Definition/General
Introduction:
Yolk sac tumor is a highly malignant non-gestational germ cell tumor of the ovary
It accounts for 15-20% of malignant ovarian germ cell tumors
Also known as endodermal sinus tumor
It demonstrates rapid growth and early metastasis.
Origin:
Originates from extraembryonic endoderm of the yolk sac
Recapitulates the primitive yolk sac development
Shows differentiation toward endodermal structures
Produces alpha-fetoprotein (AFP) like normal yolk sac.
Classification:
Pure yolk sac tumor (30-40%)
Mixed germ cell tumors with yolk sac component (60-70%)
Reticular pattern (most common)
Endodermal sinus pattern
Solid pattern
Macrocystic pattern
Myxomatous pattern.
Epidemiology:
Peak incidence in children and young adults (median age 19 years)
Second most common malignant germ cell tumor
Unilateral in 95% cases
Aggressive behavior with rapid growth
Poor prognosis if untreated
Indian population shows similar patterns.
Clinical Features
Presentation:
Rapidly enlarging abdominal mass with pain
Abdominal distension and discomfort
Markedly elevated AFP levels
Constitutional symptoms (weight loss, fatigue)
Acute abdominal pain (hemorrhage, torsion)
Advanced disease at presentation common.
Symptoms:
Abdominal/pelvic pain (90-95%)
Palpable mass (85-90%)
Abdominal distension (75-80%)
Nausea and vomiting (60%)
Constitutional symptoms (40%)
Abnormal uterine bleeding (25%)
Urinary symptoms (pressure effects).
Risk Factors:
Young age (children, adolescents, young adults)
Previous germ cell tumors
Family history (rare)
Gonadal dysgenesis (rare association)
Intersex disorders
No established environmental factors
Genetic predisposition (unclear).
Screening:
Serum AFP (markedly elevated >1000 ng/mL)
Beta-hCG (normal unless mixed tumor)
LDH (elevated, non-specific)
CA 125 (may be elevated)
Pelvic ultrasound showing complex mass
CT/MRI for staging and metastases.
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Gross Description
Appearance:
Large, solid and cystic mass with irregular surface
Gray-yellow to hemorrhagic cut surface
Size ranges from 8-25 cm (median 15 cm)
Soft to gelatinous consistency
Extensive hemorrhage and necrosis common.
Characteristics:
Unilateral in 95% cases
Partially cystic with solid nodules
Cut surface shows variegated appearance
Mucoid areas prominent
Hemorrhagic foci throughout
Friable consistency
Capsular breach common.
Size Location:
Variable size (5-30 cm diameter)
Average size 12-20 cm
Larger than typical ovarian tumors
No specific ovarian location preference
Rapid growth pattern
Surface irregularities common
Ascites frequently present.
Multifocality:
Usually unifocal within affected ovary
Bilateral involvement rare (<5%)
Multiple cystic and solid areas within tumor
Peritoneal implants common at presentation
Omental involvement frequent
Lymph node metastases possible.
Microscopic Description
Histological Features:
Schiller-Duval bodies (pathognomonic when present)
Reticular pattern with microcystic spaces
Endodermal sinus pattern
Papillary structures with central vessels
Eosinophilic hyaline globules (AFP positive).
Cellular Characteristics:
Primitive cells with hyperchromatic nuclei
Scant to moderate cytoplasm
High nuclear-cytoplasmic ratio
Prominent nucleoli
High mitotic activity
Pleomorphic appearance
Clear to eosinophilic cytoplasm.
Architectural Patterns:
Reticular/microcystic pattern (most common)
Endodermal sinus pattern
Solid pattern
Papillary pattern
Glandular pattern
Myxomatous pattern
Macrocystic pattern
Mixed patterns common.
Grading Criteria:
Yolk sac tumor is inherently high-grade
High mitotic rate (>10/10 HPF)
Marked nuclear pleomorphism
Necrosis frequently present
Vascular invasion common
Lymphatic invasion
No formal grading system used.
Immunohistochemistry
Positive Markers:
Alpha-fetoprotein (AFP) 95-100%
SALL4 90-95%
Glypican-3 85-90%
CK8/18 80-85%
Vimentin 70-80%
CDX2 (focal)
PLAP (weak, focal)
EMA (focal).
Negative Markers:
OCT4 (negative, unlike dysgerminoma)
CD117 (negative)
Beta-hCG (negative)
Inhibin (negative)
Calretinin (negative)
WT1 (negative)
CD30 (negative)
S-100 (negative).
Diagnostic Utility:
Essential for yolk sac tumor diagnosis
AFP positivity diagnostic
SALL4 confirms germ cell origin
Distinguish from other germ cell tumors
Glypican-3 supports diagnosis
OCT4 negative excludes dysgerminoma.
Molecular Subtypes:
Isochromosome 12p i(12p) (60-70%)
KRAS mutations (20-30%)
PIK3CA mutations (15-20%)
TP53 mutations (10-15%)
CTNNB1 mutations (rare)
Chromosomal instability common.
Molecular/Genetic
Genetic Mutations:
Isochromosome 12p i(12p) (60-70%)
KRAS mutations (exons 2, 3)
PIK3CA mutations
TP53 mutations
PTEN loss
BRAF mutations (rare)
Chromosomal amplifications (MYC, CCND1).
Molecular Markers:
AFP overexpression (diagnostic)
SALL4 expression
Glypican-3 expression
MYC amplification
CCND1 amplification
p53 accumulation
Telomerase activation.
Prognostic Significance:
Stage at presentation most important factor
AFP levels correlate with tumor burden
Complete AFP normalization indicates treatment response
i(12p) associated with chemosensitivity
Age (younger patients better prognosis).
Therapeutic Targets:
Platinum-based chemotherapy (cisplatin)
Bleomycin, etoposide, cisplatin (BEP)
Vincristine, actinomycin D, cyclophosphamide (VAC)
High-dose chemotherapy (refractory cases)
mTOR inhibitors (experimental)
Immunotherapy (investigational).
Differential Diagnosis
Similar Entities:
Clear cell carcinoma (epithelial, different IHC pattern)
Embryonal carcinoma (CD30 positive, different morphology)
Dysgerminoma (OCT4 positive, AFP negative)
Juvenile granulosa cell tumor (inhibin positive)
Hepatoid carcinoma (rare, different location).
Distinguishing Features:
Yolk sac tumor: AFP positive
Schiller-Duval bodies
Reticular pattern
Clear cell carcinoma: CK7 positive
Hobnail cells
Embryonal: CD30 positive
Primitive morphology
Dysgerminoma: OCT4 positive
Uniform cells
Granulosa: Inhibin positive
Coffee-bean nuclei.
Diagnostic Challenges:
Distinguishing from other germ cell tumors
Identifying mixed components
Schiller-Duval bodies may be rare
Differentiating from clear cell carcinoma
Pattern recognition in poorly differentiated areas
AFP correlation essential.
Rare Variants:
Hepatoid yolk sac tumor (liver-like pattern)
Enteric yolk sac tumor (intestinal differentiation)
Parietal yolk sac tumor
Mixed yolk sac-embryonal tumor
Yolk sac tumor with teratomatous elements
Polyembryoma (rare).
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
Ovarian mass, [side], measuring [X x Y x Z] cm, weighing [X] grams
Diagnosis
Yolk Sac Tumor (Endodermal Sinus Tumor), [Pure/Mixed with other elements]
Classification
WHO Classification: Germ Cell Tumor, Yolk Sac Tumor
Histological Features
Shows [pattern] with [presence/absence] of Schiller-Duval bodies and hyaline globules
Architectural Patterns
Predominant pattern: [reticular/endodermal sinus/solid/other], [X]% of tumor
Special Studies
IHC: AFP [strongly positive], SALL4 [positive/negative], Glypican-3 [positive/negative]
Serum AFP: [X] ng/mL (normal <10 ng/mL)
Other markers: [specify results]
Prognostic Factors
Stage: [I/II/III/IV], AFP level: [X] ng/mL, Age: [X] years, Size: [X] cm
Final Diagnosis
Ovarian Yolk Sac Tumor, [Stage], [Side]