creat 60 slides from the pdf , for acadamic presentation for urology resident , include images from standard urology books and mention video links from youtube to be included in the slides

1. Approach to
pathology, diagnosis
and staging of
testicular tumor
Presenter - Dr . Hawi D (USRIII)
Moderator - Dr. Fitsum (Consultant
urologist)
12/14/2025
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2. Outlines
• Introduction
• Epidemiology
• Risk factors
• Histologic classification
• Pathogenesis
• Clinical presentation
• Diagnostic modalities
• Clinical staging
• Summery
• Reference
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National Burden and Trend of Cancers in Ethiopia,

4. Introduction
• Morphologically and clinically diverse group of tumors,
more than 95% are germ cell tumors (GCTs).
• GCTs are broadly categorized as seminoma and
nonseminoma (NSGCT)
• GCT is a relatively rare malignancy,
• 1% to 2% of cancers among adult males in the United
States.
• Approximately 95% of GCTs arise in the testis, and 5% are
extragondal in origin.
• GCTs - curable neoplasm (metastatic GCT is 80-90%)
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5. Epidemiology
• Most common malignancy among males aged 20 to 40
years.
• The incidence rate rises rapidly after puberty, peaking 25
- 35
• The incidence of bilateral GCT is approximately 2%.
- Majority Metachronous
- Over an average interval of 5 years
- Discordant histology occurs in 30% to 50%
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6. Epidemiology…
• Highest in Scandinavia, Western Europe, and
Australia/New Zealand
• lowest in Africa and Asia.
• The incidence of GCT appears to be increasing
worldwide.
• Only about 13% of males present with distant
metastatic disease.
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7. Risk factors
Five well established risk factors
1. White race
2. Cryptorchidism ( 4-6 x more likely to be dx with testis
cancer, 2-3 x if orchidopexy is performed before puberty).
3. Family history of testis cancer
4. Personal history of testis cancer – 12-fold increased risk
of developing GCT in the contralateral testis
5. Germ cell neoplasia in situ (GCNIS)/intratubular germ cell
neoplasia (ITGCN)
• Subfertility and infertile
• Diet and/or environmental factors
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8. Histologic classification
• GCNIS-derived and non-GCNIS–derived.
• Majority of postpubertal GCTs are GCNIS-derived.
• GCNIS- derived GCTs – seminoma (52-56%) and NSGCT(44-48%)
• NSGCTs include embryonal carcinoma (EC), yolk sac tumor, teratoma,
and choriocarcinoma subtypes, either alone(pure forms) or in
combination as mixed GCT with or without seminoma.
• Most NSGCTs are mixed tumors that are composed of two or more GCT
subtypes.
• GCTs that contain both NSGCT subtypes and seminoma are classified as
NSGCT even if component is a tiny proportion of the tumor.
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Classifications

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11. Pathogenesis
• Not well defined /Poorly understood
• Transformed primordial germ cells that develop in
utero or early infancy.
• gonocytes that failed to differentiate into
prespermatogonia, that lay dormant until puberty
when they are stimulated by increased serum (LH)
and/or testosterone levels.
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12. Pathogenesis…
• Additionally, polymorphisms of certain genes, including the
gene encoding c-KIT ligand, have been associated with an
increased risk of testis cancer.
• Gonocytes depend on KIT ligand for survival; the gene for
this protein is located on the long arm of chromosome 12,
where an increased number of copies is a universal finding
in adult GCT.
• Thus, a connection between mutations or polymorphisms in
c-KIT ligand and GCT has biological plausibility.
• Inherited alterations to susceptibility genes involved in DNA
repair may contribute to the development of adult GCT.
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Pathogensis….
• Approximately 5% of postpubertal GCTs are extragondal in origin,
- midline anatomic locations (retroperitoneum and mediastinum are most common).
first hypothesizes that
• they originate from germ cells that mis-migrated along the genital ridge and were able to
survive in an extragonadal environment.
The second theory
• reverse migration from the testis to extragonadal locations
• Primary mediastinal NSGCTs differ from those originating in the testis or
retroperitoneum.
• they are less sensitive to chemotherapy and have
• poor prognosis with a 5-year overall survival of about 45%
• likely to have yolk-sac-tumor components and thus to be associated with elevations in serum
α-fetoprotein (AFP)
They are also associated with Klinefelter syndrome and with hematologic malignancies that
carry extra copies of the short arm of chromosome 12, as seen in adult GCT

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• Mediastinal seminomas carry a similar prognosis to
testicular seminomas, and
• Mature teratomas of the mediastinum have low metastatic
potential and can
• generally be cured surgically
• Primary retroperitoneal GCTs are indistinguishable
biologically from testicular GCTs and carry the same
prognosis.

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GCNIS
• Most GCTs arise from ITGCN.(Except for spermatocytic seminoma in
adults and teratomas and yolk sac tumor in pediatric patients.)
• Characterized by proliferation of uncommitted neoplastic
germ cells within seminiferous tubules.
• Progress to GCT in ~50% of cases within 5 years.

17. Seminoma
• Seminoma is the most common type of GCT.
• most cases diagnosed in the 40-50th
• Grossly, seminoma is a soft, tan-to-white, diffuse or multi
nodular mass.
• Necrosis may be present but is usually focal and not as
prominent as other GCTs.
• Sheetlike arrangement of cells with polygonal nuclei and
clear cytoplasm, with the cells divided into nests by
fibrovascular septae that contain lymphocytes.
• Syncytiotrophoblasts, which stain positive for human
chorionic gonadotropin (hCG), - in about 15% of cases.
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18. Seminoma…
• Lymphocytic infiltrates and
granulomatous reactions are often seen…
(sarcoidosis)
• Negative for CD30, positive for CD117,
and strongly positive for placental
alkaline phosphatase (PLAP).
• Seminomas arise from GCNIS - considered
to be the common precursor for other
NSGCT sub types.
• Important therapeutic implications for the
management of seminoma
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Spermatocytic
Tumor
• Spermatocytic tumor used to be classified as a
subtype of seminoma.
• Rare and accounts for less than 1% of GCTs.
• Do not arise from GCNIS, not associated with
cryptorchidism or bilaterality, does not
demonstrate i(12p),
• Do not stain for OCT 3/4, PLAP, or glycogen
(periodic acid–Schiff [PAS] stain)
• The peak incidence is the sixth decade of life.
• It is a benign tumor and is almost always cured
with orchiectomy.
• Exceptions - “spermatocytic tumor with sarcoma,”

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Embryonal Carcinoma
• EC consists of undifferentiated malignant
cells
• resembling primitive epithelial cells from early-
stage embryos with crowded pleomorphic nuclei.
• Grossly, EC is a tan-to-yellow neoplasm
• often exhibits large areas of hemorrhage and
necrosis.
• The microscopic appearance of these tumors
varies considerably,
• they may grow in solid sheets or in papillary,
glandular-alveolar, or tubular patterns.
• In some cases, syncytiotrophoblasts are
identified.

21. Embryonal
Carcinoma…
• Aggressive tumor associated with a high rate of
metastasis,
• often in normal serum tumor markers.
• Most undifferentiated cell type of NSGCT, with
totipotential capacity to differentiate into other
NSGCT cell types (including teratoma)
o primary tumor or at metastatic sites.
• The presence and proportion of EC have been
associated with an increased risk of occult
metastasis in clinical stage (CS) I NSGCT.
• EC typically stains for AE1/AE3, PLAP, and OCT3/4
and does not stain for c-KIT
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Choriocarcinoma
• Rare and aggressive tumor - extremely highly
elevated serum hCG levels and disseminated
disease.
• They are poor risk (stage IIIC) at diagnosis
because of the serum hCG level and/or
nonpulmonary organ metastases.
• Spreads by hematogenous routes, and
common sites of metastases include lungs,
liver, and brain.
• Microscopically, the tumor is composed of
syncytiotrophoblasts and cytotrophoblasts
• stain positively for hCG.

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Choriocarcinoma…
• Areas of hemorrhage and necrosis are
prominent.
• As in gestational trophoblastic disease,
testicular choriocarcinoma is prone to
hemorrhage,
• sometimes both spontaneously and immediately
after chemotherapy is initiated, bleeding can be
catastrophic, particularly when it occurs in the
lungs or brain.
• Stimulation of receptors for thyroid-
stimulating hormone (TSH) and
luteinizing hormone (LH) by hCG (which
shares an identical a-subunit)
• hyperthyroidism and elevated androgen
production. Hyperprolactinemia.

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Yolk Sac Tumor
• Pure yolk sac tumors (endodermal sinus tumors) - very
small fraction of adult gonadal and retroperitoneal GCTs
• more common in mediastinal and pediatric GCTs
• May grow in a glandular, papillary, or micro-cystic
pattern
• A characteristic feature - Schiller-Duval body,
resembles endodermal sinuses, and is seen in roughly
half of cases.
• Cytoplasmic and extracellular eosinophilic hyaline
globules are another characteristic histologic feature
and present in up to 84% of cases.
• Yolk sac tumors almost always produce AFP but not
hCG.

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Teratoma
• contain well-differentiated or incompletely
differentiated elements of at least two of
the layers: endoderm, mesoderm, and
ectoderm.
• Well-differentiated tumors - mature
teratomas,
• incompletely differentiated - immature
teratomas.
• In adolescent and adult males, no clinical
significance to the distinction between
mature and immature teratomas

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• Mature teratomas may include elements of mature
bone, cartilage, teeth, hair, and squamous
epithelium.
• Gross appearance - depends largely on the elements
within it, with most tumors having solid and cystic
areas.
• Normal serum tumor markers, mildly elevated
serum AFP levels.
• 47% of adult mixed GCTs contain teratomas, but
pure teratomas are uncommon
• histologically benign appearance but are frequently
found at metastatic sites in patients with advanced
NSGCT.
• Teratoma is resistant to chemotherapy.
• Contain many genetic abnormalities frequently
found in malignant GCT elements - aneuploidy,
i(12p), and proliferative capacity
Teratoma…

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Teratoma…
• cystic fluid from teratoma contains hCG and AFP - malignant potential.
• genetic instability of teratoma - clinical implications.
• On rare occasions, teratoma may transform into a somatic malignancy such
as rhabdomyosarcoma, adenocarcinoma, or primitive
neuroectodermal tumor.
• These tumors are called teratoma with somatic-type malignancy or
teratoma with malignant transformation.
• Abnormalities of chromosome 12 or i(12p), indicating their origin from GCT.
• Malignant transformation is highly aggressive, resistant to conventional
chemotherapy - poor prognosis
• Only 4% of teratomas with somatic-type malignancy arise within the
testis.
• arise at metastatic sites, within 3 to 4 years after completion of
chemotherapy due to unresected teratoma.
• unresected teratomas in patients with advanced NSGCT may result in late
relapse

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29. Clinical Presentation
 Most common - Painless testicular mass
 Acute testicular pain less common; due to rapid expansion
from intratumoral hemorrhage or infarction - (NSGCT)
 Vague scrotal discomfort / heaviness
 History of trauma
Frequently reported
Usually incidental — brings mass to attention
 Symptoms from metastasis (10-20%)
Regional/distant metastasis rates at diagnosis NSGCT: ~66%
; Seminoma: ~15%
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30. Clinical Presentation
Retroperitoneal metastasis
• Palpable mass, abdominal pain, flank pain (ureteral
obstruction), back pain (psoas/nerve root involvement),
leg swelling (IVC compression), GI symptoms
Pulmonary metastasis
• Dyspnea, chest pain, cough, hemoptysis
Supraclavicular lymph node metastasis
Gynecomastia (~2%) From hCG, androgens,
↑ ↓ ↑
estrogens ( Leydig cell tumors)
Infertility
•
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P/E
• Testicular or extra testicular masses.
• Atrophy of the affected or contralateral testis, particularly in
cryptorchidism.
• A hydrocele may accompany a testis cancer and impair ability to
evaluate the testis.
• In this case, a scrotal ultrasound to evaluate the testis
• Any evidence of palpable abdominal mass or pain,
• Inguinal lymphadenopathy (particularly prior inguinal or scrotal
surgery)
• Gynecomastia
• supraclavicular lymphadenopathy, and auscultation of the chest for
intrathoracic disease

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Differential Diagnosis
• Epididymo-orchitis,
• torsion,
• hematoma,
• para-testicular neoplasm (benign or malignant).
• Other diagnostic possibilities include hernia, varicocele, or
spermatocele, though these usually can be distinguished
from a testis mass by physical examination.
• A firm intratesticular mass should be considered cancer
until proven otherwise and should be evaluated further with
a scrotal ultrasound

33. Diagnostic Delay
• Patient factor - typically, young and may be less
inclined to seek medical evaluation for symptoms
because of denial, ignorance, or limited access.
• Physician factor – misdiagnosed
• The interval of delay is associated with advanced
clinical stage, sub optimal response to
chemotherapy, and diminished survival.
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Diagnosis
• Scrotal U/S
- Should be considered an extension
of P/E
- GCT is hypoechoic, and two or more
discrete lesions may be identified
- Heterogeneous echotexture within a lesion is more
commonly - NSGCT because seminomas usually have a
homogenous echotexture.
- The presence of increased flow within the lesion on color
Doppler sonography - malignancy, though its absence not
exclude GCT.

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Diagnosis …
MRI
• Sonographic findings are equivocal or
suboptimal
• Testicular Vs extratesticular lesions and
• Neoplastic Vs non-neoplastic entities

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Serum tumor markers
• Few tumors associated with serum tumors
markers.
• (lactate dehydrogenase [LDH], AFP, and hCG) that
are essential in its diagnosis and management.
• at diagnosis before orchiectomy,
• after orchiectomy, to monitor for response to
chemotherapy,
• and to monitor for relapse in patients on
surveillance and after completion of therapy.

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AFP
• The half-life is 5 to 7 days.
• At diagnosis, AFP levels are elevated in 50-70% of low-
stage (CS I, IIA, IIB) NSGCT and 60-80% of advanced (CS
IIC, III) NSGCT.
• EC and yolk sac tumors secrete AFP.
• Choriocarcinomas and seminomas do not produce AFP.
• pure seminoma in the primary tumor with an elevated
serum AFP are considered to have NSGCT.
• High AFP in other malignancy

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HCG
• Elevated in 20-40% of low-stage NSGCT and 40-60%
of advanced NSGCT.
• The half-life of hCG is 24 to 36 hours.
• 15% of seminomas secrete hCG.
• hCG is also secreted by choriocarcinoma and EC.
• Levels >5000 IU/L are usually associated with
NSGCT.

39. HCG …
• The a-subunit of hCG is common to several pituitary
tumors immunoassays for hCG are directed at the b-
subunit.
• Cross-reactivity of the hCG assay with LH may cause false-
positive hCG elevations in patients with primary
hypogonadism.
• Elevated serum hCG results caused by hypogonadism will
normalize within 48 to 72 hrs after treatment.
• Marijuana use may also cause false-positive hCG results.
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LDH
• Elevated 20% of low-stage GCT and 20-60% of advanced GCT.
• LDH is expressed in smooth, cardiac, and skeletal muscle.
• Of the five isoenzymes of LDH, LDH-1 is the most frequently
elevated isoenzyme in GCT.
• The magnitude of LDH elevation correlates with the bulk of
disease.
• As a nonspecific marker for GCT, its main use in prognostic
assessment of GCT at diagnosis.
• The serum half life of LDH is 24 hours.

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Clinical Staging
• The prognosis of GCT and initial management decisions
are dictated by the clinical stage of the disease
- Histopathological findings
- pathological stage of the primary tumor
- postorchiectomy serum tumor marker levels,
- presence and extent of metastatic disease as
determined by P/E and staging imaging studies,classified
using the Tumor, Node, Metastases (TNM) system
• CS I - clinically confined to the testis
• CS II - regional (retroperitoneal) lymph node metastasis
• CS III - nonregional lymph node and/or visceral metastasis

42. Staging imaging
• GCT follows a predictable pattern of metastatic
spread
• The most common route of disease dissemination is
via lymphatic channels
• Primary site --> Retroperitoneum --> Distant site
• Retroperitoneum is the initial site of metastatic
spread in 70% to 80% of GCT
42

43. Staging imaging…
• Rt testis to IAC-->PC--->PA nodes
• Lt testis to PA ----> IAC nodes
• Right to left pattern of drainage
• Retrograde spread
• Cisterna chyli --> posterior
mediastinum--> lt supraclavicular LN
43

44. Staging imaging …
CT Abdomen and Pelvis/MRI
• Most effective, noninvasive means of staging the
retroperitoneum and pelvis
• Most difficult area to accurately stage clinically
• Positive LN in 10% to 20% of seminomas and 60% to
70% of NSGCT
• A size cutoff of 10 mm is frequently used
• False -ve 63%, False +ve 12-40%
• 5-9mm in 1° landing zone
• Sensitivity 91% and specificity of 50%
44

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Pathological Staging of the Abdomen and Pelvis
• Pathological N stage differs from clinical N stage in that the
former considers the number of lymph nodes involved:
• pN0: no regional lymph node metastasis;
• pN1: #5 lymph nodes involved, none >2 cm
• pN2: .5 lymph nodes involved and/or any lymph node 2 to 5
cm;
• pN3: any lymph node >5 cm.

46. Staging imaging
Chest imaging
• Chest x-ray
Chest CT
• Post-orchiectomy elevated serum tumor markers
• Evidence of metastatic disease
• Abnormal or equivocal findings on chest x-ray
• CS I NSGCT with evidence of LVI or EC predominance
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Staging
Tis GCNIS
T1 invaded tunica albugnia with out
vascular/lymphatic invasion
T2 invaded tunica vaginalis or
vascular/lymphatic invasion
T3 invaded the spermatic cord
T4 invaded the scrotum

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Staging

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Staging

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Staging

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Summary
• 95% are germ cell tumors
• GCTs are broadly categorized as seminoma and nonseminoma
• 95% of GCTs arise in the testis, and 5% are extragondal
• Most have good prognosis
• Cryptorchidism, Family history, and Personal history are the strongest risk factors
• Develop from arrested primordial germ cells
• The most common is a painless testicular mass
• Scrotal Ultrasound should be considered as an extension of the physical
examination
• Tumor markers are essential in its diagnosis and management
• GCT follows a predictable pattern of metastatic spread

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Reference
• Campbell-Walsh-Wein 13th
edition
• AUA
• Up to date 21.6
• Internet

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THANK YOU !