Definition/General
Introduction:
Dysgerminoma is the most common malignant germ cell tumor of the ovary
It accounts for 1-2% of all ovarian malignancies
It is the female counterpart of testicular seminoma
It demonstrates excellent prognosis with appropriate treatment.
Origin:
Originates from primordial germ cells that migrate to the developing gonad
These cells retain their primitive characteristics
The tumor recapitulates the early germ cell phenotype
It shows totipotential differentiation capacity.
Classification:
Pure dysgerminoma (80-90%)
Mixed germ cell tumors with dysgerminomatous component
Dysgerminoma with syncytiotrophoblast giant cells (5-10%)
Anaplastic dysgerminoma (rare)
WHO classification: Germ cell tumor, dysgerminoma.
Epidemiology:
Peak incidence in 2nd-3rd decades (median age 22 years)
Accounts for 50% of malignant germ cell tumors
Bilateral in 10-15% cases
Associated with gonadal dysgenesis (Y chromosome)
Higher incidence in Asian populations.
Clinical Features
Presentation:
Rapidly enlarging pelvic mass with abdominal pain
Abdominal distension and discomfort
Menstrual irregularities
Acute abdominal pain (torsion)
No hormonal effects (unlike other germ cell tumors)
Constitutional symptoms (rare).
Symptoms:
Abdominal/pelvic pain (85-90%)
Abdominal mass (75-80%)
Abdominal distension (60-70%)
Nausea and vomiting
Acute pain (ovarian torsion)
Weight loss (advanced cases)
Normal menstrual cycles typically.
Risk Factors:
Gonadal dysgenesis (especially 46,XY DSD)
Y chromosome material
Previous gonadal tumors
Family history (rare)
Intersex disorders
Infertility (association unclear)
Age (young reproductive years).
Screening:
Serum LDH (elevated, non-specific)
PLAP (placental alkaline phosphatase)
Beta-hCG (if syncytiotrophoblast present)
Alpha-fetoprotein (normal in pure dysgerminoma)
Pelvic ultrasound
CT/MRI for staging.
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Gross Description
Appearance:
Large, solid, bosselated mass with smooth capsule
Gray-pink to tan cut surface
Size ranges from 5-30 cm (median 15 cm)
Soft to firm consistency
Hemorrhage and necrosis may be present.
Characteristics:
Unilateral in 85-90% cases
Bilateral in 10-15% (higher than other ovarian tumors)
Encapsulated appearance
Cut surface shows solid gray-white areas
Fleshy consistency
Areas of hemorrhage common.
Size Location:
Variable size (3-40 cm diameter)
Average size 12-18 cm
Larger than benign teratomas
No specific ovarian location preference
Capsular integrity usually maintained
Surface may show lobulations.
Multifocality:
Usually unifocal within affected ovary
Bilateral involvement more common than other ovarian cancers
Multiple nodules may be present
Capsular breach indicates advanced disease
Peritoneal implants in advanced cases.
Microscopic Description
Histological Features:
Sheets of large uniform cells with clear cytoplasm
Prominent lymphocytic infiltrate in stroma
Granulomatous reaction may be present
Fibrous septa divide tumor into lobules
Syncytiotrophoblast giant cells (5-10% cases).
Cellular Characteristics:
Large cells with clear to pale eosinophilic cytoplasm
Distinct cell borders
Large, round to oval nuclei
Prominent nucleoli
Variable mitotic activity
Glycogen-rich cytoplasm (PAS positive).
Architectural Patterns:
Solid sheets and nests separated by fibrous septa
Lymphocytic infiltration throughout stroma
Granulomatous inflammation with epithelioid cells
Multinucleated giant cells
Vascular invasion may be present.
Grading Criteria:
Dysgerminoma is not routinely graded
Anaplastic variant shows high-grade features
Increased nuclear pleomorphism
High mitotic rate (>20/10 HPF)
Necrosis and vascular invasion
Loss of lymphocytic response.
Immunohistochemistry
Positive Markers:
PLAP (placental alkaline phosphatase) 95-100%
CD117 (c-kit) 85-95%
OCT4 90-95%
NANOG 80-90%
SALL4 90-95%
Vimentin
D2-40 (podoplanin)
CD30 (variable).
Negative Markers:
Alpha-fetoprotein (negative)
Beta-hCG (negative except syncytiotrophoblast)
Cytokeratin (usually negative)
EMA (negative)
Inhibin (negative)
Calretinin (negative)
WT1 (negative).
Diagnostic Utility:
Essential for germ cell tumor confirmation
PLAP and CD117 highly specific
OCT4 positivity confirms primitive germ cell origin
Distinguish from other germ cell tumors
Negative AFP excludes yolk sac tumor component.
Molecular Subtypes:
KIT mutations (15-20% cases)
Isochromosome 12p i(12p) (80% cases)
KRAS mutations (rare)
PIK3CA pathway alterations
mTOR pathway activation
p53 mutations (anaplastic variant).
Molecular/Genetic
Genetic Mutations:
Isochromosome 12p i(12p) (80%)
KIT mutations (exons 13, 17)
KRAS mutations (10-15%)
PIK3CA mutations
BRAF mutations (rare)
TP53 mutations (anaplastic)
Chromosomal instability (advanced cases).
Molecular Markers:
KIT protein overexpression
OCT4 expression (pluripotency marker)
NANOG expression
SALL4 overexpression
Telomerase activity increased
p53 accumulation (anaplastic cases).
Prognostic Significance:
Stage at presentation most important factor
Pure dysgerminoma better prognosis than mixed tumors
Bilateral disease does not worsen prognosis
KIT mutations may predict imatinib response
i(12p) associated with chemosensitivity.
Therapeutic Targets:
Platinum-based chemotherapy (cisplatin, carboplatin)
Bleomycin, etoposide, cisplatin (BEP)
KIT inhibitors (imatinib) for KIT-mutated cases
mTOR inhibitors (experimental)
Immunotherapy (checkpoint inhibitors)
Fertility-sparing surgery.
Differential Diagnosis
Similar Entities:
Clear cell carcinoma (epithelial origin, different IHC)
Embryonal carcinoma (more pleomorphic, CD30 positive)
Yolk sac tumor (AFP positive, different patterns)
Large cell lymphoma (lymphoid markers)
Granulosa cell tumor (sex cord markers).
Distinguishing Features:
Dysgerminoma: PLAP and CD117 positive
Uniform cells
Lymphocytic infiltrate
Clear cell carcinoma: CK7 positive
Hobnail cells
Embryonal: CD30 positive
High-grade morphology
Yolk sac: AFP positive
Schiller-Duval bodies
Lymphoma: CD45 positive
Lymphoid morphology.
Diagnostic Challenges:
Distinguishing from other germ cell tumors
Identifying mixed components
Syncytiotrophoblast giant cells significance
Differentiating from lymphoma
Anaplastic variant recognition
Bilateral vs unilateral assessment.
Rare Variants:
Anaplastic dysgerminoma (high-grade features)
Dysgerminoma with syncytiotrophoblast
Mixed germ cell tumor with dysgerminoma
Bilateral dysgerminoma
Dysgerminoma in gonadal dysgenesis
Recurrent dysgerminoma.
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/bilateral], measuring [X x Y x Z] cm, weighing [X] grams
Diagnosis
Dysgerminoma, [Pure/Mixed with other germ cell elements]
Classification
WHO Classification: Germ Cell Tumor, Dysgerminoma
Histological Features
Shows sheets of uniform large cells with clear cytoplasm and prominent lymphocytic infiltrate
Tumor Composition
[Pure dysgerminoma/Mixed with X% other elements], [presence/absence] of syncytiotrophoblast
Special Studies
IHC: PLAP [positive/negative], CD117 [positive/negative], OCT4 [positive/negative], AFP [negative]
Serum: LDH [X] IU/L, hCG [X] mIU/mL, AFP [normal]
Molecular: [if performed]
Prognostic Factors
Stage: [I/II/III/IV], Laterality: [Unilateral/Bilateral], Size: [X] cm, Capsule: [intact/breached]
Final Diagnosis
Ovarian Dysgerminoma, [Stage], [Unilateral/Bilateral]