This document provides a summary of testicular carcinoma and germ cell tumors. It discusses the classification, spread, clinical features, investigations, and staging of testicular tumors. The majority are germ cell tumors, with seminomas and non-seminomatous germ cell tumors being the most common. Metastatic sites vary between seminomas and non-seminomas. Prognostic factors are important for determining treatment. Screening is recommended for high risk groups to detect tumors early.

1. Testicular Carcinoma II
By-Dr Satyajeet Rath
Guide-Prof Kamal Sahni

2. Testicular Tumours
• Classification
• Spread of tumour
• Clinical features
• Investigations
• Staging

3. Importance
• Relatively rare cancer accounting for approx. 1 % cancer in males
• Important in field of oncology as it represents a highly curable neoplasm
• Incidence is focused on young patients at their peak of productivity

4. Classification
• Can arise from either intratesticular or paratesticular cells
• Vast majority are Germ cell origin
• Three major classification schemes have been in use worldwide
• Dixon & Moore-1953
• WHO Classification
• Pugh-1976
• The Dixon and Moore Classification as modified by Mostofi has been
adopted by WHO and is the most widely used classification
Gunderson & Tepper , Clinical Radiation Oncology,4th edition

6. Pathological classification
3:Classification of Sex-Cord Stromal
Tumors of the Testis 2-3%
• Leydig cell tumor
• Sertoli cell tumor
• Granulosa cell tumor
• Fibroma-thecoma stromal tumor
• Gonadoblastoma
• Sex cord-stromal tumor
unclassified type
1:Intra tubular germ-cell
neoplasia(IGCN)
2:GERM CELL TUMORS 95%
Seminoma (60%)
Classic type
Anaplastic
Spermatocytic type
Non seminomatous germ-cell
tumors 35-40%
• Embryonal carcinoma 20-25%
• Teratoma 25-35%
• Yolk sac (endodermal sinus)
tumor
• Choriocarcinoma 1%
• Mixed germ-cell tumor
4: others 5%
• lymphoma
• rabdomyosarcoma
• melanoma

7. Germ cell tumors

8. Metastatic testicular Tumour
In decreasing order
Prostate
Lung
Gut
Melanoma
Kidney

9. Intratubular Germ Cell Neoplasia

10. ITGCN
• Danish studies suggest that all cases of adult ITGCN will ultimately
progress to Invasive cancer.
• ITGCN is widely regarded as the pre-invasive precursor of all testicular
GCTs except spermatocytic seminoma
• The incidence of CIS in the male population is 0.8%.
Gunderson & Tepper,4th edition

11. Screening Recommendations
• Screening is recommended for:
• EGCT
• All adolescent with intersex bearing y- chromosome
• Cryptorchid males
• Select patients with contralateral GCT( age< 40 yrs & testicular
vol<12 ml)
• Screening of contralateral testis in patients with GCT is not
advocated because:
• Protracted course of CIS,
• Side effects of therapy, and
• Second primary germ cell tumor responds well to treatment
Gunderson & Tepper,4th edition

12. Screening tools:
• Presently there are no established tumor markers for CIS
• Testicular USG is unreliable for diagnosing CIS
• ITGCN cells may or may not be present in the seminal fluid.

13. Germ Cell Tumours

14. Seminoma
• The commonest variety of testicular tumour
• Adults are the usual target (4th and 5th decade)
• Right > Left Testis
• Starts in the mediastinum: compresses the surrounding structure.
• Patients present with painless testicular mass
• 30 % have metastases at presentation, but only 3% have symptoms related to
metastases
• 90% of patients stain for PLAP.
• AFP is normal
• Classification
a) Classical – 85%
b) Anaplastic – 5-10%
c) Spermatocytic

15.  Anaplastic
• 5% - 10
• Middle age
• Aggressive - lethal
• Greater mitotic activity
• Higher local invasion
• Higher metastatic potential
• Higher rate of β-HCG production
 Typical/ Classical
• 82% - 85%
• Middle age
• PLAP – 90%
• Syncytiotrophoblsts – ↑Beta HCG(10%)
• Very slow growth
Spermatocytic
• 2% - 12% of seminomas
• Old age > 50 yr
• Does not arise from ITGC
• PLAP negative
• Extremely low metastatic potential
• Good prognosis

16. Laterality and Bilaterality:
• Slightly more common in the right testis.
• 2-3% of tumors are bilateral, occurring either simultaneously or
successively.
• Similar histology predominates with bilateral tumors
• Germinal tumors with different histology were present in 15%.

17. Non seminomatous Germ Cell Tumours

18. Embryonal Carcinoma
• 2nd most common germ cell tumor
• Most common component of mixed germ cell tumors
• Age Range – 25-30 yrs
• Highly malignant tumours
• High degree of metastasis
• Serum AFP is positive in 33 %, & beta HCG is elevated in 20% of cases
• About 40 % of GCT contain these tumours

19. Yolk Sac Tumour
• Most common germ cell tumor ( & most common testicular tumor ) in
children, where it occurs in its pure form.
• 60% of GCT in children.
• Mainly in first 2 years of life.
• Pure yolk sac tumor <2% of testicular tumors in adults
• Found in mixed germ-cell tumors.
• Elevated serum levels of alpha-fetoprotein. ( 90% cases )
• Microscopically, Schiller-Duval bodies are a characteristic feature
• Testicular mass the most usual presentation.

20. Choriocarcinoma
• A rare and aggressive tumour (5yr OS is 5%)
• Typically elevated hCG
• Presents with disseminated disease
• Metastasis to lungs and brain
• Primary is very small and often exhibit no testicular enlargement
• Small palpable nodule may be present.
• Prone to hemorrhage, sometimes spontaneous (lungs and brain)

21. 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
• Both mature and immature teratoma are considered malignant with ability to
metastasize
• Immature teratoma - partial somatic differentiation, whereas
• Mature teratoma - terminally differentiated tissues such as cartilage, skeletal muscle, or
nerve tissue, and frequently forms cystic structures
• Teratomas can give rise to secondary somatic malignancy, such as rhabdomyosarcoma,
poorly differentiated carcinoma, or primitive neuroectodermal tumor
• Normal serum markers.
• Mildly elevated AFP levels
Ehrlich Y, Beck SD, Ulbright TM, et al. Outcome analysis of patients with transformed teratoma to primitive neuroectodermal tumor. Ann Oncol
2010;21:1846–1850.

22. OTHERS

23. Interstitial cell tumors
1. Leydig cell tumors
• Most common of the sex cord mesenchymal lesions
• May affect 20-60yrs of age
• A masculinising tumor, produces androgens
• No association with crytochordism
• Presents with painless testicular mass
• Precocious puberty
• Prominent external genitalia
• Deep masculinised voice
• Pubic hair
• Gynacomastia and decreased libodo due to oestrogen production by
increased peripheral conversion

24. Interstitial cell tumors
2. Sertoli Cell Tumor
• can occur in any age group including infants
• No association with crytochordism
• Excess estrogen production
• Gynacomastia in 1/3rd of cases
• 10 % are malignant

25. Interstitial cell tumors
3. Gonadoblastoma
• Mixed germ cell/sex cord/stromal tumor
• Composed of seminoma like germ cells and Sertoli cells
• Exclusively in patients with dysgenic gonads and intersex syndromes
• 80% are phenotype females with primary amenorrhoea , lower
abdominal mass and streak gonads
• 20% are males with crytochIdism and dysgenic gonads and hypospadias
• Considered in-situ malignant form of GCT
• Risk of bilateral tumours

26. Secondary Tumors of Testis
• Lymphoma –
• most common secondary tumor
• most common testicular tumor in patients above 50 years
• clinical feature: painless enlargement of testis
• Leukamic Infilteration of testis
• primary site of relapse after ALL remission
• occurs mainly in the interstitial space
• Metastases to testis
• rare

27. Extragonadal germ cell tumors
• 3-5% of all GCTs are of extragonadal origin.
• The most common sites of origin in decreasing order of frequency:
• mediastinum,
• retroperitoneum,
• sacrococcygeal region
• pineal gland mainly
• the majority of adults with EGCT present with advanced local disease
and distant metastasis.

28. Adenocarcinoma of the rete testis:
• rare but highly malignant tumors.
• age range: 20-80 years.
• present with painless scrotal mass, and hydrocele.
• RPLND in the absence of distant metastasis.

29. Carcinoid of testis:
• Very few cases have been recorded.
• can be primary or metastatic.
• present as a slow, progressive, painless testicular enlargement.
• metastatic testis carcinod has poor prognosis.

30. Prognostic Factors
International Germ Cell Cancer Collaborative Group (IGCCCG) : A prognostic factor-based staging system for metastatic germ cell cancers., J Clin
Oncol 15(2):594-603, 1997.
For nonseminomatous
5-year OS
•good-prognosis group -92%
•intermediate-prognosis - 80%
•poor-prognosis-48%
For seminoma,
(only two prognostic groups were
identified)
5-year OS
•good-prognosis - 86%
•intermediate-prognosis -72%.

31. Spread

32. Direct Spread
• This spread occurs by invasion.
• Whole of testis in involved and restricted
• Tunica albuginea is rarely penetrated
• May be crossed by “blunder biopsy”
• Scrotal skin involvement
• Fungation on the anterior aspect
• Spread to spermatic cord and epidedymis
may occur : points towards bad prognosis

33. Lymphatic spread:
• Seminoma metastasize exclusively through
lymphatics
• They drain primarily to para-aortic lymph nodes
• From RPLN drain into cysterna chili, thoracic
duct ,posterior mediastinum & left
supraclavicular Lymph
• from medial side of testes run along the artery to
the vas to drain to nodes at the bifurcation of
common iliac
• No inguinal nodes until scrotal skin involvement
• Cross metastasis more common in rt side
tumour
• Right inter aortocaval at L2  precaval  preaortic  Right common iliac  Right
ext. iliac
• Left  Paraortic at renal hilium  preaortic  common iliac  Left ext. iliac

34. Hematogenous Spread
• NSGCT spread through blood route
• Lungs, liver, bones, brain , kidney, adrenal , GIT , spleen are the
usual sites usually involved
• In a review of over 5000 patients with metastatic GCT
• pulmonary metastases - 44%
• liver metastases - 6%
• all other areas of hematogenous spread - 1% or less
• Mediastinal and neck node involvement - 11% to 12%
International Germ Cell Consensus Classification: A prognostic factor-based staging system for metastatic germ cell cancers. International
Germ Cell Cancer Collaborative Group, J Clin Oncol 15(2):594-603, 1997.

35. Clinical Features

36. 1.Due to primary tumor
• Most commonly as a painless testicular lump
• Pain - 45 %
• Sensation of heaviness if size > than 2-3 times
• Rarely dragging pain is complained of (1/3rd cases)
• May mimic epidedymo-orchitis
• Sudden pain and enlargement due to hemorrhage mimicking torsion
• History of trauma (co-incidental)
• Gynaecomastia
• Burnt out Primary with metastases

37. DICTUM FOR ANY SOLID SCROTAL SWELLINGS
• All patients with a solid, Firm Intratesticular Mass that
cannot be Trans illuminated should be regarded as
Malignant unless otherwise proved.

38. 2.Due to metastasis
• Abdominal ( retrodudodenal mets ) pain
• Lumbar pain (due to involvement of psoas muscle)
• Dyspnoea, hemoptysis and chest pain with lung mets
• Jaundice with liver mets
• Hydronephrosis by para-aortic lymph nodes enlargement
• Pedal oedema by IVC obstruction – u/l or b/l
• Troiser’s sign
• Bone pain ( skeletal mets )
• 3.5% may have features of hypothyroidism due to raised HCG

39. Diagnosis

40. Perez & Brady , Principles of Oncology , 6th edition

41. • Bimanual Testis Examination
• Enlarged testis (except choriocarcinoma)
• Nodular testis
• Firm to hard in consistency
• Loss of testicular sensation
• Secondary hydrocele
• Flat and difficult to feel epididymis
• General examination for metastasis
• In patients who present with no obvious evidence of metastasis, a diagnostic and
therapeutic radical orchiectomy is usually performed after a solid mass is detected
on physical examination or by ultrasonography.

42. USG
• Ultrasonography is the standard imaging technique used to identify testicular
carcinoma.
• High sensitivity, but it must be combined with physical examination to achieve
the best specificity.
• More than 95% of testicular parenchymal abnormalities are identifiable on
routine sonograms, but several other lesions commonly mimic testicular cancer
• More specific in the presence of a palpable mass.
• Ultrasonography of the scrotum (7.5MHZ) is a rapid, reliable technique to
exclude
• Testicular and other scrotal swelling
• Solid & cystic swelling
• Hydrocele & epididymitis.
Soh E, Berman LH, Grant JW, Bullock N, Williams MV. Ultrasound-guided core-needle biopsy of the testis for focal indeterminate
intratesticular lesions. Eur Radiol. 2008 Dec. 18(12):2990-6.

43. CT
• Imaging technique of choice in staging testicular GCT
• Although the diagnosis of large-volume disease is readily made on CT, the
diagnosis of small-volume metastatic disease (distinguishing stage I from stage
II disease) may be extremely difficult.
• Using a size criterion of 8 mm or larger in the maximum short-axis diameter to
define a suspicious retroperitoneal node is associated with a high specificity( 85
% ) but a low sensitivity (62 % )
• Results of 2 large studies have established that between 25% and 30% of
patients harbor occult microscopic metastases that cannot be detected by CT
• CT remains the primary imaging technique for assessing response to treatment
1. Hilton S, Herr HW, Teitcher JB, Begg CB, Castellino RA. CT detection of retroperitoneal lymph node metastases in patients with clinical stage I testicular
nonseminomatous germ cell cancer: assessment of size and distribution criteria. AJR 1997; 169:521-525
2. Nicolai N, Pizzocaro G. A surveillance study of clinical stage I nonseminomatous germ cell tumors of the testis: 10-year followup. J Urol 1995;
154:1045-1049

44. MRI
• MRI is useful for the detection and characterization of CNS disease as
well as musculoskeletal and hepatic metastases.
• MRI may be valuable as a problem-solving technique in the presence of
equivocal CT findings
• MRI with lymphotrophic nanoparticles has been shown to be an effective
method for evaluating lymph nodes in different cancers

45. PET
• Studies comparing FDG PET with CT in primary staging of GCT show
that FDG PET is useful for detecting viable tumor in lesions that are
visible on CT and may prevent false-positive diagnosis on CT in clinical
stage II disease
• However, FDG PET does not improve staging in patients with clinical
stage I disease because, similar to CT, it is poor at detecting small-
volume (i.e., subcentimeter) disease
• FDG PET is not able to identify mature teratoma; therefore, FDG PET is
not recommended in the primary staging of testicular GCT
De Santis M, Becherer A, Bokemeyer C, et al. 2-18fluoro-deoxy-D-glucose positron emission tomography is a reliable predictor for viable tumor
in postchemotherapy seminoma: an update of the prospective multicentric SEMPET trial. J Clin Oncol 2004; 22:1034-1039

46. • SEMPET trial
• FDG PET was used to assess residual tumors in patients with seminoma
treated with chemotherapy
• FDG PET was more accurate than other modalities for assessment
• FDG PET correctly identified
• all cases of residual tumor in lesions greater than 3 cm
• 95% of residual tumor in lesions less than 3 cm
• Specificity – 100% and sensitivity - 80% for FDG PET
(as compared with 74% and 70% for CT.)
De Santis M, Becherer A, Bokemeyer C, et al. 2-18fluoro-deoxy-D-glucose positron emission tomography is a reliable predictor for viable tumor in
postchemotherapy seminoma: an update of the prospective multicentric SEMPET trial. J Clin Oncol 2004; 22:1034-1039

47. • In stage II and III seminomas, especially in patients with bulky
retroperitoneal disease, a bone scan should also be performed
• Patients with extensive metastatic disease, nonpulmonary visceral
metastases (NPVMs), or very high tumor marker levels are at risk for
brain metastases, and CT or MRI of the brain should be performed

48. Tumor markers
TWO MAIN CLASSES
• Onco-fetal Substances : AFP & HCG
• Cellular Enzymes : LDH & PLAP
AFP - Trophoblastic Cells
HCG - Syncytiotrophoblastic Cells
( PLAP- placental alkaline phosphatase, & LDH lactic acid dehydrogenase)

49. AFP –( Alfafetoprotein)
NORMAL VALUE: Below 16 ngm / ml
HALF LIFE OF AFP – 5 and 7 days
Raised AFP :
• Pure embryonal carcinoma
• Teratocarcinoma
• Yolk sac Tumor
• Combined tumors,
• AFP not raised in pure choriocarcinoma , & in pure seminoma

50. HCG – ( Human Chorionic Gonadotropin)
Has  and  polypeptide chain
NORMAL VALUE: < 1 ng / ml
HALF LIFE of HCG: 24 to 36 hours
RAISED  HCG -
100 % - Choriocarcinoma
60% - Embryonal carcinoma
55% - Teratocarcinoma
25% - Yolk Cell Tumour
7% - Seminomas

51. Other tumor markers
LDH:
• Has low specificity.
• There is a direct relationship between tumor burden and LDH levels.
PLAP:
• Raised in 40% of patients with advanced disease.
GGTP:
• Raised in one third of patients with active seminoma.
CD30:
• possible marker for embryonal carcinoma.

52. ROLE OF TUMOUR MARKERS
• Helps in Diagnosis - 80 to 85% of Testicular Tumours have Positive Markers
• Most of Non-Seminomas have raised markers
• Only 10 to 15% Non-Seminomas have normal marker level
• After Orchidectomy if Markers Elevated means Residual Disease or Stage II or
III Disease
• Negative Tumour Markers becoming positive on follow up usually indicates -
Recurrence of Tumour

53. AJCC TNM Staging

54. Requirements for staging
• To properly Stage Testicular Tumours following are pre-requisites:
(a) Pathology of Tumour Specimen
(b) History
(c) Clinical Examination
(d) Radiological procedure - USG / CT / MRI /Bone Scan
(e) Tumour Markers -  HCG, AFP
• In stage I disease, one of the most important determinants of outcome is the presence of vascular
invasion in the primary tumor
• In stage II disease, the extent of retroperitoneal adenopathy and serum tumor marker level
determines treatment and outcome.
• Staging not changed from AJCC 6th edition

55. T Staging
• pTX: The primary tumor cannot be evaluated.
• pT0: There is no evidence of a primary tumor in the testicles.
• pTis: Intratubular germ cell neoplasia, also called carcinoma in situ (CIS).
• pT1: Tumor limited to testis or 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
• Except for pTis and pT4, extent of primary tumor is classified by radical orchiectomy.
• TX may be used for other categories in the absence of radical orchiectomy.

56. 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
Pathological
• 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 less
than or equal to five 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

57. Distant Metastasis (M)
• M0 : No distant metastasis
• M1 : Distant metastasis
• M1a : Nonregional nodal or pulmonary metastasis
• M1b : Distant metastasis other than to nonregional lymph nodes and lung

58. Serum tumour Markers
LDH hCG (mIU/ml) AFP (ng/ml)
S0 ≤ N ≤ N ≤ N
S1 <1.5 x N < 5000 < 1000
S2 1.5-10 N 5000 – 50000 1000-10,000
S3 > 10 N >50,000 > 10,000
•Serum tumor marker levels should be measured prior to orchiectomy for assignment of S
category.
•The only exception is for stage grouping classification of Stage IS in which persistent
elevation of serum tumor markers following orchiectomy is required.

59. Staging – AJCC (American Joint Comittee on Cancer)
• Stage 0 – CIS
• Stage I – T1-4 / N0 / M0
• IA – T1
• IB – T2-4
• IS – ANY T, S1-3
• Stage II – Any T / N1-3 / M0
• IIA – N1
• IIB – N2
• IIC – N3
• Stage III – Any T /Any N / M1

60. “I always had the size difference
there, but I didn’t know…I would’ve
still been waiting if it hadn’t started
hurting, it just got so painful I
couldn’t sit on my bike anymore.”
-Lance Armstrong
“I always had the size difference there, but I didn’t
know…I would’ve still been waiting if it hadn’t
started hurting, it just got so painful I couldn’t sit on
my bike anymore.”
-Lance Armstrong
“I always had the size difference there, but I didn’t
know…I would’ve still been waiting if it hadn’t
started hurting, it just got so painful I couldn’t sit on
my bike anymore.”
-Lance Armstrong

61. Thank You