2. Moderators:
Professors:
• Prof. Dr. G. Sivasankar, M.S., M.Ch.,
• Prof. Dr. A. Senthilvel, M.S., M.Ch.,
Asst Professors:
• Dr. J. Sivabalan, M.S., M.Ch.,
• Dr. R. Bhargavi, M.S., M.Ch.,
• Dr. S. Raju, M.S., M.Ch.,
• Dr. K. Muthurathinam, M.S., M.Ch.,
• Dr. D. Tamilselvan, M.S., M.Ch.,
• Dr. K. Senthilkumar, M.S., M.Ch.
Dept of Urology, GRH and KMC, Chennai. 2
3. INTRODUCTION
• 1% of male neoplasms
• 5% of urological tumours
• three to ten new cases occurring per 100,000 males/per year in
Western societies
• Tumors with very good prognosis, one of the most curable solid tumors!
• Affects mainly young productive population
3
Dept of Urology, GRH and KMC, Chennai.
4. • Most common malignancy in men in the age group 15-35 yrs
• Incidence- 0.2 -1%
• Age group
-late adolescence-early adulthood(20-40 yrs)
-late adulthood (>60 yrs)
-infancy(0-10 yrs)
• Higher incidence -upper and middle socio economic class
-professional men
• Race – more in whites, rare in blacks
• Laterality– common in right testis
Bilateral – 2 – 3%
4
Dept of Urology, GRH and KMC, Chennai.
5. Etiology :
•Familial clustering noted; not well proved beyond
doubt
•An isochromosome of the short arm of chromosome
12, i(12p) is found in virtually all germ cell tumors,
regardless of their histologic type.
•association between genetic polymorphism in the
PTEN tumour suppressor gene and testicular germ
cell tumours (TGCT) has been recently described .
5
Dept of Urology, GRH and KMC, Chennai.
6. • Alterations in the p53 locus have been identified in 66% of cases of
GCNIS
• A deregulation in the pluripotent programme of foetal germ cells
(identified by specific markers, M2A, C-KIT and OCT4/NANOG) is
likely responsible for the development of GCNIS and germ cell
neoplasia.
• single nucleotide polymorphisms (SNPs) associated with an increased
risk of developing TGCT, in particular at 15q21.3
6
Dept of Urology, GRH and KMC, Chennai.
7. Epidemiological risk factors
• testicular dysgenesis syndrome (i.e. cryptorchidism, hypospadias,
decreased spermatogenesis evidenced by sub- or infertility)
• familial history of testicular tumors among first-grade relatives
• contralateral tumour or GCNIS
• body height (TGCT risk with an odds ratio of 1.13 per 5 cm increase in body
height)
( four well-established risk factors for testis cancer:cryptorchidism,family history
of testis cancer,a personalhistoryof testis cancer,and intratubulargerm cell
neoplasia(ITGCN).)
7
Dept of Urology, GRH and KMC, Chennai.
8. Cryptorchidism
• four to six times more likely to have testis cancer
• the relative risk decreases to two to three times more likely if orchidopexyis
performed before puberty
• 7 – 10% of pts with testicular tumors have h/o cryptorchidism / maldescent
• 5 – 10% of pts with cryptochidism will developtesticular tumor in later life
Factors-
abnormal germ cell morphology
elevated temperature
interferencewith blood supply
endocrine dysfunction
gonadal dysgenisis
8
Dept of Urology, GRH and KMC, Chennai.
11. Intra tubular germ cell neoplasia,
unclassified (IGCNU)
• Incidence- 0.8%
• Precedes invasive GCT in all
adult cases
• Absent in prepubertal
presentations, EGGCT and
Spermatocytic seminoma
• Median time for progression
– 5 yr- 50%
11
Dept of Urology, GRH and KMC, Chennai.
12. Patients at risk of CIS
•History of testicular carcinoma (5% to 6%),
• Extra gonadal GCT(40%),
• Cryptorchidism (3%),
•Contralateral testis with unilateral testis cancer (5%
to 6%),
•Somatosexual ambiguity (25% to 100%)
•Atrophic testis 30 %
•Infertility (0.4% to 1.1%)
TESTICULAR BIOPSY Gold standard for diagnoses of CIS
12
Dept of Urology, GRH and KMC, Chennai.
13. • Testicular CIS develops
from fetal gonocytes & is
characterized
histologically by
seminiferous tubules
containing only Sertoli
cells and malignant germ
cells.
13
Dept of Urology, GRH and KMC, Chennai.
16. Type Incidence
• GCT 90-95%
• Sex cord or gonadal
stromal tumors 2-4%
• Mixed 0.5%
• Miscellaneous 0.5-1%
• Secondary tumors 5%
Lymphoid
hematopoietictumors
metastatic
16
Dept of Urology, GRH and KMC, Chennai.
17. Germcelltumors-GCT
Incidence Age
Group
• Seminoma 40-50% 35-39 yrs
• Non seminomatous GCT
Embryonal carcinoma 15-20% 25-35
Yolk sac tumors 1-2% infants ,children
Trophoblastic tumors 1% 20-30 yrs
Teratoma 20-25% infants ,children
17
Dept of Urology, GRH and KMC, Chennai.
18. Seminoma
•40% of GCTs
•Fourth decade of life
•Classic seminoma
•Anaplastic seminoma
•Atypical seminoma
•Spermatocytic seminoma
18
Dept of Urology, GRH and KMC, Chennai.
19. Classical Seminoma:
• Large cell sheets with
abundant cytoplasm
• round hyperchromatic nuclei
with abundant nucleoli
• Lymphocytic infiltrate
• Trophoblastic giant cells that
produce hCG – 10%
• Atypical Seminoma:
More necrosis and higher nuclear
- cytoplasmic ratio and Keratin
positivity
19
Dept of Urology, GRH and KMC, Chennai.
21. Spermatocytic seminoma
• 2-12% of seminomas
• >50 yrs
• No cases of metastatic disease reported
• Good prognosis
(Older men not ass. with IGCNU or Bilaterality no special IHC marker
expression )
•Microscopy
Cells vary in size-different stages of maturing spermatogonia
Deeply pigmented cytoplasm
Rounded nuclei
Characteristic filamentous chromatin
21
Dept of Urology, GRH and KMC, Chennai.
22. NSGCT
• 55% of GCTs
• Third decade of life
• Most tumor types are mixed including seminoma
• All have equal prognosis
22
Dept of Urology, GRH and KMC, Chennai.
23. Embryonal carcinoma
Gross
Small rounded irregular mass
Invading tunica vaginalis , cord structures
Cut surface
Variegated grayish white fleshy tumor
Areas of necrosis and hemorrhage
Poorly defined capsule
23
Dept of Urology, GRH and KMC, Chennai.
24. microscopy
• Malignant epithelioid cells as tubules
• In distinct cell borders
• Cytoplasm – pale or vacuolated
• Round nuclei with coarse chromatin
Highly malignant tumors
Pleomorphism
Mitotic figures
Giant cells
24
Dept of Urology, GRH and KMC, Chennai.
25. Choriocarcinoma
• 1-2% of GCTs
• 20-30yrs
• Produces Beta-hCG
• Pure form - rare
• Wide spread hematogenous mets which are hemorrhagic
(Brain)
• Palpablenodule
• Distantmetastasis withsmallintra testicularlesion
Cut surface
Central h`ge
Viable grayish white tumor at periphery
25
Dept of Urology, GRH and KMC, Chennai.
26. Microscopy
Syncytiotrophoblast-
• Large multinucleated cells
• Abundant vacuolated eosinophilic
cytoplasm
• Large heperchromatic irregular nuclei
Cytotrophoblast-
• Closely packed uniform cells
• Distinct cell borders , clear cytoplasm
26
Dept of Urology, GRH and KMC, Chennai.
27. Teratoma
• 20-25%
• Derived from a pluripotent malignant precursor
• Teratoma with malignant transformation
• Non-ALL
• Rhabdomyosarcoma
• Carcinoma (enteric)
• PNET
• children
• More than one germcelllayer
• Gross
Large lobulated nonhomogenous
• In various stages of maturation
mature
immature
27
Dept of Urology, GRH and KMC, Chennai.
28. Mature
•Consists of adult type
differentiated cells from
all three elements-
ectoderm, mesoderm
and endoderm
•Cartilage ,glandular
epithelium and nerve
tissue
28
Dept of Urology, GRH and KMC, Chennai.
30. Contd…
Cut surface
• Cysts- gelatinous,mucinous,hyalinised
• Islands of solid tissue-
cartilage or bone
Intestinal ,liver ,pancreatic tissue
Smooth or skeletal muscle
Neural or connective tissue
Microscopy
• Cysts are lined by Squamous, cuboidal ,columnar ,transitional
epithelium
cartilage
mature
immature
30
Dept of Urology, GRH and KMC, Chennai.
31. Yolk sac tumors
Edodermalsinstumors
Adenocarcinomaof infantiletestis
Juvenileembryonalcarcinoma
orchioblastoma
•Infantsand children
•Pure form – uncommon in adult
•AFP
•Gross:
Papillary, glandular, microcystic or solid appearance
31
Dept of Urology, GRH and KMC, Chennai.
32. Microscopy
• Epitheloidcells in colums
• Embryoid bodies – resembling1-2 week old embryos
• perivascular arrangements of epithelialcells with an intervening
extra-cellular space (Schiller-Duval Bodies)
Yolk sac tumor
o Ebryoid body
f
embryo
32
Dept of Urology, GRH and KMC, Chennai.
35. Leydig’s cell tumors
•1-3% of testicular tumors
•Focal or diffuse interstitial cell hyperplasia
Gross
•Small yellow to brown , well circumscribed
Microscopy
• Uniform closely packed cells with eccentric nuclei and eosinophilic granular
cytoplasm
• Reinke’s crystals
• 10% are malignant
• Benign-goodprognosis
35
Dept of Urology, GRH and KMC, Chennai.
36. Sertoli’s cell tumors
•< 1%
•Any age group
•10% malignant
Gross
•1-20 cm
Cut surface
•Gray white to yellow with cystic changes
Microscopy
• Nodules of immature seminiferous tubules
• Lumen is lined by undifferentiatedcells
36
Dept of Urology, GRH and KMC, Chennai.
37. Mixed tumors-gonadoblastoma
• 0.5%
•All age groups
Gross
Round smoothsurface
Soft and fleshy-firm and hard
Cut surface
Grayish white to yellow with calcification
Microscopy
Sertolicells, germcells, interstitialcells
37
Dept of Urology, GRH and KMC, Chennai.
39. Lymphoma
•Most common secondary neoplasm
•Later manifestation of disseminated disease
•Initial manifestation of occult disease
•Gross
4-5 cm, gray to pink
Foci of necrosis & h’ge
Extention to epididymis
•microscopy
Diffusereplacementof normalpatternby reticuloendothelialcells
focalSparingof seminiferoustubules
39
Dept of Urology, GRH and KMC, Chennai.
40. Leukemic infiltartion
• Initialsiteof relapsein ALL
• Deathin 5m-2yrs
• Infitration at intertsitialspaceswithdestructionof tubules
• Biopsy
40
Dept of Urology, GRH and KMC, Chennai.
43. EXTRA GONADAL GERM CELL TUMORS
• Primary tumors of
extragonadal origin
are rare
• 3-5% of all GCTs are
extragonaldal
• Most common sites:
1. Mediastinum
2. Retroperitoneum
3. Sacrococcygeal region
4. Pineal gland
43
Dept of Urology, GRH and KMC, Chennai.
44. EXTRA GONADAL GERM CELL TUMORS
• Histologically all germ cell types
are represented
• Pure seminoma accounting for
nearly half
• May reach large size with
relatively few symptoms
• High potential for local invasion
and distant metastasis
• Primary retroperitoneal GCTs
are indistinguishable biologically
from testicular GCTs and carry
the same prognosis
44
Dept of Urology, GRH and KMC, Chennai.
45. Primary mediastinal NSGCTs
• less sensitive to chemotherapy
• have a poor prognosis with a 5-year overall survival of about 45%
• more likely to have yolk sac tumor components (elevations in serum
AFP)
• associated with Kleinfelter syndrome and with hematologic
malignancies that carry extra copies of the short arm of chromosome
12,
• In contrast, mediastinal seminomas have a prognosis similar to
testicular seminomas,
• mature teratomas of the mediastinum have low metastatic potential
and can generally be cured surgically
45
Dept of Urology, GRH and KMC, Chennai.