Definition/General
Introduction:
Seminoma is a malignant germ cell tumor of the testis
Represents 50% of testicular germ cell tumors
Shows uniform cellular morphology
Derived from primordial germ cells
Radiosensitive tumor.
Origin:
Arises from germ cells via germ cell neoplasia in situ (GCNIS)
Shows blocked differentiation
Maintains pluripotent characteristics
Associated with isochromosome 12p.
Classification:
WHO 2022: Seminoma
Classic seminoma (most common)
Seminoma with syncytiotrophoblastic cells
Anaplastic seminoma (rare)
Part of germ cell tumor family.
Epidemiology:
Peak incidence 3rd-4th decades
Later age than nonseminomatous GCT
White population predominance
Cryptorchidism risk factor
Bilateral in 2-5%.
Clinical Features
Presentation:
Painless testicular enlargement
Firm, non-tender mass
Gradual onset
Does not transilluminate
May present with metastases
Retroperitoneal lymphadenopathy.
Symptoms:
Testicular swelling
Heaviness in scrotum
Dull ache (20%)
Back pain (retroperitoneal disease)
Dyspnea (pulmonary metastases)
Weight loss.
Risk Factors:
Cryptorchidism (5-10x risk)
Family history
Infertility
Klinefelter syndrome
Testicular dysgenesis syndrome
Previous germ cell tumor.
Screening:
Testicular self-examination
Clinical examination
Scrotal ultrasound
Tumor markers (LDH, βhCG)
CT imaging for staging.
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Gross Description
Appearance:
Well-demarcated, lobulated mass
Homogeneous tan-gray cut surface
Soft consistency
Replaces testicular parenchyma
Minimal necrosis
Fibrous septa.
Characteristics:
Fleshy appearance
Fish-flesh consistency
Uniform coloration
Well-circumscribed
Lobulated pattern
Granular surface.
Size Location:
Variable size 2-10 cm
Usually unilateral
Replaces normal testis
May involve epididymis
Spermatic cord extension
Scrotal wall invasion.
Multifocality:
Usually unifocal
Bilateral synchronous (2%)
Bilateral metachronous (1-3%)
Associated GCNIS in adjacent testis
Higher bilateral risk with cryptorchidism.
Microscopic Description
Histological Features:
Uniform large cells
Clear to eosinophilic cytoplasm
Distinct cell borders
Large nuclei with prominent nucleoli
Lymphocytic infiltrate
Granulomatous reaction.
Cellular Characteristics:
Large polygonal cells
Abundant clear cytoplasm
Glycogen-rich
Well-defined cell membranes
Large vesicular nuclei
1-2 prominent nucleoli.
Architectural Patterns:
Sheets and lobules
Fibrous septa with lymphocytes
Granulomatous inflammation
Syncytiotrophoblastic giant cells (some cases)
No glandular formation
Solid growth.
Grading Criteria:
No formal grading
Anaplastic seminoma (high mitotic rate, pleomorphism)
Presence of GCNIS
Lymphovascular invasion
Rete testis invasion.
Immunohistochemistry
Positive Markers:
OCT3/4 - positive (nuclear, sensitive/specific)
D2-40 (PODOPLANIN) - positive
CD117 - positive
Placental alkaline phosphatase - positive
SALL4 - positive
SOX17 - positive.
Negative Markers:
CD30 - negative (vs embryonal carcinoma)
Cytokeratin - negative
EMA - negative
S-100 - negative
Vimentin - negative
TTF1 - negative.
Diagnostic Utility:
OCT3/4 most useful (nuclear staining)
D2-40 highly sensitive
CD117 supports diagnosis
Negative CD30 excludes embryonal carcinoma
SALL4 germ cell marker
SOX17 specific for seminoma.
Molecular Subtypes:
Classic seminoma: OCT3/4+, D2-40+, CD117+
With syncytiotrophoblastic cells: βhCG+
All seminomas: SALL4+, SOX17+
Anaplastic: Same markers, high proliferation.
Molecular/Genetic
Genetic Mutations:
Isochromosome 12p (i(12p)) - pathognomonic
12p amplification
KIT mutations (rare)
KRAS mutations
PIK3CA mutations
Aneuploidy common.
Molecular Markers:
Chromosome 12p gain
KIT/PDGFRA pathway
PI3K/AKT pathway
p53 wild-type
DNA hypomethylation
MicroRNA-371/372/373 cluster.
Prognostic Significance:
Stage most important
Tumor size >4 cm: adverse
Rete testis invasion: intermediate risk
Lymphovascular invasion: adverse
Age >40: intermediate risk
Anaplastic: rare, poor prognosis.
Therapeutic Targets:
Radiation therapy (radiosensitive)
Platinum-based chemotherapy (BEP, EP)
Surveillance (stage I)
Immunotherapy (refractory)
High cure rates (>95%).
Differential Diagnosis
Similar Entities:
Embryonal carcinoma
Large cell lymphoma
Metastatic carcinoma
Leydig cell tumor
Spermatocytic tumor
Solid variant yolk sac tumor.
Distinguishing Features:
Seminoma: OCT3/4+, CD30-, lymphocytic infiltrate
Embryonal carcinoma: CD30+, necrosis, glandular pattern
Lymphoma: CD45+
Carcinoma: Organ-specific markers
Leydig cell: Inhibin+
Spermatocytic: Older age, OCT3/4-.
Diagnostic Challenges:
Seminoma vs embryonal carcinoma
Burned-out seminoma
Seminoma with extensive necrosis
Anaplastic seminoma
Mixed germ cell tumors.
Rare Variants:
Seminoma with syncytiotrophoblastic cells
Anaplastic seminoma
Microcystic seminoma
Tubular seminoma.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Radical orchiectomy specimen, testis measuring [X] cm
Tumor Description
Seminoma measuring [X] cm with tan-gray homogeneous cut surface
Microscopic Features
Uniform large cells with clear cytoplasm, distinct borders, and lymphocytic infiltrate. [Syncytiotrophoblastic cells present/absent]
GCNIS
Germ cell neoplasia in situ: [present/absent] in adjacent testicular parenchyma
pT Stage
pT[stage] - [staging details]
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
Immunohistochemistry
OCT3/4: Positive (nuclear), D2-40: Positive, CD30: Negative, CD117: Positive
Final Diagnosis
Seminoma, pT[stage], [size] cm, [risk stratification]