mgt2 patho

1. Male Genital System(Part-II)

2. Congenital anomalies of Testis
• Cryptorchidism :
Failure of descent of testis from the abdominal cavity through the
inguinal canal.
• Causes
- Most common  idiopathic
• Epidemiology
– about1% of males
– right > left, 25% bilateral
• Pathogenesis
– Hormonal abnormalities
– Testicular abnormalities
– Mechanical problems

3. • Clinical course
– Testicular descent occurs in two morphologically and hormonally distinct
phases.
– During the first, the 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, or the inguinoscrotal, phase, the testes descend through
the inguinal canal into the scrotal sac. This phase is androgen dependent
– When unilateral, may see atrophy in contralateral testis.
– sterility
– concomitant inguinal hernia
– increased risk of testicular malignancy

4. • Morphology
– Atrophic changes by 2 yrs of age;
– Arrest in the development of germ cells
– Hyalinization and thickening of seminiferous
tubules & interstitial fibrosis
– Sparing Leydig cells which become prominent
– With progressive tubular atrophy the testis
becomes small and firm in consistency.
– Similar changes - contralateral descended testis

5. Cryptorchid testis from a 17-year-old. Postpubertal seminiferous tubules are lined by
Sertoli cells. The tubule at the right also has primary spermatocytes. Tubules at bottom
left are lined by immature Sertoli cells and are persistent immature tubules.

6. Orchiopexy ( Placement in the scrotal sac)
• May help prevent atrophy
• May not decrease risk of malignancy.

7. Testicular Atrophy(REGRESSIVE
CHANGES )
Atrophy is a regressive change affecting scrotal testis.
It is the end stage of an inflammatory orchitis
Possible causative factors:
– Atherosclerotic narrowing of the blood supply in old age
– Cryptorchidism
– hypopituitarism
– generalized malnutrition or cachexia
– irradiation
– prolonged administration of female sex hormones, as in
treatment of patients with carcinoma of the prostate
– Cirrhosis
– klinefelter’s syndrome.

8. Clinical features:
Associated with decreased fertility,
hypospermatogenesis, maturation arrest and
sometimes vas deferens obstruction.
Histology:
– Hyalinization of seminiferous tubules & interstitial
fibrosis
– Sparing of Leydig cells.

9. REGRESSIVE CHANGES(Testicular
Atrophy)

10. INFLAMMATION
• Inflammations are distinctly more common in
the epididymis than in the testis.
• Of the three major specific inflammatory
states that affect the testis and epididymis,
gonorrhea and tuberculosis almost invariably
arise in the epididymis, whereas syphilis
affects first the testis.

11. Nonspecific Epididymitis and Orchitis
• Epididymitis and possible subsequent orchitis are commonly related
to infections in the urinary tract (cystitis, urethritis, prostatitis),
which reach the epididymis and the testis through either the vas
deferens or the lymphatics of the spermatic cord.
• The cause of epididymitis varies with the age of the patient. Though
uncommon in children, epididymitis in childhood is usually
associated with a congenital genitourinary abnormality and
infection with gram-negative rods .
• In sexually active men younger than age 35 years, the sexually
transmitted pathogens C. trachomatis and Neisseria gonorrhoeae
are the most frequent culprits. In men older than age 35 the
common urinary tract pathogens, such as E. coli and Pseudomonas,
are responsible for most infections.

12. • Morphology. The bacterial invasion induces
nonspecific acute inflammation characterized by
congestion, edema, and infiltration by neutrophils,
macrophages, and lymphocytes.
• Although the infection, in the early stage, is more or
less limited to the interstitial connective tissue, it
rapidly extends to involve the tubules and may
progress to frank abscess formation or complete
suppurative necrosis of the entire epididymis
• Such inflammatory involvement of the epididymis and
testis is often followed by fibrous scarring, which in
many cases leads to sterility.

13. Acute epididymitis caused by gonococcal infection. The
epididymis is replaced by an abscess. Normal testis is seen on
the right.

14. Granulomatous (Autoimmune)
Orchitis
• Idiopathic granulomatous orchitis presents in
middle age as a moderately tender testicular
mass of sudden onset sometimes associated
with fever.
• It may appear insidiously, however, as a
painless testicular mass mimicking a testicular
tumor, hence its importance.
• Histologically the orchitis is distinguished by
granulomas restricted to spermatic tubules.

15. Specific Inflammations
• Gonorrhea
Extension of infection from the posterior urethra to the prostate,
seminal vesicles, and then to the epididymis is the usual course of a
neglected gonococcal infection.
Inflammatory changes similar to those described for nonspecific
infections occur, with the development of frank abscesses in the
epididymis, which may lead to extensive destruction of this organ.
• Mumps
Mumps is a systemic viral disease that most commonly affects
school-aged children. Testicular involvement is extremely
uncommon in this age group.
In postpubertal males, however, orchitis may develop and has been
reported in 20% to 30% of male patients. Most often, acute
interstitial orchitis develops about 1 week after the onset of
swelling of the parotid glands.

16. • Tuberculosis
Tuberculosis almost invariably begins in the epididymis and may
spread to the testis.
The infection invokes the classic morphologic reactions of caseating
granulomatous inflammation characteristic of tuberculosis
elsewhere.
• Syphilis
The testis and epididymis are affected in both acquired and
congenital syphilis, but almost invariably the testis is involved first
by the infection. In many cases, the orchitis is not accompanied by
epididymitis.
The morphologic pattern of the reaction takes two forms: the
production of gummas or a diffuse interstitial inflammation
characterized by edema and lymphocytic and plasma cell infiltration
with the characteristic hallmark of all syphilitic infections

17. VASCULAR DISEASES(Torsion of testis)
• Twisting of the spermatic cord which typically cuts off the venous
drainage of the testis
• Bilateral anatomic defect where the testis has increased mobility
giving rise to “bell-clapper” abnormality
• Infracted testicle and epididymis due to torsion
• Neonatal torsion occurs either in utero or shortly after birth. It lacks
any associated anatomic defect to account for its occurrence.
• Adult torsion is typically seen in adolescence presenting as sudden
onset of testicular pain. It often occurs without any inciting injury;
sudden pain heralding the torsion may even occur during sleep.
• Morphology. Depending on the duration of the process, the
morphologic changes range from intense congestion to widespread
extravasation of blood into the interstitial tissue to hemorrhagic
testicular infarction

18. Torsion of testis- testis is markedly enlarged and is converted
virtually into a sac of soft, necrotic, hemorrhagic tissue.

19. TESTICULAR TUMORS
WHO CLASSIFICATION
 GERM CELL TUMORS
SEMINOMATOUS
• Classical Seminoma
• Spermatocytic seminoma
NON-SEMINOMATOUS
• Embryonal carcinoma
• Embryonal carcinoma and
teratoma (‘teratocarcinoma’)
• Teratoma-Mature,Immature,
With malignant transformation
• Choriocarcinoma
• Yolk sac tumour
 SEX CORD STROMAL
TUMORS
1. Leydig cell tumor
2. Sertoli cell tumor
3. Granulosa cell tumor
4. Mixed forms

20. TESTICULAR TUMORS
• COMBINED GERM
CELL – SEX CORD
TUMORS
1. Gonadoblastoma
• OTHER TUMORS
1. Malignant lymphoma
2. Rare tumors

21. SEMINOMA
1. Most common germ cell tumor
2. Mean age is 30-40 yrs
3. Very rare in children
4. Patients present with painless testicular mass
5. 30 % have metastases at presentation, but only 3% have
symptoms related to metastases.

22. Gross appearance of seminoma. The tumor in A is very small,
whereas that in B has replaced most of the testis

23. Gross appearance of combined tumor of testis. In both instances, the solid
homogeneous gray areas correspond to the seminoma, and the variegated foci with
hemorrhage to the nonseminomatous component

24. SEMINOMA-microscopic picture
• MICROSCOPIC :
1. Tumor cells are
monomorphic, arranged in
solid nests separated by
fibrous septa
2. Cells are round to polygonal
having round to oval nuclei
with one to several nucleoli
& clear to eosinophillic
cytoplasm
3. Cell borders are well
defined
4. Granulomatous infiltrate in
50 % cases

25. Seminoma associated with marked granulomatous reaction. Only a few tumor cells are
visible in this field

26. This seminoma has increased nuclear pleomorphism and a
plasmacytoid appearance-anaplastic variant

27. Seminoma with trophoblastic giant cells. (A, Hematoxylin and eosin); B, hCG
immunostain

28. SEMINOMA-IHC
• IMMUNOHISTO CHEMISTRY
• Cells are OCT3,4+ve,
• PLAP +ve, &
• c-kit +ve
• Contains cytokeratins, although only
36 % cases are +ve.
• EMA -ve

29. SEMINOMA Strong
reactivity for PLAP

30. strong nuclear and weaker cytoplasmic reactivity for OCT3/4 in this seminoma

31. SPERMATOCYTIC SEMINOMA
1. Occurs only in testis & represents 2 % of germ cell
tumors
2. Patients are in 60s & present with testicular mass
3. Very rarely metastasize.

32. SPERMATOCYTIC SEMINOMA-
Gross
• MACROSCOPIC
1. Tumors are soft
multinodular & have a
pale gray to yellow
edematous appearance
2. Hemorrhage &
mucoid cystic change
can be present

33. spermatocytic seminoma shows fleshy, gelatinous, and hemorrhagic nodules

34. SPERMATOCYTIC
SEMINOMA
• MICROSCOPIC :
1. Characterized by
polymorphous cell
population composed of
small cells, intermediate
cells which is predominant &
few multinucleate giant cells
2. Cells are arranged in sheets
& microcysts are present
3. Nests & pseudo glandular
structures are also identified
4. Mitotic figures can be
numerous
5. Lymphoid & granulomatous
infiltrates are absent

35. Spermatocytic seminoma showing admixture of medium-sized cells
(predominating), giant cells, and small lymphocyte-like cells

36. SPERMATOCYTIC SEMINOMA-IHC
• IMMUNOHISTO CHEMISTRY
• Cells are PLAP –ve,
• vimentin –ve,
• muscle marker –ve,
• cytokeratin –ve, AFP –ve,
• HCG –ve,
• EMA –ve

37. EMBRYONAL CARCINOMA
1. 2nd most common germ cell tumor,
comprising approx. 20 % cases
2. Present in majority of mixed germ cell
tumors
3. Most men present in their 20s to 30s with a
testicular mass
4. More than 2/3rds of patients have
metastases, but only 10 % have symptom
related to metastases.

38. EMBRYONAL CARCINOMA-Gross
• MACROSCOPIC
:
1. Smaller than
seminoma,
2. C/S- fleshy gray
white tumor with
prominent
necrosis &
hemorrhage

39. EMBRYONAL CARCINOMA-
microscopy
• MICROSCOPIC :
1. Cells are large with vesicular nuclei, prominent nucleoli, &
indistinct cell borders
2. Tumor cells are arranged in sheets, cords & glandular
structure
3. Necrosis & hemorrhage may be prominent
4. May be intimately admixed with a yolk sac tumor

40. Embryonal carcinoma. The pattern of growth is diffuse , The high-power
view shows the typical large, irregularly shaped, overlapping nuclei with
multiple prominent nucleoli

41. EMBRYONAL CARCINOMA-
IHC
• IMMUNOHISTO CHEMISTRY
• Tumor cells are CD 30 +ve, a finding unique to
Embryonal carcinoma, and useful in ruling out solid
pattern of Embryonal carcinoma, which can simulate
Seminoma .
• OCT 4 +ve,
• PLAP +ve,
• cytokeratin +ve,
c-kit –ve, and EMA -ve

42. CD30 highlights the cytoplasmic membranes of an embryonal carcinoma

43. Choriocarcinoma
• Choriocarcinoma is a highly malignant form of testicular tumor. In
its “pure” form choriocarcinoma is rare, constituting less than 1% of
all germ cell tumors.
• Morphology. Often they cause no testicular enlargement and are
detected only as a small palpable nodule. Typically, these tumors
are small, rarely larger than 5 cm in diameter. Hemorrhage and
necrosis are extremely common.
• Histologically the tumors contain two cell types- cytotrophoblasts
and syncytiotrophoblasts
• Syncytiotrophoblast appears as a large cell having many irregular or
lobular hyperchromatic nuclei and an abundant eosinophilic
vacuolated cytoplasm
• Cytotrophoblasts are more regular and polygonal with distinct
borders and clear cytoplasm.

44. Choriocarcinoma shows clear cytotrophoblastic cells with central nuclei and
syncytiotrophoblastic cells with multiple dark nuclei embedded in
eosinophilic cytoplasm. Hemorrhage and necrosis are also seen

45. Yolk Sac Tumor
• The most common testicular tumor in infants and
children up to 3 years with very good prognosis
• Lace-like (reticular) network of medium-sized
cuboidal or elongated cells.
• Pathognomonic lesion is the presence of Schiller-
Duval bodies, which resemble the primitive
glomeruli and other endodermal sinuses
(perivascular formation around tumor cells).

46. 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 globule.

48. Teratoma
• The designation teratoma refers to a group of
complex testicular tumors having various cellular
or organoid components reminiscent of normal
derivatives from more than one germ layer.
• They may occur at any age from infancy to adult
life. Pure forms of teratoma are fairly common in
infants and children, second in frequency only to
yolk sac tumors.
• In adults, pure teratomas are rare, constituting
2% to 3% of germ cell tumors.

49. • Morphology. Grossly, teratomas are usually large, ranging
from 5 to 10 cm in diameter. Because they are composed of
various tissues, the gross appearance is heterogeneous
with solid, sometimes cartilaginous, and cystic areas.
Hemorrhage and necrosis usually indicate admixture with
embryonal carcinoma, choriocarcinoma, or both.
• Microscopically,Teratomas are composed of a
heterogeneous, helter-skelter collection of differentiated
cells or organoid structures, such as neural tissue, muscle
bundles, islands of cartilage, clusters of squamous
epithelium, structures reminiscent of thyroid gland,
respiratory epithelium, and bits of intestinal wall or brain
substance, all embedded in a fibrous or myxoid stroma.
• Elements may be mature (resembling various adult tissues)
or immature (sharing histologic features with fetal or
embryonal tissue).

50. Immature teratoma testis. Microscopy shows a variety of incompletely
differentiated tissue elements

51. • “teratoma with malignant transformation,”
where there is malignancy in derivatives of
one or more germ cell layers. Thus, there may
be a focus of squamous cell carcinoma, mucin-
secreting adenocarcinoma, or sarcoma.

52. Tumors of Sex Cord–Gonadal Stroma
• Sex cord–gonadal stroma tumors are subclassified
based on their presumed histogenesis and
differentiation. The two most important members of
this group—Leydig cell tumors and Sertoli cell tumors.
Leydig Cell Tumors
• Tumors of Leydig cells are particularly interesting,
because they may elaborate androgens and in some
cases both androgens and estrogens, and even
corticosteroids.
• They may arise at any age, although most cases occur
between 20 and 60 years of age.
• As with other testicular tumors, the most common
presenting feature is testicular swelling, but in some
patients gynecomastia may be the first symptom.

53. • Morphology. These neoplasms form circumscribed
nodules, usually less than 5 cm in diameter. They have a
distinctive golden brown, homogeneous cut surface.
Histologically, neoplastic Leydig cells usually are
remarkably similar to their normal counterparts in that
they are large and round or polygonal, and they have an
abundant granular eosinophilic cytoplasm with a round
central nucleus.
The cytoplasm frequently contains lipid granules, vacuoles,
or lipofuscin pigment, and, most characteristically, rod-
shaped crystalloids of Reinke occur in about 25% of the
tumors.
Approximately 10% of the tumors in adults are invasive
and produce metastases; most are benign.

54. Sertoli Cell Tumors
• Most Sertoli cell tumors are hormonally silent
and present as a testicular mass.
• Morphology. These neoplasms appear as firm,
small nodules with a homogeneous gray-white to
yellow cut surface.
Histologically the tumor cells are arranged in
distinctive trabeculae that tend to form cordlike
structures and tubules.
Most Sertoli cell tumors are benign, but
occasional tumors (∼10%) pursue a malignant
course.

55. Gonadoblastoma
• Gonadoblastomas are rare neoplasms containing 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.
Testicular Lymphoma
• Although an uncommon tumor of the testis, testicular lymphoma is included here
because affected patients present with only a testicular mass, mimicking other,
more common, testicular tumors.
• Aggressive non-Hodgkin lymphomas account for 5% of testicular neoplasms, and
are the most common form of testicular neoplasms in men over the age of 60. In
most cases, the disease is already disseminated at the time of detection.
• The most common testicular lyphomas, in decreasing order of frequency, are
diffuse large B cell lymphoma, Burkitt Lymphoma, and EBV-positive extranodal
NK/T cell lymphoma.
• Patients with testicular lymphomas have a higher incidence of central nervous
system involvement than those similar tumors located elsewhere.

56. MISCELLANEOUS LESIONS OF TUNICA
VAGINALIS
• Tunica vaginalis is a mesothelial-lined surface exterior to the testis that
may accumulate serous fluid (hydrocele) causing considerable
enlargement of the scrotal sac. By transillumination it is usually possible to
define the clear, translucent character of the contained fluid. Hydrocele
sacs are frequently lined by mesothelial cells.
• Rarely, malignant mesotheliomas also can be seen arising from the tunica
vaginalis.
• Hematocele indicates the presence of blood in the tunica vaginalis. It is an
uncommon condition usually encountered only when there has been
either direct trauma to the testis or torsion of the testis.
• 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 by filariasis.
• Spermatocele refers to a small cystic accumulation of semen in dilated
efferent ducts or ducts of the rete testis.
• Varicocele is a dilated vein in the spermatic cord.

57. THANK YOU….