Transcript GERM CELL

Testicular carcinoma
Epidemilogy
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90-95% are germ cell
Incidence five times higher among white
men
Most common solid tumor in males ages
15-35
often is in right
What is Testicular Cancer?
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Germ cell tumors (GCT): ~95% of TC
 Seminomas:
most common subtype (~50%);
slow growing and radiosensitive
 Nonseminomas: often occur in third decade;
rapid metastasis to lymph nodes and lung
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Non-Germ Cell Tumors (Non-GCTs)
 Stromal:
~4% of adult TC
 Secondary tumors: arise in another organ
Risk factor
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Gonadal Dysgenesis
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Trauma
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prompts evaluation
Hormones
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20-30% develop cancer (gonadoblastoma)
DES/OCP probably do not increase risk
Atrophy (mumps orchitis)
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Cryptorchidism: 7-10% of patients with
testicular cancer have a history of
cryptorchidism
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Abnormal germ cell morphology
Elevated temperature
Interference with normal blood supply
5-10% of patients with testicular cancer and a
history of cryptorchidism develop cancer in the
contralateral testis
Orchidopexy does not prevent development of
cancer – just allows for detection
Clinical manifestation
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Patients often present with a painless testicular
mass
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Gynecomastia
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Pain, swelling, or hardness in scrotum a less frequent
complaint
About 10% report recent testicular trauma
Swelling in lower extremities, back pain, cough, or
dyspnea may indicate advanced disease
5% germ cell
30-50% Sertoli/Leydig
1-2% have bilateral disease at diagnosis
More common on the right
Diffrentiated Diagnosis
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Torsion
Epididymitis
Epididimoorchitis
Hydrocele
Hernia
Hematoma
Spermatocele
Syphilitic gumma
Work-up
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Exam
U/S
CXR +/- Chest CT
Abdominal CT
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Can identify small nodal deposits <2 cm
MRI and PET scan no advantage over CT
Markers
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Elevation after orchiectomy generally
represents metastatic disease
Conversely normalization does not rule out
metastatic disease
Alpha-Fetoprotein
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Expressed by the early embryo (also liver and
GI tract)
Single chain
Half-life: 5-7 days
Produced by pure embryonal, teratocarcinoma,
yolk sac, mixed tumors (NOT pure
choriocarcinoma or seminoma)
Falsely elevated in liver dysfunction, viral
hepatitis
Human Chorionic Gonadotrophin
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Secretory product of the placenta
Alpha unit (LH,FSH,TSH) and beta unit
Half-life: 24-36 hours
Produced by syncytiotrophoblastic tissue
All choriocarcinomas, 40-60% embryonal,
5-10% seminoma
Falsely elevated in hypogonadism and
marijuana use
Lactic Acid Dehydrogenase
Presents normally in smooth, cardiac and
skeletal muscle, liver and brain
 Most useful in advanced seminoma or tumors
where other markers are not elevated
 Many false positives
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Testis cancer
GERM CELL
 Seminoma 30-60%
 Non-seminoma
Embryonal 3-4%
Yolk sac
Teratoma 5-10%
Choriocarcinoma 1%
Mixed 40%
NONGERM CELL
 Leydig 1-3%
 Sertoli <1%
 Gonadoblastoma 0.5%
Seminoma:
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Most common germ cell tumor
Pure seminomas never secrete AFP
5-10% secrete HCG (usually classic)
At diagnosis:
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65-75% confined to the testis
10-15% with regional retroperitoneal nodes
5-10% with advanced juxtorenal or visceral disease
Seminoma
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Classic 82-85%
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Anaplastic 5-10%
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Age 30s
Islands /sheets of cells with
syncytiotrophoblasts (5-10%)
Stage for stage no different than classic
Spermatocytic 2-12%
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Low metastatic potential
Older population (>50)
6% bilateral
Emberional
 Peak
age 25-35
 May secrete both
AFP and B-HCG
 Metastatic deposits
usually contain
teratoma (80%)
Yolk Sac (Infantile embryonal)
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Peak age: infants and children
Also may spread hematogenously
Secretes AFB and B-HCG
Embryoid bodies (Schiller-Duvall bodies)
resemble 1-2 week old embryos surrounded
by syncytiotrophoblasts and cytotrophoblasts
Choriocarcinoma
 Peak
age 20-30
 Worst prognosis of all testis
tumors
 Hematogenous spread (especially
to lungs)
 Always secrete B-HCG
Teratoma
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Peak age 25-35
Poor response to chemotherapy and XRT
Pure forms should not secrete AFB or B-HCG
Can arise from malignant transformation after
chemotherapy for NSGCT
Contains all 3 germ layers in the mature form
and is undifferentiated in immature form
TNM Staging of Testicular
Tumour
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T0
T1s
T1
T2
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T3 =
T4 =
No evidence of Tumour
Intratubular, pre invasive
Confined to Testis
Invades beyond Tunica Albuginea or into
Epididymis
Invades Spermatic Cord
Invades Scrotum
N1 =
N2 =
N3 =
Multiple< 5 node/Single < 2 cm
Multiple < 5 node / Single 2-5 cm
Any node > 5 cm
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PRINCIPLES OF TREATMENT
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Treatment should be aimed at one stage above
the clinical stage
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Seminomas Radiotherapy.
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Non-Seminomas are Radio-Resistant and best
treated by Surgery
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Advanced Disease or Metastasis - Responds
Radio-Sensitive.
well to Chemotherapy
Treat
with
PRINCIPLES OF TREATMENT
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Radical INGUINAL ORCHIDECTOMY is Standard
first line of therapy
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Lymphatic spread initially goes to
RETRO-PERITONEAL NODES
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Early hematogenous spread RARE
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Bulky Retroperitoneal Tumours or Metastatic
Tumors Initially “DOWN-STAGED” with
CHEMOTHERAPY
Treatment of Seminomas
Stage I, IIARadical Inguinal Orichidectomy followed by
radiotherapy to Ipsilateral Retroperitonium
& Ipsilateral Iliac group Lymph nodes
(2500-3500 rads)
Bulky stage II and III Seminomas Radical Inguinal Orchidectomy is followed by
Chemotherapy
Treatment of Non-Seminoma
Low Grade
RADICAL ORCHIDECTOMY
followed by RETROPERITONEAL LYMPH
DISSECTION
High Grade:
Initial CHEMOTHERAPY followed by
SURGERY for Residual Disease
Radical Orchiectomy
Survival at 5 years
Seminoma
Stage I
Stage II A
Stage II B-III
Non-seminoma
98%
96-100%
92-94%
>90%
33-75%
55-80%
NON_GERM CELL
Leydig Cell
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1-3% of all testis tumors
Bimodal age distribution: ages 5-9 and 25-35
Bilateral in 5-10%
No association with cryptorchidism
Prepubital children may present with virilization and
elevated urinary 17-ketosteroid levels; adults are
usually asymptomatic (25% gynecomastia)
Treatment: radical orchiectomy and RPLND for
malignant tumors (10% malignant)
Sertoli Cell
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Less than 1% of all testicular tumors
Bimodal age of distribution: < 1 year and
20-45 years old
10% lesions are malignant
Virilization seen in children and
gynecomastia in adults
Treatment: Radical orchiectomy with
RPLND in malignant disease
Gonadoblastoma
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0.5% of testicular tumors
Seen in patients with gonadal dysgenesis
4/5 patients are phenotypic females with
streak gonads
Treatment: Radical orchiectomy with
gonadectomy of the contralateral gonad
(bilateral in 50%)
Secondary testicular tumor
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Lymphoma
Large without pain
50% bilatral
¼ with systemic symptom
treatment:
radical orciectomy+chemotherapy
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Leukemia:
in 50% bilatral
Dx : biopsy
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Metastatic tumor:
very rarely
source: prostat
lung
GI
melanoma
kidney