Definition/General
Introduction:
Immature teratoma is a malignant germ cell tumor containing immature embryonic tissues
It accounts for 10-20% of ovarian teratomas
Contains tissues from all three germ cell layers
Distinguished by presence of immature neuroectodermal tissue.
Origin:
Originates from totipotent germ cells with trilineage differentiation
Shows differentiation into ectoderm, mesoderm, and endoderm
Contains immature embryonic elements
Predominantly neuroectodermal components determine malignant potential.
Classification:
Graded based on immature neuroectodermal tissue quantity
Grade 1: <1 low-power field per slide
Grade 2: 1-3 low-power fields per slide
Grade 3: >3 low-power fields per slide
Mixed with mature teratoma components common.
Epidemiology:
Peak incidence in children and young adults (median age 18 years)
More common in first two decades
Unilateral in 95% cases
Better prognosis in children than adults
Indian population shows similar age distribution.
Clinical Features
Presentation:
Rapidly enlarging pelvic mass with abdominal pain
Abdominal distension and discomfort
May present with acute abdominal pain (torsion, hemorrhage)
No specific hormonal effects
Constitutional symptoms in advanced cases.
Symptoms:
Abdominal/pelvic pain (80-90%)
Palpable abdominal mass (70-80%)
Abdominal distension (60-70%)
Nausea and vomiting (40%)
Urinary frequency (pressure effects)
Acute severe pain (complications)
Weight loss (advanced disease).
Risk Factors:
Young age (children, adolescents)
Previous germ cell tumors
Family history (rare)
Gonadal dysgenesis (rare)
No established environmental factors
Genetic predisposition unclear
Reproductive age group most affected.
Screening:
Serum AFP (elevated in 50-60%)
Beta-hCG (may be elevated if choriocarcinomatous elements)
LDH (elevated, non-specific)
CA 125 (variable)
Pelvic ultrasound showing complex mass
CT/MRI for tissue characterization.
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Gross Description
Appearance:
Large, multilocular cystic mass with solid areas
Variegated cut surface with multiple tissue types
Size ranges from 10-25 cm (median 15 cm)
Hair, teeth, bone, cartilage may be visible
Soft tissue areas represent immature elements.
Characteristics:
Unilateral in 95% cases
Smooth capsule with areas of irregularity
Cut surface shows cystic and solid areas
Sebaceous material and hair
Calcified structures (teeth, bone)
Brain-like tissue (neuroectodermal areas).
Size Location:
Variable size (5-30 cm diameter)
Average size 12-20 cm
Larger than mature teratomas typically
No specific ovarian location preference
Rapid growth pattern
Surface may show nodular areas.
Multifocality:
Usually unifocal within affected ovary
Bilateral involvement rare (<5%)
Multiple cystic areas within tumor
Peritoneal implants may occur (gliomatosis peritonei)
Lymph node involvement in advanced cases.
Microscopic Description
Histological Features:
Mature and immature tissues from all three germ layers
Immature neuroectodermal tissue (primitive neural tubes, rosettes)
Mature elements (skin, hair, teeth, cartilage, bone)
Embryonic mesenchyme
Immature glandular structures.
Cellular Characteristics:
Immature areas show primitive small cells with high nuclear-cytoplasmic ratio
Hyperchromatic nuclei with prominent nucleoli
High mitotic activity in immature areas
Primitive neural rosettes
Mature areas show well-differentiated tissues.
Architectural Patterns:
Neural tube formation (primitive)
Rosette patterns (Homer Wright, Flexner-Wintersteiner)
Immature glandular structures
Primitive mesenchymal tissue
Well-formed mature tissues (skin, cartilage, bone, teeth).
Grading Criteria:
Based on immature neuroectodermal tissue quantity per slide
Grade 1: Rare immature foci (<1 LPF/slide)
Grade 2: 1-3 low-power fields/slide
Grade 3: >3 low-power fields/slide
Only neuroectodermal tissue counted for grading.
Immunohistochemistry
Positive Markers:
SALL4 (germ cell origin, 90-95%)
AFP (if yolk sac elements present)
Neural markers (synaptophysin, neurofilament in neural areas)
Cytokeratin (epithelial components)
Vimentin (mesenchymal areas)
Glial markers (GFAP in glial tissue).
Negative Markers:
OCT4 (negative, unlike dysgerminoma)
CD117 (negative)
Inhibin (negative)
Calretinin (negative)
PLAP (usually negative)
Beta-hCG (negative unless trophoblastic elements)
EMA (variable).
Diagnostic Utility:
Tissue-specific markers confirm differentiation
SALL4 confirms germ cell origin
Neural markers identify immature neuroectodermal tissue
AFP if yolk sac component present
Cytokeratin patterns vary by tissue type.
Molecular Subtypes:
Isochromosome 12p i(12p) (70-80%)
KRAS mutations (20-30%)
PIK3CA mutations (15-25%)
TP53 mutations (higher grade tumors)
PTEN loss
Chromosomal instability common.
Molecular/Genetic
Genetic Mutations:
Isochromosome 12p i(12p) (70-80%)
KRAS mutations
PIK3CA mutations
TP53 mutations (grade-dependent)
PTEN deletions
BRAF mutations (rare)
Chromosomal gains and losses.
Molecular Markers:
SALL4 overexpression
Neural differentiation markers
Tissue-specific protein expression
p53 accumulation (high-grade)
Ki-67 proliferation index variable
Chromosomal instability markers.
Prognostic Significance:
Grade most important prognostic factor
Age (better prognosis in children)
Stage at presentation
Completeness of resection
Response to chemotherapy
i(12p) associated with chemosensitivity.
Therapeutic Targets:
Platinum-based chemotherapy (cisplatin, carboplatin)
Bleomycin, etoposide, cisplatin (BEP)
Vincristine, actinomycin D, cyclophosphamide (VAC)
Surgery (complete resection)
Fertility-sparing approaches (young patients).
Differential Diagnosis
Similar Entities:
Mature teratoma (no immature elements)
Yolk sac tumor (AFP positive, different morphology)
Embryonal carcinoma (CD30 positive)
Mixed germ cell tumor
Primitive neuroectodermal tumor (pure neural).
Distinguishing Features:
Immature teratoma: Mixed mature and immature elements
Graded by neural tissue
Mature teratoma: Only mature tissues
No immature neural elements
Yolk sac: AFP positive
Reticular pattern
Embryonal: CD30 positive
Primitive morphology
PNET: Pure neural tumor.
Diagnostic Challenges:
Distinguishing mature from immature elements
Grading accuracy (neural tissue quantification)
Identifying mixed germ cell components
Peritoneal implants assessment
Recurrence vs new primary
Sampling adequacy important.
Rare Variants:
Immature teratoma with yolk sac tumor
Immature teratoma with embryonal carcinoma
Solid immature teratoma
Predominantly neural immature teratoma
Growing teratoma syndrome
Malignant transformation in mature areas.
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
Immature Teratoma, Grade [1/2/3]
Classification
WHO Classification: Germ Cell Tumor, Immature Teratoma
Histological Features
Shows mature and immature tissues from all three germ layers with [amount] of immature neuroectodermal tissue
Grading
Grade [1/2/3] based on [X] low-power fields of immature neuroectodermal tissue per slide
Tissue Components
Mature: [list tissues], Immature: [list tissues]
Special Studies
IHC: SALL4 [positive/negative], Neural markers [positive in neural areas]
Serum: AFP [X] ng/mL, hCG [X] mIU/mL
Other studies: [specify if performed]
Prognostic Factors
Grade: [1/2/3], Age: [X] years, Stage: [I/II/III/IV], Size: [X] cm
Final Diagnosis
Ovarian Immature Teratoma, Grade [1/2/3], [Stage], [Side]