Seminoma testis

1. TESTICULAR CANCER

2. ANATOMY
• Male Gonads
• Homologous to ovary
• Lies obliquely in scrotum, suspended by
spermatic cord.
• Left testes slightly lower than right
• Shape : Oval
• Appx 3.75 x 2.5 x 1.8 cms is size

3. DESCENT OF TESTES
• Develops from Genital Ridge at LV-2 level
• Begins to descent by 2nd month of IUL
• 3rd month of IUL reaches Iliac Fossa
• 4th – 6th month of IUL crosses Deep Inguinal
Ring
• 7th month of IUL traverses Inguinal Canal
• 8th month passes Superficial Inguinal Ring
• 9th month reaches scrotum

4. • CRYPTORCHIDISM :
Failure of testes to reach scrotum before
birth.
• Most of the time reaches by 01 year of age.
• Orchidopexy to be done, if it doesn’t.

5. • Coverings of Testes
- Skin
- Dartos muscle
- Ext Spermatic Fascia
- Cremastric Fascia
- Int Spermatic Fascia
- Tunica vaginalis
- Tunica albuginea

6. • 200-300 lobules
• Each lobule has 2-3
seminiferous tubules
• Each seminiferous
tubules lined by cell in
different stages of
spermatogenesis
• Among the seminiferous
tubules are Sertoli cells.
• Between the loops of the
seminiferous tubules are
interstitial cells, produce
testosterone.
• Seminiferous tubules join
to form 20-30 straight
tubules.

7. • Rete testis: network of
tubules located in the hilum
of the testicle(mediastinum
testis) that carries sperm
from the seminiferous tubules
to the efferent ducts
• Rete testis give rise to 12-30
efferent ductules
• Epididymis: tube about 20
feet (6 m) long that is coiled
on the posterior surface of
each testis connect efferent
duct to vas deferens
• Ductus deferens :extends
from the epididymis in the
scrotum on its own side into
the abdominal cavity through
the inguinal canal

8. BLOOD SUPPLY
• Areterial supply
The testicular artery
branch of abdominal aorta
.
The testis has collateral
blood supply from
1. the cremasteric artery
2. artery to the ductus
deferens

9. • Venous drainage
- The veins emerge from the
back of the testis, and
receive tributaries from the
epididymis.
- they unite and form
convoluted plexus, called
the pampiniform plexus.
- Plexus to form a single
vein, which opens, on the
right side, into the inferior
vena cava ,on the left side
into the left renal vein

10. LYMPHATIC DRAINAGE
• Drain into the
retroperitoneal lymph
glands between the levels
of T11 and L4, but they are
concentrated at the level of
the L1 and L3 vertebrae.
• Lymph nodes located lateral
or anterior to the inferior
vena cava are called
paracaval or precaval nodes,
respectively.
• Interaortocaval nodes are
located between the
inferior vena cava and the
aorta.
• Nodes anterior or lateral to
the aorta are preaortic or
paraaortic nodes,
respectively

11. LYMPHATIC DRAINAGE
• On the right:
- Interaortocaval region,
followed by the paracaval,
preaortic, and paraaortic
lymph nodes.
• On the left:
- Preaortic and para-aortic
nodes and thence to the
interaortocaval

12. NERVE SUPPLY
• Sympathetic nerves arising from segment T10
of the spinal cord.
• Both afferent for testicular sensation and
efferent to the blood vessels(vasomotor).

13. INTRODUCTION
• Comprise a morphologically and clinically diverse
group of tumors
• Predominantly affects young males.
• Testicular cancer forms about 1% of all malignancies
in males in India.
• Incidence (ASR)– 0.6 per 100000
• Mortality (ASR)– 0.3 per 100000
• 95% are Germ Cell Tumours (GCTs)
• 90% GCT are in testes,2-10% in extra gonadal (eg
retropreitoneum, mediastinal)

14. EPIDEMOLOGY OF TESTICULAR
CANCER
• Age: for GCT median age at diagnosis is 34
years
• In a man age: 50 years or older solid testicular
mass is usually lymphoma
• Geographic: Highest incidence in Denmark,
Norway, and Switzerland and the lowest in
eastern Europe and Asia.
• Race: more common in young white men ,less
in African Americans

15. PREDISPOSING FACTORS
1. Cryptorchidism
2. Klinefelter syndrome
3. Positive family history
4. Positive personal history
5. Intratubular germ cell neoplasia
6. Trauma
7. Viral infection
8. Hormonal factors
9. Exposure to environmental oestrogen

16. CRYPTORCHIDISM
For inguinal cryptorchidism odds ratio is 5.3 for seminoma 3
for non seminoma
• This risk is further increased if the testis is intra-abdominal.
• Abdominal testis is more likely to be seminoma, testis
brought to scrotum by orchiopexy is more likely to be
NSGCT.
• There is still an increased risk of developing a tumour in
the contralateral normally descended testicle in pt. with
cryptorchidism
• Prepubertal orchidopexy fails to prevent the subsequent
development of malignancy

17. PREDISPOSING FACTORS
• KLINEFELTER SYNDROME
• Characterised by testicular atrophy, absence
of spermatogenesis, eunuchoid habitus,
gynecomastia
• Karyotype: 47XXY
• Pt. are at increased risk of mediastinal GCT

18. PREDISPOSING FACTORS
• Positive family history
• Men with first degree relative with testicular
cancer
• Median age being less by 2-3 yrs
• Brother of men with testicular tumor: 8-10
times more risk of developing TGCT
• Relative risk to father and sons: 2-4 times

19. PREDISPOSING FACTORS
• Positive personal history
• 12 folds increased risk of developing GCT in
the contralateral testis
• Higher risk for contralateral tumor if
- Younger age
- Seminoma

20. PATHOLOGICAL CLASSIFICATION
1:Intra tubular germ-cell neoplasia(IGCN)
2:GERM CELL TUMORS 95%
- Seminoma >50%
-Classic type
- (?Anaplastic)
- Spermatocytic type
- Non seminomatous germ-cell tumors <50%
- Embryonal carcinoma 20-25%
- Teratoma 25-35%
- Yolk sac (endodermal sinus) tumor
- Choriocarcinoma 1%
- Mixed germ-cell tumor

21. PATHOLOGICAL CLASSIFICATION
3 Classification of Sex-Cord Stromal Tumors of the
Testis(2-3%)
- Leydig cell tumor
- Sertoli cell tumor
- Granulosa cell tumor
- Fibroma-thecoma stromal tumor
- Gonadoblastoma
- Sex cord-stromal tumor unclassified type

22. PATHOLOGICAL CLASSIFICATION
4: Others
- Lymphoma
- Rabdomyosarcoma
- Melanoma

23. SEMINOMA
• Typical/ Classical
- 82% - 85% of seminomas
- Middle age
- PLAP – 90%
- Syncytiotrophoblsts – ↑Beta HCG(15-30%)
- Very slow growth

24. SEMINOMA
• Spermatocytic
- 2% of seminomas
- Old age > 50 yr
- Does not arise from ITGC
- PLAP negative
- Extremely low metastatic potential
- Good prognosis

25. SEMINOMA
• Anaplastic
- 5% - 10 of seminomas
- Middle age
- Aggressive - lethal
- Greater mitotic activity
- Higher local invasion
- Higher metastatic potential
- Higher rate of β-HCG production

26. EMBRYONAL CARCINOMA
- 2nd most common germ cell tumor, 90% of NSGCT
- Present in majority of mixed germ cell tumors
- Most men present in their 20s to 30s with a
testicular mass
- Highly malignant tumours; may invade the cord
stuctures
- High degree of metastasis
- Serum AFP is positive in 30%, & beta HCG is
elevated in 20% of cases

27. YOLK SAC TUMOUR
Most common germ cell tumor ( & most common
testicular tumor ) in children, where it occurs in its
pure form.
– 60% of GCT in children in first 2 years of life.
– Pure yolk sac tumor <2% of testicular tumors in
adults
– 40% of mixed germ-cell tumors.
– Elevated serum levels of alpha-fetoprotein.
– Microscopically, Schiller-Duval bodies are a
characteristic feature
- Testicular mass the most usual presentation.

28. CHORIOCARCINOMA
• A rare and aggressive tumour (5yrs survival is 5%)
• Composed of cytotrophoblasts and syncytiotrophoblasts
• Typically elevated hCG
• Presents with disseminated disease
• Metastasis to lungs and brain
• Primary is very small and often exhibit NO TESTICULAR
ENLARGEMENT
• Small palpable nodule may be present.
• Prone to haemorrhage, sometimes spontaneous (lungs and
brain

29. TERATOMA
• Teratoma in greek means “monster tumor”
• Contain at least two and mostly all three germ layers
with varying degree of differentiation.
• Occurs in its pure form in pediatric age group with a
mean age of diagnosis at 20 months
• In adults, occur as a component of mixed germ cell
tumor & is identified in > 47 % of mixed tumors.
• 2 – 3% of GCTs as pure Tertoma.
• Normal serum markers.
• Mildly elevated AFP levels

30. INTERSTITIAL CELL TUMORS
1. Leydig cell tumors
• May affect 20-60yrs of age
• A masculinising tumor, produces androgens
• No association with crytochordism
• Presents with painless testicular mass
• Precocious puberty
• Prominent external genitalia
• Deep masculinised voice
• Gynacomastia and decreased libodo due to
oestrogen production by increased peripheral
conversion

31. INTERSTITIAL CELL TUMORS
2. Sertoli Cell Tumor
• can occur in any age group including infants
• No association with crytochordism
• Excess estrogen production
• Gynacomastia in 1/3rd of cases
• 10 % are malignant

32. INTERSTITIAL CELL TUMORS
• 3. Gonadoblastoma
• Mixed germ cell/sex cord/stromal tumor
• Composed of seminoma like germ cells and Sertoli
differentiation
• Exclusively in patients with dysgenic gonads and
intersex syndromes
• 80% are phenotype females with primary
amenorrhoea
• 20% are males with crytochordism and dysgenic
gonads and hypospadias
• Considered in-situ malignant form of GCT
• Bilateral orchidectomy because of risk of bilateral
tumours

33. SECONDARY TUMORS OF TESTIS
• Lymphoma – most common secondary tumor
- most common testicular tumor in patients
above 50 years
- most common variety is histiocytic
• Leukamic Infilteration of testis
-Primary site of relapse after ALL remission
- Occurs mainly in the interstitial space
• Metastases to testis
- rare

34. SPREAD
• 1. Direct Spread:
-This spread occurs by invasion.
-Tunica albuginea is rarely penetrated
-May be crossed by “blunder biopsy”
-Scrotal skin involvement
-Fungation on the anterior aspect
-Spread to spermatic cord and epididymis
may occur : points towards bad prognosis

35. SPREAD
2. Lymphatic spread:
-Seminoma metastasizes exclusively through lymphatics
-They drain primarily to para-aortic lymph nodes
-From RPLN drain into cysterna chili, thoracic duct,
posterior mediastinum & left supraclavicular LN
-Lymph from medial side of testes run along the
artery to the vas to drain to nodes at the bifurcation of
common iliac
-No inguinal nodes until scrotal skin involvement

36. LYMPHATIC SPREAD
RIGHT LEFT

37. SPREAD
• Metastatic nodal
disease to the
common iliac,
external iliac, or
inguinal lymph
nodes is usually
secondary to a large
volume of disease
with retrograde
spread.

38. SPREAD
• If the patient has undergone a herniorrhaphy,
vasectomy, or other transscrotal procedure,
metastasis to the pelvic and inguinal lymph
nodes is more likely.
• Through the thoracic duct to lymph nodes in
the posterior mediastinum and supraclavicular
fossae and occasionally to the axillary nodes.
• Contralateral spread is mainly seen with right-
sided tumors.
• In 15% to 20%, bilateral nodes are involved

39. SPREAD
• 3. Blood Spread
-NSGCT spread through blood route
-Lungs, liver, bones and brain are the usual
sites usually involved

40. CLINICAL FEATURES
1. Due to primary tumor
a) Painless testicular lump
b) Sensation of heaviness if size > than 2-3 times
c) Rarely dragging pain is complained of (1/3rd cases)
d) May mimic epidedymo-orchitis
e) Sudden pain and enlargement due to hemorrhage
mimicking torsion
f) History of trauma (co-incidental)

41. DICTUM FOR ANY SOLID SCROTAL
SWELLINGS
• All patients with a solid, Firm Intratesticular
Mass that cannot be Trans-illuminated should
be regarded as Malignant unless otherwise
proved.

42. CLINICAL FEATURES
2. Due to metastasis
- Abdominal or lumbar pain (lymphatic spread)
- Dyspnoea, hemoptysis and chest pain with lung mets
- Jaundice with liver mets
- Hydronephrosis by para-aortic lymph nodes
enlargement
-Pedal oedema by IVC obstruction
-Troiser’s sign

43. CLINICAL FEATURES
Clinical examination:
a) Enlarged testis (except choriocarcinoma)
b) Nodular testis
c) Firm to hard in consistency
d) Loss of testicular sensation
e) Secondary hydrocele
f) Flat and difficult to feel epididymis
g) General examination for metastasis

44. TUMOR MARKERS
TWO MAIN CLASSES
• AFP - Trophoblastic Cells
• HCG - Syncytiotrophoblastic Cells
AFP, BHCG & LDH are included in TNM staging of
testicular cancers

46. HUMAN CHORIONIC
GONADOTROPIN
Has alpha and beta polypeptide chain
-NORMAL VALUE: < 1 ng / ml
-HALF LIFE of HCG: 24 to 36 hours
-RAISED beta HCG -
-100 % - Choriocarcinoma
-60% - Embryonal carcinoma
-55% - Teratocarcinoma
-25% - Yolk Cell Tumour
-15 – 30% - Seminomas

47. AFP –ALFA FETO PROTEIN
• normal value: below 16 ngm/ml
• half life of AFP – 5 to 7 days
• Raised AFP :
-Pure embryonal carcinoma
-Teratocarcinoma
-Yolk sac Tumor
-Combined tumors,
• AFP not raised in pure choriocarcinoma & in
pure seminoma

48. SERUM TUMOR MARKERS (S)

49. ROLE OF TUMOUR MARKERS
• Helps in Diagnosis - 80 to 85% of Testicular
Tumors have Positive Markers
• Most of Non-Seminomas have raised markers.
• Indicate Histology of Tumor:
• If AFP elevated in Seminoma - Means Tumour
has Non-Seminomatous elements
• Degree of marker elevation appears to be
directly proportional to tumor burden

50. ROLE OF TUMOUR MARKERS
• may predict the responsiveness of nonseminomas to
treatment
- The level of beta-HCG should decrease by 90% or more
every 21 days with each successful treatment cycle of
chemotherapy.
- The decline of AFP is less predictable
- Normalization of tumor marker after high inguinal
orchidectomy does not ensure complete disease removal
however after Orchiectomy if Markers Elevated means
Residual Disease
- Negative Tumor Markers becoming positive on follow
up usually indicates -Recurrence of Tumor
- Markers become Positive earlier than radiological
studies

51. WORK UP
• History (document cryptorchidism and
previous inguinal or scrotal surgery)
• Physical examination
• Laboratory Studies
-CBC, LFT, RFT, LDH
• Serum assays
-Alpha fetoprotein (AFP)
-Beta human chorionic gonadotropin

52. WORK UP
• Diagnostic Radiology
– Chest x-ray films, posterior/anterior and lateral
views
– Computed tomography (CT) scan of abdomen and
pelvis
– CT scan of chest for non seminomas and stage II
seminomas
– Ultrasound of contralateral testis
- WB PET CT Scan has better sensitivity (40% vs
66%) and comparable specificity (95% vs 98%) in
comparison to CECT Abd/pelvis for
Retroperitoneal LN involvement.
- MRI Brain if clinically indicated

53. WORK UP
• SCROTAL ULTRASOUND
-Ultrasonography of the scrotum (7.5MHZ) is a rapid,
reliable technique to exclude
- Testicular and other scrotal swelling
- Solid & cystic swelling
- Hydrocele & epididymitis.
• Ultrasonography of the scrotum is basically an
extension of the physical examination.
• Hypoechoic area within the tunica albuginea is
markedly suspicious for testicular cancer.

54. PROGNOSTIC FACTORS

55. PROGNOSTIC FACTORS

56. PROGNOSTIC FACTORS

57. STAGING

58. STAGING

59. STAGING

60. MANAGEMENT
• Initial sperm banking to be considered before
starting treatment as clinically indicated.
• Modalities of treatment
- Surgery
- Surveillance
- Radiotherapy
- Chemotherapy

61. MANAGEMENT
• Surgery
– Radical Inguinal Orchidectomy
– Diagnostic as well therapeutic
– Scrotal violation increases risk of local recurrence

62. STAGE I SEMINOMA
• Surveillance-

63. FOLLOW UP AFTER SURGERY

64. WHETHER ALL PTs SHOULD BE ON
SURVIELLANCE

65. ADJUVANT RADIOTHERAPY
FOR SATGE I
• Historically, the standard postoperative
management of patients with stage I seminoma
has been adjuvant radiotherapy to the para-aortic
and ipsilateral pelvic lymph nodes (the “dogleg”
or “hockey stick” radiation field).
• This is a highly effective treatment, with a
reported relapse rate between 1% and 5% and a
disease-specific survival of 100% in many mature
studies.

66. ADJUVANT RADIOTHERAPY
FOR SATGE I
• RCT Comparing Only Para-aortic RT & including
Pelvic RT by MRC
- Toxicity profile better in PA arm
- No difference in DFS & OS at 4.5 yrs
- Pelvis most frequent site of relapse in PA arm

67. ADJUVANT CHEMOTHERAPY FOR
SATGE I
• Adjuvant chemotherapy using single-agent
carboplatin is proposed as a less toxic
approach than radiotherapy for stage I
seminoma.

68. ADJUVANT TREATMENT FOR SATGE II
• ADJ RT vs 3xBEP / 4xEP
• Based on 2 large studies (i.e, Glaser et al &
Poly et al) ADJ RT preferred over ADJ Chemo in
Stage IIA disease.
• However no 5 year survival benefit seen in
Stage IIB. Hence RT kept in reserve only for
bulky disease.

69. RADIOTHERAPY TECHNIQUE
• Dog-leg or Hockey Stick Field-
-Superior border between the T9 and T10.
Inferior border at the top of the obturator
foramen.
- Modified approach is now commonly used
wherein the superior border is placed between
T11 and T10 and the inferior border is placed at
the superior aspect of the acetabulum

70. RADIOTHERAPY TECHNIQUE
- Field is approximately 9 cm wide in the
para-aortic region and usually covers the
transverse processes.
-On the left, the lateral border is extended to
include the left renal hilum, and customized
shielding is positioned to reduce the amount of
kidney irradiated. Field width here is typically 11 to
12 cm.
- At the mid-L4 level, the field is extended
laterally to cover the ipsilateral external iliac nodes.

71. RADIOTHERAPY TECHNIQUE

72. Dose and Fractionation
• Stage I Seminoma
-Radiation dose of between 20 and 40 Gy
at 1.25 to 2 Gy per fraction have been
reported.
- A dose of 25 Gy in 20 fractions is the
most commonly used dose/fractionation.

73. Dose and Fractionation
• MRC TE-18 RCT
- 20Gy/10# vs 30Gy/15#
- Relpase free survival similar in both groups
- Significant lethargy and weakness in
30Gy/15# arm.

74. Dose and Fractionation
• Stage II Seminoma
-The optimal radiation dose in stage II
seminoma is yet to be determined, and several
regimes are used.
-One regime of 25 Gy in 20 fractions is
frequently used with a boost (10 Gy in 5 to 8
fractions) to the residual mass for
lymphadenopathy >2 to 3 cm.
- Alternatively, 30 Gy in 15 fractions for stage
IIA and 36 Gy in 18 fractions for stage IIB seminoma
have been shown to provide excellent local control.

75. MANAGEMENT OF NSGCT
• Stage I A
- Surveillance, or
- Nerve sparing RPLND, or
- Chemotherapy (EP/BEP)
• Stage I B
- Nerve sparing RPLND, &
1 x BEP
- Surveillance (CAT 2B)

76. MANAGEMENT OF NSGCT
• Stage I S
- 3 x BEP/ 4 x EP
• Stage II A
- RPLND followed by
pN0 - Surveillance
pN1 – Surveillance (preferred) OR
2 x EP/BEP
pN2 & pN3 - 3 x BEP/ 4 x EP
• Stage II B - Similar to Stage IIA

77. THANK YOU