Testes pathology. Male infertility, inflammatory causes and tumors

1. TESTES PATHOLOGY.
NIRAV HITESH KUMAR VALAND

2. Anatomy of the testes.
• The testes (testicles) are the male gonads, paired ovoid
reproductive glands that produce sperms (spermatozoa)
and male hormones, primarily testosterone.
• The testes are suspended in the scrotum by the
spermatic cords, with the left testis usually suspended
(hanging) more inferiorly than the right testis.
• The epididymis is attached to the posteroinferior surface
of the testes, this is important in distinguishing between
swellings of the two parts.

3. Anatomy of the testes.
•The surface of each testis is covered by the
visceral layer of the tunica vaginalis, except
where the testis attaches to the epididymis and
spermatic cord.
•The tunica vaginalis is a closed peritoneal sac
partially surrounding the testis, which represents
the closed-off distal part of the embryonic
processus vaginalis. The visceral layer of the
tunica vaginalis is closely applied to the testis,
epididymis, and inferior part of the ductus
deferens.

4. • The testes have a tough fibrous outer surface, the
tunica albuginea, that thickens into a ridge on its
internal, posterior aspect as the mediastinum of the
testis.
• From this internal ridge, fibrous septa extend inward
between lobules of minute but long and highly coiled
seminiferous tubules in which the sperms are produced.
• The seminiferous tubules are joined by straight
tubules to the rete testis (L. rete, a net), a network of
canals in the mediastinum of the testis.
Continued….

6. • During its development, each testis descends from the posterior
abdominal wall to the scrotum, carrying with it a covering layer of
peritoneum which forms the tunica vaginalis, a closed serous cavity
around the testis. Blood vessels and lymphatics enter and leave the
testis on its posterior surface at the hilum, which is not covered by
tunica vaginalis.
• The descent from the abdominal wall starts by the 7th week. By the
12th week, the testis is in the pelvis, and by 28 weeks (7th month),
it lies close to the developing deep inguinal ring. The testis begins
to pass through the inguinal canal during the 28th week and takes
approximately 3 days to traverse it. Approximately 4 weeks later,
the testis enters the scrotum
Continued….

7. • Blood is supplied by the spermatic artery, a branch of the aorta,
which passes along the spermatic cord. The venous return surrounds
the spermatic artery as a network of intercommunicating veins, the
pampiniform plexus. This plexus becomes the main testicular vein
which, on the right side, drains to the inferior vena cava and, on the
left, joins the left renal vein. Lymphatic drainage of the testis is to the
iliac and para-aortic lymph nodes.
Continued….

8. Robbins and Cotran, Atlas of Pathology, 3rd edition, Page 310

9. Histology of the testes.
• The seminiferous tubules are formed of a lamellar
connective tissue membrane.
• 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.

10. • 2. Sertoli cells which are larger and act as supportive cells
to germ cells, they secrete androgen binding protein
(ABP), which keeps a high concentration of testosterone in
the germ cell environment.
• The seminiferous tubules have several layers of cells;
the outermost layer consists the Spermatogonia,
these divide to form the next layer i.e. of primary
spermatocytes these divide to form the secondary
spermatocytes
Continued….

11. • 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.
Continued….

12. •The location of the testes in the scrotum is important for sperm
production, which is optimal at 2°C to 3°C below body
temperature (35°C to 37.4°C). Two mechanisms maintain the
temperature of the testes at a level consistent with sperm
production.
•One is the pampiniform plexus of testicular veins that
surround the testicular artery. This plexus absorbs heat from
the arterial blood, cooling it as it enters the testes.
•The other is the dartos and cremaster muscles, which
respond to decreases in testicular temperature by moving
the testes closer to the body

15. Robbins and Cotran, Atlas of Pathology, 3rd edition, Page 311

16. Congenital anomalies of the testis.
Cryptorchidism.
• Cryptorchidism is a complete or partial failure of the
intra-abdominal testes to descend into the scrotal sac
and is associated with testicular dysfunction and an
increased risk of testicular cancer.
• Testicular descent occurs in two morphologically and
hormonally distinct phases;

17. During the first transabdominal, phase, the testis
comes to lie within the lower abdomen or brim of the
pelvis. This phase is believed to be controlled by a
hormone called müllerian inhibiting substance.
In the second inguinoscrotal, phase, the testes descend
through the inguinal canal into the scrotal sac. This
phase is androgen-dependent and is possibly mediated
by androgen-induced release of calcitonin gene related
peptide from the genitofemoral nerve.

18. •Although testes may arrest anywhere along their
pathway of descent, the most common site is in the
inguinal canal; arrest within the abdomen is
uncommon, accounting for approximately 5% to 10%
of cases.
•Even though testicular descent is controlled by
hormonal factors, cryptorchidism is only rarely
associated with a well-defined hormonal disorder.
•This condition is unilateral in most cases, however, 25%
of the cases are bilateral.

19. Morphology
• Gross
– The testis is small, fibrotic and firm;
– Appears pale white on cut section.
• Microscopy
– These changes start within the 2nd year, and its marked
by arrested germ cell development.
– Hyalinization and thickening of the basement
membrane
– Prominent Leydig cells.

21. Clinical features/significance.
There’s an increased incidence of infertility and germ cell
neoplasms.
Those with a unilateral cryptorchidism have oligospermia (i.e.
a sperm count of less than 20 million/ mL. Those with bilateral
cryptorchidism have azoospermia and are infertile.
Inguinal hernia.
Diagnosis.
Examination
Laparoscopy
Ultrasonography
MRI

22. Male infertility.
oInfertility is empirically defined as inability to conceive after
1 year of coital activity with the same sexual partner without
contraception. (Rubin’s Pathology, 7th edition, 2015, Page
979).
oThe causes of male infertility can be divided in to 3 groups
i.e. Pretesticular (Supratesticular), Testicular and Post-
testicular.

23. Male infertility.
PRETESTICULAR
CAUSES.
•Hypothalamic disorders
(deficiency of GnRH)
•Hypopituitarism
(deficiency of FSH and
LH)
•Endocrine diseases of
the adrenal, thyroid and
also diabetes.
•Hyperestrogenism
•Major organ diseases
e.g. the kidneys, liver,
and the heart
•Chronic and debilitating
diseases e.g. AIDs and
TB
•Drugs and substance
use.

24. TESTICULAR CAUSES.
•Idiopathic causes e.g.
Hypospermatogenesis or
azoospermia
•Developmental causes
e.g. Cryptorchidism,
gonadal dysgenesis
•Inflammatory causes e.g.
orchitis
•Iatrogenic testicular
injury e.g. by radiation
• Trauma to the testis.
• Genetic disorders e.g.
Klinefelter syndrome

25. POSTTESTICULAR
CAUSES
•Iatrogenic defects of the
excretory ducts
•Inflammation and
scarring of the excretory
ducts
•Congenital anomalies of
the excretory ducts e.g.
absence or atresia of
the vas deferens
•Acquired block e.g. due
to gonorrhea and
surgical intervention.
•Impaired sperm motility
in the presence of
normal sperm counts
e.g. immotile cilia
syndrome

26. Regressive changes
• Atrophy - Testicular atrophy may be caused by
one of several conditions, including (1)
progressive atherosclerotic narrowing of the
blood supply in old age, (2) the end stage of an
inflammatory orchitis, (3) cryptorchidism, (4)
hypopituitarism, (5) generalized malnutrition or
cachexia, (6) irradiation,

27. (7) prolonged administration of antiandrogens
(treatment for advanced carcinoma of the
prostate), and (8) exhaustion atrophy, which may
follow persistent stimulation by high levels of
follicle-stimulating pituitary hormone.
•The gross and microscopic alterations follow the
pattern already described for cryptorchidism.
Atrophy occasionally occurs as a primary failure
of genetic origin, such as in Klinefelter syndrome

28. INFLAMMATORY CONDITIONS OF THE TESTES.
oInflammation of the
testis is termed as orchitis
and of epididymis is
called as epididymitis;
the latter being more
common. A combination
epididymo-orchitis may
also occur.
 Non-specific
epididymitis and orchitis.
Is acute or chronic
inflammation of the
epididymis and the testes.
Commonly related to
infections of the urinary
tract i.e. cystititis, urthritis
or prostititis, the
microorganisms get to the
epididymis through the
vas deferens or the
lymphatics.

29. The etiological agents vary with age;
In children its usually due to congenital
abnormalities and usually through gram
negative rods.
In the sexually active adults <35 years its usually
due to Clostridium trachomatis and Neisseria
gonorrheae
In those >35years its usually as a result of E.coli
and Pseudomonas

30. •Morphology
Gross
- In the acute stages, testis
are firm, swollen (due to
edema) and congested.
- In cases of gonorrhea,
there may be multiple
abscesses.
- In chronic cases, the testis
may become atrophic and
fibrotic.
Microscopic
- Congestion, edema and
diffuse infiltration of
neutrophils.
- In the early stages the
infection is limited to the
interstial tissue however,
in the later stages, it may
spread to involve the
tubules and progress to
formation of an abscess or
complete suppurative
necrosis of the entire
epididymis.
- From the epididymis, the
reaction spreads to the
testis to evoke a similar
response.

31.  Granulomatous (Autoimmune) orchitis
•This idiopathic form of orchitis mainly affects the
middle aged men, who present with a moderately
tender testicular mass and sometimes with fever.
•May appear suddenly as a painless swelling similar
to testicular tumor.
•It is a type of Type IV hypersensitivity reaction
with a non-caseating granuloma.

32. Morphology.
Gross
oAffected testis is enlarged with a thickened tunica.
The cut surface is greyish-white to tan-brown.
Microscopic
oNon-caseating granulomas that are restricted to the
seminiferous tubules. The granuloma is composed of
epithelioid cells (originate from Sertoli cells),
neutrophils, plasma cells, some lymphocytes and
large multinucleated giant cells.
oThe lesions closely resemble tubercles but differ in
that the granulomatous reaction is present diffusely
throughout the testis and is confined to the
seminiferous tubules

33.  Tuberculous epididymo-orchitis
 Unilateral, painless, testicular enlargement that may
clinically resemble testicular tumor.
 Occurs mostly in middle aged men and is usually a
secondary TB from the genitourinary tract, the lungs and
the kidneys.
 It starts from the epididymis and spreads to the testis.
It manifests as palpable enlargement of the epididymis and
beading of the vas deferens, with confluent caseating
granulomas.

34. Morphology
Gross. – discrete, yellowish caseating necrotic areas.
Chronically may cause discharging sinuses on the scrotal
skin.
Microscopic - Caseating granulomas and mass
destruction of the epididymis.

35. Spermatic granuloma
These are inflammatory lesions in the testis as a
result of spermatozoa invasion of the stroma.
These lesion arise as a result of;
Trauma
Inflammation
Loss of ligation after a vasectomy.

36. Morphology.
Gross – the granuloma is a small nodule that
measures 3mm –3cm in diameter and is firm and
white-yellowish brown.
Microscopy – A granuloma that is composed of
epithelioid cells, histiocytes, lymphocytes,
macrophages and some neutrophils. The center is
composed of spermatozoa and necrotic debris.
– In the late stages there’s fibroblast proliferation at the periphery
and there’s hyalinization.

37.  Elephantiasis.
• This is the thickening of the scrotal skin and ultimately
results in the enlargement of the scrotum.
•This condition results from the parasitic infection,
Filariasis, in which the adult form lives in the
lymphatics and the larvae are found in the blood. The
most common filarial worm is the Wuchereria
bancrofti, which is transmitted by the culex mosquito.
•Presentation; May be asymptomatic or may present
with fever, tender lymphadenopathy, rash, blood
eosinophilia and local pain.

38. Morphology
• Gross – the affected leg and scrotum are thickened with
enlargement of the lymph nodes. The affected leg also
shows dilated dermal lymphatics and varicose.
• Microscopy – The worm in the dead, alive or calcified form
is found in the dilated lymphatics and lymph nodes.
- Lymphangitis as a result of the dead or calcified
form, this is evident with intense infiltration of
eosinophils.
- In advanced cases, chronic lymphedema with
tough subcutaneous fibrosis and epidermal
hyperkeratosis develops which is termed
elephantiasis.

39.  Specific inflammatory causes;
Gonorrhea
• Is as a result of extension from the posterior urethra to
prostate , seminal vesicles and finally to the epididymis.
• In advanced cases, there’re epididymal abscesses that
leads to extensive destruction and fibrosis.
• The testis are then involved causing a suppurative
orchitis.

40. Mumps
•Is a systemic viral disease, this majorly affects the
children, however testicular involvement in this
age group is rare.
•In post-puberty males, there’s acute orchitis after
1 week after the onset of parotid swelling.

41. Syphilis
•The testis and epididymis may be affected in
both acquired and congenital syphilis, but
almost invariably the testis is involved first.
• The morphologic pattern of the reaction takes
two forms:
(1)the production of gummas (these are characteristic of the tertiary
stage) or
(2)a diffuse interstitial inflammation that produces the histologic
hallmark of syphilitic infections, obliterative endarteritis
associated with perivascular cuffs of lymphocytes and plasma
cells.

42. Vascular Disorders.
• Torsion.
•Twisting of the spermatic cord typically cuts off the
venous drainage of the testis. If untreated, it leads to
testicular infarction.
• The thick-walled arteries remain patent, producing
intense vascular engorgement followed by
hemorrhagic infarction.

43. • Is of 2 types;
Neonatal torsion – this may occur in utero or
shortly after birth. There’s usually no anatomic
defect.
Adult torsion – happens in adolescence and is
characterized by a sudden onset of testicular pain.
There’s no inciting injury and may also occur at
night.
There’s a bilateral anatomical defect that
causes an increased mobility of the testes, this
is called the bell clapper abnormality.

44. Morphology
• Depending on the duration, there maybe congestion to
widespread hemorrhage and testicular infarction.
• In the advanced stages, the testis is enlarged, and is soft,
necrotic and hemorrhagic.
• Undergoes coagulative necrosis along with the epididymis.

47. Varicocele.
• Varicocele is the dilatation, elongation and tortuosity of the
veins of the pampiniform plexus in the spermatic cord. It is
of 2 types: primary (idiopathic) and secondary.
• Primary or idiopathic form is more frequent and is more
common in young unmarried men. It is nearly always on
the left side as the loaded rectum presses the left vein.
Besides, the left spermatic 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 spermatic
vein by enlarged liver, spleen or kidney. It is commoner in
middle-aged people.

48. • The increased blood flow makes this lesion a radiant heat
device that increases the temperature of testicular tubules,
inhibiting normal spermatogenesis.

49. Hydrocele
• Is the collection of serous fluid in the tunica vaginalis. This
fluid is straw colored, however maybe slightly hemorrhagic
and turbid.
• Can be classified as being acute or chronic, congenital or
acquired.
• Causes include; trauma and systemic edema as seen in
cardiac and renal failure.
• Is also a complication of TB, syphilis and gonorrhea.

50. • The sac may have a single loculus (cavity) or multiple loculi.
• The sac contains fibrous tissue and infiltrated by lymphocytes and
plasma cells.

51. HAEMATOCELE
• Haematocele is haemorrhage 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 a recent haematocele, 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 organized
haemorrhage and occasionally may get partly
calcified.

53. • CHYLOCELE refers to the accumulation of lymph in
the tunica and is almost always found in patients
with elephantiasis who have widespread, severe
lymphatic obstruction caused, for example, by
filariasis.
•SPERMATOCELE refers to a small cystic accumulation
of semen in dilated efferent ducts or ducts of the
rete testis.

54. TUMORS
•SPERMATIC CORD TUMORS.
The most common are the lipomas.
It is not exactly a tumor, it is retroperitoneal fat
that is pulled in through the inguinal canal.

55. •PARATESTICULAR TUMORS.
Benign tumor
Most common are adenomatoid tumors and are
mesothelial in nature.
These tumors are small nodules near the upper poles
of the epididymis.
Grossly is well circumscribed, and microscopically they
maybe minimally invasive to the adjacent testis.
Malignant tumors
•The most common one in adults is Rhabdomyosarcoma
and in children is liposarcomas.

56. Testicular tumors
•These are of 2 types;
• Germ cell tumors
• Sex cord-stromal tumors.
•Germ cell tumors are further divided into seminomas and
non-seminomas. These tumors are very aggressive cancers
capable of rapid and wide dissemination.
•Sex cord-stromal tumors are benign tumors.
•Risk factors include; cryptorchidism, genetic factors and also
developmental disorders.

58. •Often the rst sign of testicular cancer is a slight enlargement of
the testicle that may be accompanied by some degree of
discomfort. This may be an ache in the abdomen or groin or a
sensation of dragging or heaviness in the scrotum.
•Frank pain may be experienced in the later stages, when the
tumor is growing rapidly and hemorrhaging occurs. Testicular
cancer can spread when the tumor may be barely palpable.
•Approximately 10% of men present with symptoms related to
metastatic disease.
•Signs of metastatic spread include swelling of the lower
extremities, back pain, neck mass, cough, hemoptysis, or
dizziness. Gynecomastia (breast enlargement) may result from
human chorionic gonadotropin (hCG)-producing tumors and
occurs in about 5% of men with germ cell tumors.

59. Germ cell tumors
• Are the most common in the age group of 15-35.
Etiology.
• Environmental factors
Testicular germ cell tumors are associated with a
spectrum of disorders collectively known as testicular
dysgenesis syndrome (TDS).
Components of this syndrome include cryptorchidism,
hypospadias, and poor sperm quality. It has been
proposed that these conditions are increased by in utero
exposures to pesticides and nonsteroidal estrogen.

60. • Genetic factors.
• There is a high familial predisposition for testicular germ cells.
• Several genetic loci have been linked to familial germ cell
tumor risk, including the genes encoding the ligand for the
receptor tyrosine kinase KIT and BAK, which is an important
inducer of apoptotic cell death. These genes are also thought
to play a role in gonadal development.

61. • Classification.
• There are two groups;
• Seminomatous tumors are composed of cells that resemble
primordial germ cells or early gonocytes.
• The non-Seminomatous tumors may be composed of
undifferentiated cells that resemble embryonic stem cells, as
in the case of embryonal carcinoma
• NB. The malignant cells may also differentiate along other
lineages, generating yolk sac tumors, choriocarcinomas and
teratomas.
Germ cell tumors may have a single tissue component, but in
approximately 60% of cases the tumors contain mixtures of
Seminomatous and non-Seminomatous components and
multiple tissues.

63. Pathogenesis.
• Most testicular germ cell tumors originate from a precursor lesion
called intratubular germ cell neoplasia (ITGCN). The exceptions to
this rule are pediatric yolk sac tumors and teratomas, and adult
spermatocytic seminomas, all of which are of uncertain origin.
• The ITGN arises in utero but remains dormant till adolescence
when the seminoma or non-seminoma starts to develop.
• Activating mutations in the gene encoding the KIT receptor
tyrosine kinase, which may be present in seminomas, are also
frequently present in ITGCN.
• Particularly important is the reduplication of the short arm of
chromosome 12 (12p) in the form of an isochromosome i(12p), a
cytogenetic alteration that is invariably found I invasive germ cell
tumors regardless of histological type.

64. Clinical features.
• Gradual gonadal enlargement and dragging sensation in the
testes.
• Metastatic involvement may produce secondary symptoms
such as pain, lymphadenopathy, hemoptysis and urinary
obstruction.
Spread.
• Spread is by 2 routes i.e. the lymphatic and the hematogenous
route.
• Lymphatic spread occurs to the para-aortic, mediastinal and
supraclavicular lymph nodes.
• Hematogenous spread occurs to the lungs, liver, brain and
bones.

65. NB
•Metastases from seminomas typically involve lymph
nodes. Hematogenous spread occurs later in the
course of dissemination. NSGCTs not only
metastasize earlier but also use the hematogenous
route more frequently.
•The rare pure choriocarcinomas is the most
aggressive NSGCT. It may not cause any testicular
enlargement but instead spreads predominantly and
rapidly by the bloodstream. Therefore, lungs and
liver are involved early in virtually every case

66. Tumor markers.
• Germ cell tumours of the testis secrete polypeptide hormones and
certain enzymes which can be detected in the blood. Two tumour
markers widely used in the diagnosis:
1. hCG is synthesized by placental syncytio-trophoblast such as in
various non-Seminomatous germ cell tumours of the testis (e.g. in
choriocarcinomas, yolk sac tumour and embryonal carcinoma).
However, ectopic hCG production may occur in a variety of non-
testicular non-germ cell tumours as well.
2. AFP is normally synthesized by the fetal liver cells, yolk sac and fetal
gut. Its levels are elevated in testicular tumours associated with yolk
sac components. However, elevated serum AFP levels are also found in
liver cell carcinoma.
In addition, carcinoembryonic antigen (CEA), human placental
lactogen (HPL), placental alkaline phosphatase, testosterone,
oestrogen and luteinizing hormone may also be elevated.

67. Prognosis.
• These tumors are staged in 3 stages;
• Stage I – the tumor is confined to the testes.
• Stage II – distant spread confined to the retroperitoneal lymph nodes
below the diaphragm.
• Stage III – there is distant spread beyond the diaphragm.
• Seminomas are generally in stage I.
• Non-Seminomas can be in either stage II or III.
• Seminomas are extremely radiosensitive while non-
Seminomatous germ cell tumours are radio-resistant.
• In general, seminomas have a better prognosis with 90% cure
rate while the non-Seminomatous tumours behave in a more
aggressive manner and have poor prognosis.

68. Classic Seminoma
• Most common type of germ cell tumor.
• Peak incidence is the third decade and almost doesn't occur
infants.
Morphology.
Gross.
• The testes are 10 times the normal size and bulky but maintain
the normal contours.
• The typical seminoma has a homogeneous, gray-white, lobulated
cut surface, usually devoid of hemorrhage or necrosis.
• The larger tumour replaces the entire testis, whereas the smaller
tumour appears as circumscribed mass in the testis.

69. Microscopic.
• Tumour cells – the seminoma cells generally lie in cords, sheets or
columns forming lobules.
• The classic seminoma cell is large and round to polyhedral and
has a distinct cell membrane. The cytoplasm contains variable
amount of glycogen that stains positively with PAS reaction.
• The nuclei are centrally located, large, hyperchromatic and
usually contain 1-2 prominent nucleoli.
• Tumour giant cells may be present.
• Stroma – the stroma of seminoma is a delicate fibrous tissue
which divides the tumour into lobules. The stroma shows a
characteristic lymphocytic infiltration, indicative of immunologic
response of the host to the tumour. About 20% of the tumours
show granulomatous reaction in the stroma

70. • Microscopically, there are two variants;
• Seminoma with syncytiotrophoblast giant cells. These are
best demonstrated by antibodies against hCG. Although
they produce hCG, the blood levels of hCG are low.
• Rarely, the cells may show increased mitotic activity and
nuclear morphism, this is anaplastic seminoma.

72. Spermatocytic Seminoma
•Is a slow-growing tumor that usually occur in the 6th
decade.
•Doesn't metastasize.
•Is a benign tumor.
Morphology.
Gross.
•Spermatocytic seminoma tends to have a soft, pale gray,
cut surface that sometimes reveal mucoid cysts.

73. Spermatocytic Seminoma
Microscopic.
•Spermatocytic seminomas contain three cell populations,
all intermixed:
• Medium-sized cells, the most numerous, containing a
round nucleus and eosinophilic cytoplasm;
• Smaller cells with a narrow rim of eosinophilic
cytoplasm resembling secondary spermatocytes; and
• Scattered giant cells, either uninucleate or
multinucleate.
•The stroma lacks lymphocytic and granulomatous reaction
seen in classic seminoma.

74. Embryonal carcinoma
• Common in 20 – 30 years age group.
• Much more aggressive than the Seminomas.
• About 90% cases are associated with elevation of AFP or hCG or
both.
Morphology.
Gross.
• Smaller than seminoma and affect the contour of the testes due to
invasion of the tunica albuginea and epididymis.
• On cut surfaces, the tumor is often variegated, poorly demarcated
at the margins, and punctuated by foci of hemorrhage or necrosis

75. Microscopic.
• Histologically the cells grow in alveolar or tubular patterns,
sometimes with papillary convolutions.
• More undifferentiated lesions may display sheets of cells. Well
formed glands are absent.
• The neoplastic cells have an epithelial appearance, are large and
anaplastic, and have hyperchromatic nuclei with prominent
nucleoli and an amphophilic cytoplasm.
• The cell borders are usually indistinct, and there is considerable
variation in cell and nuclear size and shape.
• Mitotic figures and tumor giant cells are frequently seen.
• The stroma is not as distinct as in seminoma and may contain
variable amount of primitive mesenchyme.

78. Yolk sac tumors.
• Also called Endodermal Sinus Tumour, Orchioblastoma, Infantile
Embryonal Carcinoma.
• Is common in infants and children up to 3 years.
• In adults the pure form of this tumor is rare; instead, yolk sac
elements frequently occur in combination with embryonal
carcinoma.
Morphology.
Gross
• Are nonencapsulated.
• Have a homogenous, yellow-white and mucinous appearance.

79. Microscopically.
• They are composed of a lacelike (reticular) network of medium-sized
cuboidal or flattened cells.
• In addition, papillary structures, solid cords of cells, and a multitude
of other less common patterns may be found.
• In approximately 50% of tumors, structures resembling endodermal
sinuses (Schiller-Duval bodies) may be seen; these consist of a
mesodermal core with a central capillary and a visceral and parietal
layer of cells resembling primitive glomeruli.
• Present within and outside the cytoplasm are eosinophilic, hyaline-
like globules in which α-fetoprotein (AFP) and α1- antitrypsin can be
demonstrated by immunocytochemical staining.
• The presence of AFP in the tumor cells is highly characteristic, and
underscores resemblance to yolk sac cells.

81. CHORIOCARCINOMA
•It is a highly malignant form of testicular tumor.
•In its “pure” form, choriocarcinoma is rare,
constituting less than 1% of all germ cell tumors.
•It is composed of elements consisting of
syncytiotrophoblast and cytotrophoblast.
•The primary tumour is usually small and the
patient may manifest initially with symptoms of
metastasis.
•The serum and urinary levels of hCG are greatly
elevated in 100% cases.

82. MORPHOLOGY
GROSSLY,
•These tumors are soft, small, rarely larger than
5 cm in diameter.
•Hemorrhage and necrosis are extremely
common.
MICROSCOPICALLY,
•The characteristic feature is the identification of
intimately related syncytiotrophoblast and
cytotrophoblast without formation of definite
placental type villi.

83. Syncytiotrophoblasts are large with many irregular
and bizarre nuclei and abundant eosinophilic
vacuolated cytoplasm which stains positively for
hCG.
• These cells often surround masses of
cytotrophoblastic cells.
Cytotrophoblasts are more regular and tend to be
polygonal, with distinct borders and clear or
eosinophilic cytoplasm with hyperchromatic nuclei;
they grow in cords or masses and have a single, fairly
uniform nucleus.

85. TERATOMA
•Teratomas are complex tumours composed
of tissues derived from more than one of the
three germ cell layers—endoderm,
mesoderm and ectoderm.
•Testicular teratomas are more common in
infants and children and constitute about
40% of testicular tumours in infants, whereas
in adults they comprise 5% of all germ cell
tumours.

86. •However, teratomas are found in combination
with other germ cell tumours (most commonly
with embryonal carcinoma) in about 45% of
mixed germ cell tumours. About half the
teratomas have elevated hCG or AFP levels or
both.
MORPHOLOGY
Testicular teratomas are classified into 3 types:
1. Mature (differentiated) teratoma
2. Immature teratoma.
3. Teratoma with malignant transformation.

87. GROSSLY,
•They 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.
•Dermoid tumours commonly seen in the ovaries
are rare in testicular teratomas.

88. MICROSCOPICALLY,
The three categories of teratomas show different
appearances:
1. Mature (differentiated) teratoma
•It is composed of disorderly mixture of a variety of
well differentiated structures such as cartilage,
smooth muscle, intestinal and respiratory
epithelium, mucus glands, cysts lined by squamous
and transitional epithelium, neural tissue, fat and
bone.
•This type of mature or differentiated teratoma is the
most common, seen more frequently in infants and
children and has favorable prognosis.

89. •It is believed that all testicular teratomas in the
adults are malignant.
2. Immature teratoma
• Immature teratoma is composed of incompletely
differentiated and primitive or embryonic tissues
along with some mature elements.
•Primitive or embryonic tissue commonly present are
poorly-formed cartilage, mesenchyme, neural
tissues, abortive eye, intestinal and respiratory tissue
elements etc.
•Mitoses are usually frequent.

90. 3. Teratoma with malignant transformation
•This is an extremely rare form of teratoma in
which one or more of the tissue elements
show malignant transformation.
• Such malignant change resembles
morphologically with typical malignancies in
other organs and tissues and commonly
includes rhabdomyosarcoma, squamous cell
carcinoma and adenocarcinoma.

92. TUMORS OF SEX CORD-GONADAL STROMA
Sex cord-gonadal stroma tumors are
subclassifed based on their presumed
histogenesis and differentiation.
There are two types:
i. Leydig cell tumors
ii. Sertoli tumors

93. LEYDIG CELL TUMORS
•These cells secrete androgens and in some
cases both androgens, estrogens and rarely
corticosteroids.
•They may occur at any age but more
frequent in the age group of 20 and 60
years.
•Bilateral tumors may occur typically in
congenital Adrenogenital syndrome.

94. MORPHOLOGY
GROSS
• they appear as small, well-demarcated and forms
circumscribed nodules, usually less than 5 cm in
diameter.
• They have a distinctive golden brown, homogenous
cut surface.
MICROSCOPICALLY,
• They are large in size and have round or polygonal
cell outlines, abundant granular eosinophilic
cytoplasm, and round central nucleus.

95. •The cytoplasm frequently contains lipid
droplets, vacuoles, or lipofuscin
pigment, and, most characteristically,
rod-shaped crystalloids of Reinke,
which are seen in about 25% of the
tumors.
• Approximately 10% of the tumors in
adults are invasive and produce
metastases; most are benign.

97. SERTOLI CELL TUMORS (ANDROBLASTOMA)
•These tumors are hormonally silent and
present as a testicular mass.
•They correspond to arrhenoblastoma of the
ovary.
•They occur at all ages but more frequent in
infants and children.
•These tumors elaborate estrogen or androgen
and may account for gynecomastia in an adult,
or precocious sexual development in a child.

98. MORPHOLOGY
GROSSLY,
•The tumor is fairly large, firm, round, and well
circumscribed nodules.
•Cut surface of the tumor is yellowish or yellow-
grey.
MICROSCOPICALLY,
•The tumor cells are arranged in distinctive
trabeculae that tend to form cordlike structures
and tubules.
•Majority of sertoli cell tumors are benign but only
10%may metastasize to regional lymph nodes.

100. GONADOBLASTOMA
• They are rare neoplasms comprised of a mixture of
germ cells and gonadal stromal elements that almost
always arise in gonads with some form of testicular
dysgenesis.
• In some cases the germ cell component becomes
malignant, giving rise to seminoma.
• The patients are commonly intersexual, particularly
phenotypic females.
• They secrete androgen and therefore produce
virilisation in female phenotype.

101. MORPHOLOGY
GROSSLY,
•The tumor is of variable size, yellowish-white and
soft.
MICROSCOPICALLY,
•It is composed of 2 principal cell types:
large germ cells resembling seminoma cells,
 small cells resembling immature Sertoli, Leydig
and granulosa cells.
•Call-Exner bodies of a granulosa cell tumour may be
present.

102. TESTICULAR LYMPHOMA
•Aggressive non–Hodgkin lymphomas account
for 5% of testicular
neoplasms, and are the most common form of
testicular neoplasms in men older than age 60
years.
•testicular lymphoma may present with only a
testicular mass, mimicking other, more
common, testicular tumors.

103. •In most cases, the disease is already
disseminated at the time of detection.
•The most common testicular lymphomas,
in decreasing order of frequency, are
diffuse large B-cell lymphoma, Burkitt
lymphoma, and EBV-positive extranodal
NK/T cell lymphoma.
•Testicular lymphomas have a higher
propensity for central nervous system
involvement than do similar tumors arising
at other sites.

104. Mixed tumors.
•About 60% of testicular tumors are composed of more
than one of the “pure” patterns. Common mixtures
include:
• teratoma, embryonal carcinoma, and yolk sac tumor;
• seminoma with embryonal carcinoma;
• and embryonal carcinoma with teratoma (teratocarcinoma).
•In most instances the prognosis is worsened by the
presence of the more aggressive element.