1. The Male Genital System pathology

2. The Male Genital System
Penis
scrotum and testes
prostate

3. Disease Categories Malformations Inflammatory conditions & STDs
Neoplasms

4. Penis Malformations
Hypospadias
epispadias

5. Hypospadias more common (1 in 250 live male births)
urethral opening along ventral aspect
urinary tract obstruction
risk of infections
other anomalies:
Inguinal hernias
UDTs

7. Epispadias Orifice on dorsal aspect of penis
Lower urinary tract obstruction
Urinary incontinence
Commonly associated with bladder extrophy.

9. Penis Inflammatory Lesions
balanitis :
glans penis
balanoposthitis :
glans penis & prepuce by smegma
Phimosis
paraphimosis
congestion, swelling & pain
Urinary retention
Candidiasis

11. Neoplasms of the Penis >95% originate from squamous epithelium
Higher rates in developing countries
Most cases are uncircumcised & older than 40
Pathogenesis:
Poor hygiene (smegma)
Smoking
HPV 16 and 18

12. Intraepithelial neoplasia (carcinoma in situ)
Three clinical variants :
1-Bowen disease
Older uncircumcised males
Solitary, plaquelike lesion on shaft
Malignant cells throughout epidermis
No invasion of stroma
Invasive SCC in 33% .

13. Bowen disease (carcinoma in situ)
Hyperchromatic
Dysplastic
Dyskeratotic
epithelial cells
scattered mitoses

14. Intraepithelial neoplasia (carcinoma in situ)
2-Erythroplasia of Queyrat
Erythematous patch on glans

15. Intraepithelial neoplasia (carcinoma in situ)
3-Bowenoid papulosis
young, sexually active males
multiple reddish brown papules
on glans
most often transient
rare progression to carcinoma in immunocompetent patients

16. Squamous cell carcinoma of penis
gray, crusted, papular lesion
on glans penis or prepuce
infiltrates underlying tissue
indurated, ulcerated lesion
irregular margins
keratinizing SCC with infiltrating margins

17. Glans penis deformed by a firm, ulcerated, infiltrative mass

18. Gray, crusted, papule on glans or prepuce that infiltrates underlying tissue

19. Most case are indolent
locally infiltrative
Regional metastases in inguinal lymph nodes (25% )
Distant metastases relatively uncommon
Overall 5-year survival rate averages 70%

20. Verrucous carcinoma a variant of SCC papillary architecture
less striking cytologic atypia
rounded, pushing deep margins

21. SCROTUM
SCC:
Sir Percival Pott observed a high incidence in chimney sweeps

22. SCROTUM Hydrocele: most common cause of scrotal enlargement
serous fluid within tunica vaginalis
causes:
infections
tumors
idiopathic

23. SCROTUM
blood : Hematoceles
Lymphatic fluid :chyloceles

24. SCROTUM Elephantiasis lymphatic obstruction (filariasis)
Scrotum & lower extremities

25. The Testes Cryptorchidism & Testicular Atrophy Inflammatory Lesions
Testicular Neoplasms

26. Cryptorchidism failure of testicular descent into scrotum
Descent from coelomic cavity into pelvis by the third month of gestation
Through inguinal canals into scrotum during the last 2 months of intrauterine life
Diagnosis difficult to establish before 1 yr

28. Cryptorchidism By 1 yr seen in 1% of the male population
10% are bilateral
Causes:
hormonal
intrinsic testicular abnormalities
mechanical (inguinal canal obstruction)
congenital syndromes (Prader-Willi)
unknown

29. Cryptorchidism Sterility Risk of testicular malignancy x3-5 times
unilateral cryptorchidism :
1- cancer risk in contralateral, descended testis
2- atrophy of contralateral gonad and sterility

30. Orchiopexy
Surgical placement of UDT into scrotum before puberty decreases likelihood of atrophy,cancer and infertility

31. Cryptorchidism Right >left 10% bilateral normal size early in life
at 5 to 6 yrs: tubular atrophy
at puberty:
hyalinization
hyperplasia of Leydig cells
intratubular neoplasia

32. Atrophic changes Cryptorchidism chronic ischemia Trauma Radiation
antineoplastic chemotherapy
chronic elevation in estrogen levels (cirrhosis)

34. Inflammatory Lesions epididymis > testis
Acute gonococcal epididymitis (abscess)

35. Inflammatory Lesions Nonspecific epididymorchitis :
begins as a primary UTI
secondary ascending infection of testis
testis is swollen and tender with PMNs

36. Inflammatory Lesions mumps orchitis 20% of infected adults
rarely in children
testis is edematous and congested
lymphoplasmacytic infiltrate
tubular atrophy, fibrosis & sterility

37. Inflammatory Lesions Testicular TB:
most common cause of testicular granulomas
epididymitis testis
granulomas & caseous necrosis

38. Testicular Neoplasms Firm, painless enlargement 5 /100,000 males
peak yrs

39. Testicular Neoplasms cause unknown
Cryptorchidism (10%): X3-5 in both sides
syndromes: androgen insensitivity
gonadal dysgenesis
isochromosome 12p
risk in siblings of patients
risk in contralateral testis
whites >blacks
Caucasians

40. Heterogeneous group:
1-germ cell tumors
(95%,all are malignant)
2-sex cord/stromal tumors
(uncommon,usually benign)

41. Classification of Germ Cell Tumors
One Histologic Pattern (60%)
Seminoma
nonseminoma
Embryonal carcinoma
Yolk sac tumor
Choriocarcinoma
Teratomas Mature
Immature
malignant transformation
More Than One Histologic Pattern

42. Intratubular germ cell neoplasia
most tumors arise from in situ lesions
in situ foci are adjacent to germ cell tumors in almost all cases

43. Seminoma 1-classic: 50% of germ cell neoplasms
identical to dysgerminomas & CNS germinomas

44. Large
Soft
well-demarcated
Homogeneous
gray-white
bulge from cut surface
confined to testis
intact tunica albuginea
foci of coagulation necrosis
usually without hemorrhage

45. Large,uniform cells
distinct cell borders
Clear,glycogen-rich cytoplasm
round nuclei
conspicuous nucleoli
small lobules
intervening fibrous septa
lymphocytic infiltrate
granulomatous reaction

46. cells staining positively for hCG in 25 %
similar to syncytiotrophoblasts
elevated serum hCG concentrations

47. Seminoma 2-spermatocytic occur in older patients medium-sized cells
large uninucleate or multinucleate cells
small cells with round nuclei
no association with intratubular germ cell neoplasia
metastases are exceedingly rare

48. Embryonal carcinomas Ill-defined,invasive masses Hemorrhage & necrosis
primary lesions may be small,even in cases with metastases
may invade epididymis & spermatic cord

49. Embryonal carcinomas Large,primitive cells basophilic cytoplasm
indistinct cell borders
large nuclei
prominent nucleoli

50. Embryonal carcinomas undifferentiated, solid sheets
glandular structures & irregular papillae
other patterns are admixed with embryonal areas

51. Embryonal carcinomas
Pure forms 2% to 3% of all testicular germ cell tumors
foci of intratubular germ cell neoplasia frequently present in adjacent tubules

52. Yolk sac tumors (endodermal sinus tumors)
the most common primary testicular tumor in children <3
In adults,often admixed with embryonal carcinoma

53. Yolk sac tumors often large and well demarcated
low cuboidal to columnar epithelial cells
microcysts, sheets, glands, and papillae

54. structures resembling primitive glomeruli, Schiller-Duvall bodies
Eosinophilic hyaline globules (AFP)

55. Choriocarcinomas Trophoblastic differentiation
primary tumors often small & nonpalpable
May have extensive systemic metastases
small cuboidal cytotrophoblastic cells
large, eosinophilic syncytiotrophoblastic cells (multiple dark & pleomorphic nuclei)
hCG within cytoplasm of syncytiotrophoblasts
Well-formed placental villi not seen

56. Choriocarcinomas
Hemorrhage
necrosis c s

57. Teratomas Differentiation along somatic cell lines
in prepubertal boys :
usually benign
Pure forms
In adults:
metastases in 37% of cases
often contain other malignant elements

58. Teratoma: variegated cut surface with cysts

59. 1-Mature teratomas one or more germ cell layers
neural, cartilage, adipose, bone & epithelial
haphazard array

60. neural
glandular
cartilaginous
squamous

61. 2- Immature teratomas
immature somatic elements reminiscent of those in developing fetal tissue

62. Teratoma disorganized collection of glands, cartilage, smooth muscle & immature stroma

63. 3-Teratomas with somatic-type malignancies
frank malignancy in preexisting teratomatous elements
usually scc or adenocarcinoma

64. Mixed germ cell tumors 40% of all testicular germ cell neoplasms
Combinations of any of described patterns
teratoma, embryonal carcinoma & yolk sac tumors

65. Clinical Features Seminomas often remain confined to testis
may reach considerable size
Metastases to iliac and para-aortic nodes
Hematogenous metastases occur later

66. Clinical Features non-seminomatous widespread metastases at diagnosis
with no palpable testicular lesion
metastasize earlier
lymphatic & hematogenous (liver & lungs)

67. Testicular germ cell neoplasms staging
Stage I:
confined to testis
Stage II:
Regional LN only
Stage III:
Nonregional and/or distant metastases

68. Assay of tumor markers role in primary diagnosis & staging
Serially measured to monitor patients

69. hCG syncytiotrophoblastic cells always elevated in choriocarcinoma
Seminoma: 10-25%

70. AFP Glycoprotein fetal yolk sac & other fetal tissues
reliable indicator of a nonseminomatous component (yolk sac)
most nonseminomatous tumors have elevations of both hCG and AFP
also elevated in hepatocellular carcinoma.

71. treatment Seminomas Radiosensitive respond well to chemotherapy
nonseminomatous germ cell tumors
platinum-based chemotherapy

72. PROSTATE
Prostatitis
nodular hyperplasia
carcinoma

73. Acute bacterial prostatitis
E.coli & other gram-negative rods
Most patients have acute urethrocystitis
direct extension from urethra or bladder
vascular channels from more distant sites

74. Chronic prostatitis bacterial episodes of acute prostatitis
may also develop insidiously
abacterial
account for most cases
nonbacterial agents:
Chlamydia trachomatis
Ureaplasma urealyticum,

75. Granulomatous prostatitis
not a single disease
a reaction to a variety of different insults
disseminated TB
Sarcoidosis
fungal infections
Wegener granulomatosis
reaction to inspissated prostatic secretions
Following TURP

76. Morphology Acute prostatitis: neutrophilic inflammatory infiltrate
Congestion
stromal edema
glandular epithelium may be destroyed
Microabscesses
Gross abscesses uncommon (in diabetics).

77. Morphology chronic prostatitis nonspecific in most cases
lymphoid infiltrate
glandular injury
concomitant acute inflammation
tissue destruction
fibroblastic proliferation

78. Morphology granulomatous prostatitis multinucleate giant cells
foamy histiocytes
sometimes eosinophils
Caseous necrosis only in TB prostatitis

79. Clinical Features of Prostatitis
acute:
Dysuria
urinary frequency
lower back pain
suprapubic or pelvic pain
fever and leukocytosis
chronic:
recurrent UTI in men
silent

80. normal prostate:
glandular
stromal
parenchyma:
1-Peripheral
2-Central
3-Transitional
4-periurethral

81. most hyperplastic lesions arise in inner transitional & central zones
most carcinomas (70-80%) arise in peripheral zones

82. Nodular Hyperplasia of the Prostate
glandular & stromal hyperplasia
extremely common abnormality
a significant number of men by age 40
its frequency rises progressively with age (90% by the 8th decade)

83. "Benign prostatic hypertrophy" (BPH)
a synonym for nodular hyperplasia
redundant and a misnomer
the lesion is a hyperplasia rather than a hypertrophy

84. Cause remains incompletely understood androgens have a central role
not seen in males castrated before puberty
Not in men with genetic diseases
(blocked androgen activity)

85. pathogenesis of nodular hyperplasia
local, intraprostatic concentrations of androgens and their receptors
increases in estrogens may increase expression of DHT receptors on prostatic parenchymal cells ( age-related )

87. currently 5α-reductase inhibitors are used to treat symptomatic nodular hyperplasia

88. Morphology periurethral glands of prostate
prostate is enlarged even >300 gm
cut surface well-circumscribed nodules
solid or with cystic spaces
urethra is usually compressed
(slit-like orifice)
may project into bladder lumen

89. Well-defined nodules compress urethra into a slitlike lumen

90. Microscopical appearance
Glands
tall columnar epithelial cells
flattened basal cells
crowding of epithelium (papillary projections)
corpora amylacea
Infarction (advanced cases)
squamous metaplasia in adjacent glands

91. Microscopical appearance
fibromuscular stroma surround glands
Spindle cells & connective tissue nodules

92. basal cell and secretory cell layers

94. Clinical Features in only about 10% of patients
lower urinary tract obstruction & infections
Hesitancy
intermittent interruption of urinary stream
painful distention of bladder
hydronephrosis
bladder irritation
( frequency, nocturia & urgency)

95. Carcinoma of the Prostate
the most common visceral cancer in males
2nd cancer-related death cause in men >50
peak incidence between 65 and 75 years
overall frequency >50% in men above 80

96. Pathogenesis Hormones: not seen in males castrated before puberty
androgens probably contribute
growth inhibited by orchiectomy or DES
Genes:
Higher risk among 1st-degree relatives
Environment:
American blacks >whites, Asians or Hispanics
A high animal fat diet is suggested as a risk factor

97. prostatic intraepithelial neoplasia (PIN)
frequent coexistence with infiltrating carcinoma
probable precursor to carcinoma
high-grade and low-grade patterns
degrees of atypia vary
an intermediate between normal & malignant tissue

98. Gross pathology 70-80 % in periphery irregular hard nodules
less likely to cause urethral obstruction
ill-defined masses
firm, gray-white to yellow
Infiltrative margins

99. Microscopy adenocarcinoma small glands lie "back to back"
single layer of cuboidal cells
basal cell layer absent
conspicuous nucleoli

100. perineural invasion by malignant glands

101. Low-grade (Gleason score 2)
back to back
uniformly sized glands

102. Anaplasia irregular, ragged glands papillary or cribriform structures
sheets of poorly differentiated cells

103. Moderately differentiated
(Gleason score 6)
variably sized
widely dispersed
Moderately differentiated
(Gleason score 10)
Poorly differentiated sheets of malignant cells

104. Clinical Features often clinically silent during early stages
may be discovered by routine rectal exam
10% found in histologic examination of tissue removed for nodular hyperplasia
autopsy studies,30% in men 30 to 40 years
Prostatism when more extensive :
local discomfort
lower urinary tract obstruction

105. Clinical Features
More aggressive cases come to attention because of metastases
regional pelvic LN
seminal vesicles
periurethral zones
bladder wall
Invasion of rectum less common

106. Clinical Features Bone metastases axial skeleton common:
osteolytic (destructive)
osteoblastic (bone-producing)
osteoblastic metastases in an older male strongly suggests advanced carcinoma

107. Metastatic osteoblastic prostatic carcinoma within vertebral bodies

108. prostate-specific antigen (PSA)
proteolytic enzyme
secreted into prostatic acini and seminal fluid
increases sperm motility
serum level 4.0 ng/L is the upper limit of normal
Cancer cells produce more PSA
also elevated in :
nodular hyperplasia
prostatitis

109. prostate-specific antigen
limited value when used as an isolated screening test for cancer
diagnostic value enhanced when used with digital rectal examination
transrectal sonography
needle biopsy

110. prostate-specific antigen
great value in monitoring patients after treatment for cancer
rising levels indicate recurrence and/or metastases

111. prostate-specific antigen
useful refinements PSA (4 to 10)
gray zone:
PSA velocity
PSA density
free vs bound forms of PSA
Free PSA
level >25% indicate a lower risk
level <10% are worrisome

112. staging

113. Treatment combinations:
Surgery
Radiation
Hormonal ( advanced carcinomas)

114. Quiz

115. 1-In Bowen disease which statement is true
A)it is seen in young uncircumcised males
B)it is a solitary, plaquelike lesion.
C)it has invasion of stroma
D)invasive SCC never develops in such patients

116. 2-in Epispadias which sentence is false?
A) The orifice is on ventral aspect of penis.
B) Lower urinary tract obstruction is seen
C) Urinary incontinence may occur
D) Bladder extrophy is commonly noted

117. 3-AFP is A)A Glycoprotein B)Produced by fetal yolk sac & other tissues
C)A reliable indicator of yolk sac tumor
D)All of the above.

118. 4-in acute prostatitis which change is not present?
A) neutrophilic inflammatory infiltrate
B) Congestion & stromal edema
C) glandular epithelium destruction
D) granulomas.

119. 5-prostate cancer is associated with :
A)irregular soft nodules
B)well-defined masses
C)High serum PSA level.
D)All of the above

120. The End