Definition/General
Introduction:
Ovarian germ cell tumors (GCT) represent neoplasms derived from primordial germ cells of the developing ovary
They constitute 15-20% of all ovarian tumors and 60-70% of ovarian tumors in patients under 20 years
These tumors recapitulate various stages of embryonic development
They range from benign mature teratomas to highly malignant subtypes.
Origin:
Originate from primordial germ cells that migrate from the yolk sac to the developing gonad
These cells normally differentiate into oogonia and eventually mature oocytes
Neoplastic transformation can occur at various stages of germ cell development
Tumors may show totipotential differentiation into embryonic and extraembryonic tissues
Some retain primitive characteristics while others show mature differentiation.
Classification:
Classified based on WHO 2020 guidelines
Primitive GCTs: Dysgerminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma
Biphasic/Triphasic GCTs: Immature teratoma, mixed GCT
Mature GCTs: Mature teratoma (dermoid cyst), monodermal teratomas
Mixed forms contain multiple GCT components.
Epidemiology:
Peak incidence in children and young adults (10-30 years)
Dysgerminoma peak in 2nd-3rd decades
Yolk sac tumor in infants and children
Immature teratoma in adolescents and young adults
Mature teratoma in reproductive age
Indian population shows similar age distribution with slightly earlier presentation.
Clinical Features
Presentation:
Rapidly growing pelvic mass (characteristic of malignant GCTs)
Abdominal pain and distension
Acute abdomen due to torsion or rupture
Precocious puberty (hormone-producing tumors)
Amenorrhea or irregular bleeding
Mass effect symptoms
Emergency presentation with ovarian torsion common.
Symptoms:
Abdominal pain (acute or chronic)
Rapid abdominal distension
Nausea and vomiting
Urinary frequency
Constipation
Early satiety
Hormonal symptoms (hCG-producing tumors)
Respiratory symptoms (large masses)
Weight loss (malignant cases).
Risk Factors:
Young age (most important risk factor)
Gonadal dysgenesis (increased dysgerminoma risk)
Turner syndrome with Y chromosome
Previous germ cell tumor
Family history (rare)
Genetic syndromes (rare associations)
Cryptorchidism in males (not applicable to ovary).
Screening:
No routine screening protocols
Pelvic examination in symptomatic patients
Tumor markers: AFP (yolk sac tumor, immature teratoma), hCG (choriocarcinoma, embryonal carcinoma), LDH (dysgerminoma)
Imaging studies: Ultrasound, CT, MRI
Age-appropriate evaluation in pediatric patients.
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Gross Description
Appearance:
Variable size from 5-40 cm in diameter
Unilateral in majority of cases (90-95%)
Solid, cystic, or mixed appearance depending on subtype
Dysgerminoma: Gray-pink, solid, lobulated
Teratoma: Multilocular cystic with hair, teeth, sebaceous material
Yolk sac tumor: Gray-yellow, solid-cystic, hemorrhagic.
Characteristics:
Mature teratoma: Cystic with hair, teeth, cartilage, sebaceous material
Immature teratoma: Solid areas mixed with cystic components
Dysgerminoma: Solid, gray-pink, fish-flesh appearance
Yolk sac tumor: Gelatinous, hemorrhagic, necrotic areas
Mixed GCT: Heterogeneous appearance with multiple tissue types.
Size Location:
Size varies from microscopic to >40 cm
Unilateral involvement in 90-95% cases
Bilateral occurrence: Dysgerminoma (10-15%), mature teratoma (10-15%), other GCTs (<5%)
Right ovary slightly more commonly affected
Large size common due to rapid growth.
Multifocality:
Bilateral disease more common in certain subtypes
Dysgerminoma: 10-15% bilateral
Mature teratoma: 10-15% bilateral
Yolk sac tumor: rarely bilateral
Multifocal involvement within same ovary possible
Peritoneal spread in malignant cases
Lymph node involvement (dysgerminoma).
Microscopic Description
Histological Features:
Dysgerminoma: Uniform large cells with clear cytoplasm, prominent nucleoli, lymphocytic infiltrate
Yolk sac tumor: Schiller-Duval bodies, microcystic pattern, primitive epithelium
Immature teratoma: Immature neural tissue, primitive mesenchyme
Mature teratoma: Mature tissues from all three germ layers
Embryonal carcinoma: Large pleomorphic cells, high mitotic rate.
Cellular Characteristics:
Cell morphology varies dramatically by subtype
Dysgerminoma cells: Large, round, clear cytoplasm, prominent nucleoli
Yolk sac tumor cells: Primitive appearance, high N:C ratio, pleomorphic
Teratoma: Multiple cell types representing different tissues
Trophoblastic elements: Syncytiotrophoblasts, cytotrophoblasts
High mitotic activity in malignant forms.
Architectural Patterns:
Dysgerminoma pattern: Solid nests with fibrous septa and lymphocytes
Yolk sac pattern: Reticular, microcystic, solid, papillary, glandular patterns
Teratoma pattern: Organized tissue structures (skin, brain, cartilage)
Embryonal pattern: Solid sheets and glandular structures
Mixed patterns common in combined tumors.
Grading Criteria:
Immature teratoma grading: Grade 0 (mature), Grade 1 (minimal immature neural), Grade 2 (moderate immature neural), Grade 3 (abundant immature neural)
Other GCTs: Generally not graded but classified by differentiation
Mature teratoma: Benign by definition
Malignant transformation in mature teratoma (rare).
Immunohistochemistry
Positive Markers:
OCT4 (primitive germ cell marker, positive in dysgerminoma, embryonal carcinoma)
NANOG (pluripotency marker)
CD117 (dysgerminoma)
PLAP (placental alkaline phosphatase)
AFP (yolk sac tumor, immature teratoma)
hCG (choriocarcinoma, syncytiotrophoblasts)
SALL4 (broad germ cell marker).
Negative Markers:
Cytokeratins (usually negative except in teratomatous epithelium)
EMA (epithelial membrane antigen)
Inhibin (sex cord-stromal tumors)
Calretinin (sex cord-stromal tumors)
CD45 (lymphoma)
S-100 (melanoma, nerve sheath tumors)
Chromogranin (neuroendocrine, except in teratoma).
Diagnostic Utility:
OCT4 and NANOG identify primitive germ cell tumors
CD117 specific for dysgerminoma among ovarian tumors
SALL4 broad marker for germ cell differentiation
AFP immunostaining correlates with serum levels
Panel approach essential for mixed tumors
Helps distinguish from somatic tumors.
Molecular Subtypes:
Isochromosome 12p [i(12p)] common in malignant GCTs
KIT mutations in dysgerminoma (rare)
KRAS mutations in mature teratoma
TP53 mutations associated with malignant transformation
Microsatellite instability (rare)
Chromosome 12 abnormalities characteristic.
Molecular/Genetic
Genetic Mutations:
Isochromosome 12p [i(12p)] in 80% of malignant GCTs
KIT mutations (dysgerminoma, 25%)
KRAS mutations (mature teratoma, 50%)
TP53 mutations (malignant transformation in teratoma)
PIK3CA mutations (teratoma, 20%)
ARID1A mutations (clear cell carcinoma arising in teratoma)
Chromosome 12 gain common.
Molecular Markers:
12p amplification (oncogenes CCND2, MDM2)
OCT4 expression (primitive germ cells)
NANOG expression (pluripotency)
SOX2 expression (embryonic stem cells)
LIN28 expression (germ cell tumors)
miR-302 cluster (pluripotency-associated)
Telomerase activity (malignant GCTs).
Prognostic Significance:
Stage most important prognostic factor
Histological subtype determines behavior
i(12p) associated with cisplatin sensitivity
Immature teratoma grade correlates with outcome
Mixed histology follows most malignant component
Age influences prognosis (better in children)
Tumor markers guide treatment response.
Therapeutic Targets:
Cisplatin-based chemotherapy (BEP, EP regimens)
KIT inhibitors (imatinib for KIT-mutated dysgerminoma)
mTOR pathway (potential target)
PARP inhibitors (BRCA-deficient cases)
Immunotherapy (PD-1/PD-L1 inhibitors under study)
Targeted therapy based on molecular profiling.
Differential Diagnosis
Similar Entities:
Sex cord-stromal tumors (especially in young patients)
Epithelial ovarian tumors (clear cell carcinoma)
Metastatic tumors (gastrointestinal, breast)
Lymphoma (especially in pediatric patients)
Small round blue cell tumors (Ewing sarcoma, rhabdomyosarcoma)
Krukenberg tumor (metastatic signet ring cell carcinoma).
Distinguishing Features:
GCT: OCT4, NANOG, SALL4 positive
GCT: Young age predilection
GCT: Elevated tumor markers (AFP, hCG)
Sex cord-stromal: Inhibin, calretinin positive
Epithelial: Cytokeratin strongly positive
Lymphoma: CD45 positive
Metastases: Clinical history and organ-specific markers
Small round blue cell: Specific translocations.
Diagnostic Challenges:
Distinguishing primitive GCT subtypes in mixed tumors
Immature teratoma grading (neural tissue quantification)
Mature teratoma with malignant transformation
Yolk sac tumor vs clear cell carcinoma in young patients
Dysgerminoma vs lymphoma
Immunohistochemistry and molecular studies essential.
Rare Variants:
Polyembryoma (multiple embryoid bodies)
Choriocarcinoma (pure ovarian, very rare)
Mixed malignant germ cell tumor
Mature teratoma with malignant transformation
Struma ovarii (thyroid tissue in teratoma)
Carcinoid tumor (arising in teratoma)
Sarcoma (arising in teratoma).
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 specimen, [left/right/bilateral], measuring [size] cm
Diagnosis
Ovarian germ cell tumor, [specific subtype]
Classification
WHO 2020: [specific subtype], [grade if immature teratoma]
Histological Features
Shows [specific morphological features] consistent with [subtype]
Size and Extent
Size: [X] cm, [confined/extends beyond ovary]
Surface and Capsule
Surface involvement: [present/absent], capsular rupture: [present/absent]
Special Studies
IHC: OCT4 [+/-], SALL4 [+/-], CD117 [+/-], AFP [+/-]
Serum markers: AFP [level], hCG [level], LDH [level]
Molecular: [test performed]: [result]
Staging
FIGO Stage: [stage], TNM: [classification]
Prognostic Factors
Stage: [stage], Subtype: [subtype], Size: [size], Age: [age]
Final Diagnosis
Ovarian germ cell tumor, [complete subtype and grade]