ureteropelvic Junction (UPJ) Obstruction

 Most common cause of hydronephrosis in infants and children.
 Bilateral, associated with other anomalies, more common in male
 Agenesis of the contralateral kidney in minor cases.
 In adults, more common in women and most often unilateral.
Sclerosing Retroperitoneal Fibrosis
 Abnormal organization of smooth muscle bundles at the UPJ, to
 Uncommon, fibrotic proliferative inflammatory process encasing
excess stromal deposition of collagen between smooth muscles.
the retroperitoneal structures and leading to hydronephrosis.
 Middle age to late age, more common in males.
Diverticula
 A subset is related to IgG4-related disease, with elevated serum
 Saccular outpouchings of the ureteral wall.
IgG4 and fibroinflammatory lesions w/ IgG4 plasma cells.
 Most are symptomatic, but urinary stasis may lead to infections.
 Often involves pancreas and salivary glands.
 Dilation (hydroureter), elongation, and tortuosity of the ureters.
 Fibrous tissue containing a prominent infiltrate of lymphocytes
with germinal centers, plasma cells (IgG4) and eosinophils.
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Urinary Bladder
 Cystitis is common in young women of reproductive age.
CONGENITAL ANOMALIES
Vesicoureteral Reflux
 Most common and serious congenital anomaly.
 Major contributor to renal infection and scarring.
 Abnormal connections between the bladder and the vagina,
rectum, or uterus may create congenital vesicouterine fistulae.
Diverticula
 Pouch-like evaginations of the bladder.
 Congenital Diverticula – focal failure of development of the
normal musculature during fetal development.
 Acquired Diverticula – Most often seen with prostatic
enlargement, producing obstruction to urine outflow and marked
thickening of the bladder wall, the increase in intravesical
pressure causes outpouching of the wall.
 Frequently multiple and have narrow necks located between the
interweaving hypertrophied muscle bundles.
 Urinary stasis may lead to infection or calculi formation
Exstrophy of the Bladder
 Developmental failure in the anterior wall of the abdomen and
bladder, the bladder either communicates directly via a large
defect or lies as an open sac.
 Exposed mucosa may undergo colonic glandular metaplasia and is
subject to infections.
 Increased risk of adenocarcinoma.
Urachal anomalies
 The urachus (canal that connects the fetal bladder with the
allantois) is normally obliterated after birth.
 Sometimes remain in part or in whole.
 When totally patent, a fistulous urinary tract connects the
bladder with the umbilicus.
 Sometimes, only the central region persists give rise to urachal
cysts, lined by urothelium or metaplastic glandular epithelium.
 Carcinomas, mostly glandular tumors, may arise from such systs.
INFLAMMATION
Acute and Chronic Cystitis
 Bacterial pyelonephritis is frequently preceded by infection of the
urinary bladder with retrograde spread of bacteria.
 Women are more likely to develop cystitis due to short urethra.
 Common etiologic agents are:
 Coliforms: Escherichia coli
 Proteus, Klebsiella, Enterobacter
 Tuberculous cystitis is always a sequel to renal TB.
 Candida albicans, cryptococcal may also cause cystitis particularly
in immunocompromised patients receiving antibiotics.
 Schistosomiasis (S. haematobium) common in middle eastern.
 Chlamydia, Mycoplasma may also cause cystitis.
 Radiation cystitis may also happen due to irradiation.
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Morphology
 Most cases produce non-specific acute or chronic inflammation.
 In acute cystitis there is hyperemia and neutrophilic infiltrates.
 Patients receiving cytotoxic antitumor drugs or infection with
Adenovirus may develop hemorrhagic cystitis.
 Chronic cystitis is associated with mononuclear infiltrates.
 Follicular Cystitis is characterized by presence of lymphoid
follicles within the bladder mucosa and underlying wall.
 Eosinophilic Cystitis is manifested as infiltration with submucosal
eosinophils.
 All forms of cystitis are characterized by triad of symptoms
1. Frequency – urination every 15-20 minutes.
2. Lower abdominal pain localized in suprapubic area
3. Dysuria – pain of burning sensation of urination
Special forms of cystitis
Interstitial Cystitis (Chronic Pelvic Pain Syndrome)
 Occurs most frequent in women characterized by intermittent,
often severe suprapubic pain, frequency, urgency, hematuria, and
dysuria and cystoscopic findings of fissures and hemorrhages.
 Etiology is unknown.
 Associated with chronic mucosal ulcers (Hunner ulcers), termed
the late phase.
 Increase numbers of mucosal mast cells.
 Transmural fibrosis may appear late in the course.
Malakoplakia
 Inflammatory reaction that appears to stem from defects in
phagocyte function arises in the setting of bacterial infection,
mostly in E. coli or Proteus species.
 Increased frequency in immunosuppressed patients.
 Soft, yellow, slightly raised mucosal plaques filled with large,
foamy macrophages mixed with multinucleate giant cells.
 The macrophages have abundant granular cytoplasm.
 Laminated mineralized concretions due to deposition of calcium
in enlarged lysosomes known as Michaelis-Gutmann bodies.
Polypoid Cystitis
 Inflammatory lesions resulting from irritation of the mucosa.
 Indwelling catheters are the most common culprits.
 Urothelium is thrown into broad bulbous polypoid projections as
a result of submucosal edema.
METAPLASTIC LESIONS
Cystitis Glandularis and Cystitis Cystica
 Common lesions in which nests of urothelium (Brunn nests) grow
downward to the lamina propria.
 Epithelial cells undergo metaplasia and take on a cuboidal or
columnar appearance (cystitis glandularis) or retract to produce
cystic spaces lined by flattened urothelium (cystitis cystica).
 Since they coexist they are called cystitis cystica et glandularis.
 In a variant, goblet cells exist, resembling intestinal mucosa
(intestinal or colonic metaplasia)
Squamous Metaplasia
 Response to injury, urothelium is replaced by non-keratinizing
squamouse epithelium.
 Should be distinguished from glycogenated squamous epithelium
which is normally found in women at the trigone.
Nephrogenic Adenoma
 Results from implantation of shed renal tubular cells at sites of
injured urothelium.
 The overlying urothelium may be focally replaced by cuboidal
epithelium, which can assume papillary growth pattern.
 Tubular proliferation can infiltrate the underlying lamina propria
and superficial detrusor muscle, mimicking malignant process.
NEOPLASMS
 Most epithelial tumors are urothelial type, thus interchangeable
called urothelial or transitional tumors.
Urothelial Tumors
 90% of all bladder tumors.
 Multifocal at presentation.
 May be seen in any site where there is urothelium such as in renal
pelvis and the distal urethra.
 Two distinct precursor lesions to invasive urothelial carcinoma:
 Non-invasive papillary tumors – most common
 Flat non-invasive urothelial carcinoma – carcinoma in situ
 Most common ones originate from papillary urothelial hyperplasia
 Grading system:
 Once muscularis propria is invaded, there is 30% 5-year survival.
Epidemiology and Pathogenesis
 Higher in men, 3:1, in developed countries, 50-80 y/o.
 Factors:
 Cigarette smoking – most important, 5-7-fold increase.
 Industrial exposure to aryl amines - 2-naphthylamine
 Schistosoma haematobium
 Long-term analgesic use
 Long-term exposure to cyclophosphamide
 Irradiation
 Several acquired genetic mutations, strongly associated with gain-
of-function mutation in FGFR3 found in non-invasive low-grade
papillary carcinomas as its result in receptor tyrosine kinase.
 Loss-of-function mutations in TP53 and RB are seen in high-grade
and often invasive tumors.
 Common are losses on chromosome 9 (deletions, monosomy)
 9p deletions (9p20) span region includes CDKN2A.
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Morphology
 Varies from purely papillary to nodular to flat.
 Most arise from lateral or posterior walls of the bladder base.
 Papillary lesions are red, elevated excrescences.
 Multiple discrete tumors are often present.
 Overall, majority of papillary tumors are low grade.
 Papillomas
 1% or less, seen in younger patients, arise singly as small,
delicate structures, superficially attached to mucosa by a
stalk, referred as exophytic papillomas.
 The finger-like papilla have central core of loose fibrovascular
tissue covered by epithelium identical to the urothelium.
 Inverted papillomas are completely benign consisting of
inter-anastomosing cords of bland urothelium extending
down the lamina propria.
 Papillary urothelial neoplasm of low malignant potential
 Share histologic features papilloma, differs only with having a
thicker urothelium.
 Low-grade papillary urothelial carcinomas
 Cells are evenly spaced and cohesive.
 Mild degree of nuclear atypia consisting of hyperchromatic
nuclei, infrequent mitotic figure frequently towards the base
 Although infrequent, these type may invade
 High-grade papillary urothelial carcinoma
 Dyscohesive cells with large hyperchromatic nuclei.
 Highly anaplastic.
 Mitotic figures, including atypical ones are frequent.
 Disarray and lost of polarity.
 Higher incidence of invasion, metastasis.
 Less than 10% are low-grade, but 80% are high-grade.
 40% metastasize to regional lymph nodes.
 Hematogenous spread to the liver, lungs, and bone marrow.
 Carcinoma in situ (flat urothelial CA)
 Cytologically malignant cells with flat urothelium.
 May be full-thickness or scattered (pagetoid spread)
 Common feature shared with high-grade papillary urothelial
CA is lack of cohesiveness leading to shedding of malignant
cells in the urine.
 Appears as mucosal reddening, granularity, or thickening
without evident intraluminal mass, usually multifocal.
 Invasive Urothelial Cancer
 Usually associated with high grade urothelial CA or adjacent
carcinoma in situ.
 Extent of invasion into muscularis mucosa is prognostic.
 The extent of spread (staging) at the time of initial diagnosis
is most important for determining the outlook.
Variants of Urothelial CA
 Unusual variants include nested urothelial CA, with bland
cytology, lymphoepithelioma-like CA and micropapillary CA.
Other Epithelial Bladder Tumors
 Squamous Cell CA – resemble those occurring at other sites, make
up 3% to 7%, more frequent in countries where schistosomiasis is
endemic.
 Pure SCCA is almost always associated with chronic irritation
and infection.
 Mixed Urothelial CA with areas of SCCA are more frequent, most
are invasive, fungating tumors or are infiltrative and ulcerative.
 Adenocarcinomas are rare, identical to those seen AdenoCA of
the GIT; some arise from urachal remnants in association with
extensive intestinal metaplasia.
 Small-cell carcinoma – indistinguishable from SCC of the lungs,
arise in the bladder in association with urothelial, squamous, or
adenocarcinoma.
Clinical Manifestations
 Classically produce painless hematuria.
 Frequency, urgency, and dysuria occasionally company hematuria.
 60% when first discovered are single, 70% localized to the bladder
 Recurrence is common in whatever grade, recurrent mays how
higher grade.
 Risk of recurrence is related to the size, stage, grade,
multifocality, prior recurrence, and associated dysplasia.
 Most recurrence arises at different site from original lesion.
 Recurrence may be independent of the new tumors, but in others
they share the same clonal abnormality.
 Squamous cell carcinoma and Adenocarcinoma are associated
with a worse prognosis than urothelial CA, yet stage for stage,
they are all similar.
 Clinical challenge is early detection and adequate follow up.
 Selection of treatment depends on the grade, stage, and whether
the lesion is flat or papillary.
 Small, localized low grade tumors, the diagnostic
transurethral resection is the only surgical procedure done.
 High-risk patients receive intravesical instillation of
attenuated strains of Mycobacterium bovis called Bacillus
Calmette-Guerin (BCG) that destroy tumor cells.
 Radical cystectomy is reserved for tumors invading the
muscularis propria, CIS, high-grade papillary CA refractory to
BCG, CIS extending to prostatic urethra.
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Mesenchymal Tumors
 Benign Tumors – most common is Leiomyoma.
 All tend to grow as isolated, intramural, encapsulated, oval-to-
spherical masses,
 Sarcomas – True sarcomas are uncommon, inflammatory
myofibroblastic tumors may assume sarcomatoid growth patterns
and be mistaken for a sarcoma.
 Most common sarcoma is embryonal rhabdomyosarcoma in
childhood and manifest as polypoid grape-like mass (sarcoma
botryoides).
 Most common sarcoma in adults is leiomyosarcoma.
Secondary Tumors
 Malignant involvement of the bladder is most often by direct
extension from a primary lesion.
 Lymphomas of the bladder may be a component of systemic
disease or may arise as primary bladder lymphoma.
OBSTRUCTION
 In males, most common cause is prostate gland enlargement due
to nodular hyperplasia.
 Less common in females, most commonly caused by cystocele.
 Infrequent causes are:
 Congenital urethral strictures
 Inflammatory strictures
 Inflammatory fibrosis and contraction
 Bladder tumors
 Invasion of the bladder neck by tumors.
 Mechanical obstruction due to foreign body or calculi
 Injury to nerve controlling bladder contraction (neurogenic
bladder)
 In the early stages there is only thickening due to smooth muscle
hypertrophy, in course of time may form crypts and diverticula.
 Enlarged bladder may reach the brim or umbilicus, the wall this
time is markedly thinned and lacks trabeculations.
Urethra
INFLAMMATION
 Classically divided into:
 Gonoccocal
 Non-gonococcal
 Gonococcal urethritis is one of the earliest manifestations of
venereal infection.
 Non-gonococcal urethritis is common, can be caused by
Chlamydia trachomatis (25-60%), and Mycoplasma urealyticum.
 Urethritis is often accompanied by cystitis in women and
prostatitis in men.
 Some are non-infectious in origin, example is reactive arthritis
(triad: arthritis, conjunctivitis, urethritis).
 Changes are entirely typical of inflammation.
TUMORS AND TUMOR-LIKE LESIONS
 Urethral Caruncle – inflammatory lesion presents as a small, red,
painful mass about the external urethral meatus, typically in older
females.
 Consists of inflamed granulation tissue covered by intact but
extremely friable mucosa.
 May ulcerate and bleed with slightest trauma.
Benign Epithelial Tumors
 Include squamous and urothelial papillomas
 Inverted urothelial papillomas and condylomas.
Primary Carcinoma of Urethra
 Uncommon.
 Tumors in the proximal urethra are analogous to those arising
within the bladder.
 Tumors in the distal urethra are more often squamous CA.
 AdenoCA are infrequent, generally occur in women.
 Cancer arising within the prostatic urethra are dealt within the
section on the prostate.
MALE GENITAL TRACT
Penis
 Affected by congenital anomalies, inflammations and tumors
 Tumors and inflammations are the most important
CONGENITAL ANOMALIES
Hypospadias and Epispadias
 Malformation of the urethral groove and urethral canal creating
an abnormal urethral opening:
 Hypospadias – ventral surface
 Epispadias – dorsal surface
 Either may be associated with failure of normal descent of the
testes and malformations of the urinary tract
 Hypospadias are most common of the two
 The abnormal opening is often constricted resulting to obstruction
and increased risk of ascending UTI
 Orifices situated near the base of the penis cause infertility by
hampering normal ejaculation and insemination
Phimosis
 Orifice of the prepuce is too small to permit normal retraction
 May result from anomalous development or more frequently the
result of repeated attacks of infection that cause scarring of the
preputial ring
 Interferes with cleanliness and permits the accumulation of
secretions and detritus under the prepuce
 May lead to development of secondary infections and carcinoma
INFLAMMATION
 Involve the glans and prepuce and include specific and non-
specific infections
 Specific infections are sexually transmitted: syphilis, gonorrhoea,
chancroid, granuloma inguinale, lymphopathia venereal, genital
herpes
 Non-specific infections: balanoposthitis
Balanoposthitis
 Infection of the glans and prepuce
 Common agents include: Candida albicans, anaerobic bacteria,
Gardnerella and pyogenic bacteria
 Consequence of poor local hygiene in uncircumcised males
 Smegma – acts as a local irritant composed of accumulated
desquamated epithelial cells, sweat and debris
 Persistence of infections lead to inflammatory scarring
 A common cause of phimosis
Page 5 of 13
Tumors
 Uncommon, but most frequent neoplasms are carcinomas and
condyloma acuminatum (a benign tumor)
BENIGN TUMORS
Condyloma Acuminatum
 Benign sexually transmitted wart caused by HPV
 Related to the common wart and occur on any moist
mucocutaneous surface of the external genitals on both sexes
 HPV type 6 and type 11 (less frequent) are most common agent
Morphology
 Occur on the external genitalia or perineal areas
 On the penis, most frequently found on the coronal sulcus and
inner surface of the prepuce
 Consist of single or multiple sessile or pedunculated, red
papillary excrescences
 Acanthosis – branching, villous, papillary connective tissue stroma
covered by epithelium with considerable superficial
hyperkeratosis and thickening of underlying epithelium
 Maturation of epithelial cells is preserved
 Koilocytosis – cytoplasmic vacuolization of the squamous cells,
characteristic of HPV infection
 Tend to recur but rarely progress into malignancy
Peyronie Disease
 Fibrous bands involving the corpus cavernosum of the penis
 Some classify it as a variant of fibromatosis, etiology remains an
enigma
 Results in penile curvature and pain during intercourse
MALIGNANT TUMORS
Carcinoma in Situ (CIS)
 Strong association with infection by high risk HPV type 16
 Two distinct histologic features:
 Bowen Disease – occurs in the genital region of both sexes
 >35 years old
 Tends to involve the skin of the shaft of the penis and the
scrotum
 A solitary, thickened, gray-white, opaque plaque
 Can also manifest on the glans and prepuces as a single or
multiple shiny red, velvety plaques
 Epidermis is hyperproliferative containing numerous atypical
mitoses
 Cells are markedly dysplastic with larger hyperchromatic
nuclei and lack of maturation
 Dermal-epidermal border is delineated by an intact
basement membrane
 Transforms into squamous cell carcinoma in 10% of patients
 Bowenoid Papulosis – occurs in sexually active adults
 Occurs in younger patients
 Multiple reddish brown papular lesions
 Histologically indistinguishable from Bowen disease
 Never develops into invasive carcinoma and regresses
spontaneously
Invasive Carcinoma
 Squamous cell carcinoma of the penis is associated with poor
genital hygiene and high-risk HPV infection
 40-70 years old
 More common in Asia, Africa and South America (10-20% of male
malignancies)
 Circumcision confers protection
 HPV 16 is the most frequent culprit, type 18 is also implicated
 Vaccine to both low risk (6,11) and high risk (16, 18) subtypes of
HPV help reduce the incidence as well as condyloma acuminatum
 Cigarette smoking also elevates the risk
Morphology
 Begins on the glans or the inner surface of the prepuce near the
coronal sulcus
 Two macroscopic patterns: papillary and flat
 Papillary lesions simulate condyloma acuminatum and may
produce a cauliflower-like fungating mass
 Flat lesions appear as areas of epithelial thickening with graying
and fissuring of the mucosal surface
 Ulcerated papule develops on progression
 Verrucous carcinoma – an exophytic well-differentiated variant of
SCC that are locally invasive but rarely metastasize
 Other less common subtypes of SCC: basaloid, warty and papillary
variants
Clinical Features
 Slowly growing, locally invasive lesion that may be present for a
year or more before medical attention is given
 Nonpainful lesions until secondary ulceration and infection arises
 Metastases to inguinal LN may occur early but widespread
dissemination is extremely uncommon until far advanced
 Assessment of regional LN is inaccurate
 50% of inguinal nodes only present with carcinoma, other
half present with reactive lymphoid hyperplasia
 Prognosis is related to stage of the tumor
 Without metastasis, 5 year survival rate is 66%, metastasis 27%
Testis and Epididymis
 Inflammatory diseases are most important in epididymis
 Tumors for the testis
CONGENITAL ANOMALIES
 Extremely rare except for cryptorchidism
 Other anomalies are absence of one testes and fusion of the
testes (synorchism)
Cryptorchidism
 Complete or partial failure of the intra-abdominal testes to
descend into the scrotal sac
 Associated with testicular dysfunction and increased risk of
testicular CA
 Found in 1% of 1 y/o boys
 Occurs as an isolated anomaly but may be accompanied by other
malformations of the GUT (e.g. hypospadias)
 Occurs in two morphologically and hormonally distinct phases
 Transabdominal phase – the testis comes to lie within the lower
abdomen or brim of the pelvis
Page 6 of 13
 Controlled by: mullerian inhibiting substance
 Inguinoscrotal phase – the testes descends through the inguinal
canal into the scrotal sac
 Androgen-dependent
 Mediated by: androgen-induced release of calcitonin gene-
related peptide from the genitofemoral nerve
 Most common site of testicular arrest is in the inguinal canal but
may arrest anywhere along the pathway of descent
 Arrest within the abdomen is uncommon (5-10%)
 Only rarely associated with a well-defined hormonal disorder
Morphology
 Unilateral in most cases, bilateral in 25%
 Histologic changes in malpositioned testis begin at 2y/o
 Characterized by arrested germ cell development with marked
hyalinization and thickening of the basement membrane of the
spermatic tubules
 Tubules appear as dense cords of hyaline connective tissue with
prominent basement membranes
 Concomitant increase in interstitial stroma
 Leydig cells appear to be prominent
 Cryptorchid testis is small in size and is firm in consistency as a
result of fibrotic changes
 Similar histologic changes are seen in the descended testis in
males with unilateral cryptorchidism
Clinical Features
 Completely asymptomatic and comes into attention when the
scrotal sac is discovered empty by the patient or physician
 Undescended testis is prone to trauma injuries, CAs and cause
sterility
 Accompanied by inguinal hernias (10-20%)
 Majority spontaneously descends into the scrotum in the first
year of life, those that remains require surgical correction
(orchiopexy) but does not guarantee fertility
 Cryptorchidism is a marker of some intrinsic defect in testicular
development or function
REGRESSIVE CHANGES
Atrophy and Decreased Fertility
 Caused by the following factors:
 Progressive atherosclerotic narrowing of the blood supply in
old age
 End stage of an inflammatory orchitis
 Cryptorchidism
 Hypopituitarism
 Generalized malnutrition of cachexia
 Irradiation
 Prolonged administrations of antiandrogens
 Exhaustion atrophy
 Factors are followed by persistent stimulation of high levels of
FSH
 Gross and microscopic patterns are same with cryptorchidism
 Occur as a primary failure of genetic origin (e.g. Klinefelter
syndrome)
INFLAMMATION
 More common in the epididymis than the testis
 Gonorrhea and tuberculosis arise in the epididymis, syphilis
affects the testis first
Nonspecific Epididymitis and Orchitis
 Commonly related to infections of the UT (e.g. cystitis, urethritis,
prostatitis) via the vas deferens or lymphatics of the spermatic
cord
 Cause varies with the age of the patient
 Childhood epididymitis (uncommon) is usually associated with a
congenital GUT abnormality and infection with gram negative
rods
 In sexually active men <35 y/o, most common culprits are
Chlamydia trachomatis and Neisseria gonorrhoea
 >35y/o, culprits are E. coli and Pseudomonas
Morphology
 Nonspecific acute inflammation characterized by congestion,
edema, and infiltration neutrophils, macrophages and
lymphocytes
 Rapidly extends to involve the tubules and progress to abscess
formation or complete suppurative necrosis of entire epididymis
and extends to the testis
 Scarring leads to sterility
 Leydig cells are not totally destroyed and androgen production by
the testis is not affected
Granulomatous (Autoimmune) Orchitis
 Presents in middle age as a moderately tender testicular mass of
sudden onset sometimes with fever
 May appear insidiously as a painless testicular mass mimicking a
testicular tumor
 Distinguished by granulomas restricted to the spermatic tubules
 Resemble tubercles but granulomatous reaction is present
diffusely throughout the testis and is confined to the seminiferous
tubules
Specific Inflammations
Gonorrhea
 Extension of infection from the posterior urethra to the prostate,
seminal vesicles and to the epididymis
 Epididymal abscesses may occur in severe cases leading to
extensive destruction and scarring
 May spread to the testis and produce suppurative orchitis
Mumps
 Systemic viral disease commonly affecting school-aged children
 Testicular involvement is uncommon in children, but occurs in 20-
30% of post-pubertal males
 Acute interstitial orchitis develops 1 week after onset of swelling
of the parotid glands
Tuberculosis
 Involvement of the genital tract begins at the epididymis then
spreads to the testis
 Invokes classic morphologic reactions of caseating granulomatous
inflammation
Page 7 of 13
 Syphilis
 Testis and epididymis may be affected in both acquired and
congenital form of syphilis but almost always, the testis is
involved first
 Morphologic patterns:
 Production of gummas
 Diffuse interstitial inflammation that produces the histologic
hallmark of syphilis (obliterative endarteritis associated with
perivascular cuffs of lymphocytes and plasma cells)
VASCULAR DISORDERS
Torsion
 Twisting of spermatic cord cutting of venous drainage of the testis
 Leads to infarctions when untreated
 Arteries remain patent producing intense vascular engorgement
followed by hemorrhagic infarction
 Neonatal torsion – occurs in utero or after birth and lacks any
associated anatomic defect
 Adult torsion – seen in adolescence and presents with sudden
onset of testicular pain
 Often occurs without inciting injury and may occur during
sleep
 If testis is untwisted within 6hours of onset of torsion, testis
may remain viable
 Bell-clapper abnormality – bilateral anatomic defect that
leads to increased mobility of the testis
 To prevent torsion of unaffected testis, it is surgically fixed to the
scrotum (orchiopexy)
Morphology
 Changes range from intense congestion to widespread
hemorrhage to infarction
 In advanced stages, testis is enlarged and consists of soft,
necrotic, hemorrhagic tissue
Spermatic Cord and Paratesticular Tumors
 Lipomas are common involving the proximal spermatic cord,
usually indentified at the time of hernia repair
 Represent retroperitoneal adipose tissue pulled into the
inguinal canal along with the hernia rather than a true
neoplasms
 Adenomatoid Tumor – most common benign paratesticular tumor
 Small nodules, occurring at the upper pole of the epididymis
 Well circumscribed and may be minimally invasive into
adjacent testis
 One of the few benign tumors that occur near the testis
 Most common malignant tumors are rhabdomyosarcomas (in
children) and liposarcomas (in adults)
Testicular Tumors
 Divided into two major categories: germ cell tumors (95%) and sex
cord-stromal tumors
 Germ cell tumors are subdivided into seminomas and
nonseminomas
 Most GC tumors are aggressive CAs capable of rapid, wide
disseminations, although most can be cured
 Sex cord-stromal tumors are generally benign
Germ Cell Tumors Seminoma
 Most common type of GC tumors (50%)
 Classic or typical
rd
 Peaks at the 3 decade of life and almost never occur in infants
 In the ovary, it is termed as dysgerminoma
 Contain i(12p) and express OCT3/4 and NANOG
 25% of tumors have KIT activating mutations, amplification and
overexpression

Morphology
 Produce bulky masses, ten times the size of normal testis
 The most common tumor of men in the 15-34 age group and  Typical seminoma has a homogenous, gray-white, lobulated cut
approx 10% of all cancer deaths surface, devoid of hemorrhage or necrosis
 More common in whites than in blacks (5:1)  Tunica albuginea is not penetrated
 Extension to the epididymis, spermatic cord or scrotal sac occurs
Environmental Factors  Composed of sheets of uniform cells divided into poorly
 Associated with a spectrum of disorders collectively known as demarcated lobules by delicate fibrous septa containing a
testicular dysgenesis syndrome (TDS) lymphocytic infiltrate
 Components of the syndrome include: cryptorchidism (most  Cell is large and round to polyhedral and has a distinct cell
important association seen in 10% of GC tumors), hypospadias membrane; clear or watery-appearing cytoplasm; and a large,
and poor sperm quality central nucleus with one or two prominent nucleoli
 Conditions are increased in utero by exposure to pesticides and  Cytoplasm contain varying amounts of glycogen
nonsteroidal estrogens  Anaplastic seminoma – frequent tumor giant cells and greater
 Klinefelter syndrome is associated with a great increased risk for mitotic activity, does not necessarily mean poor prognosis
development of mediastinal GC tumor but not testicular tumors  Immunohistochemistry: (+) KIT, OCT4 and PLAP
 15% contain syncytiotrophoblast resulting to increase HCG levels
Genetic Factors
 Ill-defined granulomatous reaction may also be seen
 Strong familial predisposition
 Four times higher than the normal in fathers and sons of affected Spermatocytic Seminoma
patients and 8-10x in brothers
 Rare, slow-growing GC tumor affecting older men (>65)
 Genes encoding for the ligand of the receptor tyrosine kinase KIT
 Distinctive to classic seminoma hystologically and clinically
and BAK which are important inducer of apoptosis and plays a
 Uncommon (1-2%) of testicular germ cell neoplasms
role in gonadal development are usually involved
 Does not metastasize, excellent prognosis
Classification
Morphology
 Seminomatous tumors are composed of cells that resemble
 Soft, pale gray, cut surface revealing mucoid cyst
primordial germ cells or early gonocytes
 Three cell populations, all intermixed:
 Nonseminomatous tumors may be composed of undifferentiated
 medium-sized cells, the most numerous, round nucleus and
cells that resembles embryonic stem cells (e.g. embryonal
eosinophilic cytoplasm
carcinoma) or may also differentiate along other lineages (e.g.
 smaller cells with a narrow rim of eosinophilic cytoplasm
yolk sac tumors, choriocarcinomas and teratomas)
resembling secondary spermatocytes
 60% of GC tumors are mixtures of seminomatous and
 scattered giant cells, uninucleate or multinucleate
nonseminomatous components and multiple tissues
 Lack lymphocytes, granulomas, syncytiotrophoblast, extra-
testicular sites of origin, admixture with other GC tumors and
Pathogenesis
association with ITGCN
 Most GC tumors originate from a precursor lesions called
intratubular germ cell neoplasia (ITGCN) except for yolk sac
Embryonal Carcinoma
tumors, teratomas and adult spermatocytic seminomas
 20-30 age group
 ITGCN is believed to arise in utero and stay dormant until puberty
 More aggressive than seminomas
 Consists of atypical primordial germ cells with large nuclei and
clear cytoplasm twice the size of normal germ cells
Morphology
 Cells retain the expression of transcription factors OCT3/4 and
 Primary tumors are smaller than seminoma and do not replace
NANOG important in maintenance of pluripotent stem cells
entire testis
 One important alteration is the reduplication chromosome 12p in
 Extension through the tunica albuginea into the epididymis or
the form of an isochromosome i(12)p, invariably found in invasive
cord occurs
GC tumors regardless of type
 Variegated, poorly demarcated at the margins and punctuated by
 Mutations in the genes encoding for KIT receptors are also found
foci of hemorrhage or necrosis
 50% of individuals with ITGCN develop invasive GC tumors within
five year after diagnosis.
Page 8 of 13
 Cells grow in alveolar or tubular patterns, with papillary
convolutions
 Undifferentiated lesions may display sheets of cells
 Well formed glands are absent
 Neoplastic cells have epithelial appearance, large and anaplastic,
hyperchromatic nuclei with prominent nucleoli
 (+) Mitotic figures and tumor giant cells
 (+) OCT 3/4, PLAP, cytokeratin and CD30
 (-) KIT
Yolk Sac Tumor
 Endodermal sinus tumor
 Most common testicular tumor in <3 years, good prognosis
 In adults, occur in combination with embryonal carcinoma
Morphology
 Nonencapsulated and have a homogenous, yellow-white,
mucinous appearance
 Composed of lacelike (reticular) network of medium-sized
cuboidal or flattened cells
 Papillary structures, solid cord of cells may also be found
 Schiller-Duval bodies – consists of mesodermal core with a
central capillary and a visceral and parietal layer of cells
resembling primitive glomeruli and endodermal sinuses, found in
50% of tumors
 Within and outside the cytoplasm are eosinophilic hyaline-like
globules with (+) α-fetoprotein (highly characteristic) and α1-
antitrypsin
Choriocarcinoma
 Highly malignant
 Pure form is rare
Morphology
 No testicular enlargement and are detected only as small palpable
nodules
 Small, rarely larger than 5cm in diameter
 Hemorrhage and necrosis are extremely common
 Contains syncytiotrophoblast and cytotrophoblasts
 Syncytiotrophoblast are large multinucleated cells with
abundance eosinophilic vacuolated cytoplasm containing
HCG and detected by immunohistochemisty
 Cytotrophoblasts are more regular and polygonal with
distinct borders and clear cytoplasm. Grow in cords or
masses with a single, uniform nucleus
 Can also arise in the female GUT
Teratoma
 Occur at any age
 Pure forms are common in infants, second in frequency to yolk
sac tumors
 In adults, pure teratomas (2-3%), mixed with other tumors (45%)
 In the child, usually benign
 In post pubertal male are regarded as malignant and capable of
metastatic element whether immature or mature
Page 9 of 13
Morphology
 Large (5-10 cm), heterogeneous with solid, cartilaginous and
cystic areas
 Hemorrhage and necrosis indicates mixture with embryonal CA,
choriocarcinoma or both
 Composed of neural tissue, muscle bundles, cartilages, squamous
epithelium, thyroid gland structures, bronchial epithelium,
intestinal wall or brain substance
 Maybe mature or immature
 Rarely, malignant non-germ cell tumors arise in teratomas known
as “teratoma with malignant transformation” in the form of SCC,
mucin-secreting adenoCA, sarcoma or other cancers
Mixed Tumors
 Mixtures include: teratoma, embryonal CA, yolk sac tumor;
seminoma with embryonal CA and embryonal CA with teratoma
(teratocarcinoma)
 Prognosis is worsened by presence of more aggressive element
Clinical Features of Testicular Germ Cell Tumors
 Characteristic feature is painless enlargement of testis
 Standard management of a solid mass is radical orchiectomy
 Lymphatic spread is common to all forms. Retroperitoneal para-
aortic nodes are involved first then spreads to mediastinal and
supraclavicular nodes
 Hematogenous spread is primarily to the lungs, but liver, brain
and bones may also be involved
Difference between Seminomas and Nonseminomas (NSGCT)
 Seminomas remain localized to the testis (stage I) for a long time,
non seminomas are advanced clinical disease (stages II and III)
 Seminomas spread late with a preference of L>H, while
nonseminomas spread early H>L
 Choriocarcinoma is the most aggressive NSGCT, which does not
cause testicular enlargement but spread may involve the lungs
and liver in every case
 Nonseminomas are more aggressive and have a poorer prognosis
Staging:
 Stage I: tumor confined to the testis, epididymis or spermatic cord
 Stage II: distant spread confined to retroperitoneal nodes below
the diaphragm
 Stage III: metastases outside the retroperitoneal nodes or above
the diaphragm
Biomarkers
 HCG, AFP and LDH
 Elevation of LDH – correlates with the mass of tumors cells and
provides assessment of tumor burden
 Elevation of AFP and HCG – yolk sac tumor and choriocarcinoma,
respectively. Both markers are elevated in NSGCT
 Seminomas have minimal elevation of HCG levels which does not
affect prognosis
 Functions of biomarkers:
 Evaluation of mass
 Staging
 Assessing tumor burden
 Monitoring the response to therapy
Tumors of Sex Cord-Gonadal Stroma
 Sub classified based on their presumed histogenesis and
differentiation
 Leydig cell tumors and sertoli cell tumors
Leydig Cell Tumors
 May elaborate androgens, estrogens and corticosteroids
 Arise at any age, most between 20-60 years of age
 Most common presenting feature is testicular swelling, but in
some gynecomastia is the first symptom
 In children, hormonal effects manifested as sexual precocity is the
dominant feature
Morphology
 Form circumscribed nodules, less than 5cm in diameter
 Distinctive golden brown, homogenous cut surface
 Large in size and round or polyglonal cell outlines, abundant
granular eosinophilic cytoplasm and round central nucleus
 Cytoplasm contains lipid droplets, vacuoles, or lipofuscin pigment
and rod-shaded crystalloids of Reinke
 Most are benign, 10% are invasive and metastasis in adults
Sertoli Cell Tumors
 Hormonally silent and present as testicular mass
 Firm, small nodules with a homogenous gray-white to yellow cut
surface
 Tumor cells are arranges in distinctive trabeculae that form
cordlike structures and tubules
 Most are benign, 10% are malignant
Gonadoblastoma
 Rare, composed of mixture of germ cells and gonadal stromal
elements that almost always arise in gonads with some form of
testicular dysgenesis
 Germ cell may in sue malignant transformation giving rise to
seminoma
Testicular Lymphoma
 Aggressive non-Hodgkin lymphomas (5%) – most common form in
men >60 years old
 May present only with a testicular mass, mimicking other more
common testicular tumors
 Disease has already disseminated at the time of detecting
 Most common testicular lymphomas in decreasing order of
frequency:
 Diffuse large B cell lymphoma
 Burkitt lymphoma
 EBV-positive extranodal NK/T cell lymphoma
 Has a higher propensity for CNS involvement
MISCELLANEOUS TUMORS OF TUNICA VAGINALIS
 Hydrocele – accumulation of serous fluid causing considerable
enlargement of the scrotal sac detected by transillumination
 Malignant mesotheliomas can also arise from the tunica vaginalis
 Hematocele – indicates the presence of blood, uncommon
condition following trauma or torsion or due to systemic bleeding
disorders
Page 10 of 13
 Chylocele – accumulation of lymph in the tunica and is almost
always found in patients with elephantiasis
 Spermatocele – small cystic accumulation of semen in dilated
efferent ducts or ducts of the rete testis
 Varicocele – dilated vein in the spermatic cord, asymptomatic,
implicated in some men as a contributing factor of infertility
 All can be corrected by surgical repair
Prostate
 Normally weighs approximately 20g
 A retroperitoneal organ encircling the neck of bladder and urethra
and devoid of a distinct capsule
 Divided into four distinct zones or region: peripheral, central,
transitional and periurethral zones
 Most hyperplasias arise in the transitional zone, most carcinomas
originate in the peripheral zone
 Composed of glands lined by a basal layer of low cuboidal
epithelium covered by a layer of columnar secretory cells with
small papillary infolding of the epithelium
 Glands are separated by abundant fibromuscular stroma
 Testicular androgens control growth and survival of prostatic cells
 Castration leads to atrophy of prostate by widespread apoptosis
 Benign nodular enlargements are the most common and occurs
in advanced age
 Prostatic carcinoma is also common in men
INFLAMMATION
 Prostatitis is divided into several categories: acute and chronic
bacterial prostatitis, chronic abacterial prostatitis, and
granulomatous prostatitis
Acute Bacterial Prostatitis
 Results from bacteria similar to those that cause UTIs (e.g. E. coli,
other gram-negative rods, enterococci and staphylococci)
 Organisms become implanted in the prostate by intraprostatic
reflux of urine from the posterior urethra or urinary bladder or
via lymphohematogenous routes from distant foci of infection
 Follows surgical manipulation of the urethra or prostate gland
itself (e.g. catheterization, cystoscopy, urethral dilation or
resection of the prostate)
 Associated with fever, chills and dysuria
 On DRE, the prostate is exquisitely tender and boggy
 Diagnosis is by urine culture and clinical features
Chronic Bacterial Prostatitis
 Difficult to diagnose and treat
 Present with low back pain, dysuria and perineal and suprapubic
discomfort or may be virtually asymptomatic
 Patient often have a history of UTI caused by the same organism
 Diagnosis depends on demonstration of leukocytosis in the
expressed prostatic secretions, along with positive bacterial
cultures
 In most cases, there is no antecedent acute attack, disease
appears insidiously without obvious provocation
 Organs involve is same with ABP
Granulomatous Prostatitis
 Specific (etiologic agent identified) and non-specific
 Most common cause is instillation of BCG within the bladder for
treatment of superficial bladder cancer
 Fungal granulomatous prostatitis is seen in immunocompromised
hosts
 Nonspecific granulomatous prostatitis is relatively common and
represents a reaction to secretions from ruptured prostatic ducts
and acini, (-) bacteria within the tissue
Morphology:
 Acute prostatitis appear as minute, disseminated abscesses or
large coalescent focal areas of necrosis or diffuse edema,
congestion and boggy suppuration of the entire gland
 Biopsy in suspected acute prostatitis is contraindicated as it may
lead to sepsis
 Prostate specimens are diagnosed using terms such as: acute
inflammation, chronic inflammation and not as prostatitis
BENIGN ENLARGEMENT
Benign Prostatic Hyperplasia or Nodular Hyperplasia
 BPH is the most common benign prostatic disease in men >50
years old
 Results from nodular hyperplasia of prostatic stromal and
epithelial cells and often leads to obstruction
 Formation of large, fairly discrete nodule in the periurethral
region of the prostate
 Nodular hyperplasia is not considered to be a premalignant lesion
Incidence
 Seen in 20% of men age 40, increase to 70% by 60 and 90% to 80
 No direct correlation between histologic changes and clinical
symptoms
 50% have detectable enlargement of prostate and only 50% of
these develop clinical symptoms
Etiology and Pathogenesis
 Hyperplasia stems from impaired cell death resulting in the
accumulation of senescent cells in the prostate
 Androgens not only increase cellular proliferation but also inhibit
cell death
 Dihydrotestosterone (DHT) is formed in the prostate from
testosterone through the enzyme called type 2 5α-reductase
(almost entirely found in stromal cells and few basal cells)
 Stromal cells are responsible for androgen-dependent prostatic
growth
 Type 1 5α-reductase is located in the liver and skin and may act by
endocrine mechanism
 DHT binds to nuclear androgen receptor (AR) present in both
stromal and epithelial prostate cells, stimulating transcription of
androgen-dependent genes including growth factors and
receptors
 Most important growth factors: FGF, TGF-β
Morphology
 Prostate weights 60-100gm
 Originates almost exclusively in the inner aspect of the prostate
(transition zone) where epithelial nodules arise
Page 11 of 13
 Encroach laterally to the walls of the urethra to compress it to a
slit like orifice
 Median lobe hypertrophy – enlargement projection into the floor
of the urethra as a hemispheric mass beneath the mucosa of the
urethra
 Nodules that contains mostly glands are yellow-pink and soft, and
exude a milky white prostatic fluid
 Nodules with fibromuscular stroma are pale grey and though and
do not exude fluid and less clearly demarcated
 Glandular proliferation takes the form of aggregations of small to
large cystically dilated glands lined by an inner columnar and
outer cuboidal or flattened epithelium
Clinical Features
 Major clinical problem is urinary obstruction which stems from
increased size and smooth muscle contraction
 Increased resistance to urinary outflow leads to bladder
hypertrophy and distention, accompanied by urine retention
 Increased urinary frequency, nocturia, difficulty in starting and
stopping the stream of urine, overflow dribbling, dysuria and
increased risk of bacterial infection
 Mild cases are treated by decreasing fluid intake before bedtime,
moderate intake of alcohol and caffeine and timed voiding
 Common medications: α-blockers, 5-α-reductase inhibitors
 Transurethral resection of the prostate (TURP) is the gold
standard for reducing symptoms
 Alternative procedures: high-intensity focused ultrasound, laser
therapy, hyperthermia, transurethral electrovaporization,
transurethral needle ablation using radiofrequency
TUMORS
Adenocarcinoma
 Most common form of cancer on men
 Very aggressive lethal cancers to incidentally discovered clinically
insignificant cancers
Incidence
 Common in men older than 50
 Common in Asians and most frequent among blacks
Etiology and Pathogenesis
 Age, race, family history, hormone levels and environmental
influences are considered factors
 Dietary factors: charred red meat, lycopenes, soy products and
vitamin D
 Androgens play an important role in prostate cancer
 X-linked AR gene contains a polymorphic sequence composed of
repeats of the codon CAG (glutamine)
 Kennedy disease – neurodegenerative disorder characterized
by large expansion of CAG repeats
 The length of repeats is inversely related to rate at which prostate
cancer develops
 The importance of androgens in maintaining the growth and
survival of prostate cancer cells are seen in therapeutic effects of
castration or treatment with antiandrogens inducing disease
regression
 Most tumors become resistant to androgen blockage,
mechanisms include:
  Acquisition of hypersensitivity of low levels of androgen (AR  α-methylacyl-coenzyme A-racemase (AMACR) is up-regulated in
gene amplification) prostate cancer (sensitivity is 82%-100%), must be used in
 Ligand-dependent AR activation (splice variants that lack the conjunction with routine hematoxylin and eosin-stained sections
ligand binding domain)
 Mutations in AR that allow it to be activated by non- Grading and Staging
androgen ligands  Best prognostic predictors
 Epigenetic changes that activate alternative signaling  Prostate cancer uses the Gleason system which stratifies
pathways (increased activation of PI3K/AKT signaling the cancer into five grades:
pathway)
 Occurs at an earlier age with familial history
 Germ line mutation of BRCA2 and HOXB13 have increased risk
 Most common structural genetic change is chromosomal
rearrangement that juxtapose the coding sequence of an ETS
family transcript factor gene (ERG or ETV1) next to TMPRSS2
promoter
 Genomic deletions (PTEN, RB and TP53) and amplifications
(androgen receptor gene locus and 8q24 locus containing MYC
oncogenes) are more common than point mutations involving
oncogenes
 Most common epigenetic alteration is hypermethylation of
glutathione S-transferase (GSTP1) gene located on chromosome
11q13
 Other silenced genes: RB, CDKN2A, MLH1, MSH2 and APC
 Prostatic intraepithelial neoplasia (PIN) – precursor lesion
 PIN and cancer predominate in the peripheral zone
 Higher frequency and extent of PIN is often seen in cancer  Staging uses the TNM system:
 PIN glands are surrounded by a patchy layer of basal cells
and an intact basement membrane

Morphology
 70% arise in the peripheral zone, classically posterior in location
 Neoplastic tissue is gritty and firm, but when embedded within
the prostatic substance, it may be extremely difficult to visualize
and be more readily apparent on palpation
 Extension most commonly involves periprostatic tissue, seminal
vesicles, and base of the bladder
 Metastases spread via the lymphatics to the obturator nodes and
the para-aortic nodes
 Hematogenous spread occurs chiefly to the bones (osteoblastic)
and may spread to the viscera (exemption rather than the rule)
 Bone involvement in descending order: lumbar spine,
proximal femur, pelvis, thoracic spine and ribs
 Most lesions are adenocarcinomas that are well defined,
demonstrable glandular patterns
 Lined by single uniform layer of cuboidal or low columnar
epithelium and are more crowded and lack branching and
papillary infolding
 Outer basal cell layer typical of benign glands is absent
 Cytoplasm ranges from pale-clear to amphophilic appearance,
nuclei are large and contain one or more large nucleoli
 Pleomorphism is not marked, mitotic figures are uncommon
 Biopsy is challenging due to scant amount of tissue available in
needle biopsies and admixed with numerous benign glands
 Specific biopsy findings: perineural invasion
 Diagnosis is made based on architectural, cytologic and ancillary
findings

Page 12 of 13
Clinical Course
 Stage T1a found on TURP do not progress when followed for 10 or
more years
 Stage T1b are more ominous and are treated, mortality rate is
20% if untreated
 Localized prostatic CA is asymptomatic and discovered by
detection of nodule on DRE or elevated serum PSA (insensitive
and organ specific but not cancer specific)
 PSA Density – ratio between the serum PSA and volume of
prostate gland
 PSA Velocity – rate of change in PSA value with time
 Use of age specific reference ranges
 Ratio of free and bound PSA in the serum
 Finding of osteoblastic metastases by skeletal surveys or the the
much more sensitive radionuclide bone scan is is diagnostic of
prostatic cancer
 Transrectal needle biopsy is required for confirmatory diagnosis
 DRE and Transrectal US has low sensitivity and unspecific
 Biomarkers:
 PSA (prostate specific antigen)
 PCA3 (noncoding RNA which is overexpressed in 95% of
prostate CA)
 Combination of PCA3 with screening of urine for TMPRSS2-ERG
fusion DNA have increased sensitivity and specificity compared to
PSA screening alone
 Most common treatment for localized cancer is radical
prostatectomy
 Alternatives include external-beam radiation therapy or
interstitial radiation therapy

Miscellaneous Tumors and Tumor-like Conditions

 Same mesenchymal tumors that involve the bladder may also
manifest in the prostate
 Existence of unique mesenchymal tumors of the prostate derived
from the prostatic stroma

Ductal Adenocarcinomas
 CAs arising in the peripheral ducts follow the same fashion as
prostatic cancer
 While in the periurethral ducts may follow urothelial cancer
(causing hematuria and obstruction), poor prognosis
 Squamous differentiation following hormone therapy de novo

Colloid Carcinoma of the Prostate

 Abundance mucinous secretions

Small-Cell Cancer
 Neuroendocrine carcinoma
 Most aggressive variant, rapidly fatal

Urothelial Cancer
 Most common tumor to secondarily involve the prostate
 Two distinct patterns:
 Large invasive urothelial cancers can directly invade from
the balder into the prostate.
 Carcinoma in situ of the bladder can extend into the “Ziry kivio darilaros issa, se z hon suvio perzo vaedar issa”
prostatic urethra and down into the prostatic ducts and (He is the prince that was promised, and he is the song of fire and ice)
acini

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