1. Dr. Saket Singh
Guide:
Dr. Prabha Om

5. Histologic classifications, grading systems, and staging
evaluations have traditionally provided a major clinical
basis for therapeutic decisions.
The World Health Organization (WHO) has standardized
pathologic criteria for the diagnosis of testicular cancer.

6. Germ cell tumors:
Precursor lesions- intratubular malignant germ cell tumor (carcinoma
in situ)
Tumors of one histologic type (pure forms)
Seminoma
variant- seminoma with syncitiotrophoblastic cells
Spermatocytic seminoma
variant- spermatocytic seminoma with sarcoma
Embryonal carcinoma
Yolk sac tumor
Polyembryoma
Trophoblastic tumors- choriocarcinoma
Teratoma
Mature teratoma
Dermoid cyst
Immature teratoma
Teratoma with malignant areas
Mixed tumors

7. Sex cord/ Gonadal Stromal Tumors:
-Pure forms
Leydig’s cell tumor
Sertoli’s cell tumor
large cell calcifying
lipid rich cell
-Granulosa cell tumor
Adult type granulosa cell tumor
Juvenile type granulosa cell tumor
-Tumors of thecoma/ fibroma group
-Incompletely diffrentiated sex cord/ gonadal stromal tumors
-Mixed forms.

8. -Unclassified forms
-Tumors containing both germ cell and sex cord/ gonadal stromal
elements
-Gonadoblastoma
-Mixed germ cell- sex cord/ gonadal stromal tumors,
unclassified
-Miscellaneous tumors
-Carcinoid tumors
-Tumors of ovarian epithelial types.

9. -Lymphoid and hematopoietic tumors:
-Lymphoma
- Plasmacytoma
- Leukemia
-Tumors of collecting duct and rete:
-Adenoma
-Carcinoma
-Tumors of tunica, epididymis, spermatic cord, supporting
structures, and appendices:
-Adenomatoid tumor
- Mesothelioma
- Adenoma
-Carcinoma
-Melanotic neuroectodermal tumor.

10. -Soft tissue tumors,
-Unclassified tumors, and
-Secondary tumors.

13. Histology:
Testicular CIS develops from fetal gonocytes and is
characterized histologically by seminiferous tubules
containing only sertoli cells and malignant germ cells.
It is postulated that malignant initiation of germ cells
take place in-utero since fetal cell surface
glycoprotein antigens have been expressed by them.

16. Screening tools:
•
•
Open surgical biopsy: “gold standard”
since CIS is evenly distributed throughout the
testis, open surgical biopsy under L.A, 3mm3 from
lateral part of the cranial pole of the testis.
Immunostaining of cell markers for ITGCN:
Polyclonal antibody, PLAP can be used
formaldehyde fixed material.
Monoclonal antibodies against M-2A and 43-9F.
on

17. Screening tools:
•
Presently there are no established tumor markers for CIS
•
Testicular USG is unreliable for diagnosing CIS
•
ITGCN cells may or may not be present in the seminal
fluid.

18. Management:
Management depends on factors:
•
Age,
•
Bilateral or unilateral,
•
Associated testicular atrophy, and
•
Philosophy of the treating physician.
Treatment options:
Observation, radiation therapy, chemotherapy, and
orchiectomy.

24. FREQUENCY OF HISTOLOGIC TYPE:Germinal tumors: 90-95%
of all
primary testicular
malignancies.
Seminoma: 30-60%.
Embryonal carcinoma: 3-4% (pure form),
40% (mixed form).
Teratoma: 5 – 10%.
Pure Choriocarcinoma: 1%.
Mixed GCT: 60%.

31. Scrotal Sonography:
USGof the scrotum is basically an extension of the physical
examination.
Any hypoechoic area within the tunica albuginea is
markedly suspicious for testicular cancer.
In patients with a diagnosis of EGCT, ultrasound of the
testis is mandatory to be certain that one is not dealing
with a primary GCT.

35. 



Abdominal CT:
Most effective means to identify
retroperitoneal lymph node involvement.
Excellent for visualization of kidney, ureters,
retro-crural space in the para-aortic region.
However cannot sufficiently distinguish
between fibrosis, teratoma, and malignancy
by size criteria alone.

36. 




MRI:
Testicular tumors are hypointense on T2
weighted images, and show brisk and early
enhancement after I.V Gadolinium.
PET:
To detect radiographic abnormalities after
chemotherapy.
Neither PET nor CT has the ability to detect
microscopic nodal disease.

37. 



Applied to body fluid and tissue sections.
Oncofetal substances: associated with
embryonic development (AFP, HCG),
Cellular enzymes: LDH, PLAP.
Capable of detecting small tumor burdens
(105 cells) that are not detectable by
currently available imaging techniques.

38. 





AFP:
Not produced by pure choriocarcinoma or
pure seminoma.
HCG:
Choriocarcinoma (all patients),
Embryonal carcinoma (40-60%),
Pure seminoma (5-10%).

39. LDH:
 Has low specificity.
 There is a direct relationship between tumor
burden and LDH levels.
PLAP:
 Raised in 40% of patients with advanced disease.
GGTP:
 Raised in one third of patients with active
seminoma.
CD30:
 possible marker for embryonal carcinoma.

40. 

10- 15% of patients with NSGCT can be
expected to have normal marker levels even
in advanced stage of disease.
Persistently elevated tumor markers after
orchiectomy reflect systemic metastasis, and
warrant the use of chemotherapy.

41. 
The rate of tumor marker decline relative to
expected marker half-life after treatment
has been proposed as a prognostic index.

Moreover normalization of markers after
treatment cannot be equated with the
absence of residual disease.

45. Serum tumor markers (S)
LDH
hCG (mIU/ml)
AFP (ng/ml)
S0
≤N
≤N
≤N
S1
<1.5 x N
< 5000
< 1000
S2
1.5-10 N
5000 – 50000
1000-10,000
S3
> 10 N
>50,000
> 10,000

46. Stage grouping
T
N
M
S
Stage 1
1a
1b
T1-T4
T1
T2
T3
N0
N0
M0
M0
Sx
S0

47. Seminoma constitute 35-70% of germ cell
tumor.
 It is most common in men in their thirties.
 90% of patients stain for PLAP.
 10% of patients stain for hCG.
Anaplastic Seminoma:
5-10% of all seminoma.
It is more aggressive and potentially more
lethal.


49. 





Radiation therapy:
Today most centers administer 25Gy to paraaortic nodes only.
This has a 5 year survival in excess of 95%.
Primary Chemotherapy:
Single agent carboplatin compare favorably
with adjuvant radiation therapy.
2 courses of carboplatin were associated
with no relapse and favorable toxicity
profile.

50. Surveillance:
Appropriate for patients with:
1. tumors smaller than 6 cm,
2. absence of vascular invasion, and
3. normal hCG levels.
in motivated and reliable patients.

53. Radiation therapy:
N1 disease receive 30 Gy, and N2 disease receive 35 Gy.
Patients with stage II seminoma have 5 year survival rates
of 70% to 92%.
Chemotherapy:
Irradiation to kidney is avoided- parenchyma is sensitive.
So, chemotherapy is preferred in this region.

55. Cisplatin based chemotherapy:
>90% of patients achieve a complete response.
Residual masses are resected if on CT scan:
-if they are well delineated,
-distinct from surrounding structures, and
-diameter is larger than 3 cm.

56. Embryonal carcinoma:
• Age range: 25-35 years.
• Constitute 3-6% of germ cell tumors.
• About 40% of GCTs contain this tumor.
• Positive for CD30, keratin, and occasionally PLAP.
• Syncitiotrophoblastic cells commonly found adjacent to
EC cells stain positive for hCG.
Yolk cell tumor:
• Most common testis tumor in pre-pubertal boys.
• Yolk cell elements are present in 33% of mixed GCTs.
• AFP is positive in >90%.

57. Teratoma:
• Composed of two or more embryonic germ cell layers.
• Constitute 3% of adult and 38% of child GCTs.
• Age range: 1st, 2nd, and 3rd decades.
• AFP in 20-25% of this tumor.
Choriocarcinoma:
• 1-2% of all GCTs.
• Age range: 2nd and 3rd decade.
• Stain positive for hCG in >90%, and also for PLAP.

59. Retro-peritoneal lymph node dissection:
• Capable of eradicating resectable disease in the majority
of N1-N2 tumors.
• 5 year survival for stage 1 is 95%.
• 5-10%
experience relapse: high cure rates with
chemotherapy.
Modified (template) RPLND:
• Complete dissection in the most likely area, and
modification in less likely area.
• Ejaculation is preserved in 100%, and fertility noted in
75% of patients.

60. Primary radiation therapy:
• 5 year survival for stage 1: 80-95% when chemotherapy is
used to treat relapses.
• Relapse rate after radiation therapy: 24%.
The main objections to radiation therapy:
• Inaccuracy of clinical staging,
• Lack of survival data,
• Prior radiation makes it difficult for future surgical or
pharmacological intervention, and
• Risk of second malignancy: 18% in 25 years.

61. Prognostic factors for clinical stage 1 tumors:
• Invasion of testicular veins,
• Invasion of lymphatics,
• Absence of yolk sac elements,
• presence of embryonal cell carcinoma, and
• Angiogenesis: factor VIII stain positive.

62. Surveillance:
Surveillance is indicated in stage 1 disease:• without any risk factors for relapse,
• in motivated patients, and
• who fully understands the risk of failure to comply.

63. 



Surveillance protocol:
Physical examination, chest radiographs, and
tumor markers: monthly for 1st year, every 2
months for second year, and every 3-6
months thereafter.
CT abd: every 2-3 months for the first 2
years, and every 6 months thereafter.
Finally, surveillance is necessary for
minimum of 5 years, possibly 10 years after
orchiectomy.

64. Primary chemotherapy:
2 cycles of bleomycin, cisplatin, and etoposide are used.
5 year survival: 95%-100%.
Added advantage of treating metastatic disease outside
the retroperitoneum.
Suitable for centers where expertise for RPLND are not
available.

67. Primary chemotherapy:
• If nodes are larger than 3 cm on CT.
• Avoids ejaculatory failure.
Disadvantages: azoospermia, secondary malignancy.
17% of stage IIa patients and 39% of stage IIb patients
require RPLND after chemotherapy for relapse.

70. Contraindication to adjunctive surgery in patients after
chemotherapy: The presence of elevated levels of tumor
markers.
Salvage Chemotherapy:
• residual
cancer that has been resected after
chemotherapy,
• who do not respond to traditional courses of induction
therapy.

71. Patients who failed initial chemotherapy regimens:
Ifosfamide in combination with vinblastine and cisplatin.
Patients who failed 1st and 2nd line therapy:
Autologous bone marrow transplant or stem cell support
with high dose chemotherapy regimens.

72. 



3-5% of all GCTs are of extragonadal origin.
The most common sites of origin in
decreasing order of frequency:
mediastinum, retroperitoneum,
sacrococcygeal region, and pineal gland
mainly.
the majority of adults with EGCT present
with advanced local disease and distant
metastasis.

73. mediastinal and retroperitoneal disease:
complete local excision is rarely feasible.
cisplatin based chemotherapy for extragonadal
seminoma is effective.
nonseminomatous EGCT do poorly despite
surgery, radiation therapy, and
chemotherapy.

74. sacrococcygeal germ cell tumors:
wide local excision is the treatment of choice
because most are benign.
pineal tumors:
primary radiation therapy and a cerebrospinal
shunt may be required.

75. also known as leydig’s cell tumors.
most common of the sex cord mesenchymal
lesions.
1-3% of all testis tumors.
age range: pre-puberty, and 20-60years.
no association with cryptorchidism.
10% are malignant.

76. 



prepubertal cases present with isosexual
precocity.
in adults majority show manifestations of
hormonal imbalance.
Radical inguinal orchiectomy is the initial
procedure of choice.
these tumors are relatively radioresistant.

77. <1% of testicular malignancy.
age range: any age group, including infancy.
nearly 10% are malignant.
Can be found associated with cryptorchidism.
clinical features: testicular mass, and
feminizing feature.
management: radical inguinal orchiectomy.
RPLND (if malignant).

78. 




0.5% of all tsticular neoplasm.
age range: all age group.
clinical features:
80% are phenotypic females: primary
amenorrhea, lower abdominal mass and
streak gonads.
remainder are phenotypic males:
cryptorchidism, hypospadias, and some
female internal genitalia.

79. 




90% of patients are sex chromatin negative.
management:
radical inguinal orchiectomy.
since 50% are bilateral, so contralateral
gonadectomy when gonadal dysgenesis is
present.
prognosis is excellent.

80. 



1% of testicular tumors.
age range: twenties.
considered as a monolayer teratoma.
management: radical inguinal orchiectomy.

81. 




rare but highly malignant tumors.
age range: 20-80 years.
present with painless scrotal mass, and
hydrocele.
management: radical orchiectomy.
RPLND in the absence of distant
metastasis.

82. 





23 cases have been recorded.
can be primary or metastatic.
present as a slow, progressive, painless
testicular enlargement.
management:
primary testis carcinoid: inguinal
orchiectomy.
metastatic testis carcinod has poor
prognosis.

83. 




constitute 5% of all testis tumors.
this is the most common secondary neoplasm
of the testis.
age range: most frequent of all testis tumors
in patients older than 50 years. median age
is 60 years.
clinical feature: painless enlargement of
testis.
management: radical orchiectomy, and then
chemotherapy.

84. 


testis is the prime initial site of relapse in
boys with ALL.
biopsy: is essential for diagnosis.
management: testicular irradiation.

85. age range: 50-60 years.
common primary sources in decreasing order of
frequency:
prostate, lung, GIT, melanoma, and kidney.