PATHOLOGY OF MALE

GENITAL SYSTEM
• PENIS
• SCROTUM, TESTIS, & EPIDIDYMIS
• PROSTATE
 PENIS
• MALFORMATIONS
• INFLAMMATORY LESIONS
• NEOPLASMS
MALFORMATIONS OF THE PENIS

Abnormal location of urethral orifice

along penile shaft
– Hypospadias (ventral aspect)
• Most common (1/300 live male births)
– Epispadias (dorsal aspect)
Hypospadias
Epispadias
HYPOSPADIAS AND EPISPADIAS
– May be associated with other genital
abnormalities
• Inguinal hernias
• Undescended testes
– Clinical consequences
• Constriction of orifice
• Urinary tract obstruction
• Urinary tract infection
• Impaired reproductive function
INFLAMMATORY LESIONS OF
THE PENIS
• Sexually transmitted diseases
• Balanitis (balanoposthitis)
– Inflammation of the glans (plus prepuce)
– Associated with poor local hygiene in
uncircumcised men
• Smegma
– Distal penis is red, swollen, tender
• +/- Purulent discharge
INFLAMMATORY LESIONS OF
THE PENIS
• Phimosis
– Prepuce cannot be easily retracted
over glans
– May be congenital
– Usually associated with balanoposthitis
and scarring
– Paraphimosis (trapped glans)
• Urethral constriction
INFLAMMATORY LESIONS OF
THE PENIS
• Fungal infections
– Candidiasis
• Especially in diabetics
• Erosive, painful, pruritic
• Can involve entire male external
genitalia
 NEOPLASMS OF THE PENIS
• SQUAMOUS CELL CARCINOMA (SCC)
– EPIDEMIOLOGY
• UNCOMMON – LESS THAN 1 % OF CA IN US MEN
• UNCIRCUMCISED MEN BETWEEN 40 AND 70
– PATHOGENESIS
• POOR HYGIENE, SMEGMA
• HUMAN PAPILLOMA VIRUS (16 AND 18)
• CIS FIRST, THEN PROGRESSION TO INVASIVE
SQUAMOUS CELL CARCINOMA
Squamous Cell Carcinoma
 SCC OF THE PENIS
• Clinical course
– Usually indolent
– Locally invasive
– Has spread to inguinal lymph nodes in 25% of
cases at presentation
– Distant mets rare
– 5 yr survival
• 70% without ln mets
• 27% with ln mets
 LESIONS INVOLVING THE
SCROTUM
• Inflammation
– Tinea cruris (jock itch)
• Superficial dermatophyte infection
• Scaly, red, annular plaques, pruritic
• Inguinal crease to upper thigh
• Squamous cell carcinoma
– Historical significance
– Sir percival pott, 18th century english
physician
– Chimney sweeps
 LESIONS INVOLVING THE
SCROTUM
• Scrotal enlargement
– Hydrocele - most common cause
• Accumulation of serous fluid within tunica
vaginalis
• Infections, tumor, idiopathic
– Hematocele
– Chylocele
• Filiariasis - elephantiasis
– Testicular disease
Hydrocele
LESIONS OF THE TESTES

• CONGENITAL
• INFLAMMATORY
• NEOPLASTIC
 CRYPTORCHIDISM AND
TESTICULAR ATROPHY

• Failure of testicular descent

• Epidemiology
– About 1% of males
– Right > left, 25% bilateral
• Pathogenesis
– Hormonal abnormalities
– Testicular abnormalities
– Mechanical problems
 Phase of testicular descent
• Transabdominal phase (arrested in 5-
10%)
– Located in lower abdomen or pelvis brim
– Controlled by mullerian-inhibiting
substance
• Inguinoscrotal phase (common finding)
– Decent to scrotal sac
– Androgen-dependent
Atrophic testes
secondary to
cryporchidism
 CRYPTORCHIDISM AND
TESTICULAR ATROPHY
• Clinical course
– When unilateral, may see atrophy in contralateral
testis
– Sterility
– Increased risk of malignancy (4-10x)
– Orchiopexy
• May help prevent atrophy
• May not decrease risk of malignancy
OTHER CAUSES OF TESTICULAR
ATROPHY
• Chronic ischemia
• Inflammation or trauma
• Hypopituitarism
• Excess female sex hormones
– Therapeutic administration
– Cirrhosis
• Malnutrition
• Irradiation
• Chemotherapy
 INFLAMMATORY LESIONS OF
THE TESTIS
• Usually involve the epididymis first
• Sexually transmitted diseases
• Nonspecific epididymitis and orchitis
– Secondary to UTI (urinary tract infection)
• Bacterial and non-bacterial
– Swelling, tenderness
– Acute inflammatory infiltrate
 INFLAMMATORY LESIONS OF
THE TESTIS
• Mumps
– 20% of adult males with mumps
– Edema and congestion
– Chronic inflammatory infiltrate
– May cause atrophy and sterility
• Tuberculosis
– Granulomatous inflammation
– Caseous necrosis
• Autoimmune granulomatous orchitis
– Rare finding in middle aged men
 TESTICULAR NEOPLASMS
• Epidemiology
– Most important cause of painless
enlargement of testis
– 2/100,000 males, whites > blacks (us)
– Increased frequency in siblings
– Peak incidence 15-34 yrs
– Most are malignant
– Associated with germ cell maldevelopment
• Cryptorchidism
• Testicular dysgenesis(xxy)
TESTICULAR NEOPLASMS
• Pathogenesis
– 95% arise from germ cells
• ISOCHROMOSOME 12, i(12p), IS A
COMMON FINDING
• Intratubular germ cell neoplasms
– Rarely arise from sertoli cells or leydig cells
• These are often benign
– Lymphoma
• Men > 60 yo
 WHO CLASSIFICATION OF
TESTICULAR TUMORS
• ONE HISTOLOGIC PATTERN (40%)
– SEMINOMAS (30%)
– EMBRYONAL CARCINOMA
– YOLK SAC TUMOR
– CHORIOCARCINOMA
– TERATOMA
• MULTIPLE HISTOLOGIC PATTERNS
(60%)
– EMBRYONAL CA + TERATOMA
– CHORIOCARCINOMA + OTHER
– OTHER COMBINATIONS
 HISTOGENESIS OF TESTICULAR
NEOPLASMS (PEAK INCIDENCE)
GERM CELL PRECURSOR

GONADAL TOTIPOTENTIAL
DIFFERENTIATION DIFFERENTIATION
(NONSEMINOMA)
SEMINOMA EMBRYONAL CA
(40-50 Y) (UNDIFFERENTIATED) SOMATIC
(20-30 Y) DIFFERENTIATION

TROPHOBLASTIC YOLK SAC TERATOMA

DIFFERENTIATION DIFF (ALL AGES)

CHORIOCARCINOMA YOLK SAC TUMOR MATURE

(20-30 Y) (< 3 Y)
hCG + AFP + IMMATURE
MALIGNANT TX
Seminoma, with focal hemorrhage and
necrosis
Normal testicular tissue
Seminoma
Seminoma

Syncytiotrophoblast
Dermoid Cyst
Immature Teratoma

With Embryonal Carcinoma

 CLINICAL COURSE OF
TESTICULAR TUMORS
• Usually present with painless enlargement of
testis
• May present with metastases
– Nonseminomas (more common)
• Lymph nodes, liver and lungs
– Seminomas
• Usually just regional lymph nodes
• TUMOR MARKERS (hCG AND AFP)
• Treatment success depends on histology and
stage
– Seminomas very sensitive to both radio- and
chemotherapy
DISEASES OF THE PROSTATE

• Prostatitis
• Nodular hyperplasia
• Cancer
 PROSTATITIS
• Acute bacterial prostatitis
• Chronic bacterial prostatitis
• Chronic abacterial prostatitis
 ACUTE BACTERIAL
PROSTATITIS
• Etiology
– Same organisms that cause UTI
• E coli, OTHER GNR
• Pathogenesis
– Organisms ascend from urethra and urinary
bladder
– Rarely, hematogenous spread
 ACUTE BACTERIAL
PROSTATITIS
• MORPHOLOGY
– ACUTE INFLAMMATION, ESPECIALLY IN
THE GLANDS, WITH MICROABSESSES
– CONGESTION, EDEMA
• CLINICAL COURSE
– DYSURIA, FREQUENCY, LOW BACK PAIN,
PELVIC PAIN
– ENLARGED, EXQUISITELY TENDER
– +/- FEVER OR LEUKOCYTOSIS
– USUALLY RESOLVES WITH WITH AB RX
 CHRONIC PROSTATITIS
• Etiology
– May follow acute prostatitis
– May develop insidiously
– Culture positive (bacterial)
• Same organisms that cause acute prostatitis
– Culture negative (abacterial)
• May be related to
– Chlamydia trachomatis
– Ureaplasma urealyticum
• Most common form of chronic prostatitis
 CHRONIC PROSTATITIS
• Morphology
– Lymphocytic infiltrate
– Neutrophils and macrophages
– Some evidence of tissue destruction
• Clinical course
– Similar to ap
• Less acute symptoms
• More resistant to ab rx
– Cbronic prostatitis often associated with
recurrent UTI
PROLIFERATIVE LESIONS OF THE PROSTATE
PERIURETHRAL
AND URETHRA
TRANSITIONAL
ZONES PERIPHERAL
ZONE
NORMAL PROSTATE

NODULAR HYPERPLASIA CARCINOMA

 NODULAR HYPERPLASIA
• Other terms used
– Glandular and stromal hyperplasia
– Benign prostatic hypertrophy (hyperplasia)
• Epidemiology
– Occurs in 20% of men over 40
– Occurs in 90% of men over 70
PATHOGENESIS OF NODULAR
HYPERPLASIA
• Proliferation of both epithelial and stromal
elements
• Both androgens and estrogens may play a role
– Not seen in males castrated before
puberty
– Inhibitors of testosterone metabolism
useful in treatment
– Relative increase in estrogens in older
men may increase dht receptors in
prostate
CLINICAL COURSE OF NODULAR
HYPERPLASIA

• Symptoms occur in only 10% of men with

nodular hyperplasia
• Hesitancy
• Urinary retention
– Urgency, frequency, nocturia, uti
• Treatment
– Medical
– Surgical
• Common cause for elevated prostate specific
antigen (PSA)
 CARCINOMA OF THE
PROSTATE
• Epidemiology
– Most common visceral cancer
• About 70/100,000 men in USA
• 200,000 new cases/yr in USA
• 20% are lethal
– Second most common cause of cancer death
in men
– Peak incidence of clinical cancer is 65-75 yo
– Latent CA is even more prevalent
• >50% in men > 80 yo
 Carcinoma of the prostate
• Pathogenesis
– Hormonal factors
• Does not occur in eunuchs
• Orchiectomy and/or estrogen treatment inhibits
growth
– Genetic factors
• Increased risk in first order relatives (2-time
increased risk)
• Blacks > whites (symptomatic ca)
– Environmental factors
• Geographic differences in incidence of clinical
cancer (not of latent ca)
• Change in incidence with migration
 Molecular mechanisms
• Increased CAG repeat in promotor of
AR gene
– Long repeat-> decreased risk (Asian)
• ETS gene rearrangement under control
of TMPRSS2 promoter gene -> andorgen
reponsive
• Hypermethylation of GSTP1 promoter
• PTEN, Rb, p16, MLH1, MSH2 and APC
 Molecular markers
• PSA
• EZH-2 -> suppress e-cadherin
• AMACR
• PCA3 is a regulatory RNA
 Precursor lesion
• PIN = High grade Prostate Intraepithelial
Neoplasia
• Found in 80% of prostate cancer cases
• Also have ETS gene rearrangement
(similar to prostate cancer)
PIN (High Grade Prostate
Intraepithelial Neoplasia)
CARCINOMA OF THE PROSTATE
• Clinical course
– Often clinically silent
– Digital rectal exam (dre)
– Prostate specific antigen (PSA)
• > 4 ng/ml IN PERIPHERAL BLOOD
• Free psa < 25%
– Transrectal ultrasound
– Needle biopsy
– Prostatism (like bph)
– Metastases
• Osteoblastic
– Treatment- surgery, radiation, hormones,
chemo
 PSA as the screening test
• Increased serum PSA
– Normal PSA is varies with age
• 2.5 ng/ml in 40-49 year-old man
• 3.5 ng/ml in 50-59 year-old man
• 4.5 ng/ml in 60-69 year-old man
• 6.5 ng/ml in 70-79 year-old man
• PSA velocity
– More than 0.75 ng/ml per year
• Free/total PSA
– Most PSA bound to alpha1-
antitrypsin
– >25% ->low risk of cancer
– <10% -> high risk of cancer
 Diagnostic procedures in
suspected cases (high PSA)
• Digital rectal examination (lack
sensitivity)
• Transrectal ultrasound
• Transperineum needle biopsy (most
recommended)
Prostate cancer
Needle bx of prostate
CARCINOMA OF THE PROSTATE

• Staging
A (T1) MICROSCOPIC ONLY
B(T2) MACROSCOPIC (PALPABLE)
C(T3 &T4) EXTRACAPSULAR
D(N1-3,M1) METASTATIC
• Prognosis dependent on stage and histologic
grade
– 90% 10 yr survival for a and b
– 10-40% 10 yr survival for c and d
 Grading
• Gleason score
– Grade varies from 1-5
– Two number and the sum
– First number indicates the grade of the
dominant pattern
– Second number indicates the secondary
pattern
– Example: 2+2=4, 3+2=5
• Grade 1 = well-differentiated
adenocarcinoma with well-defined
border
• Grade 5 = Poorly differentiation without
gland formation