Download Germ Cell Tumors

TESTICULAR
CANCER
GÖZDE AKAN
BERFİN GİZEM USLU
ANATOMY
 Paired, ovoid male
reproductive organ
 4 x 3 x 2.5cm
approximately 25 ml
 250-350 lobules
 Lies obliquely within the
scrotum suspended by the
spermatic cord
FUNCTIONS
 Produce sperms and
male hormones,
primarily
testosterone
LYMPHATIC DRAINAGE
 On the right :
along the IVC - interaortacaval region - preartic
and paraaortic lymph nodes ,with possible crossover within the retroperitoneum
 On the left :
preaortic and paraaortic nodes around the left
renal hilum - interaortacaval nodes mostly without
cross-over
EPIDEMIOLOGY
 Uncommon malignancy, accounting for 1–2% of all
tumours in men
 However, it is important because its incidence is
increasing worldwide
 Most common malignancy in young men (aged 15–34
years) in many populations worldwide
 The peak age of men with seminomas is 30–40 years,
compared with 20–30 years for nonseminomatous GCT
 Contrary to the trends in incidence, the testicular cancer
mortality rate has been decreasing in most European
countries, largely attributable to the advent of platinumbased chemotherapy regimens and multidisciplinary
approach to testicular cancer management
RISK FACTORS
1. Cryptorchidism -four to eight times greater risk
2. Prior Testicular Cancer- 500-fold higher rate than in
the general population
3. Genetics-
Klinefelter syndrome (47XXY)
Down syndrome
Androgen insensitivity syndrome
4. Family history
5. Infertility
6.Environmental exposure
7.Scrotal trauma
8.Inguinal hernia
9.Smoking
10.Race-more common among Caucasian males
Highest rates in Scandinavia,
Germany and New Zealand
11.HIV
CLINICAL FEATURES
•
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•
•
•
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• Due to metastasis;
Due to primary tumor;
• Abdominal or lumbar pain
Painless testicular lump
(lymphatic spread)
Sensation of heaviness
• Dyspnea, hemoptysis and
Rarely pain (1/3rd cases)
chest pain with lung
May mimic
metastasis
epidedymoorchitis
• Jaundice with liver metastasis
Gynaecomastia appears in
• Hydronephrosis by para-aortic
7% of cases
lymph nodes enlargement
• Pedal edema by IVC
obstruction
PHYSICAL EXAMINATION:
• Enlarged testis (except
choriocarcinoma)
• Nodular testis
• Loss of testicular sensation
• Flat and difficult to feel
epididymis
• General examination for
metastasis
CLASSIFICATION OF TESTICULAR
TUMORS
 Germ Cell Tumors (%90)
A. Seminomas (%60)
1. Classical
2. Spermatocystic
3. Anaplastic
B. Non-Seminomatous Tumors
(%40)
1. Embryonal Carcinoma
2. Yolk Sac Tumor
3. Choriocarcinoma
4. Teratoma
5. Mixed Tumors
 Non-Germ Cell Tumors
A. Sex-Cord Stromal Tumors (%2)
1. Leydig Cell Tumor
2. Sertoli Cell Tumor
3. Granulosa Cell Tumor
4. Mixed Type
5. Unclassified
B. Mixed Germ Cell and Stromal
Tumor
C. Adnexal and Paratesticular
Tumors
D. Miscellaneous Tumors (%5)
(Metastatic tumors,
Carcinoid,Lymphoma)
GERM CELL TUMORS
1) Seminoma testicular cancer
• The commonest variety of testicular tumour
• Adults are the usual target (4th and 5th decade); never seen in infancy
• Patients present with painless testicular mass
• 30 % have metastases at presentation, but
only 3% have symptoms related to metastases
• Serum alpha fetoprotein is normal
• Beta HCG↑30% of patients
with Seminoma
• Highly sensitive to radiotherapy
among testis tumors
SEMINOMA

CLASSICAL (%85)

Middle age (30-50)
↑BetaHCG(10%)
Very slow growth
 Spermatocytic(2% - 12% )
yrs
ANAPLASTIC (5% - 10)

Middle age

Aggressive - lethal

Greater mitotic activity

Higher local invasion
 Higher metastatic potential
Old age (> 50 yr)
Most common GCT in men > 65  Higher rate of β-HCG production
Extremely low metastatic potential
Good prognosis
2)NON-SEMİNOMATOUS GERM CELL
TUMORS
2. a) Embryonal Carcinoma:
 2nd most common germ cell tumor
 90% of NSGCT
 Present in majority of mixed germ cell tumours
 Most men present in their 20s to 30s with a testicular mass
 Highly malignant tumours; may invade the cord structures epididymis
 High degree of metastasis
 Serum AFP is positive in 30%, beta HCG is elevated in 20% of cases
2)NON-SEMİNOMATOUS GERM CELL
TUMORS
2.b) Choriocarcinoma:
• A rare and aggressive tumour (5years survival is 5%)
 Typically elevated B-Hcg > 99%
 Usually present with distant mets – lung and /or brain
 Primary is very small and often exhibit NO TESTICULAR
ENLARGEMENT, small palpable nodule may be present.
 Hematogenous mets most common
2)NON-SEMİNOMATOUS GERM CELL
TUMORS
2.c) Yolk sac tumor:
• Most common prepubertal GCT in children.
• Pure yolk sac tumor <2% of testicular tumors in adults
• 40% of mixed germ-cell tumors.
• AFP ↑ >90% of pts
• Testicular mass the most usual presentation
• Respond very well to chemotherapy, even if they have spread
• Microscopically, Schiller-Duval bodies are
a characteristic feature
2)NON-SEMİNOMATOUS GERM CELL
TUMORS
2.d) Teratoma:
 Teratoma in greek means “monster tumor”
 Contain all three germ layers with varying degree of diffrentiation
 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
 Normal serum markers.
◦ Mildly elevated AFP levels
3)SEX CORD STROMAL TUMORS
1. Sertoli cell:
3. Granulosa cell
-Excess estrogen production
4. Mixed types
-Gynecomastia in 1/3rd of cases
-10 % are malignant
-Androgen insensitivity syndrome
-Peutz-Jeghers syndrome
2. Leydig cell:
-Produces androgens
-Reinke crystals
-Klinefelter’s syndrome
METASTATIC TUMORS OF TESTIS
 Lymphoma
-most common secondary tumor
-most common testicular tumor in patients above 50 years
 Leukemia
 Prostate cancer
SPREAD
1. Direct Spread:
 This spread occurs by invasion.
 Tunica albuginea is rarely penetrated
 Scrotal skin involvement
 Spread to spermatic cord and epidedymis may occur :
points towards bad prognosis
2. Lymphatic spread:
Seminoma metastasize exclusively through lymphatics
They drain primarily to para-aortic lymph nodes
3. Blood Spread
 NSGCT spread through blood route
 Lungs, liver, bones and brain are the usual sites usually involved
TUMOR MARKERS
 AFP (alpha-fetoprotein): Trophoblastic Cells
-upper limit of normal serum AFP<10-15 microg/L
-serum AFP concentrations >10,000 microg/L are found almost
exclusively in patients with (NSGCTs) or hepatocellular carcinoma
 B-HCG: Syncytiotrophoblastic Cells
-most commonly elevated tumor marker in testicular cancer
-normal value in men is less than 5 to 10 IU/L
-Increased levels of beta-HCG can be found in seminoma or
nonseminoma
TUMOR MARKERS
 Lactate Dehydrogenase (LDH):
-elevated in 40 to 60 percent of men with testicular germ cell tumors
-less sensitive and less specific tumor marker than (beta-hCG) or (AFP)
for men with NSGCTs
- increased levels reflect tumor burden, growth rate, and cellular
proliferation
AFP, BHCG & LDH are included in TNM staging of testicular cancers
DIAGNOSIS
 Painless swelling or a nodule in one testicle is the most common
presenting sign
 In any man with a solid, firm mass within the testis, testicular cancer
must be the considered diagnosis until proven otherwise
Physical examination
Scrotal USG
Blood test: CBC + AFP , B-HCG , LDH
 CT Scan, MRI, PET Scan
 Radical inguinal orchiectomy
 Contralateral testicular biopsy
 Retroperitoneal lymph node dissection
DDx
 Epididymo-orchitis
 Hematoma
 Torsion
 Paratesticular neoplasm
(most commonly benign)
 Hernia
 Varicocele-spermatocele
 Tuberculosis and other
testicular infections
STAGING(for all patients)
 Serum tumour markers
-AFP
-hCG
-LDH
 Abdominopelvic CT
 Chest X-ray/ CT
 Testis ultrasound (bilateral)
TNM STAGING
Testicular cancer is staged using the TNM
system created by the American Joint
Committee on Cancer (AJCC).
T refers to how much the main (primary) tumor
has spread to tissues next to the testicle.
N describes how much the cancer has spread to
regional (nearby) lymph nodes.
M indicates whether the cancer has
metastasized (spread to distant lymph nodes or
other organs of the body).
S indicates the serum (blood) levels of tumor
markers that are made by some testicular
cancers.
ROYAL MARSDEN
CLASSIFICATION
Stage I: Cancer is found only in the testicle.
Stage II: Cancer has spread to the
retroperitoneal lymph nodes in the belly.
-IIA: <2 cm in size or < 6 positive nodes
-IIB: 2-5 cm in size or > 6 positive nodes
-IIC: large and bulky abdominal mass, usually >
5-10 cm
Stage III: Cancer has spread beyond the lymph
nodes in the belly. There may be cancer in parts
of the body far away from the testicles such as
the lungs, brain, bones and liver.
Stage IV: Hematogenous spread
GENERAL MANAGEMENT
 After obtaining serum AFP & B-Hcg levels in
suspected case of malignant germ cell tumour
 Radical inguinal orchietectomy with high ligation of
spermatic cord is done, it is both diagnostic &
therapeutic
 Further management depends on, pathology & stage
of disease.
Radical inguinal orchietectomy
 Testicular tumors are diagnosed,
staged and locally controlled by
inguinal orchiectomy.
 Scrotal biopsy is irrelevant and
contraindicated.
TREATMENT
 Radical Inguinal Orchiectomy
 Surveillance
 Retro Peritoneal Lymph Node Dissection(RPLND)
 Radiotherapy
 Chemotherapy
SEMINOMAS TX
 1. Early Stage
 Radiation therapy (gold standard)
 Surveillance (selected cases)
 2. Advanced Stage
 Chemotherapy
NONSEMINOMAS TX
 Early Stage (Stage I)
 Retroperitoneal Lymph Node Dissection
 Open / Laparoscopic
 Surveillance (low-risk patients)
 Chemotherapy (2 courses) (high-risk patients*)
* angio-lymphatic invasion
>%50 presence of embryonal cell carcinoma
Absence of yolk sac component
 Advanced Stage (>IIB)
 Chemotherapy (BEP : Bleomycin/etoposide
Cisplatin)
PROGNOSIS
High-risk prognostic features include any of the
following:
 Mediastinal primary tumor
 Nonpulmonary visceral metastases
 AFP > 10,000 ng/mL
 hCG > 50,000 IU/L
 LDH > 10 times the upper limit
A good prognosis can typically be expected in patients
with the following:
 Testicular or retroperitoneal primary tumor
 No nonpulmonary visceral metastases
 Alpha-fetoprotein < 1000 ng/mL
 Human chorionic gonadotropin < 5000 IU/L
 Lactate dehydrogenase (LDH) < 1.5 times the upper
limit
FOLLOW-UP
 At least 5 years with:
-periodic x-rays
-CT scans
-blood tests for tumor markers
 Also, since there is an increased risk (about 2%) of a
second tumor, it is important to continue monthly
testicular self-exams.
REFERENCES
 "What Is Testicular Cancer?" American Cancer Society. N.p., n.d. Web. 01 Apr.
2017. <https://www.cancer.org/cancer/testicular-cancer/about/what-is-testicularcancer.html>.
 "Testicular Cancer." Background, Pathophysiology, Epidemiology. N.p., 13 Mar.
2017. Web. 01 Apr. 2017. <http://emedicine.medscape.com/article/279007overview>.
 "Testes and Epididymis Anatomy." Overview, Gross Anatomy, Microscopic Anatomy.
N.p., 28 Oct. 2016. Web. 01 Apr. 2017.
<http://emedicine.medscape.com/article/1949259-overview#a2>.