Male Genital System

Hiroshani Kulatunga
BSc(hons)MLS
Objectives
At the end of this lecture students should be able to,
• describe the normal histology of the testis
• describe the normal histology of prostate
• identify the features of different testicular tumours
• identify the features of different prostate tumours
• develop the capacity to differentiate each tumour type
Recall the basic structure of Male genital
system
Testicle and epididymis
considered as a single organ as
the epididymis is attached to
body of the testis posteriorly.

Scrotal sack contains the testicle

and epididymis along with lower
end of the spermatic cord and
the tunica vaginalis that forms
the outer serous investing layer.
Recall the basic structure of Male genital
system Cont…
• Main component of testicles is the seminiferous tubules.
• Cell lining of the seminiferous tubules include,

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
oestrogen.
• Recall the memory on
testis…..
Testicular Tumors
• More frequent in white males
• Responsible for 1% of cancer deaths
• This has trimodal age distribution. There are peaks in,
infancy
adolescence and early adulthood
after 60 years of age
 Testicular Tumors Cont…

• Etiological factors are not clearly known. But following factors have been
implicated
1. Cryptorchidism (undescended testis)
2. Disgenetic gonads due to endocrine problems
3. Genetic factors
4. Other factors –
Oorchitis (due to previous exposure to mumps virus)
Trauma
Carcinogens
Classification of Testicular Tumors
• According to histogenic classification proposed by WHO , There are 03
types of testicular tumors.
1. Germ cell tumors (95% of tumors)
In clinical site of view, these tumors again divide into 02 groups
seminomatous tumors
non-seminomatous tumors
2. Sex-cord stromal tumors
3. Mixed forms
Germ Cell Tumors

• Accounts 95% of testicular tumors

• More frequent before 45years of age

• Almost always malignant

• Nearly half of them contain more than one histologic type. Besides
their counterparts in the female gonads, germ cell tumours are also
found at the extragonadal sites such as the retroperitoneum,
mediastinum, base of the brain, coccyx etc
Classic Seminoma
• Commonest malignant tumor in testis.
• This corresponds to the dysgerminoma of females
• Classic seminoma is found in 45% of germ cell tumors & 15 % from
mixed germ cell tumours
• From seminomas , classic seminoma accounts 95% of cases.
• There is a high incidence in 40s of age. (4th decade) & this is rare
before puberty.
• Undescended testis is the frequent cause for seminoma & 10% of
seminomas are due to high hCG levels in serum.
Classic Seminoma
• Gross Morphology
Enlarged testis (upto 10 times its normal size)
But normal contour doesn’t change as the tumour rarely invades the
tunica.
Cut section of an affected testis shows homogenous, grey-white
lobulated appearance.
Necrosis and haemorrhage are rare.
Seminoma testis. The testis is enlarged but without distorting its contour. Sectioned surface shows replacement

of the entire testis by lobulated, homogeneous, grey-white mass.

Classic Seminoma
• Microscopy
1. Tumour cells
• Seminoma cells normally lie in cords, sheets or columns forming lobules.
• In classic seminoama tumor cells ,
- fairly uniform in size with clear cytoplasm
- well defined cell borders.
- cytoplasm contains variable amounts of glycogen(can visualized by PAS stain)
- Centrally located, large, hyperchromatic nuclei with 1-2 prominent nucleoli
• There can be tumor giant cells
• Mitotic figures infrequent
Classic Seminoma
• Microscopy
2. Stroma
This is a delicate fibrous tissue that divides the tumor in to lobules.
Shows a characteristic lymphocytic infiltration (indicative of
immunologic response of the host)
About 20% of the tumour show granulomatous reaction in stroma.
Seminoma testis. Microscopy of the tumour shows lobules of monomorphic seminoma cells separated by
delicate fibrous stroma containing lymphocytic infiltration.
Classic Seminoma

• Has a better prognosis than other germ cell tumours

• Highly radiosensitive
Spermatocytic Seminoma

• Uncommon type of tumor (5% of all germ cell tumors)

• This is clinically and morphologically distinct from clinical seminoma

• Common in older pts, generally in 6th decade of life.

• In 10% of patients tumor is bilateral. (What is meant by bilateral????)

Spermatocytic Seminoma
Gross morphology
• Homogenous, larger, softer and more yellowish and gelatinous testis.
Microscopy
1. Tumour cells
Vary in size from the size of a lymphocyte to huge mononucleate
or multinucleate giant cell. But majority are in medium size
Eosinophilic cytoplasm devoid of glycogen
Nuclei of large and intermediate cells have filamentous pattern
Mitoses are often frequent
Spermatocytic Seminoma
2. Stroma
Stroma lacks lymphocytic and granulomatous reaction seen in classic
seminoma

• Prognosis is excellent & better than classic seminoma as tumor is

slow-growing and rarely metastasizes.
• Tumour is radiosensitive.
Spermatocytic seminoma
Activity……

• Compare and contrast the feature of classic seminoma &

Spermatocytic Seminoma
Embryonal Carcinoma

• Pure embryonal carcinoma constitutes 30% of germ cell tumours. But

areas of embryonal carcinoma are present in 40% of various other
germ cell tumours.

• More common in 2nd and 3rd decades of life.

• 90% of cases are due to elevations of AFP or HCG or both.

• More aggressive than seminomas.

Embryonal Carcinoma
• Morphological Features
Gross appearance
• Small tumour in testis
• Distorts the contour as it frequently invades
the tunic and epididymis.
• Cut surface of the tumour is grey-white,
soft with areas of haemorrhage and
necrosis.
 Embryonal carcinoma. Area showing more Embryonal carcinoma. Solid sheets of
obvious epithelial differentiation with irregular primitive cells with characteristic large
slit like spaces lined by primitive cells vesicular nuclei and prominent nucleoli
Embryonal Carcinoma
Microscopy
1. The tumour cells are arranged in a variety of patterns— glandular,
tubular, papillary and solid.
2. The tumour cells are highly anaplastic carcinomatous cells having
large size, indistinct cell borders, amphophilic cytoplasm and prominent
hyperchromatic nuclei showing considerable variation in nuclear size.
Mitotic figures and tumour giant cells are frequently present.
Haemorrhage and necrosis are common.
3. The stroma is not as distinct as in seminoma and may contain
variable amount of primitive mesenchyme.
Embryonal Carcinoma

• More aggressive

• Radiosensitive than seminoma

• Chemotherapy is more effective in treating this tumour.

Yolk Sack Tumour

• This is the most common type of tumour of infants and children up to

04 years.

• In adults, yolk sac tumour in pure form is rare but may be present as
the major component in 40% of germ cell tumors.

• In almost all the cases AFP (alpha feto protein) levels are elevated.
Yolk Sack Tumour
• Gross appearance
Generally soft, yellow-white, mucoid with areas of necrosis and
hemorrhages
Yolk Sack Tumour
Microscopy
• 1. The tumour cells form a variety of patterns—loose reticular network,
papillary, tubular and solid arrangement.
2. The tumour cells are flattened to cuboid epithelial cells with clear
vacuolated cytoplasm.
3. The tumour cells may form distinctive perivascular structures resembling
the yolk sac or endodermal sinuses of the rat placenta called Schiller-Duval
bodies.
4. There may be presence of both intracellular and extracellular PAS-positive
hyaline globules, many of which contain AFP.
Yolk sac tumour testis.
The tumour has
microcystic pattern and
has highly anaplastic
tumour cells. Several
characteristic Schiller-
Duval bodies are present.
Inset shows intra- and
extracellular hyaline
globules.
Choriocarcinoma

• Pure choriocarcinoma is a highly malignant tumour

• But, pure form is extremely rare & occurs more often in combination
with other germ cell tumors.

• Usually found in the 2nd decade of the life.

• The serum & urinary levels of hCG are greatly elevated in 100% of
cases.
Teratoma
• These are complex tumors composed of tissues derived from more
than one of the 03 layers of germ cell layers. (endoderm, mesoderm
and ectoderm)
• Common in infants & children
• Usually found in combination with other germ cell tumours.(mainly
with embryonated carcinoma)
• About half of the teratomas have hCG or AFP levels or both.
Teratoma
• Morphologically there are 03 types of testicular teratomas
1. Mature (differentiated) teratoma
2. Immature teratoma
3. Teratoma with malignant transformation

Macroscopic appearance is almost same in all the 03 types but, there

are different appearances in microscopic appearance.
1. Mature teratoma -
• Most common type
• More frequent in infants and children
• Mixture of mature elements from ecto, meso and endoderm
• Have a favorable prognosis
2. Immature teratoma
• Primitive or embryonic tissue along with some mature elements
3. Teratoma with malignant transformation
• Very rare
Teratoma
Macroscopy,

most teratomas are large, grey-white masses enlarging the involved

testis. Cut surface shows characteristic variegated appearance—grey-
white solid areas, cystic and honey-combed areas, and foci of cartilage
and bone
Immature teratoma testis. The testis is enlarged and nodular distorting the testicular contour. Sectioned
surface shows replacement of the entire testis by variegated mass having grey-white solid areas, cystic areas,
honey-combed areas and foci of cartilage and bone.
Immature teratoma testis. Microscopy shows a variety of incompletely
differentiated tissue elements.
Mature teratoma
Mixed Germ Cell Tumours
• About 60% of germ cell tumours have more than one of the above
histologic types (except spermatocytic seminoma) and are called
mixed germ cell tumours.
• Clinical behavior of this type of tumours worsened by inclusion of
more aggressive tumour components in a less malignant tumors.
• Metastases of the mixed germ cell tumours may not exactly
reproduce the histologic types present in the primary tumour.
Mixed Germ Cell Tumours

• The most common combinations of mixed germ cell tumours are as

under:

1. Teratoma, embryonal carcinoma, yolk sac tumour and

syncytiotrophoblast.

2. Embryonal carcinoma and teratoma (teratocarcinoma).

3. Seminoma and embryonal carcinoma.

Sex Cord Stromal Tumours

• Tumours arising from specialized gonadal stroma are classified on the

basis of histogenesis.

• Primitive mesenchyme is the one which gives rise to specialized

stroma of gonads in either sex.
 Sertoli cells
Males
Leydig cells

Primitive
Mesenchyme Theca cells

Females Granulosa
cells

Lutein cells
Sex Cord Stromal Tumours

• Since the primitive mesenchyme is identical, sertoli & interstitial

Leydig cell tumours may also present in the ovaries. (in adition to
theca calls, granulosa cells & lutein tumour cells). Vise versa also can
happen.

• All these tumours secrete various hormones.

Leydig Cell Tumors
• Quite uncommon

• Can occur at any age but, more frequent in 20-50 years.

• Most are benign, only 10% may invade and metastasise.

• Characteristically, these cells secrete androgen, or both androgen &

oestrogen, & rarely corticosteroids.

• Bilateral tumours may occur typically in congenital adrenogenital

syndrome.
Sertoli Cell Tumours (Adroblastoma)

• Can occur in any age but, more frequent in infants and children.

• Sertoli cell tumours are correspond to arrhenoblastoma of the ovary.

• These tumours may elaborate oestrogen or androgen

• May account for gynaecomastia in an adult, or precocious sexual

development in a child
Mixed Germ Cell – Sex Cord Stromal Tumours

Gonadoblastoma
• Dysgenetic gonads and undescended testis are predisposed to
develop such combined proliferations of germ cells and sex cord-
stromal elements.
• These patients are commonly intersexuals, particularly phenotypic
females.
• Most of the gonadoblastomas secrete androgen and therefore
produce virilisation in female phenotype. A few, however, secrete
oestrogen.
Gonadoblastoma cont…

• Composed of principal cell types : large germ cells resembling

seminoma calls and small cells resembling immature Sertoli, Leydig &
granulosa cells.

• Other tumours
• Malignant lymphoma – most common tumor of testis in the elderly
Summary on Testicular
Tumors
Summary
• Testicular tumours are divided into 3 groups: germ cell tumours
(95%), sex cord-stromal tumours (~5%) and mixed forms (rare).
• Cryptorchidism and dysgenetic gonads are implicated in the
etiology of testicular tumours.
• AFP and hCG are commonly used as tumour markers in their
diagnosis, staging and monitoring.
• Testicular tumours may spread by lymphatic and haematogenous
route.
• Summary
• Seminoma is the commonest malignant tumour of the testis; spermatocytic
seminoma is a variant with better prognosis.
• Teratomas are composed of tissues derived from three germ cell layers—
endoderm, mesoderm and ectoderm. They may be mature, immature and with
malignant change.
• Other primary germ cell tumors are yolk sac tumour seen in children, embryonal
carcinoma in young adults and choriocarcinoma, a highly malignant tumour.
• Leydig cell, Sertoli cell and granular cell tumours are uncommon sex-cord stromal
tumours.
Prostate Gland
Prostate
• There are 03 distinct lobes at
birth
• Two major
lateral lobes
• Small median
lobe
Prostate
Histology
• Prostate is composed of tubular alveoli (acini) embedded in a
fibromuscular mass.
• Glandular epithelium forms infoldings and consists of 02 layers
- A basal layer of low cuboidal cells
- inner layer of mucus secreting tall columnar cells
• Alveoli are separated by thick fibromuscular septa containing
abundant smooth muscle fibers.
Prostate

• This has numerous blood vessels & nerves.

• Also prostate is an endocrine dependent organ.

oInner periurethral part – sensitive to oestrogen &
androgen
oOuter sub capsular part - sensitive to Androgen
Prostate

• There are 02 main growth abnormalities

1. Nodular hyperplasia

2. Cancer
Normal prostate, benign nodular hyperplasia and prostatic carcinoma. The nodule in case of benign nodular
hyperplasia (B) is located in the inner periurethral part and compresses the prostatic urethra while prostatic
carcinoma (C) generally arises in the peripheral glands and, thus, does not compress the urethra.
Nodular Hyperplasia
• This is a non-neoplastic tumour like enlargement of the prostate.
• Commonly called as benign nodular hyperplasia (BNH) or benign
enlargement of prostate (BEP).
• Very common condition
• More frequent above 50years of age, 75-80% of cases are above
80years of age.
• But, only 5-10% of cases are symptomatic which require surgeries
(due to obstructions in urinary tract).
Nodular Hyperplasia
• Etiology
• Haven’t identified the exact cause.
• But suggest following may be the causes.
oEndocrinologic factors - this may be the main cause
according to investigations
oRacial factors
oInflammation
oArteriosclerosis
Nodular Hyperplasia
Histology
Enlarged prostate is nodular, smooth & firm.
Appearance of cut section varies depending on whether the
hyperplasia is predominantly of the glandular or fibromuscular tissue.
Primary glandular BEP – firm, homogenous & doesn’t exude milky fluid.
Primary fibromuscular hyperplasia - firm, white, homogenous
Nodular Hyperplasia
• Surrounding uninvolved peripheral tissue forms a false capsule.
• Therefore surgical removal is easy
• Clinical features are due to urethral obstruction and secondary effects
on bladder
Nodular enlargement of the prostate.
Sectioned surface of enlarged prostate
shows soft to firm, grey-white, nodularity
with microcystic areas.
Nodular Hyperplasia
• Microscopy
In every case, there is hyperplasia of all three tissue elements in varying
proportions – Glandular, fibrous & muscular
Nodular hyperplasia of the prostate.
There is hyperplasia of fibromuscular elements. There are areas of intra-acinar papillary infoldings
(convolutions) lined by two layers of epithelium with basal polarity of nuclei.
Nodular Hyperplasia
• Clinical features
Symptomatic cases develop symptoms due to complications like urethral
obstructions and secondary effects on the bladder (hypertrophy, cystitis) ,
ureter (hydroureter) and kidneys (hydronephrosis).

Presenting features,
Nocturia, difficulty on micturition, pain, haematuria & sometimes acute
retention of urine
Carcinoma of Prostate

• Second most commonest type of cancer in males

• Normally seen in males above 50 years of age & prevelance increases

with the increase of their age.

• 50% of males asymptomatic (latent) carcinoa.

• These are microscopic. Therefore, in most instances we can identify

after a removal of prostate for a BEP or in an autopsy.
Carcinoma of Prostate
• Etiology
Still the etiology is obscured.
Following factors have been suspected.
1. Endocrine factors – androgens
2. Racial & geographic influence
3. Environmental influence
4. Nodular hyperplasia
5. Heredity
Carcinoma of Prostate
Morphologic Features
Macroscopy,
Enlarged / normal or smaller in size.
Normally occur in the peripheral zone, specially in the posterior
lobe.
Firm and fibrous.
Cut section is homogeneous & contain irregular yellowish areas
 Microscopy

Carcinoma of the prostate. The field shows microacini of small malignant cells
infiltrating the prostatic stroma. Inset in the photomicrograph shows perineural
invasion by prostatic adenocarcinoma
Carcinoma of Prostate
• 04 histologic types
- adenocarcinoma – 96% of prostate cancers. This is generally
referred as prostate cancer
- transitional cell carcinoma
- squamous cell carcinoma
- undifferentiated carcinoma
Carcinoma of Prostate
• Gland pattern – small glands / cribriform / solid or traberculae

Moderately
Poorly
Well differ differenciated
differentiated

• Tumour cells - single cell layer, Mild nuclear atypia , outer basal
layer is lost
• Invasion – Invasion of the malignancy to perineural spaces.
Lymphatic and vascular invasion also available. But difficult
to detect
• Metastasis
Spread occurs through lymphatic and haematogenous routes.
Haematogenous spread leads to characteristic osteoblastic Osseous
metastases to pelvis, lumbae spine

Other mesasstasis sites are lungs, kidneys, breast and brain.

Clinical features of Prostate Cancer
• Urinary symptoms/ back ache
• Palpable in PR examinations
• Elevation of Prostatic Acid Phosphotase (PAP)
• Elevation of Prostate Specific Antigen (PSA) – normal 0 to 4 ng/ml
• Radiology
• Biopsy/ FNA
• Gleason’s histologic grading – based on degree of gland
• differentiation and growth pattern
• TNM staging
Summary on
Prostate
Summary
• Prostate is divided into inner periurethral female part (sensitive to
oestrogen and androgen) and outer subcapsular true male part
(sensitive to androgen).
• Nodular hyperplasia of prostate is common and involves hyperplasia
of glandular, fibrous and muscular tissues in varying proportions.
• Cancer of the prostate is the second most common form of cancer in
males in older age group.
Summary
• Androgens are considered essential for development and
maintenance of prostatic epithelium.
• Prostatic adenocarcinoma is the most common type of prostatic
cancer. It may spread directly to adjacent tissues or may metastasise,
especially to bones.
• Diagnosis of prostatic cancer requires DRE, PSA determination and
histopathologic examination of core needle biopsy.
• Gleason’s histologic grading and TNM clinical staging are followed for
assessing clinical course of prostate cancer.
Mandatory Question

•Prepare a table and compare the different

types of testicular tumours.
If you need to know more details……
• Please refer Harsh Mohan text book for pathology..
Thank
You….