Definition/General
Introduction:
NSGCT represents diverse group of testicular germ cell tumors
Comprises 60% of testicular GCTs
More aggressive than seminoma
Contains multiple histologic components
Shows earlier metastases.
Origin:
Arises from primordial germ cells
Shows pluripotential differentiation
Embryonic and extraembryonic patterns
Associated with GCNIS (germ cell neoplasia in situ).
Classification:
WHO 2016: Embryonal carcinoma
Yolk sac tumor
Choriocarcinoma
Teratoma (mature/immature)
Mixed NSGCT
Combined with seminoma.
Epidemiology:
Peak incidence 2nd-3rd decades
Earlier than seminoma
Caucasian predominance
Associated with cryptorchidism
Testicular dysgenesis syndrome.
Clinical Features
Presentation:
Testicular mass
Pain/discomfort (30%)
Testicular swelling
Gynecomastia (β-hCG elevation)
Metastatic symptoms
Back pain (retroperitoneal nodes).
Symptoms:
Scrotal mass
Testicular heaviness
Acute pain (hemorrhage/necrosis)
Abdominal pain
Supraclavicular lymphadenopathy
Shortness of breath (pulmonary metastases).
Risk Factors:
Cryptorchidism
Family history
Testicular dysgenesis
Klinefelter syndrome
Previous GCT
Infertility.
Screening:
Testicular examination
Tumor markers: AFP, β-hCG, LDH
Scrotal ultrasound
CT chest/abdomen/pelvis
Brain MRI (choriocarcinoma).
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Gross Description
Appearance:
Variegated appearance
Soft to firm
Hemorrhage and necrosis
Cystic areas (teratoma)
Solid nodules
Replace testicular parenchyma.
Characteristics:
Heterogeneous cut surface
Multiple colors
Soft friable areas
Firm nodules
Extensive necrosis
Cartilage/bone (teratoma).
Size Location:
Variable size (1-15 cm)
Replace testicular parenchyma
Extension to epididymis
Spermatic cord involvement
Scrotal extension rare.
Multifocality:
Usually unifocal
Adjacent GCNIS
Bilateral GCT (5%)
Scar formation (post-chemotherapy)
Burned-out tumor.
Microscopic Description
Histological Features:
Multiple histologic patterns
Embryonal carcinoma: Large pleomorphic cells
Yolk sac tumor: Schiller-Duval bodies
Choriocarcinoma: Syncytiotrophoblast and cytotrophoblast
Teratoma: Mature/immature tissues.
Cellular Characteristics:
Embryonal carcinoma: Large cells, prominent nucleoli
Yolk sac: Reticular pattern, hyaline globules
Choriocarcinoma: Dimorphic population
Teratoma: Differentiated tissues.
Architectural Patterns:
Solid sheets (embryonal)
Glandular/papillary (yolk sac)
Biphasic pattern (choriocarcinoma)
Organoid structures (teratoma)
Mixed patterns.
Grading Criteria:
No formal grading
Component assessment important
Immature teratoma: Neural elements
High-grade features in embryonal carcinoma.
Immunohistochemistry
Positive Markers:
Embryonal carcinoma: CD30+, OCT4+
Yolk sac tumor: AFP+, Glypican-3+
Choriocarcinoma: β-hCG+, inhibin+
Teratoma: Tissue-specific markers.
Negative Markers:
PLAP - variable
CD117 - negative (vs seminoma)
D2-40 - negative.
Diagnostic Utility:
Component identification critical
OCT4 distinguishes embryonal carcinoma
AFP specific for yolk sac
β-hCG for choriocarcinoma
Lineage markers for teratoma.
Molecular Subtypes:
Embryonal carcinoma: OCT4+, CD30+
Yolk sac tumor: AFP+, SALL4+
Choriocarcinoma: hCG+, syncytiotrophoblast
Mixed NSGCT: Multiple markers.
Molecular/Genetic
Genetic Mutations:
Isochromosome 12p (80%)
12p amplification
KIT mutations
KRAS mutations
PIK3CA mutations
TP53 mutations (teratoma).
Molecular Markers:
12p gain (CCND2, KRAS)
Pluripotency factors (OCT4, NANOG)
DNA hypomethylation
Chromosomal instability.
Prognostic Significance:
Stage most important
Tumor markers (AFP, hCG)
Histologic components
Vascular invasion
Risk stratification (good/intermediate/poor).
Therapeutic Targets:
Platinum-based chemotherapy (BEP/EP)
Surgical resection
Retroperitoneal lymph node dissection
High-dose chemotherapy (refractory)
Salvage surgery.
Differential Diagnosis
Similar Entities:
Seminoma
Sex cord-stromal tumors
Lymphoma
Metastatic carcinoma
Spermatocytic tumor.
Distinguishing Features:
NSGCT: Diverse morphology, AFP/hCG+
Seminoma: Uniform cells, OCT4+, PLAP+
Sex cord: Inhibin+, Calretinin+
Lymphoma: CD45+
Metastatic: Organ-specific markers.
Diagnostic Challenges:
Mixed components
Post-chemotherapy changes
Burned-out GCT
Sampling adequacy
Component quantification.
Rare Variants:
Polyembryoma
Diffuse embryoma
Teratoma with malignant transformation
Growing teratoma syndrome.
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 with tumor
Tumor Description
Mixed non-seminomatous germ cell tumor measuring [X] cm
Histologic Components
Components: [Embryonal carcinoma ([%]), Yolk sac tumor ([%]), Teratoma ([%]), Choriocarcinoma ([%])]
Vascular Invasion
Lymphovascular invasion: [present/absent]
Rete Testis
Rete testis invasion: [present/absent]
Spermatic Cord
Spermatic cord involvement: [present/absent]
pT Stage
pT[stage] - [staging details]
GCNIS
Germ cell neoplasia in situ (GCNIS): [present/absent] in adjacent testicular parenchyma
Immunohistochemistry
OCT4: [Positive in embryonal carcinoma], AFP: [Positive in yolk sac tumor], β-hCG: [Positive in choriocarcinoma]
Tumor Markers
Correlate with serum AFP and β-hCG levels
Final Diagnosis
Mixed non-seminomatous germ cell tumor, pT[stage]