2. MALE REPRODUCTIVE PATHOLOGY
1. TESTIS AND EPIDIDYMIS
2. TESTICULAR NEOPLASMS
3. PENIS
4. TUMORS OF PENIS
5. PROSTRATE
6. CARCINOMA OF PROSTRATE
3. TABLE OF CONTENTS
• TESTIS AND EPIDYDIMIS
o Normal structure
o Developmental disorders
o Male infertility
o Inflammations
o Miscellaneous lesions
o Testicular tumors
• PENIS
• PROSTRATE
4. TESTIS AND EPIDIDYMIS
NORMAL STRUCTURE
Contents of the scrotal sac:
1. Testicle and epididymis
2. Lower end of the spermatic cord
3. Tunica vaginalis.
The epididymis is attached to body of the testis posteriorly, thus, may be regarded as one organ.
Structurally, the main components of the testicle are seminiferous tubules which when uncoiled are of
considerable length.
HISTOLOGICALLY,
The seminiferous tubules are formed of a lamellar connective tissue membrane and contain several layers of
cells.
In the adult, the cells lining the seminiferous tubules are of 2 types:
1. Spermatogonia or germ cells which produce spermatocytes (primary and secondary), spermatids and mature
spermatozoa.
2. Sertoli cells which are larger and act as supportive cells to germ cells, produce mainly androgen
(testosterone) and little estrogen.
5. Cont…
The seminiferous tubules drain into collecting ducts which form the rete testis from
where the secretions pass into the vasa efferentia.
Vasa efferentia opens at the upper end of the epididymis.
The lower end of the epididymis is prolonged into a thick muscular tube, the
vas/ductus deferens, that transports the secretions into prostatic urethra.
The fibrovascular stroma present between the seminiferous tubules contains varying
number of interstitial cells of Leydig.
Leydig cells have abundant cytoplasm containing lipid granules and elongated
Reinke’s crystals.
These cells are the main source of testosterone and other androgenic hormones in
males.
Thus, Sertoli and Leydig cells are hormone-producing cells homologous to their
ovarian counterparts (granulosa-theca cells) and are termed specialised stromal
cells of the gonads.
Thus, the main functions of the testis are to produce sperms and testosterone.
6.
7. Cont…
Coverings of testis
(From superficial to deep)
1. Tunica vaginalis. (Parietal &
visceral layers)
2. Tunica albuginea.
3. Tunica vasculosa.
Layers of scrotum (SDESCIS)
1. Skin
2. Dartos muscle
3. External spermatic fascia
4. Cremasteric muscle and
fascia
5. Internal spermatic fascia
8. BLOOD, NERVE SUPPLY & LYMPHATIC DRAINAGE
ARTERIAL SUPPLY
Testicular artery, a branch of abdominal aorta.
The artery to vas deferens from the superior or
inferior vesical artery
Cremasteric artery from the inferior epigastric
artery.
VENOUS DRAINAGE
Many small testicular veins emerge from the
testis to form the pampiniform plexus, which
forms the main bulk of the spermatic cord.
At the deep inguinal ring the plexus is
replaced by testicular vein which drains into
the left renal vein (left side) and IVC (right
side)
LYMPHATIC DRAINAGE
• Drained by lymphatics to Pre-aortic and para-aortic
or lateral aortic lymph nodes on the posterior
abdominal wall.
• Enlargement of these lymph nodes may be the only
sign of carcinoma
NERVE SUPPLY
Sympathetic efferent nerve supply through celiac
and testicular plexuses from T10 to T12 segments
of spinal cord.
Sympathetic afferent nerve supply travel in
sympathetic nerves in celiac and testicular plexuses
to the lesser and least splanchnic nerves, which
carry them to T10 to T12 segments of spinal cord.
Testicular pain is referred to the middle and lower
abdominal wall.
10. DEVELOPMENTAL DISORDERS
• Cryptorchidism
• Male infertility
CRYPTORCHIDISM
Incomplete or failure of testis to descend
into the scrotum (undescended testis)
Incidence
• 1% in adult male population.
• Bilateral in 10% of cases
Location
In 70% of cases, the undescended testis
lies in the inguinal ring
In 25% in the abdomen
In the remaining 5%, in other sites along
its descent from intra-abdominal location
to the scrotal sac.
Etiology
Unknown in most cases, but has been attributed to;
1. Mechanical factors e.g. short spermatic cord,
narrow inguinal canal, adhesions to the
peritoneum.
2. Genetic factors e.g. trisomy 13, maldevelopment
of the scrotum or cremaster muscles.
3. Hormonal factors e.g. deficient androgenic
secretions.
N/B
Because undescended testes become atrophic,
bilateral cryptorchidism results in sterility.
For some unclear reasons, even unilateral
cryptorchidism may be associated with atrophy of
the contralateral descended gonad.
But generally, unilateral cryptorchidism leads to
infertility whereas bilateral cryptorchidism leads
to sterility
11. Cont…
Morphologic features
Unilateral in 80% cases and bilateral in the rest.
Grossly,
The cryptorchid testis is small in size, firm and fibrotic.
Histologically,
Changes of atrophy begin to appear by about 2 year of age as
under:
Seminiferous tubules:
Loss of germ cell elements.
The tubular basement membrane is thickened.
Hyalinised tubules.
Few Sertoli cells surrounded by prominent basement
membrane.
Interstitial stroma:
Increase in the interstitial fibrovascular stroma.
Conspicuous presence of Leydig cells, seen singly or
in small clusters.
CLINICAL FEATURES
Asymptomatic and is discovered only on physical
examination.
However, if orchiopexy is not undertaken by about 2 years
of age, significant adverse clinical outcome may result:
1. Sterility-infertility
2. Testicular atrophy
3. Inguinal hernia
4. Malignancy
Cryptorchid testis is at 30-50 times increased risk of
developing testicular malignancy
Risk of malignancy is greater in intra abdominal
testis than in testis in the inguinal canal (Easy and
early detection)
Treatment
• Surgical placement of the undescended testis into the
scrotum (orchiopexy) by 2 years of age to decrease the
likelihood of testicular atrophy, infertility, and testicular
cancer.
12. INFERTILITY
Causes of male infertility
Pre-testicular
Testicular
Post testicular
Can be congenital or acquired
Pre-testicular causes
1. Hypopituitarism
2. Estrogen excess
3. Glucocorticoid excess
4. Other endocrine disorders; DM &
hypothyroidism (both associates with
Hypospermatogenesis)
Testicular causes
1. Agonadism
2. Cryptorchidism
3. Maturation arrest
4. Hypospermatogenesis
5. Sertoli cell-only syndrome
6. Klinefelter’s syndrome
7. Mumps orchitis
8. Irradiation damage
Post-Testicular Causes
1. Congenital block
2. Acquired block
3. Impaired sperm motility
-ve feedback effects
on both GnRH & LH
13. INFLAMMATIONS
• Inflammation of the testis is termed as orchitis and of epididymis is called as
epididymitis
• Epididymitis is more common.
• A combination epididymo-orchitis may also occur.
Important types:
1. Non-specific epididymitis and orchitis
2. Granulomatous (autoimmune) orchitis
3. Tuberculous epididymo-orchitis
4. Spermatic granuloma
5. Elephantiasis
14. Non-specific epididymitis & orchitis
Non-specific epididymitis and orchitis, or their
combination, may be acute or chronic.
Refers to inflammation of testis and epididymis
when spread of infection are via the vas
deferens, or via lymphatic and hematogenous
routes.
Most frequently, the infection is caused by
urethritis, cystitis, prostatitis and seminal
vesiculitis.
Other causes are mumps, smallpox, dengue
fever, influenza, pneumonia and filariasis.
The common infecting organisms in sexually-
active men under 35 years of age are Neisseria
gonorrhoeae and Chlamydia trachomatis.
In older individuals the common organisms are
urinary tract pathogens like Escherichia coli
and Pseudomonas.
MORPHOLOGIC FEATURES
Grossly,
Testicle is firm, tense, swollen and congested.
Multiple abscesses, especially in gonorrheal
infection.
Variable degree of atrophy
Fibrosis.
Histologically,
Congestion
Edema
Diffuse infiltration by inflammatory cells
(neutrophils, lymphocytes, plasma cells and
macrophages)
Formation of neutrophilic abscesses.
Focal or diffuse chronic inflammation
Disappearance of seminiferous tubules
Fibrous scarring
Destruction of interstitial Leydig cells.
Permanent sterility
15. Granulomatous (Autoimmune) orchitis
• Non-tuberculous granulomatous orchitis is a peculiar type of unilateral, painless testicular
enlargement in middle-aged men that may resemble a testicular tumour clinically.
• The exact etiology and pathogenesis of the condition are not known though an autoimmune
basis is suspected.
Morphologic features
Grossly,
Affected testis is enlarged
Thickened tunica.
Cut section of the testicle is greyish-white to tan-brown.
Histologically,
Circumscribed noncaseating granulomas lying within the seminiferous tubules.
These granulomas are composed of epithelioid cells, lymphocytes, plasma cells, some
neutrophils and multinucleate giant cells.
The origin of the epithelioid cells is from Sertoli cells lining the tubules.
The tubules show peritubular fibrosis which merges into the interstitial tissue that is
infiltrated by lymphocytes and plasma cells.
16. Tuberculous epididymo-orchitis
• Tuberculosis invariably begins in the
epididymis and spreads to involve the
testis.
• Tuberculous epididymo-orchitis is
generally secondary tuberculosis from
elsewhere in the body.
• It may occur either by direct spread from
genitourinary tuberculosis such as
tuberculous seminal vesiculitis, prostatitis
and renal tuberculosis, or may reach here
by hematogenous spread of infection such
as from tuberculosis of the lungs.
• Primary genital tuberculosis may occur
rarely.
Morphologic features
Grossly,
Discrete, yellowish, caseous necrotic areas are
seen.
Microscopically,
Numerous tubercles which may coalesce to
form large caseous mass are seen.
Characteristics of typical tubercles such as
epithelioid cells, peripheral mantle of
lymphocytes, occasional multinucleate giant
cells and central areas of caseation necrosis
are seen.
Numerous acid-fast bacilli can be
demonstrated by Ziehl-Neelsen staining.
The lesions produce extensive destruction of
the epididymis and may form chronic
discharging sinuses on the scrotal skin.
Healing by fibrosis
Calcification.
17. Spermatic granuloma
• Is the development of inflammation due to invasion of spermatozoa into the stroma.
• May develop due to trauma, inflammation and loss of ligature following vasectomy.
Morphologic features
Grossly,
The sperm granuloma is a small nodule, firm, white to yellowish-brown.
Histologically,
Granuloma composed of histiocytes, epithelioid cells, lymphocytes and some
neutrophils.
Centre of spermatic granuloma contains spermatozoa and necrotic debris.
Fibrosis and hyalinization.
18. Elephantiasis
• Is enormous thickening of the scrotal skin
resulting in enlargement of the scrotum.
• The condition results from filariasis in which
the adult worm lives in the lymphatics, while
the larvae travel in the blood.
• The most important variety of filaria is
Wuchereria bancrofti.
• The condition is common in all tropical
countries.
• The vector is generally the Culex mosquito.
• The patients may remain asymptomatic or
may manifest with fever, local pain, swelling,
rash, tender lymphadenopathy and blood
eosinophilia.
• An asthma-like respiratory complaint may
develop in some cases.
Morphologic features
Grossly,
Affected leg and scrotum are enormously thickened
Enlargement of regional lymph nodes.
Dilated dermal lymphatics and varicosities in affected
area of skin.
Histologically,
Lymphatic obstruction by the adult worms.
The worm in alive, dead or calcified form may be
found in the dilated lymphatics or in the lymph
nodes.
Dead or calcified worm in lymphatics is usually
followed by lymphangitis with intense infiltration by
eosinophils.
Sometimes, granulomatous reaction may be evident
Chronic lymphedema
Subcutaneous fibrosis
Epidermal hyperkeratosis (termed elephantiasis).
19. MISCELANEOUS LESIONS
1. Testicular torsion
2. Varicocele
3. Hydrocele
4. Hematocele
TESTICULAR TORSION
• May occur either in a fully-descended testis or in an
undescended testis (more common and more severe).
• Refers to sudden cessation of venous drainage and
arterial supply to the testis, following sudden
muscular effort or physical trauma.
• Common in boys and young men.
Morphologic features
The pathologic changes vary depending upon duration
and severity of vascular occlusion.
Coagulative necrosis of the testis and epididymis
Hemorrhagic infarction.
Inflammatory reaction generally not so pronounced.
VARICOCELE
• Is the abnormal dilatation, elongation and
tortuosity of the veins of the pampiniform
plexus in the spermatic cord.
2 types: primary (idiopathic) and secondary.
Primary or idiopathic form
More frequent
More common in young unmarried men.
Nearly always on the left side as the loaded
rectum presses the left testicular vein.
Besides, the left testicular vein enters the renal
vein at right angles while the right spermatic
vein enters the vena cava obliquely.
Secondary form
Occurs due to pressure on the testicular vein by
enlarged liver, spleen or kidney.
It is commoner in middle-aged people.
20. Cont…
HYDROCELE
Is abnormal collection of serous fluid in
the tunica vaginalis.
It may be acute or chronic, congenital or
acquired.
The usual causes are trauma, systemic
edema such as in cardiac failure and renal
disease, and as a complication of
gonorrhea, syphilis and tuberculosis.
The hydrocele fluid is generally clear and
straw-colored but may be slightly turbid or
hemorrhagic.
The hydrocele sac may have single loculus
or multiple loculi.
The wall of the hydrocele sac is composed
of fibrous tissue infiltrated with
lymphocytes and plasma cells.
HEMATOCELE
• Is hemorrhage into the sac of the tunica
vaginalis.
• It may result from direct trauma, from
injury to a vein by the needle, or from
hemorrhagic diseases.
• In recent hematocele, the blood
coagulates and the wall is coated with
ragged deposits of fibrin.
• In long-standing cases, the tunica
vaginalis is thickened with dense
fibrous tissue coated with brownish
material due to old organised
hemorrhage and occasionally may get
partly calcified.
21. Review
CONTENTS OF SPERMATIC CORD
Composed of the following six groups of structures
1. Ductus deferens, in the posterior part.
2. Three arteries:
(a) Testicular artery, from abdominal aorta.
(b) Cremasteric artery, from inferior epigastric artery.
(c) Artery to ductus deferens, from inferior vesical artery.
3. Veins, the pampiniform venous plexus.
4. Lymphatics, especially from testis draining into pre- and para-aortic nodes, and some
from the coverings draining into external iliac nodes.
5. Nerves, genital branch of genitofemoral nerve and sympathetic fibres which accompany
the arteries.
6. Remains of processus vaginalis.