Key points from Campbell Walsh Urology 11th edition. Will be helpful for MBBS, MS and MCH candidates.

1. Somanatha Sharma.S M.Ch Resident
Department of Urology & Renal Transplantation
Govt. Stanley Medical College

2. INTRODUCTION
Relatively rare
95 % are Germ cell tumors
Classified into Seminoma & Non
Seminomatous GCT
GCT is a curable malignancy

3. EPIDEMIOLOGY
RISK FACTORS
TUMOR BIOLOGY
CLASSIFICATION
HISTOLOGY
CLINICAL FEATURES
INVESTIGATIONS
TUMOR MARKERS
STAGING
RISK STRATIFICATION
TREATMENT
INDEX

4. EPIDEMIOLOGY
One of the most common neoplasms in men of age between 20 – 40 years
Testis tumors have three age
peaks:
Infancy,
30 to 34 years, and
Approximately age 60.

5. INCIDENCEMORTALITY

6. Incidence is increasing worldwide
Increased awareness and earlier diagnosis

7. CRYPTORCHIDISM FAMILY HISTORY
PERSONAL
HISTORY
PRESENCE OF
ITGCN
RISK FACTORS

8. RELATIVE RISK
CRYPTORCHIDISM 4 – 6 %
ORCHIDOPEXY BEFORE PUBERTY 2 – 3 %
AFFECTED BROTHER 8 – 12 %
AFFECTED FATHER 2 – 4 %
CA TESTIS – OPPOSITE TESTIS 12 %

9. Germ Cell Tumors
Precursor – ITGCN
Seminoma
• Classic
• Spermatocytic
Non – Seminomatous
• Embryonal
• Yolk Sac
• Trophoblastic ( Choriocarcinoma )
• Teratoma

10. Histology
Seminoma -
52 to 56 %
NSGCT -
44 to 48 %
Pure forms of NSGCT
are rare, and they are
always mixed with 2
or more types
GCTs that contain
both NSGCT subtypes
and seminoma are
classified as NSGCT.

11. ITGCN [INTRATUBULAR GERM CELL NEOPLASIA]
Precursor lesion, almost all invasive GCT arise from ITGCN except
Spermatocytic Seminoma
Also called Carcinoma in situ [cis]
Found in adjacent testicular parenchyma in 80 – 90 % of invasive GCT
Found in 5 – 9 % of normal contralateral testis and in 36% of contralateral
cryptorchid or atrophic testis

12. Histology - ITGCN

13. Seminoma
• Most common GCT – 50%, precursor for all other subtypes
• Female Equivalent in Ovary - Dysgerminoma
• Uniform tumor cells with abundant clear cytoplasm,
distinct cell border, and large central nuclei with prominent
1-2 nucleoli, separated by fibrous septa, with lymphocytic
infiltration in septa
• Multinucleated giant cells (syncytiotrophoblasts) may be
seen, especially in patients with elevated HCG. (15 %)
• IHC: PLAP+, Oct3/4+ and CD117+, Keratin
• D/D: Solid pattern EC, Yolk sac tumors, Sertoli cell tumors

14. Histology - Seminoma

15. SPERMATOCYTIC SEMINOMA
• Rare, less than 1%, benign, most
common in 6th decade
• Does not arise from ITGCN
• Not associated with cryptorchidism or
bilaterality
• Does not express i12p
• Does not occur as part of mixed GCT
• No tumor markers are elevated

16. Embryonal Carcinoma
• Most Undifferentiated
• Can differentiate into other NSGCT or Teratoma, in primary or
metastatic sites
• Highly aggressive and higher degree of metastasis
• Microscopically pleomorphic
• Serum AFP and HCG may be elevated
• IHC: AE1/AE3, PLAP, and OCT3/4

17. Histology - Embryonal Carcinoma

18. Choriocarcinoma
• Rare
• Aggressive
• Hematogenous spread to lungs[cannon ball mets], brain, eye, skin
• Microscopically composed of syncytio and cytotrophoblasts, with
areas of hemorrhage and necrosis
• Stain positive for HCG

19. Histology - Choriocarcinoma

20. Yolk sac tumors
• Endodermal sinus tumors
• Rare in adults, common in mediastinal and pediatric GCT
• Characteristic microscopic features are Hyaline globules (84 %) and
Schiller – Duval bodies (resembling endodermal sinuses)
• Almost always produce AFP

21. Histology – Yolk sac tumors

22. Teratoma
Monster tumor
Has derivatives from at least 2 of 3
germ layers
May cause mild AFP elevation
Usually histologically benign
Chemo resistant, require surgical
resection
May become unresectable (Growing
Teratoma syndrome)
May transform to somatic malignancy

23. Histology - Teratoma

24. Clinical features
Signs & Symptoms
• Painless testicular mass [MOST COMMON PRESENTATION]
• Pain - Intratumor hemorrhage, infarction
• Regional or distant metastases at diagnosis
• Two thirds of NSGCT
• 15 % of seminoma
• Symptomatic metastases – 10 to 20 %
• Flank mass, flank pain, ureteric obstruction, back pain, leg swelling
• Gynecomastia – 2 %
• Elevated hcg, decreased androgens, increased estrogens
• Subfertility
• Seen in two thirds, but an uncommon initial presentation
CLINICAL FEATURES

25. Examination
Testis
Presence
Relative size
Consistency
Abdominal mass
Inguinal or supraclavicular
lymphadenopathy
Chest

26. A firm intratesticular mass
should be considered
cancer until proven
otherwise

27. DIFFERENTIAL DIAGNOSIS
EPIDIDYMO- ORCHITIS TORSION
HEMATOMA
PARATESTICULAR
NEOPLASM

28. D I A G N O S T I C D E L AY
Prior studies show that up to one third of testicular tumors are initially
misdiagnosed as epididymitis or hydrocele
Diagnostic delay can be avoided by efforts to improve patient and
physician education.
Consider diagnosis of GCT in any male aged 15 to 50 years
• with a firm testicular mass,
• midline retroperitoneal mass, or mass in the left supraclavicular fossa.
• physical examination with appropriate serological & radiologic evaluations

29. PATHOGENESIS
Course of Spread of Germ Cell Tumours are predictible once
Histology of Tumour is confirmed
With the exception of choriocarcinoma, the most common route of
disease dissemination is via lymphatic channels
to the retroperitoneal lymph nodes and subsequently to distant
sites (70% to 80% of patients with GCT)

30. LYMPHATICS
LANDING ZONE
LEFT testes drains into
the LEFT PARA-
AORTIC and
INTERAORTOCAVAL
NODES.
RIGHT testes drains
into
INTERAORTOCAVAL
NODES and RIGHT
PARACAVAL NODES
and a small amount to
LEFT PARA-AORTIC
region.
Drainage is consistent with global lymphatic flow
from right to left.

31. Local involvement of
epididymis or cord:
10-15 %
Lymphatic drainage cross
over from right to left, and,
therefore, cross-metastases
occur more commonly in
patients with right-sided
tumors.

32. SCROTAL ULTRASONOGRAPHY
Extension of the physical
examination
High-frequency transducers (5 to 10
MHz)
GCT is hypoechoic (80%)and two or more
discrete lesions may be identified
NSGCT Heterogeneous echotexture within
a lesion
Seminomas homogeneous echotexture

33. SCROTAL ULTRASOUND
Bilaterality
2% incidence
At diagnosis is rare(0.5% of all
GCTs)
metachronous presentation is
more common
Association between testicular microlithiasis and GCT is not clearly defined should
not prompt further evaluation
Increased flow within the lesion on color Doppler ultrasonography is suggestive of
malignancy

34. SERUM TUMOR MARKERS
LDH AFP HCG
• Diagnosis
• Prognosis
• Treatment
• Monitoring
• response to chemotherapy,
• relapse
Essential
in

35. TUMOR MARKER SEMINOMA NONSEMINOMA
HCG RAISED IN 15-30% RAISED IN 80%
AFP - RAISED IN 80%
LDH RAISED WITH METASTATIC DISEASE RAISED WITH METASTATIC DISEASE

37. NORMAL VALUE: < 16 ng/ ml
HALF LIFE OF AFP – 5 - 7 days

38. AFP
• Raised AFP :
• Pure embryonal carcinoma
• Teratocarcinoma
• Yolk sac Tumour
• Combined Tumour
• Not raised in Pure Choriocarcinoma or Pure Seminoma

39. NORMAL VALUE: < 1 ng / ml
HALF LIFE of HCG: 24 to 36 hours
RAISED  HCG
100 % - Choriocarcinoma
60% - Embryonal carcinoma
55% - Teratocarcinoma
25% - Yolk Cell Tumour
15% - Seminomas

40. LDH
Normal Values 105 - 333 IU/L
Serum half-life of LDH - 24 hours
Correlates with the bulk of disease.
Its main use is in prognostic assessment of GCT

41. ROLE OF TUMOUR MARKERS
Helps in Diagnosis - 80 to 85% of Testicular Tumours have Positive
Markers
Most of Non-Seminomas have raised markers
Only 10 to 15% Non-Seminomas have normal marker level
After Orchidectomy if Markers Elevated is indicative of Residual
Disease or Stage II or III Disease
Elevation of Markers after Lymphadenectomy is suggestive of STAGE
III Disease

42. ROLE OF TUMOUR MARKERS
Interpret postorchiectomy tumor marker levels (staging purposes)
• Degree of Marker Elevation is directly proportional to Tumor Burden
• Markers indicate Histology of Tumor:
If AFP elevated in Seminoma - Tumor has Non-Seminomatous elements
• Negative Tumor Markers becoming positive on follow up usually indicates
recurrence of Tumor
• Markers become Positive earlier than radiologic studies

43. WHETHER TO BIOPSY CONTRALATERAL TESTIS?
Between 5% and 9% of patients with GCT have ITGCN
in the normal contralateral testis
In patients with
• An atrophic testis,
• History of cryptorchidism, or
• Age younger than 40 years,
• Suspicious lesion in USG
Risk of ITGCN in the contralateral testis has been
reported in up to 36% open inguinal biopsy

44. Extragonadal GCT
2 to 5 % of GCT  extragonadal origin
MC site-
mediastinum,retroperitoneum,sacrococcygeal
region, pineal gland
Any young male with a midline mass GCT
should be considered

45. IMAGING STUDIES
• CECT abdomen –
retroperitoneal nodes
• MRI
• Chest X ray
• PET

46. Staging of the
Abdomen and
Pelvis
Computed tomography (CT) after
administration of oral and intravenous contrast
agents
• most effective, noninvasive
• detailed anatomic assessment of the retroperitoneum
(anatomic anomalies)
Retroperitoneal LN mets range from small
discrete nodules to large confluent masses
• RPLN enlarged 10-20% of seminoma, 60-70% of NSGCT
• Sensitivity :65%-96% , specificity : 81%-100%

49. MRI
Patients in whom iodinated contrast cannot be
given
Distinguishing radiation fibrosis from residual /
recurrent tumour
Second line investigation for preoperative evaluation
of the testes when USG is inconclusive
It can distinguish germ cell tumors from benign mimics
and lymphoma & leukemia infiltrates

50. CHEST RADIOGRAPHY
Chest x-ray is sufficient for follow-up for stage I seminomas and stage2
NSGCT
Indications for CT Chest:
• Increased tumor markers,
• Evidence of metastatic disease clinically and on abdominal CT,
• Abnormal or equivocal findings in CXR,
• Evidence of Lymphovascular/ Extracapsular invasion on biopsy
Indications for CT Brain:
• HCG >10000 IU/L
• Metastatic Choriocarcinoma

51. RADIONUCLIDE IMAGING
• FDG-PET is superior to CT in the prediction of viable tumor in
postchemotherapy seminoma residuals
• helpful for follow-up stage IIB, IIC, and III seminoma who have a residual
mass >3 cm and normal markers
• there is currently no role for FDG-PET in the routine evaluation of NSGCT
and seminoma at the time of diagnosis
• Bone scans are useful in the absence of FDG-PET scans and should be used
when bone metastases are suspected.

52. Clinical Staging
Histopathologic findings and pathologic stage of the
primary tumor,
Postorchiectomy serum tumor marker levels,
Presence and extent of metastatic disease as determined
by physical examination and staging imaging studies

53. CLINICAL STAGING
Staging A or I - Tumour
confined to testis.
• IIA - Nodes <2 cm in size or < 5 Positive Nodes
• IIB - 2 to 5 cm in size or > 5 Positive Nodes
• IIC - Large, Bulky, abd.mass usually > 5 to 10 cm
Staging B or II - Spread to
Regional nodes.
Staging C or III - Spread
beyond retroperitoneal
Nodes or Above
Diaphragm or visceral disease.

54. TNM STAGING
Primary Tumor (T)
TX Primary tumor cannot be assessed (if no radical orchiectomy has been performed, TX is used)
T0 No evidence of primary tumor (e.g., histologic scar in testis)
Tis Intratubular germ cell neoplasia (carcinoma in situ)
T1 Tumor limited to the testis and epididymis and no vascular/lymphatic invasion
T2 Tumor limited to the testis and epididymis with vascular/lymphatic invasion or tumor extending
through the tunica albuginea with involvement of tunica vaginalis
T3 Tumor invades the spermatic cord with or without vascular/lymphatic invasion
T4 Tumor invades the scrotum with or without vascular/lymphatic invasion

55. Regional Lymph Nodes (N)
Clinical NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Lymph node mass 2 cm or less in greatest dimension or multiple lymph node masses, none
more than 2 cm in greatest dimension
N2 Lymph node mass, more than 2 cm but not more than 5 cm in greatest dimension, or multiple
lymph node masses, any one mass greater than 2 cm but not more than 5 cm in greatest
dimension
N3 Lymph node mass more than 5 cm in greatest dimension

56. Distant Metastases (M)
M0 No evidence of distant metastases
M1 Nonregional nodal or pulmonary metastases
M2 Nonpulmonary visceral masses
Serum Tumor Markers (S)
LDH HCG(mIU/L) AFP(ng/ml)
S0 N N N
S1 < 1.5 X N <5000 <1000
S2 1.5-10 X N 5000-50000 1000-10000
S3 >10XN > 50000 > 10000

57. IGCCCG RISK CLASSIFICATION
RISK STATUS SEMINOMA
GOOD RISK Any primary site and No non pulmonary visceral metastases and Normal AFP ,
Any HCG or LDH
(Approx 90%)
5-year PFS 82%., 5-year survival 86%
INTERMEDIATE Any primary site and Non pulmonary visceral metastases and Normal AFP ,
Any HCG or LDH
(approx 10%)
5-year PFS 67% ., 5-year survival 72%
POOR RISK No patients classified as poor prognosis

58. NONSEMINOMA
GOOD PROGNOSIS INTERMEDIATE PROGNOSIS POOR PROGNOSIS

59. TREATMENT
SURGERY
CHEMOTHERAPYRADIOTHERAPY

60. PRINCIPLES OF
TREATMENT
LYMPHATIC
SPREAD INITIALLY
GOES TO RETRO-
PERITONEAL
NODES
EARLY
HEMATOGENOUS
SPREAD RARE
Bulky
Retroperitoneal
Tumours
“DOWN-STAGED”
with
CHEMOTHERAPY
RADICAL
INGUINAL
ORCHIDECTOMY
IS STANDARD
FIRST LINE OF
THERAPY

61. INGUINAL EXPLORATION AND ORCHIDECTOMY
• High Inguinal Orchidectomy with division of the spermatic cord at the
internal inguinal ring must be performed if a malignant tumour is found.
• If the diagnosis is unclear, a testicular biopsy should be taken for frozen-
section histopathology – Chevassu’s Maneuver

62. RADICAL ORCHIDECTOMY

63. EARLY CLAMPING

64. RADICAL INGUINAL ORCHIDECTOMY
Inguinal skin crease incision
Control the spermatic cord with atraumatic clamp/ penrose drain
Deliver the testis from the scrotum and ligate the vas deferens and spermatic vessels separately.
Leave a long non absorbable silk for future identification during RPLND.
Frozen section biopsy in doubtful cases.
Never explore through scrotal incision
No trucut/ core needle biopsy.

65. Orchidectomy alone Curative in
•80% to 85% of CS I seminoma
•70% to 80% of CS I NSGCT

66. TREATMENT OF ITGCN
RADICAL ORCHIDECTOMY IS THE
DEFINITIVE PROCEDURE
LOW DOSE RADIOTHERAPY [20 Gy] IS
EQUALLY EFFECTIVE

67. TREATMENT OF NSGCT
STAGE I
LOW RISK
ORCHIDECTOMY +
SURVEILLANCE
HIGH RISK
ORCHIDECTOMY +
SURVEILLANCE + RPLND
/ CHEMOTHERAPY
STAGE 1 S [INCREASED
TUMOR MARKERS
DURING SURVEILLANCE]
– INDUCTION
CHEMOTHERAPY
CHEMOTHERAPY
REGIMEN – BEP X 2
CYCLES

68. CHEMOTHERAPY REGIMENS
BEP
• BLEOMYCIN
• ETOPOSIDE
• CISPLATIN
VIP
• ETOPOSIDE [VP-16]
• IFOSFAMIDE
• CISPLATIN
PVB
• CISPLATIN
• VINBLASTINE
• BLEOMYCIN

69. STAGE II A & B
LOW RISK: RPLND
+/- ADJUVANT
CHEMOTHERAPY
HIGH RISK:
INDUCTION
CHEMOTHERAPY
STAGE II C & III
INDUCTION
CHEMOTHERAPY
IS FIRST LINE
REGIMEN:
BEP x4 CYCLES
OR PVB x4 CYCLES

70. RPLND

71. CHEMOTHERAPY FOR NSGCT
GOOD RISK NSGCT:
BEP x3 OR EP x4 [5 YEAR SURVIVAL 91-94%]
INTERMEDIATE & POOR RISK NSGCT:
BEP x 4 OR VIP x 4 [5 YEAR SURVIVAL 83% AND 75%]

72. STAGE I SEMINOMA
PRIMARY RADIATION THERAPY
• Dose: 25-35 Gy
• Paraaortic/ Hockey stick/ Dog leg field
• INCLUDES PARA-AORTIC NODAL FIELD &
IPSILATERAL PELVIC NODAL FIELD
• 5-year survival rates in excess of 95%

73. PRIMARY CHEMOTHERAPY
Carboplatin is equally
effective for stage I
seminoma
STAGEI
SEMINOMA

74. Stage IIA
and IIB
Seminoma
NODES < 5 CM = RADIOTHERAPY
NODES > 5 CM = CHEMOTHERAPY
The Retroperitoneal lymph node groups included in
radiation treatment fields for stage II seminoma are
• Ipsilateral External Iliac
• Bilateral Common Iliac
• Paracaval
• Para-aortic node
• Cisterna chyli

75. Stage IIc and Stage III Disease: Advanced Seminoma
Cisplatin-based chemotherapy is the
treatment of choice

76. RESIDUAL
MASS
Teratoma in the residual mass is very rare.
Second, a complete RPLND is often not technically possible owing to
obliteration of tissue planes secondary to the severe desmoplastic
reaction of these tumors after chemotherapy
So perioperative morbidity is higher

77. BRAIN METASTASIS
MOST COMMONLY FROM
CHORIOCARCINOMA
TREATMENT: BEP x 4 CYCLES FOLLOWED
BY METASTASECTOMY/ GAMMA KNIFE

78. NON GERM CELL TUMORS
SEX CORD STROMAL TUMORS:
LEYDIG CELL TUMORS
SERTOLI CELL TUMORS
GRANULOSA CELL TUMOR – MOST COMMON TUMOR IN INFANTS
TREATMENT:
<3CM – TESTIS SPARING SURGERY
>3CM – RADICAL HIGH ORCHIDECTOMY

79. MISCELLANEOUS
LYMPHOMA
• NHL IS THE MOST COMMON TESTICULAR NEOPLASIA AFTER 50 YEARS
• BILATERALITY – 35%
• TREATMENT: RADICAL HIGH ORCHIDECTOMY
LEUKEMIA
• ACUTE LYMPHOCYTIC LEUKEMIA RELAPSE COMMON IN TESTES.
• TREATMENT: LOW DOSE RADIOTHERAPY. ORCHIDECTOMY IS NOT
NEEDED.

80. METASTASES
Metastases to the testis are rare. Bilateral involvement occurs
in 15% of patients.
The most common primary tumors are prostate, lung,
melanoma, colon, and kidney.
Although treatment is largely dictated by the primary tumor,
orchiectomy may be considered for palliative reasons.

81. SPERM
CRYOPRESERVATION
Sperm cryopreservation offered to
all patients before RPLND,
chemotherapy, or radiation
therapy
Sperm banking can be done before
or after radical orchiectomy.

82. TAKE HOME MESSAGE
• RELATIVELY RARE BUT INCIDENCE INCREASING
• 95% GCT [SEMINOMA AND NSGCT]
• PRECURSOR LESION IS ITGCN
• CURABLE MALIGNANCY
• SERUM TUMOR MARKERS IS INCLUDED IN STAGING
• FOR SEMINOMA, NO POOR RISK
• TREATMENT INCLUDES SURGERY, RADIOTHERAPY AND CHEMOTHERAPY

83. TREATMENT IN A NUTSHELL
SEMINOMATOUS GCT PRIMARY TREATMENT
STAGE I HIGH INGUINAL ORCHIDECTOMY RADIOTHERAPY
STAGE IIA, II B HIGH INGUINAL ORCHIDECTOMY NODES <5 CM – RADIOTHERAPY
NODES >5 CM - CHEMOTHERAPY
STAGE II C, III HIGH INGUINAL ORCHIDECTOMY CHEMOTHERAPY
NSGCT
STAGE I HIGH INGUINAL ORCHIDECTOMY SURVEILLANCE
STAGE I S CHEMOTHERAPY [BEP X 4]
STAGE II A, B HIGH INGUINAL ORCHIDECTOMY RPLND +/- CHEMOTHERAPY
STAGE II C, III HIGH INGUINAL ORCHIDECTOMY CHEMOTHERAPY

84. THANK YOU