4. LEARNING OBJECTIVES
• At the end of this presentation, the students should be able to:
• Understand embryology of the testis and testicular descent
• Understand the detailed pathology and pathophysiologic changes in
testicular cancer patients
• Work out the diagnosis and management modality in a given patient
with testicular cancer
• Identify the current area of interest and the future trend in the
management of testicular cancer
5. INTRODUCTION
• Testicular cancer is relatively rare, occur in 2-3/100,000
• More common on the right
• 94% are germ cell tumours (seminoma & non-seminoma)
• Remaining are gonadal stroma (leydig, sertoli, gonadoblastoma) and secondary
tumours
• Germ cell subtypes are less common in our environment
• 12% associated with cryptorchidism, including carcinoma in situ
• 1-2% of primary testicular tumours are bilateral, up to 50% of these are found in men
with cryptorchidism
• Orchidopexy does not prevent subsequent cancer development
6. EMBROLOGY
• The gonadal ridge is formed from the mesothelial layer of the primitive
peritoneum and the adjacent mesoderm.
• This would develop to the eventual testis in male.
• Cords are formed from the core of the primitive testis the surface of which is
covered by tunica albuginea which eventually separates the cords from the
surface epithelium
• the cords converges at the hilum eventually forming the rete testis
• The cords develops into seminiferous tubules away from the rete and are
separated by connective tissue septa
• The outgrow from the mesonephros soon join with the rete and form the
drainage of the tubules.
8. EMBRYOLOGY
• Before testicular descent, there is formation of connection between the
developing testis and the scrotum
• Then the formation of gubernaculum testis which is believe to pull the
testis to its eventual site in the scrotum
• This under the influence of testosterone
9. PATHOLOGY
• Seminoma: account for 35% of all tumours
✦ Classic Seminoma- about 85% of all seminoma, common in 4th decade of life.
Grossly it has coalescing grey nodules on cut surface.
✦ Anaplastic Seminoma- 5-10% require 3 or more mitoses per high power field for
diagnosis. has high nuclear pleomorphism, usually present at higher stage. this
subtype does not convey worse prognosis.
✦ Spermatocytic Seminoma- 5-10% Cells are of varied sizes, with dense staining
cytoplasm and chromatin. Over 50% of sufferers are 50years and older.
• Embryonal cell carcinoma: Account for 20% of the tumour
✦ Adult type- Marked pleomorphism, indistinct cell borders, high mitotic figure
and presence of giant cells.
10. PATHOLOGY
Cells are in sheets, cords, form glands or are papillary. Grossly,
hemorrhagic and necroses are seen on cut surface.
✦Infantile- Commonest in infants and children. When seen in adult its of
mixed nature histologically; secrete AFP, cells are vaculated due to fat
and glycogen, are in loose network with intervening cystic spaces.
Embryoid bodies are present containing cavity surrounded by syncytio
and cytotrophoblasts
12. PATHOLOGY
• Teratoma: 5% of all tumour can be seen in both adults and children,
have more than one germ cell layers in various stages of maturation
and differentiation. Grossly, its lobulated and cystic filled with gelatin
and mucus materials
✦Matured- May have elements resembling benign structures derived
from ectoderm, mesoderm or endoderm.
✦Immature- Characterized by undifferentiated primitive tissues
on microscopy, derivatives of the three germ layers could be seen, sq
cells, neural tissues, bone, cartilage, muscles, respiratory, intestinal or
pancreatic tissue.
13. PATHOLOGY
•Choriocarcinoma: <1% in pure form, its very rare.
Grossly seen as a small tumour within testis with central haemorrhage
Microscopy show trophoblasts must be seen.
syncytial elements are large, multinucleate cells with vaculated
oesinophilic cytoplasm, large irregular and hyper chromatic nuclei.
Cytotrophoblast elements are uniform cells with distinct cell borders,
clear cytoplasm and single nucleus.
It is clinically aggressive with hematogenous spread occurring early.
14. PATHOLOGY
•Mixed cell type: 40% of all testicular tumours. Teratocarcinoma
(teratoma + embryonal cell carcinoma) account for about 25% of all
testicular tumours.
when seminoma coexist with non seminoma germ cell tumour, the
treatment is for that of non seminoma GCT
•Carcinoma in Situ: It is found in about 5% of countralateral testis of
patients with testicular cancer. often helraded by presence of testicular
atrophy and microlith on USS.
The treatment is external beam radiation therapy.
15. PATTERN OF SPREAD
• Chorioca has early hematogenous spread to the lungs and spleen
• Others are spread mainly via lymphatics from T1 to L4, more nodal
concentration at the renal hilum
• The spread is stepwise:
✦ On the Right- Precaval to Preaortic to paracaval to Common iliac to Ext.
iliac
✦ On the left- Preaortic to Common iliac to Ext. iliac
• No crossover metastasis to the right from left is noted, however there
is commonly from right to left
16. PATTERN OF SPREAD
• Distal Ext. iliac and obturator nodes may be involved in epididymis and
spermatic cord invasion
• Scrotal violation or invasion of tunica albuginea may result in inguinal
node metastasis
• In advanced disease, viscera may be involved however, early spread is
to retroperitonium.
• Lungs, liver, brain, bone, kidney, adrenal, GIT, spleen in descending
order of occurrence.
18. CLINICAL STAGING
•TNM (1996)-AJCC:
Primary tumour;
Tx- can’t be assessed
To- no evidence
Tis- intratubular cancer
T1- limited to the testis and epididymis. No vascular invasion
T2- invasion of tunica albuginea OR vascular invasion
T3- invasion of spermatic cord
T4- scrotal invasion
19. CLINICAL STAGING
Regional nodes;
Nx- can’t be assessed
No- no evidence
N1- node not greater than 2cm OR multiple nodes non greater than
2cm and not more than 5 positive nodes
N2- node greater than 2cm but less than 6cm OR 6 and above positive
nodes.
N3- nodal mass more than 5cm
20. CLINICAL STAGING
Metastasis;
Mx- can’t be assessed
Mo- no evidence of distant spread
M1- spread to non regional nodes OR lungs involvement
M2- non pulmonary visceral spread
21. CLINICAL STAGING
Serum tumour markers
Sx- markers not available
So- marker levels within normal limits
S1- LDH <1.5 times normal OR hCG < 5,000mu/mL OR AFP <
1,000ng/mL
S2- LDH >1.5-10 times normal OR hCG 5,000-50,000 mu/mL OR AFP
1,000-10,000ng/mL
S3- LDH > 10 times normal OR hCG >50,000mu/mL OR AFP >
10,000ng/mL
22. CLINICAL FINDINGS
• Painless scrotal swelling of gradual onset
• Feeling of heaviness in the ipsilateral testicle
• Acute testicular pain if tumor bleeds or superimpose infection seen in
10% of cases
• 10% will be asymptomatic with incidental finding following trauma or
by sex partner
23. CLINICAL FINDINGS
• 10% of the patients will present with features of metastasis
✦ cough, dispnoea, hemoptysis- Lung
✦ Back pain- retroperitoneal nerve roots
✦ anorexia, vomiting, nausea- retroduodenal
✦ bone pain- skeletal
✦ leg swelling- vena cava obstruction.
24. CLINICAL FINDING
• Diffuse testicular mass, firm and non tender
• Epididymis is easily separated from the mass
• There maybe secondary hydrocele, it may mask the tumour
• Retroperitoneal nodes maybe palpable per abdomen
• Other lymph nodes are sought for- supraclavicular, scalene, inguinal
• There maybe gynecomastia in Sertoli and Laydig cell tumours up to
50% of cases, 5% in germ cell tumour
25. LAB FINDINGS
• Anaemia
• Abnormal LFT
• Elevated urea and creating in ureteral obstruction
• Tumour markers- AFP, hCG, LDH
✦ AFP- 70 kDalton glycoprotein; T1/2-4-6 days; present in fetal life; seen
in NSGCTs; not seen in seminom.
✦ hCG- 35 kDalton glycoprotein; T1/2 24hrs; alpha subunit same as in LH,
FSH and TSH; insignificant serum level in normal male; commonly seen
in NSGCTs, up to 7% seminoma will elaborate it.
26. LAB FINDINGS
✦ LDH- 134 kDalton cellular enzyme, five isoenzymes- in muscles, liver,
kidney and brain. Elevation of total of total serum LDH and
isoenzyme-I correlate with tumor burden in NSGCTs. May be elevated
in seminoma
✦ Others: Placenta alkaline phosphatase (PLAP), Gamma-glutamyl
transpeptidase (GGT)
27. IMAGING
• Ultrasound- fast and cheap, readily available. Demonstrate
intratesticular mass and any associated secondary hydrocele
★ Once the diagnosis of testicular cancer is established by inguinal
orchiectomy, careful clinical staging is mandatory
✦ Chest X-ray- Lungs Metastasis
✦ CAT Scan- abdomen and pelvis- retroperitoneal nodes metastasis
✦ Pedal lymphangiography- rarely used, invasive and less specific but
necessary in patients on surveillance protocol.
29. TREATMENT
• Inguinal exploration with cross-clamping of spermatic vasculature and
delivery of testis into the field is main stay of exploration for possible
tumour of the testis
• Radical orchiectomy is necessary if if tumor cant be rule out by
examination
• subsequent management depend on nature and stage of tumour
31. TREATMENT
• Low-Stage seminoma-
✦ Radical orchiectomy and retroperitoneal irradiation 2500-3000cGy
✦ Low volume retroperitoneal disease can be treated with irradiation,
average 5 year survival is 87%
✦ Prophylactic mediasternal irradiation is no longer employed because
of myelosupression which may undermine chemotherapy when
needed
✦ Chemo is advocated as salvage therapy for relapse following
irradiation
32. TREATMENT
• High-Stage seminoma-
✦ Bulky seminoma and seminoma with elevated AFP should be treated with
primary chemotherapy
✦ PEB: cisplatin, etoposide & bleomycin
✦ VAB-6: Vinblastine, cyclophosphomide, actinomycin D, bleomycin & cisplatin
✦ CE: cisplatin & etoposide
✴ 4 cycles is required
✴ All seminomas are given low-risk chemo: CE, PEB 3 cycles
33. TREATMENT
✴ With chemo, 90% advanced disease achieve complete response
✴ Following chemo residual retroperitoneal masses are fibrosis in 90% of
cases
✴ When circumscribed and >3cm, surgical excision of the retroperitoneal
residual mass is advocated since 40% of them will harbor tumor
34. TREATMENT
• Low-Stage NSGCT-
✦ Standard treatment for stage I disease in the USA include
retroperitoneal lymph node dissection
✦ This is modified due to the morbidity of RPLND and the fact that in
stage I disease there is cure by orchiectomy alone reported in up to
75% cases.
✦ Modification options include surveillance and modified RPLND
35. TREATMENT
• High-Stage NSGCT-
✦ There is RPLND, surveillance and adjuvant chemotherapy.
✦ PEB is the chemotherapy of choice (cisplatin, eposide, bleomycin).
36. SURVEILLANCE PROTOCOL
• Patients are considered for surveillance if:
✦ Tumour is NSGCT confined within tunica albuginea
✦ No vascular invasion
✦ Tumour markers normalizes after orchiectomy
✦ Radiologic imaging show no evidence of disease
✦ Patient is considered RELIABLE
37. SURVEILLANCE PROTOCOL
• Follow up every month for 1st 2 years and twice monthly in the 3rd year
• Tumour markers are checked every visit
• CXR, CT scan every 3-4 months
• Follow up beyond 3 years.
• Most relapse occur within 1st 8-10 months
• Most patients with relapse can be cured by chemotherapy and surgery
38. RPLND
• Usually done through a thoraco-abdominal incision OR midline transabdominal
approach
• Nodal tissues between the ureters from the renal vessels to the bifurcation of the
common iliac vessels are cleared
• Negative nodes or N1 nodal disease does not need adjuvant chemotherapy
• N2 disease is given 2 cycles of chemotherapy because relapse is up to 50%
• RPLND is associated with significant morbidity particularly ejaculation
• To preserve ejaculation, RPLND is done only on the left for left tumour. This is not
applicable to right sided tumour because crossover spread.
39. MODIFIED RPLND
• By modifying the dissection of nodal tissues below the inferior
mesenteric artery to include only ipsilateral nodal tissues preserve
ejaculation
• An alternative in Clinical stage I disease with vascular invasion in
primary tumor is 2 cycles of chemotherapy. This is associated with
neurotoxicity and fertility issues especially in young patients
40. Relapse After Chemotherapy
• Salvage chemotherapy is the treatment of choice for relapsed GCT after
chemotherapy.
• First relapse with good prognostic features (gonadal primary tumor,
initial response), 4 cycles of standard salvage chemotherapy are
proposed.
• For patients with poor prognostic factors (extragonadal primary,
incomplete response to first line chemotherapy) and subsequent
relapse, high dose chemotherapy with autologous stem cell support is
recommended.
41. Follow-up
• Aim is to detect relapse as early as possible
• To monitor contralateral testis
• To identify early non-malignant complications of therapy.
✦ Physical exam and tumor markers check should last up to 10 years.
✦ Done 4 times a year for the first two years, yearly thereafter.
