Pathology of Lower

Urinary Tract and Male

Genital Tract
Dr. Kinde Bussa (MD, Pathologist)

Kinde Bussa (MD, Pathologist) 6/28/2022 1

PENIS AND SCROTUM
Congenital Anomalies
 HYPOSPADIAS- Urethra opens onto ventral
surface of penis or scrotum; 1 in 300 live
male births
 EPISPADIAS- Urethra opens onto dorsal
surface of penis
 Penopubic epispadias is most common,
associated with urinary incontinence
 Both types are associated with undescended
testis, urinary malformation, obstruction or
infection
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Phimosis
 Orifice of foreskin is too small to permit its
retraction
 It could be congenital or repeated infections
=> scarring

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Paraphimosis
 Forceful retraction of phimotic foreskin over
glans may cause marked swelling which blocks
replacement of foreskin => painful & urinary
retention

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Inflammatory Lesions
 BALANOPOSTHITIS
 Infection of glans and foreskin
 20 to bacteria & fungi
 Common in uncircumcised newborns or men
with poor hygiene

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Sexual Transmitted Infections
 Bacterial: Chancroid, Granuloma inguinale,
Lymphogranuloma venereum, Syphilis
 Viruses: Herpes simplex virus, Molluscum
contagiosum

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PENILE TUMORS
CONDYLOMA ACUMINATUM
 Benign tumor 20 to HPV 6 and 11
 Sexually transmitted, often near coronal sulcus
and inner surface of foreskin
 Recurs but does not evolve into invasive cancer
 Gross: papillary, fungating, wart-like, often
multiple lesions, 1 mm or larger

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 Micro: complex papillary pattern with central
fibrovascular cores, hyperplastic epithelium
with preservation of orderly maturation;
koilocytosis (vacuolization of cells of prickle
cell layer near surface of papillae)

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Condyloma acuminatum

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Condyloma acuminatum

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Koilocytosis = HPV infection

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Penile Intraepithelial Neoplasia
(PeIN)
 Various classification schemes, similar to
cervix
 High grade/severe dysplasia & PIN III are
synonymous with carcinoma in situ
 75-100% are associated with HPV
 Most of PIN are associated with invasive
squamous cell carcinoma

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Carcinoma In Situ:
 All forms below are associated with HPV 16
(80% of cases)
1. Bowen’s disease (gray white lesion on the
shaft)
2. Erythroplasia of queyrat
3. Bowenoid papulosis

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Invasive squamous carcinoma

 40-70 years, median age 58 years

 10-20% of Ca. in men in Africa
 Circumcision confers protection => rare if
circumcision at birth, more common if late
circumcision (after age 10); extremely rare in
Jews & Muslems
 Risk factors: paraphimosis, phimosis, HPV 16
or 18, smoking, etc
 HPV frequency varies by histologic type
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 Most arise from glans or inner foreskin near
coronal sulcus
 Gross: exophytic or endophytic (epithelial
thickening with gray fissures in mucosa, later
ulcerated papule)
 Pattern of growth:
 Papillary, cauliflower like fungating mass
 Flat: Epithelial thickening with graying &
fissuring as well as ulcerating
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Penile Carcinoma

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Micro:
 Squamous cell carcinoma; Graded as 1-3
 Keratinizing SCC (Most common)
 Verrucous carcinoma: low malignant (rarely
metastatic)
 Not related to HPV infection
 No cytological atypia, pushing type of invasion
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Penile: squamous cell carcinoma

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Penile: squamous cell carcinoma

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Metastases
 Inguinal and pelvic lymph nodes
 Liver, lung, heart or bone
 15% have metastases at diagnosis

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Prognosis
5 yr survival related to nodal involvement
 66% (not involved) vs. 27% (involved)
 Treatment: local resection, partial/total
penectomy

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SCROTUM
 Non-neoplastic lesions of scrotum
 Fat necrosis
 Idiopathic calcinosis
 Massive localized lymphedema in morbidly
obese patients

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Scrotal calcinosis

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Lesions of tunica vaginalis
 Hydrocele – accumulation of clear serous fluid
 Hemtocele – blood
 Chylocele – lymph
 Spermatocele – accumulation of semen in dilated
efferent ducts
 Varicocele – dilated vein in the spermatic cord

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 Neoplastic lesions of scrotum
 Leiomyoma: Most common benign mesenchymal
tumor
 Paget’s disease
 Squamous cell carcinoma: associated with
chimney sweeps, paraffin workers, tar workers,
cotton mill workers

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Testis and Epididymis

 Testiscommonly affected by tumors

 Epididymis – major lesions are inflammatory

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Congenital anomalies
Cryptorchidism
 Synonymous with undescended testis
 In most patients, the undescended testis is
palpable in the inguinal canal
 Unilateral in most cases
 Histologic changes begin as early as 2 years of age

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 Arrest in development of germ cells and
hyalinization and thickening of basement
membrane
 Increase in interstitial stroma
 Consequences may be Tubular atrophy, Prone to
trauma, Sterility, Testicular cancer

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Inflammations

 Non specific epididymitis and Orchitis

 Commonly related to infection in the urinary
tract or STDs
 Granulomatous (autoimmune) orchitis
 Diffuse, and confined to the seminiferous
tubules

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 Specific inflammations
 Gonorrhea
 Mumps
 Tuberculosis – invariably begins in the
epididymis and may spread to the testis
 Syphilis – testes involved first

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Vascular disturbances

Torsion
 Twisting of the spermatic cord
 Two major types :Neonatal and adult torsion
 Neonatal torsion – no associated anatomic defect
 Adult torsion- bilateral anatomic defect in which
the testis has increased mobility

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 Adult torsion is featured by sudden onset of pain
 From intense congestion to widespread
extravasation of blood
 Late stages, hemorrhagic infarction occurs
 If untwisted with in 6 hours of torsion, the testis
may remain viable

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  Testicle, torsion - Gross

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Testicular tumors

 Germ cell tumors- highly aggressive

 Non-germ cell tumors – generally benign
 95% arise from germ cells

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Classification
 Germ cell tumors (GCT)
 Seminoma
 Embyonal carcinoma
 Yolk sac tumor
 Choriocarcinoma
 Teratoma
 Sex cord-stromal tumors
 Leydig cell tumor
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 Sertoli cell tumor

Germ cell tumors (GCT)

Histogenesis
 Neoplastic germ cells may differentiate along
gonadal lines to give rise to seminoma or
transform in to a totipotential cell population that
give rise to non seminomatous tumors

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 Totipotential cells may
 Remain undifferentiated to form embryonal
carcinomas
 May differentiate along extraembryonal lines to
form yolk sac tumors or choriocarcinomas
 Teratoma result from differentiation of
embryonic carcinoma cells

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Pathogenesis
 Predisposing factors
 Cryptorchidism
 Testicular dysgenesis – disorders of testicular
development like klinefelter syndrome,
testicular feminization

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Seminoma
 Most common type of germinal tumor (50%)
 Uniform population of cells
 Peak in the thirties
 An identical tumor in the ovary is called
Dysgerminoma

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 Morphology
 Produce bulky mass
 Gray white devoid of hemorrhage and necrosis
 Sheets of uniform cells divided into poorly
demarcated lobules by delicate septa of fibrous
tissue

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  Classic seminoma cell
 Large and round to ployhedral and has a
distinct cell membrane
 Clear or watery appearing cytoplasm
 Large central nucleus with one or two
prominent nucleoli
 Septa usually infiltrated by T-lymphocytes

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  Testicle, classic seminoma - Gross, cut surface
 Testis, classic seminoma - High power

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Embryonal carcinoma
 Occurs in the 20 to 30 year age group
 More aggressive than seminomas
 Often variegated – foci of hemorrhage and
necrosis
 Cells grow in alveolar or tubular patterns,
sometimes with papillary convolutions
 Lack well formed glands
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 The neoplastic cells have an epithelial
appearance and are large and anaplastic, with
hyperchromatic nuclei having prominent nucleoli
 Cell borders are usually indistinct
 Mitotic figures and tumor giant cells are frequent

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  Testis, nonseminomatous (mixed) germ cell tumor - Gross, cut surface
 Testis, embryonal carcinoma with syncytiotrophoblasts - Medium power
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Yolk Sac tumor
 Also known as infantile embryonal carcinoma or
endodermal sinus tumor
 Most common testicular tumor in up to 3 years of
age
 Yellow white, mucinous

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 Shciller – Duval bodies (structures resembling
endodermal sinuses) in 50%
 Mesodermal core with a central capillary and a
visceral and parietal layer of cells resembling
primitive glomeruli
 Presence of AFP is highly characteristic

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  Testis, yolk sac tumor (endodermal sinus tumor) - High power

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Choriocarcinoma
 Highly malignant
 Composed of both cytotrophoblastic and
syncytiotrophoblastic cells
 Often do not cause testicular enlargement
 HCG is easily demonstrated
 Rapidly growing with extensive hemorrhage and
necrosis
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Teratoma
 Neoplastic germ cells differentiate along multiple somatic
cell lineages and form firm masses that often contain
cysts and recognizable areas of cartilage
 Occur at any age from infancy to adult life
 Pure forms of teratoma are fairly common in infants and
children
 Elements may be mature or immature (sharing histologic
features with fetal or embryonal tissues).
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 In prepubertal males, teratomas are benign,
whereas the majority of teratomas in
postpubertal males are malignant, being
capable of metastasis regardless of whether
they are composed of mature or immature
elements.

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 Clinical feature of testicular tumors

Seminomatous GCT NSGCT

 Presentation Localized - Advanced
 Metastases Lymphatic -Hematogenous
 Therapy Radiosensitive - Radioresistant
 Prognosis Better - Poor prognosis
-More aggressive

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Prostate

 Fibromuscular and glandular organ

 Surrounds the prostatic urethra

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Inflammation

 Acute bacterial prostatitis

 From bacteria that cause urinary tract infection
 Fever, chills, dysuria
 On rectal examination, prostate tender and
boggy

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 Chronic bacterial prostatitis
 Low back pain, dysuria, perineal and suprapubic
discomfort
 Recurrent urinary tract infection

 Chronic abacterial prostatitis

 No history of recurrent urinary tract infection
 Bacterial cultures are negative
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Granulomatous prostatitis- after BCG
treatment for bladder cancer, fungal
infections

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Benign prostatic hyperplasia (BPH)

 Common in men over age 50

 Etiology and pathogenesis
 Related to the action of androgens

 Prepubertal castration prevents the development of

nodular hyperplasia

 Dihydrotestosterone (DHT) is the ultimate mediator of

prostatic growth
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Morphology
 Originates in the transitional zone

 Epithelial and fibromusculal stromal proliferation

 Variable sized glands lined two layers of ductal

and basal cells

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  Prostate gland, nodular hyperplasia - Medium power
 Prostate
Kinde Bussa (MD, Pathologist)
gland, nodular hyperplasia - Gross, cut surface
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Clinical course
 Compression of the urethra with difficulty in
urination
 Frequency, nocturia, difficulty in starting and
stopping stream of urine, overflow dribbling,
dysuria
 Retention of urine in the bladder with subsequent
distension and hypertrophy of the wall
 Nodular
Kinde Bussa (MD, Pathologist)
hyperplasia not considered to be
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Adenocarcinoma

A disease of men over age 50

 Etiology – androgens are believed to play a role

 Inhibition of these tumors can be achieved by
orchiectomy

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 Morphology
 Arises in the peripheral zone of the gland,
classically in a posterior location, rendering it
palpable on rectal examination
 Neoplastic tissue is gritty and firm
 Hematogenous spread chiefly occurs to the
axial skeleton and is osteoblastic

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 Histologically,
most lesions are adenocarcinomas
that produce glands
 Neoplastic glands are more crowded and smaller
 Glands lined by a single uniform layer of cuboidal
or low columnar epithelial cells with enlarged
nuclei and prominent nucleoli

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  Prostate gland, adenocarcinoma - High power
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  Prostate gland, adenocarcinoma - Gross, cut surface
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 Spine, prostate carcinoma metastatic to vertebrae -
Grading and staging
 Grading – the Gleason system is the best known
 Grade 1 represents the most well
differentiated tumors, in which the neoplastic
glands are uniform and round in appearance

 Grade 5 tumors show no glandular

differentiation, and the tumor cells infiltrate
the stroma in the form of cords, sheets and
nests
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Prostatic carcinoma

 Grade – Gleason score

 Predominant pattern + Secondary pattern
 Best score – 2, Worst score – 10

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 Grading is of particular importance in prostate
cancer because it is the best marker, along with
the stage, for predicting prognosis

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Clinical course
 Clinically localized disease
 No urinary symptoms and the lesion is
discovered by the finding of a suspicious nodule
on PR or elevated serum PSA

 Urinary symptoms occur late since cancers arise

peripherally

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 Prostate specific antigen (PSA) – is organ specific
but not cancer specific
 Serum PSA levels by itself can not be used for
detection of early cancer

 Serial measurements of PSA are of great value

in assessing the response to therapy

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Urinary bladder
Congenital anomalies

 Diverticula
 Exstrophy
Presence of a developmental failure in the
anterior wall of the abdomen and in the
bladder, so that the bladder either
communicates directly through a large
defect with the surface of the body or lies
as an opened sac
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 Vesico ureteral reflux

Inflammation

 Acute and chronic cystitis

 Women are more likely to develop as a result of
their shorter urethra
 Common etiologic agents- coliform bacterias
 Predisposing factors include bladder calculi,
urinary obstruction, instrumentation, immune
deficiency
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 Cystitis clinically characterized by
1.Frequency
2.Suprapubic pain
3.Dysuria
 Associated signs may be fever, chills and
general malaise
 Antecedent to pyelonephritis
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Neoplasms

 95% of tumors are epithelial origin

 Most epithelial tumors composed of transitional
type cells

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Urothelial ( Transitional cell) tumors

 90% of bladder tumors

 May be seen at any site where there is urothelium
 Two distinct precursor lesions
 Non invasive papillary urothelial neoplasms
 Flat urothelial carcinoma ( carcinoma insitu)

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 Morphology – it can be papillary or flat
Papillary urothelial neoplasms include
Papillomas
Papillary urothelial neoplasms of low
malignant potential
Low grade papillary urothelial carcinomas
High grade papillary urothelial
carcinomas
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 Flat carcinoma insitu- cytologically high
grade malignant urothelial cells

May have invasive component

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 Epidemiology and pathogenesis
 Carcinoma of the bladder more common in
men, industrialized nations, urban areas
 Male to female ratio is 3:1
 Contributors to transitional cell carcinoma
Cigarette smoking, Industrial exposure to
arylamines, Long term use of analgesics,
cyclophosphamide, Radiation
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 Clinical course
 Painless hematuria
 Frequency, urgency, dysuria
 Pyelonephritis or hydronephrosis may follow
 Recurrence after excision is common

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SEXUALLY TRANSMITTED DISEASES

Syndromes
 Urethral discharge
 Vaginal discharge
 Pelvic inflammatory disease (PID)
 Genital ulcer
 Inguinal bubo
 Neonatal conjunctivitis
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