Testicular tumors

1. Testicular tumors
Mohammad Ihmeidan PGY2

2. Introduction
• Most common malignancy of urogenital tract in
males 15-35
• Its incidence has been increasing during the last
decades especially in industrialised countries.
• More common among Caucasian men

3. Presentation
• Signs & symptoms
– Usually painless lump
– 30-40% c/o heaviness or dull ache
– 10% acute pain
– 10% present with metastatic manifestations
• Neck mass, cough, nausea, vomiting, lumbar pain, bone pain
– Gynecomastia is present in 5% of GCTs
• Any hypoechoic area on US wthin tunica is suspicious for
tumor

4. Risk factors
• Cryptorchidism (4-13x risk)
– 7-10% of tumors had cryptorchidism
– 5-10% testicular tumor had cryptorchidism in
contralateral side
– Intra-abdominal testis > Intrainguial testis
– Structural abnormalities seen in cryptorchid
testis at 3 years
– Orchiopexy does not prevent cancer, but it
allows easier clinical detection

5. • - Family History (6-8x risk)
• - Racial Origin (Highest in Scandinavia)
• - Maternal exposure of estrogen (2.8-5.3x risk)
• - Subfertility (1.6-20x risk)
• - Contralateral testicular tumour (5-10% risk)

6. • Survival
– <50% prior to 1970
– >95% in 1997
• Improved survival:
– Accurate tumor markers
– Effective chemo
– Modifications of surgical technique
– Mostly radiosensitive
– Backup treatments if primary treatments fail

8. Classification
• Germ Cell Tumors (GCT)
– Seminoma
• Classic or Typical
• Anaplastic
• Spermatocytic
– Nonseminoma
• Embryonal Cell Carcinoma
• Yolk Sac Tumor
• Teratoma
• Choriocarcinoma
• >50% GCT are mixed

9. Classic Seminoma
• 82-85% of seminomas
• Mostly men in 30’s
• Clear cytoplasm, dense nucleus
• Synctiotrophoblasts in 10-15%
– Elevated B-HCG in 10%
– hCG up to 500 ng/mL
• Lymphocytes in 20%

10. Anaplastic Seminoma
• 5-10% of seminomas
• Greater mitotic activity
• Higher rate of local invasion
• Increased rate of metastasis
• Higher rate of B-HCG production
• Stage for stage – treatment outcomes same as
classic seminoma

11. Anaplastic Seminoma
Note : Pleomorphism, hyperchromasia

12. Spermatocytic Seminoma
• 3 sizes of cells
• 9% of seminomas
• 50% older than 50
• Very low metastatic potential
– Favorable prognosis

13. Embryonal Carcinoma
• Small, hard, irregular mass
• Age 25-35
• Smallest germ cell tumor
– 40% <2cm
• Invades tunica vaginalis
• Often close to rete testis
• Highly malignant

14. Choriocarcinoma
• Commonly present with metastasis
• Must have synctiotrophoblasts &
cytotrophoblasts
• 1-2% of tumors
• hCG elevated in >99%
• Age 20-30
• Worst prognosis

15. Teratoma
Derived from 2 or more embryonic germ cell layers
in various stages of maturation
• Can contain bone, cartilage, intestinal,
pancreatic, liver, muscle, neural cells
• Lined by any cell type
• Large, lobulated, nonhomogeneous

16. Teratoma
• Classifications
– Mature
– Immature
– With malignant transformation
– Simple epidermoid cysts
• 3% of adult, 38% of children
• Elevated AFP 20-25%
• Age 25-35
• Epidermoid cysts – benign
• Metastatic teratoma resistant to chemo & radiation

17. Yolk Sac Tumor
• Most common testis tumor age 0-10
– Slow growing mass
– 25% have hydrocele
– AFP elevated in >90%
• In adult mixed tumors, 1/3 have yolk sac
elements

18. Mixed Tumors
• 60% of tumors
• Most frequent mixed tumor
– Embryonal, seminoma, yolk sac, teratoma &
syncytiotrophoblasts
• Document % of volume for each type
• AFP & hCG can be elevated
• Age 10-30
• Managed as NSGCT

19. Intratubular Germ Cell Neoplasia:
((CIS of Testis))
• Precursor to all GCTs except spermatocytic seminoma
• Risk Factors
– Contralateral testis w/ unilateral ca (2-38%)
– Cryptorchidism (5-6%)
– Infertility (1%)
– Extragonadal GCT (35-50%)
– Intersex (25-100%)
• Evenly distributed through testis
– Open biopsy is reliable
– US unreliable
• Treatment Options
– Observation – treatment of choice
– Orchiectomy
– Radiation (European treatment)
– Chemo ineffective

20. Epidemiology of GCTs
• Incidence
– Lifetime risk white male – 1 in 500
• 1/3 lower risk for American blacks
– Highest incidence – Scandinavia, Switzerland,
Germany, New Zealand
– Lowest incidence – Asia, Africa
• Laterality
– 2-3% are bilateral
– More common on Rt ?

21. Tumor Markers
• NSGCTs
– Elevated AFP 50-70%
– Elevated hCG 40-60%
– Elevated either or both 90%
– 10% of advanced disease will have normal tumor markers
• Be careful
– Elevated AFP can be from liver dysfunction
– Elevated hCG can be from hypogonadism & marijuana
– Normal markers does not mean no residual disease
• 10-20% after chemo & RPLND for bulky disease have viable tumor
despite normal markers

22. AFP
• 5-7 day half life
• Can be elevated in:
– Testis, liver, pancreas, stomach, lung ca
• Never elevated in pure choriocarcinoma or seminoma
• Can be elevated in:
– Pure embryonal
– Teratocarcinoma
– Yolk sac
– Combined

23. HCG
• 24-36 hour half life
• Elevated in all choriocarcinoma, 40-60% of embryonal,
5-10% of seminomas
• Can be elevated in:
– Marijuana smokers
– Liver, pancreas, stomach, lung, breast, kidney, bladder ca
– Elevated LH - false positive HCG

24. LDH
• High levels in muscle, liver, kidney, brain
• High false positive rate
• Most useful as a marker for bulky disease

25. Patterns of Spread
• Predictable (except for choriocarcinoma)
• Spermatic cord has 4-8 lymph channels
• Right-sided tumors
– Interaortocaval at level of L2 body
– Can cross from R to L
• Left-sided tumors
– Para-aortic between L ureter, L renal vein, aorta,
origin of IMA

26. Staging

27. Staging Systems
• American Joint Committee on Cancer (AJCC) – 1997,
2002
– TNMS system
• Stage grouping
– Stage 0, Ia, Ib, Is, IIa, IIb, IIc, III
– Stage I
• No nodes, no mets
– Stage II
• Positive regional nodes
– Stage III
• Nonregional nodes or pulmonary mets

28. STAGING OF TESTIS TUMORS BY
THE AMERICAN JOINT COMMITTEE ON CANCER (AJCC)
• Primary Tumor
• The extent of primary tumor is
classified after radical orchiectomy
• pTX Primary tumor cannot be
assessed. (If no radical orchiectomy
has been performed, TX is used.)
• pT0 No evidence of primary
tumor (e.g., histologic scar in testis)
• pTis Intratubular germ cell
neoplasia (carcinoma in situ)
• pT1Tumor limited to the testis
and epididymis without
vascular/lymphatic invasion. Tumor
may invade into the tunica albuginea
but not the tunica vaginalis.
• pT2Tumor limited to the testis and
epididymis with vascular/lymphatic
invasion, or tumor extending through
the tunica albuginea with involvement
of the tunica vaginalis
• pT3Tumor invades the spermatic
cord with or without
vascular/lymphatic invasion
• pT4Tumor invades the scrotum
with or without vascular/lymphatic
invasion

29. • Regional Lymph Nodes (N) Clinical
• NX Regional lymph nodes cannot be
assessed
• N0No regional lymph node metastasis
• N1Metastasis with a lymph node mass 2
cm or less in greatest dimension; or multiple
lymph nodes, none more than 2 cm in
greatest dimension
• N2Metastasis with a lymph node mass,
more than 2 cm but not more than 5 cm in
greatest dimension; or multiple lymph nodes,
any one mass greater than 2 cm but not
more than 5 cm in greatest dimension
• N3Metastasis with a lymph node mass
more than 5 cm in greatest dimension
• Pathologic Lymph Nodes (pN(
• pNX Regional lymph nodes cannot be
assessed
• pN0No regional lymph node
metastasis
• pN1Metastasis with a lymph node
mass 2 cm or less in greatest dimension
and five or fewer nodes positive, none
more than 2 cm in greatest dimension
• pN2Metastasis with a lymph node
mass more than 2 cm but not more than
5 cm in greatest dimension; or more
than five nodes positive, none more
than 5 cm; or evidence of extranodal
extension of tumor
• pN3Metastasis with a lymph node
mass more than 5 cm in greatest
dimension

30. • Distant Metastasis (M(
• MX Distant metastasis cannot be
assessed
• M0 No distant metastasis
• M1 Distant metastasis
• M1a Nonregional nodal or pulmonary
metastasis
• M1b Nonpulmonary visceral metastasis
• Serum Tumor Markers (S)
• SXMarker studies not available or not
performed
• S0Marker study levels within normal limits
• S1LDH <1.5 × N and
HCG (mIU/mL) <5000 and
AFP (ng/mL) <1000
• S2 LDH 1.5-10 × N or
HCG (mIU/mL) 5000-50,000 or
AFP (ng/mL) 1000-10,000
• S3 LDH >10 × N or
HCG (mIU/mL) >50,000 or
AFP (ng/mL) >10,000
• N indicates the upper limit of normal for the LDH
assay

33. Treatment of GCTs
• Radical orchiectomy for local control
– Offer sperm banking prior to surgery
• 65-85% seminomas confined to testis
• 60-70% nonseminomas present as recognizable
metastatic disease

34. Partial Orchiectomy
• Option for
– Organ confined tumor <2cm
• Especially incidentally found, nonpalpable
– Solitary testis or w/ B/L tumors
• Careful frozen sections

35. Stage I Seminoma
• No nodes, survival is same with surveillance & XRT, surveillance more
common due to increased risk of secondary malignancy
• 15-25% staging error
• Radiation – treatment of choice
– 20-25 Gy to para-aortic nodes
– 5-year disease free survival >95%
– Long-term side effects
• Infertility, GI, 2nd
malignancy
– 3% relapse (outside retroperitoneum) & need chemo
• Chemotherapy
– Carboplatin

36. Stage IIa & IIb Seminoma
• XRT
– Ipslilateral external iliac, b/l common iliac, paracaval,
para-aortic, cisterna chyli
– Avoid kidney
– Shield contralateral testis
– 5-yr disease free survival 80%
– 3% relapse
• Chemo
– If nodes close to kidney

37. Stage IIc & III Seminoma
• Cisplatin-based chemo is the treatment of
choice
– Bleomycin, Etoposide, Cisplatin (BEP) x3–4
– Etoposide, Cisplatin (EP) x4
– 90% complete response to chemo at 4yrs
– 10% relapse after initial chemo response
• Postchemo residual retroperitoneal mass
– Well-delineated, >3cm – resect
• Mass = GCT, then salvage chemo (vinblastine, ifosfamide,

38. Stage I NSGCTs
• Staging is inaccurate in at least 25% & only way to accurately stage is RPLND
• Radiation - not used in North America, relapse rate 24%
• Surveillance
– Option for low risk:
• No vascular/lymphatic invasion (<T2)
• <40% embryonal
• Motivated, reliable pts
– Relapse 28%, survival 99%
– Protocol
• CXR, tumor markers q1mo x1yr, q2mo x1yr, q3-6mo up to 10 more yrs
• CT q2-3mo x2yrs, q6mo up to 10yrs
• Chemo – BEP x2-3
– Option for low or high risk:
• T2 or higher (vascular/lymphatic invasion)
• >40% embryonal

39. • Modified template RPLND
– If negative, then observe
• 70% of RPLNDs find no disease
– If <2cm nodes (N1), observe or adjuvant chemo – BEP x2 or EP x2
– If >2cm nodes (N2), adjuvant chemo – BEP x2 or EP x2
– 5-10% relapse outside field of RPLND

40. Stage IIa & IIb NSGCTs
• Bilateral RPLND
– N1 (nodes <2cm) – observe or adjuvant chemo –
BEP x2
– N2 (nodes 2-5cm) – adjuvant chemo – BEP x2
• Chemo – BEP x3 or EP x4
– If post-orchiectomy tumor markers elevated
– If nodes >3cm

41. Stage IIc & III NSGCTs
• Low Risk
– No nonpulmonary visceral mets
– AFP <1000, hCG <5000, and LDH <1.5x normal
• Intermediate Risk
– No nonpulmonary visceral mets
– Markers between low & high risk
• High Risk
– Nonpulmonary visceral mets
– AFP >10,000, hCG >50,000, or LDH >10x normal

42. Stage IIc & III NSGCTs
• Low risk
– Chemo – BEP x3 or EP x4
– 92% 5-yr survival
• High risk
– Chemo – BEP x4 or B/isosfamide/P
– 48% 5-yr survival

43. Stage IIc & III NSGCTs
• After Chemo
– Complete response (normal tumor markers, no residual mass)
• Observe
– 10% relapse & need salvage chemo
– Partial response (normal tumor markers, residual mass)
• Full B/L RPLND & resect residual mass
– 10-20% GCT – salvage chemo
– 40-50% teratoma – observe or resect
– 40% necrosis – observe
– Poor response (elevated tumor markers or no shrinkage of mass)
• Salvage chemo, high dose chemo & autologous bone marrow transplant
– 25% long term survival

44. Chemo & XRT Toxicity
• 2nd
Malignancy
– Up to 18% 25yrs after XRT
– Chemo
• Higher long-term incidence of leukemia, lymphoma, colon, stomach,
kidney, prostate, bladder, thyroid, rectum, pancreas, connective
tissue cancers
• Bleomycin
– Pulmonary Toxicity
• Etoposide
– Myelosuppression
• Cisplatin
– Nephrotoxicity – also Carboplatin
– Low Magnesium
– Neurotoxicity & Ototoxicity

45. Other Testicular Tumors
• Leydig Cell Tumor
• Sertoli Cell Tumor
• Gonadoblastoma
• Lymphoma

46. Leydig Cell Tumors
• 1-3% of testicular tumors
• 10% malignant
– Average survival – 3 years if malignant
• Reinke’s crystals – red extracellular lobular crystals
• Presentation
– Precocious puberty in kids
– Elevated testosterone, urinary 17-ketosteroids
– Mass
– Impotence, gynecomastia
• Treatment
– Radical orchiectomy

47. Sertoli’s Cell Tumors
• <1% testicular tumors
• Most common testicular tumor
• 10% malignant
• Any age
• Radical orchiectomy
– RPLND if metastatic

48. Others
• Gonadoblastoma
– 0.5% testicular tumors
– 80% are in phenotypically female
pts
– Good prognosis
• Epidermoid Cyst
– 1% testicular tumors
– ? Monolayer teratoma
– Benign
• Rete Testis Adenocarcinoma
– Age 20-80
– Very malignant
Adrenal Rest Tumor
B/L tumor, CAH – remission w/
corticoid treatment
Lymphoma
5% testicular tumors
Most common secondary
tumor
Most common testicular tumor
in age >50
½ are B/L

49. • THE END